Therapeutic potential of Abelmoschus manihot: mechanisms of action and clinical use in traditional Chinese medicine formulas

Abstract

Abelmoschus manihot (L.) Medicus (AM), commonly known as Huangshukui in China, is a traditional medicinal herb. Its flowers serve as the primary active component of Huangkui Capsule (HKC), which has demonstrated therapeutic potential in various conditions such as chronic kidney disease (CKD), inflammatory bowel disease (IBD), ischemic cardiac/cerebral injuries, hepatic injury, and diabetes mellitus. In order to reveal that AM has extensive clinical applications and significant development value, this paper collates the pharmacological effects of AM and the clinical data of traditional Chinese medicine (TCM) formulations containing AM. This review aims to systematically summarize the pharmacological effects and clinical applications of AM, with a focus on its underlying mechanisms—including immunomodulation, antifibrotic activity, metabolic regulation, intestinal flora modulation, organ protection, antioxidant effects, and analgesia. Although most clinical data currently center on HKC, this article also examines other TCM formulations containing AM, such as Jiahua Tablets, Chuangling Liquid, Huangkui Lianchang Decoction, Huangkui Siwu Formula, Yu Kui Qing, Qikui Granules, Huangshukui paste, and Er Huang Ointment. By consolidating current evidence on the pharmacology and clinical use of AM, this review highlights its broad therapeutic potential and promote further research and development of AM-based treatments.

1 Introduction

Abelmoschus manihot (L.) Medicus (AM), known as Huangshukui in Chinese, is a versatile herbaceous plant of the Malvaceae family (Abelmoschus genus) with significant medicinal and edible value (Hong et al., 2021). Its therapeutic importance is well-established both in history and in modern medicine. Ancient Chinese medical books, such as Jiayou Materia Medica and the Compendium of Materia Medica, document AM’s use for treating conditions like carbuncles, toxic swellings, and scalds (Liu et al., 2023; Xue et al., 2023). The 2020 edition of the Pharmacopoeia of the People’s Republic of China (Chinese Pharmacopoeia) formally recognizes the AM flower for clearance of dampness and heat from the body, diminishing swelling, and eliminating toxins (Luan et al., 2020). Beyond China, AM (also known as Aibika or Sunset Muskmallow) is widely used in countries including India, Nepal, Papua New Guinea, Vanuatu, Fiji, and New Caledonia for various medicinal purposes. In these regions, its applications range from using crushed seeds to relieve pain and foot spasms, as well as to manage lactation or menorrhagia, to the practice of applying root juice for sprains (Todarwal et al., 2011; Zhong et al., 2024).

Although the dried flower is the primary part used in medicine, other plant components—such as the seeds, roots, stems, and leaves—are also utilized to address conditions like indigestion, poor appetite, and traumatic injuries (Yin et al., 2021). Phytochemical studies have identified diverse constituents in AM, such as flavonoids, polysaccharides, steroids, volatile oils, and amino acids (Liu et al., 2016; Guo et al., 2021; Xue et al., 2023). Modern pharmacological research validates and expands upon traditional uses, revealing that AM possesses various bioactivities, including antimicrobial, antioxidant, analgesic, and anti-inflammatory properties. These mechanisms contribute to the treatment of various ailments, such as the amelioration of inflammatory bowel disease (IBD), restoration of heart and brain damage, improvement of renal and liver function, and regulation of intestinal flora and glucose/lipid metabolism (Ding et al., 2013; Zhang et al., 2017; Zhu et al., 2018; Luan et al., 2020; Gao et al., 2022; Zhou et al., 2022; Wei et al., 2023; Miao et al., 2024b; Song et al., 2024; Xu et al., 2024; Zhang et al., 2024; Wen and Chen, 2017; Zhou and Chen, 2016).

The most widespread application of AM in clinical practice is Huangkui Capsule (HKC), a single-herb traditional Chinese medicine (TCM) preparation derived from AM, approved for treating chronic kidney disease (CKD) and rheumatoid arthritis by the National Medical Products Administration of China (Luan et al., 2020; Wei et al., 2023). HKC is also commonly prescribed for conditions including primary chronic glomerulonephritis, nephrotic syndrome (NS), diabetic nephropathy (DN), hepatitis B-associated glomerulonephritis, and chronic renal failure (Luan et al., 2020; Wei et al., 2023). Similarly, Huangkui Lianchang decoction (HLD), formulated with AM as the principal ingredient, has shown efficacy in alleviating ulcerative colitis (UC) (Xu et al., 2024). Other AM-containing prescriptions—such as Jiahua Tablets, Chuangling Liquid, Huangkui Siwu Formula, Yu Kui Qing, Qikui Granules, Huangshu Kuihua paste, and Er Huang Ointment—have demonstrated therapeutic effects on CKD, skin ulcers, and chronic inflammatory diseases (Guo and Wang, 2017; Yan et al., 2018; Lu T. et al., 2020). This review synthesizes current reports on the ethnobotany, phytochemistry and their bioactive properties, pharmacological activities, and potential mechanisms of AM and its formulations. It also highlights limitations in existing research and discusses prospects for future applications, underscoring AM’s potential to bridge traditional and modern medicine.

2 Literature search methods

This review used the keywords “A. manihot (L.) Medicus” to search PubMed, Science Direct, Web of Science, Sarcandra, Baidu Scholar, Google Scholar, Connected Papers, Springer Search, and CNKI databases from 1981 to 2024, and 675 pieces of information were collected. This article aligns with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021). The botanical information was obtained through the Flora of China (www.iplant.cn). The inclusion criteria for this review were the availability of relevant studies on botany, traditional uses, pharmacology, and TCM formulas of AM. This article included all published studies in Chinese and English, in vitro and in vivo trials, and clinical studies. Duplicate studies, abstracts or partial/incomplete manuscripts, lack of transparent methods and objectives, and papers on agricultural practices, engineering, and technology development were excluded (Figure 1).

FIGURE 1

3 Plant ethnobotany and distribution

Abelmoschus manihot (L.) Medicus (AM) is an annual or perennial robust, erect herb with vigorous growth of aboveground parts and a plant height of 1–2 m (Figure 2A). The root of AM is slightly conical, with many lateral roots (Shao, 2012). AM leaves are palmately divided and have irregular, coarsely toothed margins. The flower is divided into five petals; the periphery is yellowish or pale yellow, and the center is purplish. The flower diameter is 10–20 cm, flowering from bottom to top, and the ovary is 5-chambered (Figure 2B). The plant flowers from August to October and is considered highly ornamental value (Chen et al., 2016). The capsule is oblong, pointed, and hirsute, 5.0–7.5 cm long, and contains about 50 seeds per capsule. At maturity, the seeds are gray-black and kidney-shaped, with many stripes on the surface.

FIGURE 2

AM originated in the southern part of China. It prefers to be grown in warm and humid weather with abundant rainfall and adequate sunshine in good drainage and loose, fertile soil. However, it is adaptable and now is widely distributed in tropical and subtropical regions. The natural distribution of AM in China is mainly concentrated in plain areas, such as Hebei, Henan, Shandong, and Fujian (Figure 2C). AM is also distributed in India, Sri Lanka, North Queensland, and other countries (Figure 2D).

4 Phytochemistry and their bioactive properties

Chemical investigations have revealed that different parts of A. manihot (L.) Medicus (AM) contain distinct chemical components. The flowers are primarily rich in flavonoids, while the seeds are abundant in amino acids and unsaturated fatty acids. The roots, stems, and leaves mainly contain polysaccharides (Li Z. et al., 2016). While the chemical composition of AM has been well-studied, research into the pharmacological effects of its main components is still in the early stages.

4.1 Flavonoids

Flavonoids represent the primary chemical constituents and the most significant bioactive components of AM. Forty-eight flavonoids have been isolated and identified from AM flowers. These compounds can be broadly categorized into four groups: 1) Quercetin and its glycoside derivatives, including quercetin, rutin, hyperoside, quercetin-3′-O-β-D-glucoside, quercetin-3-O-β-D-glucoside, quercetin-3-O-β-D-6′-acetylglucopyranoside, quercetin-3-O-β-robinobioside, quercetin-3-O-β-rutinoside, and quercetin-3-O-β-D-xylopyranosyl (1→2)-β-D-galactopyranoside; 2) Gossypetin and its glycoside derivatives, such as gossypetin, hibifolin, and gossypetin-3′-O-β-D-glucoside; 3) Myricetin and its glycoside derivatives, exemplified by myricetin, myricetin-3-O-β-D-glucoside, cannabiscitrin, myricetin-3-O-β-D-galactopyranoside, myricetin-3-O-rutinoside, myricetin-3-O-robinobioside, and myricetin-3-O-β-D-xylopyranosyl-(1→2)-β-D-glucopyranoside; 4) Other flavonoid compounds, such as tiliroside, hibiscetin-3-O-glucoside, floramanoside B, floramanoside C, and 5-hydroxy-4′,7,8-trimethoxyflavone. Based on current literature, Table 1 summarizes the pharmacological effects and associated mechanisms of action for key representative flavonoid constituents of AM, including: hyperoside, quercetin, isoquercitrin, gossypetin-3′-O-β-D-glucoside, quercetin-3′-O-β-D-glucoside, gossypetin-8-O-β-D-glucuronide, myricetin-3-O-β-D-galactopyranoside, and abelmanihotols A-C.

4.2 Polysaccharides

AM flowers, roots, stems, and leaves are rich in soluble polysaccharides. Notably, the total polysaccharide content in the stems can reach as high as 10.86% (Li et al., 2025). Recent studies have confirmed that AM polysaccharides possess skincare, immunomodulatory, and anti-tumor activities (Liu et al., 2016; Pan et al., 2018; Wang J. et al., 2024). Specific polysaccharide fractions—such as AMPS-a, KSK-JT, S-SLAMP-a3, SLAMP-c, and SLAMP-d—contribute significantly to these immunomodulatory and anti-tumor activities (Table 1).

4.3 Other compounds

A total of 22 amino acids and 16 nucleosides have been identified in AM. Among these, the amino acid content is higher in the flowers, reaching 4.737 mg/g, while nucleoside levels in the leaves are relatively lower at 1.474 mg/g (Liu et al., 2016). Leaf composition analysis reveals 1.77% lipids, 2.20% protein, 1.61% ash, and 88.4% moisture. Steroids and triterpenoids have also been detected in AM stems (Wen et al., 2015).

AM seeds are rich in fatty acids, soluble polysaccharides, soluble proteins, amino acids, nucleosides, and mineral elements (Liu et al., 2012; Wen et al., 2015). Total fatty acids constitute 10.22% of seed composition, with unsaturated fatty acids accounting for 78.01%–79.40% of this fraction (Liu et al., 2016). Amino acids are abundant (10.08%–10.15%), and essential amino acids represent 38.42%–39.40% of total free amino acids (Liu et al., 2016). Nucleoside content is relatively low (3.01–3.11 mg/g) (Liu et al., 2016). AM seeds also contain a diverse profile of 24 mineral elements—including K, Ca, Fe, Mn, Cu, Zn, and Mo—with levels of harmful elements (Hg, As, Cd) below food hygiene standards (Wen et al., 2015). Studies report that unsaturated fatty acids from AM seeds reduce serum levels of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in hyperlipidemic rats, while increasing high-density lipoprotein (HDL) (Wu, 2011). These findings demonstrate the significant nutritional and medicinal value of AM seeds.

5 Pharmacological activities of AM

Abelmoschus manihot (L.) Medicus (AM), particularly its flowers, exhibits therapeutic potential against various diseases including CKD, IBD, ischemic cardiac/cerebral injuries, hepatic injury, and diabetes mellitus (Figure 3). Advances in research methodologies have enabled systematic investigation into the pharmacological activities of AM. This section summarizes the established pharmacology and underlying mechanisms of AM and HKC (Table 2; Figure 4).

FIGURE 3

FIGURE 4

5.1 Anti-inflammatory and immunomodulatory effects

Inflammation accelerates organ injury through multiple mechanisms, while targeted anti-inflammatory intervention can significantly delay the progression of the disease associated with the inflammation. Current evidence demonstrates that AM downregulates pivotal inflammatory mediators—including M1 macrophage-derived cytokines (IL-1β, IL-12, IL-6, MMP-12), chemokines (MCP-1), and adhesion molecules (VCAM-1)—in diabetic nephropathy (DN) models (Ge et al., 2016; Gu et al., 2020). This anti-inflammatory action appears central to AM’s therapeutic mechanism, with additional research revealing its ability to modulate ER stress through iRhom2/tumor necrosis factor-α converting enzyme (TACE)/Spliced X-box binding protein-1 (XBP1S) pathways and regulate autophagy via adenosine monophosphate-activated protein kinase (AMPK)- sirtuin 1 (SIRT1) signaling (Liu et al., 2017; Tu et al., 2020). Parallel mechanistic studies reveal that HKC attenuates inflammatory cell activation and infiltration via p38 mitogen-activated protein kinase (MAPK) pathway inhibition, thereby reducing transforming growth factor beta 1 (TGF-β1) expression in nephropathy models (Chen P. et al., 2012). Current evidence establishes AM and HKC as renal protective agents targeting pathogenic T-lymphocyte subsets including Th22 cells, with single-cell RNA sequencing revealing critical renal receptor networks mediating HKC’s suppression of T-cell activation and infiltration (Wu et al., 2024). Simultaneously, these interventions modulate TGF-β1/Smad family member 3 (Smad3) signaling to reduce immune complex deposition in IgA nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MsPGN) (Pei and Li, 2021; Wu et al., 2024), while enhancing erythrocyte-mediated clearance via redistribution of circulating complexes to erythrocyte surfaces—a mechanism shown to limit renal deposition (Hu et al., 2011). These multimodal actions collectively substantiate HKC’s clinical efficacy in IgAN through integrated immunoregulation (Pei and Li, 2021).

In addition, intestinal inflammation drives IBD progression by mediating tissue damage, fibrosis, and carcinogenesis. In 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)/dextran sodium sulfate (DSS)-induced colitis models, AM ethanol extract attenuates pro-inflammatory cytokines (IL-6, IL-1β, IL-18, IL-17, TNF-α) and reduced myeloperoxidase activity in serum and colonic tissues (Cheng et al., 2015; Xue et al., 2023). Mechanistically, AM suppresses Nod-like receptor protein 3 (NLRP3) inflammasome activation via β-arrestin1 inhibition—evidenced by reducing NLRP3/apoptosis-associated speck-like protein containing caspases recruitment domain (ASC)/caspase-1 expression (Wu et al., 2021). Immune modulation studies revealed AM’s capacity to normalize T helper 17 cell (Th17)/regulatory T cell (Treg) balance through peroxisome proliferator-activated receptor gamma (PPAR-γ)-mediated enhancement of Treg cytokines (IL-10, TGF-β) with concurrent Th17 marker suppression (Qiao et al., 2021). In vitro studies confirmed AM’s inhibition of nuclear factor kappa B (NF-κB) and MAPK signaling in lipopolysaccharide (LPS)-stimulated macrophages (Zhang D. et al., 2019). Immune cell infiltration is critical in initiating and propagating the immune response against pathogens during the progression of UC (Neurath, 2014). This process is tightly regulated by adhesion molecules that mediate interactions between vascular endothelial cells and immune cells (Besendorf et al., 2022). Recent work identified the total flavonoids of AM (TFA) suppression of tumor necrosis factor-alpha (TNF-α)-induced NF-κB activation in colonic endothelial cells, thereby reducing vascular adhesion molecule expression (ICAM-1, VCAM-1, MAdCAM-1) and monocyte recruitment (Xue et al., 2023).

5.2 Anti-fibrotic effect

When tissues are damaged (such as due to infection, toxins, ischemia, mechanical injury, or chronic inflammation), the body activates its repair mechanism. The core of fibrosis lies in the activation and proliferation of fibroblasts. By differentiating into myofibroblasts with strong contractile and synthetic capabilities, they produce and secrete extracellular matrix components, thereby isolating the damaged area and preventing the spread of inflammation (Wang et al., 2025). However, as the injury stimulus persists or the repair process becomes imbalanced, the fibrotic response will proceed excessively, persistently and eventually lead to the aggravation of the disease state.

Renal fibrosis, representing the terminal pathological endpoint in CKD, is driven primarily by myofibroblast activation triggered by inflammatory mediators (TNF-α, IL-1β), metabolic disturbances (high glucose/lipid-induced reactive oxygen species (ROS)), mechanical stress, or hypoxia. These insults activate key signaling pathways (such as TGF-β/Smad3) to induce phenotypic transformation. In DN models, HKC suppresses TGF-β1 expression and reduces α-SMA levels (Gu et al., 2021). Furthermore, in unilateral ureteral obstruction models, HKC targets calcium-permeable TRPC channels, specifically modulating TRPC6/NFAT signaling. This mechanism is critical, as the protective effect of HKC is abolished in TRPC6-knockout mice (Gu et al., 2020). The protective role of HKC in renal disease is primarily mediated through the critical TRPC6/NFAT pathway, as complemented by its suppression of the TGF-β1/α-SMA axis. In addition, mechanistic studies reveal HKC’s capacity to inhibit fibrogenesis through coordinated p38 MAPK/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway downregulation (Mao et al., 2015), NLRP3 inflammasome suppression with toll-like receptor 4 (TLR4)/NF-κB blockade to prevent epithelial-mesenchymal transition (Han et al., 2019), NOX/ROS/ERK axis modulation (Li et al., 2019), and angiogenic receptor (VEGFR, PDGFR) inhibition coupled with pericyte myofibroblast transdifferentiation suppression (Wang M. et al., 2022). These actions are further complemented by connective tissue growth factor/osteopontin reduction via Smad7/SnoN upregulation and Klotho/TGF-β1/p38 pathway normalization in renal tubular cells (Gu et al., 2021). These studies collectively demonstrate that HKC orchestrates a coordinated suppression of critical pro-fibrotic pathways—including p38 MAPK/PI3K/Akt, TLR4/NF-κB/NLRP3, and NOX/ROS/ERK—thereby counteracting fibrogenesis at multiple levels.

Intestinal fibrosis—a pivotal complication in IBD progression with over 50% incidence in Crohn’s disease—drives intestinal stenosis, obstruction, and surgical intervention through excessive ECM deposition and pathological myofibroblast activation. AM counteracts this remodeling by reducing TNBS-induced weight loss, disease activity index (DAI) scores, and collagen deposition while improving histopathological features (Zhang et al., 2017). Mechanistically, AM suppresses fibrotic markers (col1a2, col3a2, α-SMA) via dual inhibition of TGF-β and IGF-1 signaling (Qiao et al., 2021; Zhang et al., 2024), remodels ECM through altered MMP/TIMP balance (elevated MMP-9/MMP-2 with suppressed TIMP-1), and attenuates TGF-β1-induced epithelial-mesenchymal transition (EMT) by blocking Smad2/3 phosphorylation and MAPK cascades (Yang et al., 2018). In vitro evidence confirms AMPK/mTOR-regulated autophagy mediates AM’s inhibition of IGF-1-driven collagen synthesis in intestinal fibroblasts (Zhang H. et al., 2022), establishing a multi-target therapeutic profile against fibrogenesis.

5.3 Metabolic and anti-oxidant regulation

The ethanol extract showed superior efficacy and reduced hyperglycemia-induced ROS in pancreatic β-cells (Wang S. W. et al., 2024). AM total flavonoids, TFA, enhanced glucose metabolism through dose-dependent promotion of glucose uptake in 3T3-L1 adipocytes and exerted hypoglycemic effects in diabetic murine models. TFA administration elevated superoxide dismutase (SOD) activity while reducing malondialdehyde (MDA) levels in diabetic rats, suggesting β-cell protection against oxidative damage (Zhou and Chen, 2016).

The ethanol extract of AM inhibited TG accumulation in 3T3-L1 adipocytes and lowered serum TC, TG, low-density lipoprotein cholesterol (LDL-C), and ox-LDL levels in hyperlipidemic rats, achieved through downregulation of PPARγ and CCAAT/enhancer-binding protein alpha (C/EBPα) mRNA to inhibit adipogenesis (An et al., 2011; Li J. et al., 2016). At the molecular level, AM ethanol extract orchestrates lipid homeostasis by normalizing adipogenic regulators (PPARα/γ, C/EBPα, SREBP-1), correcting adipokine imbalances (adiponectin/resistin), and alleviating ER stress-induced lipid dysmetabolism. Synergistically, TFA combined with glipizide reduced plasma lipids, blood urea nitrogen (BUN), creatinine, urinary microalbumin, and blood viscosity in DN rats (Li et al., 2018). Metabolic profiling reveals HKC’s systemic modulation of circulating metabolites including methionine sulfoxide, branched-chain amino acids, and cis-7-hexadecenoic acid (Shi et al., 2023). Complementary renal protection involves improved sodium handling via inhibition of renal medullary Na⁺-K⁺-ATPase activity, reducing pathological edema and lipid deposition in diabetic kidneys (Cai et al., 2016; Li et al., 2018; Qian et al., 2023).

AM also has a significant antioxidant effect. AM accelerates scald wound healing by modulating MDA/SOD via nuclear factor erythroid 2-related factor 2 (Nrf2) (Song et al., 2024), protects NIH-3T3 fibroblasts from H₂O₂ damage through the same pathway, and alleviates gastric mucosal injury by boosting glutathione synthesis (Hsuan et al., 2024). Furthermore, AM flower extracts enhance human fibroblast proliferation through cyclin D1 upregulation (Park et al., 2020) and HKC reduces ROS/NO in LPS-activated macrophages and increases lung catalase (CAT)/glutathione peroxidase (GSH-Px) activity in acute lung injury models (Deng et al., 2021). Several studies have revealed that AM exhibits antioxidant activity through scavenging DPPH/ABTS/OH radicals while enhancing antioxidant enzymes (GSH-Px, CAT, SOD, T-AOC) and reducing MDA levels (Qiu et al., 2017; Liu et al., 2021c; Sun et al., 2024). Its total flavonoid fraction TFA activates Nrf2 signaling to upregulate heme oxygenase-1 (HO-1)/NAD(P)H dehydrogenase quinone 1 (NQO1), mitigating D-galactose-induced hepatocyte cytotoxicity (Qiu et al., 2017).

5.4 Regulation of intestinal flora

The intestinal microbiota’s pivotal role in IBD pathogenesis is increasingly recognized, with microbial dysbiosis driving immune activation through commensal flora infiltration into lamina propria. Clinical observations reveal reduced microbial diversity in IBD patients, where therapeutic strategies like probiotics and fecal microbiota transplantation (FMT) demonstrate clinical efficacy by restoring ecological balance (Weingarden and Vaughn, 2017; Tao P. et al., 2024; Zhao H. et al., 2024). In DSS-induced colitis models, AM intervention reverses Firmicutes depletion and Bacteroidetes expansion while enriching beneficial taxa (Akkermansia muciniphila, Lachnospiraceae, Bifidobacterium) and suppressing pathogens (Escherichia coli, Proteobacteria) (Zhang W. et al., 2019; Bu et al., 2021). Cohousing experiments demonstrate AM-treated mice attenuate colitis severity in cohabited counterparts (Gao et al., 2022), with fecal microbiota transplantation confirming microbiota-dependent protection via increased Bacteroides and Ruminiclostridium [sp. cluster 9] in UC recipients (Wu et al., 2021). Notably, AM selectively enhances butyrate-producing Lachnospiraceae to boost short-chain fatty acid (SCFA) production—critical for mucosal integrity and inflammation suppression (Zhang W. et al., 2019) —and directly stimulates A. muciniphila proliferation in vitro (Bu et al., 2021). In addition, AM polysaccharides enhance mucin production via IL-10-dependent pathways, with bacterial transfer studies confirming A. muciniphila as a key mediator of this protective effect (Wang Y. et al., 2024), establishing microbial-metabolic modulation as a viable barrier rehabilitation strategy.

5.5 Organ protection

Cerebral ischemia, characterized by insufficient cerebral blood flow leading to oxygen/glucose deficiency, underlies pathologies like cerebral infarction and vascular dementia with high disability/recurrence rates (Chen et al., 2025). AM administration mitigates cerebral edema, attenuates infarct volume, and improves blood-brain barrier integrity while reducing serum biomarkers (LDH, MDA, and PGE2) of neuronal damage in cerebral ischemia-reperfusion injury model (Guo and Chen, 2002; Gao et al., 2003; Wen and Chen, 2006). AM further enhances hippocampal neuron survival by inhibiting intracellular Ca²⁺ overload and lactate dehydrogenase (LDH) release during hypoxia/reoxygenation, while its total flavonoids (TFA) suppress N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity via non-competitive receptor desensitization—validated by patch-clamp electrophysiology (Cheng et al., 2006; Wen and Chen, 2017). In post-stroke depression (PSD) models, TFA enhances locomotor activity and improves hemorheological parameters by reducing blood viscosity while increasing erythrocyte deformability. Concurrently, it elevates SOD/GSH-Px activities and reduces levels of MDA, adrenocorticotropic hormone (ACTH), and cortisol in both brain tissue and the hypothalamus (Hao et al., 2007; Hao and Zhou, 2009). These effects are achieved by TFA’s suppression of lipid peroxidation and upregulation of brain-derived neurotrophic factor (BDNF)/cAMP response element-binding protein (CREB) neurotrophic pathways (Liu et al., 2009). In neuronal oxidative stress models, AM ethanol extract directly protects neuronal PC12 cells against oxidative stress through antioxidant enzyme induction, glutathione (GSH) synthesis promotion, DNA repair enhancement, and ROS reduction (Wang S. W. et al., 2022). Critically, AM modulates the gut-brain axis to alleviate depression-associated intestinal barrier damage and microbial dysbiosis, concurrently ameliorated depressive behaviors and DSS-induced colitis (Wang et al., 2021).

AM, traditionally used in Jiangsu and Anhui provinces for jaundice and hepatitis management, exerts hepatoprotection primarily through its total flavonoid component (Liu et al., 2010). In CCl₄-induced liver injury models, TFA significantly reduces serum markers (ALT, AST, ALP, γ-GT) and hepatic MDA while elevating GSH content, concurrently enhancing antioxidant enzyme activities (SOD, GSH-Px, CAT, GST) and suppressing inflammatory mediators (TNF-α, IL-1β, NO) (Hu et al., 2011; Ai et al., 2013). TFA’s dose-dependent cytoprotection in CCl₄-exposed hepatocytes, evidenced by improved cell viability and reduced ALT/AST/ALP leakage (Ai et al., 2013). In cholestatic models, TFA upregulates bile transporters (BSEP, MRP2, NTCP) at protein/mRNA levels (Yan et al., 2015). In D-galactose-induced aging models, TFA activates the Nrf2 pathway to boost antioxidant capacity (CAT, T-SOD, GSH-Px, T-AOC) and inhibit peroxidation (Qiu et al., 2017). In vitro analyses confirm AM’s ethyl acetate fraction protects HepG2 cells from H₂O₂-induced damage through ROS scavenging, membrane stabilization, and apoptosis modulation via Nrf2/HO-1/NQO1 pathway activation and caspase-3/9/Bax regulation (Liu et al., 2021c).

5.6 Antiviral, antibacterial, and ulcer repair

AM and its total flavonoid component exhibit broad-spectrum antimicrobial activity against viral and bacterial pathogens. TFA potently inhibits herpes simplex virus types 1/2 (HSV-1 IC₅₀ = 1.01 mg/L; HSV-2 IC₅₀ = 1.21 mg/L) with high therapeutic indices (>10), indicating selective antiviral action (Jiang et al., 2006). Gao et al. found that AM ethanol extract reduces influenza A viral loads and suppresses pulmonary IL-1β/IL-6/TNF-α via MAPK pathway modulation in murine models (Gao et al., 2022). Against bacterial pathogens, AM demonstrates efficacy against Gram-positive/negative species, particularly Neisseria gonorrhoeae, with TFA exhibiting bactericidal activity against Staphylococcus epidermidis and Staphylococcus aureus (MIC = 3.125 g/L) and fungistatic effects on Candida albicans (MIC = 1.562–3.125 g/L) (Zhang et al., 2006). These properties translate to therapeutic efficacy in mucosal infections: TFA accelerates healing of C. albicans- or S. epidermidis-induced oral ulcers in guinea pigs, and AM flower extract reduces inflammation in S. aureus-infected rabbit oral mucosa (Li et al., 2006; Zhang et al., 2006).

5.7 Antipyretic and analgesic effects

AM and its total flavonoid component exhibit antipyretic and analgesic properties through distinct biological pathways. In rabbit fever models induced by turpentine oil or E. coli, TFA reduced body temperature within 150 minutes—albeit with slower onset than aspirin due to delayed systemic absorption and hepatic metabolism (Fan et al., 2003b). For analgesia, TFA (5–20 mg/kg) significantly inhibited acetic acid-induced writhing responses (42.81%–57.53% reduction) and attenuated potassium chloride-evoked nociception without inducing addictive behaviors even at 280 mg/kg (Fan et al., 2003a). TFA significantly reduced pain responses in rabbits following potassium chloride injections (Fan et al., 2003a). Petroleum ether and methanol extracts of AM also exhibited a dose-dependent inhibition on thermopain (Jain et al., 2011), and AM extracts alleviate burn-induced inflammatory exudation and elevate pain thresholds in scalded models (Song et al., 2024).

6 Traditional Chinese medicine formulas containing AM

Currently, the only drug related to A. manihot (L.) Medicus (AM) approved for production by the National Medical Products Administration is HKC. Given that there have been a large number of systematic reviews and meta-analyses on the efficacy and safety of HKC (Li et al., 2017; An et al., 2021; Li Y. et al., 2024), we have sorted out the clinical application status of other TCM compounds containing AM (such as Jiahua Tablets, Chuangling Liquid, Yu Kui Qing, etc.), as shown in Table 3. In addition, this section summarizes the traditional prescriptions that contain AM, along with their pharmacological effects (Table 4).

6.1 Jiahua tablets

Jiahua Tablets are semi-extracted TCM tablets made from the raw powder and extracts of AM flowers, containing 10% starch slurry and an appropriate amount of ethanol. These tablets have been clinically used for over a decade and have been demonstrated to display significant therapeutic efficacy (Lin et al., 2020a; Zha et al., 2020). Both HKC and Jiahua Tablets are derived from the single medicinal ingredient of AM flowers. They share properties that clear heat, promote diuresis, support kidney function, and eliminate toxins, primarily addressing acute and chronic nephritis (Zhang and Zhou, 2012). According to the Chinese Pharmacopoeia, the recommended dosage of AM flowers is 10–30 g/day, with both HKC and Jiahua Tablets containing a daily dosage of 30 g of AM flowers.

In addition to conventional early DN treatments, Jiahua Tablets can reduce serum inflammatory factors such as C-reactive protein (CRP) and TNF-α. It also lowers levels of Cystatin C (Cys-C) and urinary albumin-to-creatinine ratio (UACR), thereby improving kidney function (Cha et al., 2020). In patients undergoing coronary intervention, those treated with Jiahua Tablets exhibited significantly lower levels of serum creatinine (SCr), BUN, Cys-C, IL-6, IL-8, high-sensitivity C-reactive protein (hs-CRP), urinary N-acetyl-β-D-glucosaminidase (NAG), and urinary β-galactosidase (GAL) 72 h post-operation compared to the control group. Additionally, the estimated glomerular filtration rate (eGFR) was significantly higher in the treatment group than in the control group, indicating that Jiahua Tablets can effectively prevent contrast-induced nephropathy. The underlying mechanism likely involves inhibiting inflammatory responses and protecting renal tubules, thereby repairing kidney damage and preserving renal function (Wu et al., 2020).

6.2 Chuangling liquid

Chuangling Liquid was developed by the Jiangsu Provincial Hospital of TCM in the 1980s. Its formulation including A. manihot (Huang Shu Kui), Rheum palmatum (Da Huang), Carthamus tinctorius (Hong Hua), and Terminalia chebula (He Zi) (Yang, 1997; Xu, 2010; Huang and Chen, 2012; Miao, 2013; Yin et al., 2013; Cao et al., 2014; Sheng, 2014; Teng and Ji, 2016; Wang et al., 2016; Li, 2017; Liu, 2019; Wang et al., 2020; Xue et al., 2020; Ye et al., 2021). The primary active components of Chuangling Liquid include gallic acid, hyperoside, isoquercitrin, myricetin, quercetin, rhein, emodin, chrysophanol, and physcion (Shu et al., 2016). This preparation promotes blood circulation and removes blood stasis, effectively treating various types of infectious ulcers with significant inflammation (Chen et al., 2017).

Chuangling Liquid has demonstrated a range of therapeutic properties in various experimental and clinical settings. Zhang et al. showed that it can counteract acute exudative inflammation induced by croton oil in mice and inhibit granulation tissue proliferation in cotton pellet granuloma models (Zhang et al., 1997). In rabbit ulcer models, Chuangling Liquid promotes early wound healing processes such as epithelial tissue proliferation, granulation formation, and accessory regeneration, while inhibiting collagen fiber scar formation, leading to faster healing with less scarring (Zhang et al., 1997). Additionally, it exhibits strong antibacterial activity against S. aureus, methicillin-resistant S. aureus (MRSA), and Proteus species, being particularly effective at eliminating MRSA from infected wounds and promoting recovery (Liu et al., 2018). Moreover, Chuangling Liquid also inhibits thrombosis and platelet aggregation, thereby improving blood circulation and alleviating blood stasis (Chen et al., 2017). Clinically, it has been proven effective in treating postoperative infected wounds, chronic ulcers, diabetic foot ulcers, venous ulcers of the lower limbs, and anal fistulas (Hu, 2016; Li, 2016; Xu, 2017). Furthermore, modifying the formulation process and incorporating collagen into Chuangling Liquid enhances its anti-inflammatory effects, wound healing, angiogenesis, and overall recovery (Zhao and Zhu, 2013). Recent studies have also found that Chuangling Liquid promotes the proliferation of immortalized melanocytes in mice and activates tyrosinase activity, enhancing melanin synthesis. This suggests potential applications in treating pigmentary disorders such as vitiligo (Zhou et al., 2019).

6.3 Huangkui Lianchang decoction

Huangkui Lianchang Decoction (HLD) is a traditional Chinese medicinal formulation used to treat UC. It consists of six key ingredients: the primary herb is A. manihot (Huang Shu Kui), combined with Euphorbia humifusa Willd (Di Jin Cao), Pteris multifida Poir (Feng Wei Cao), Lithospermum erythrorhizon Siebold & Zucc (Zi Cao), Rubia cordifolia L. (Qian Cao), and Rhus chinensis Mill (Wu Bei Zi) (He et al., 2019; Yang et al., 2023). HLD is rich in flavonoids, including rutin, isoquercitrin, gossypetin, and quercetin (Cheng et al., 2022). The proposed functions of HLD are to clear heat and dampness, activate blood circulation, protect the intestines, and detoxify the body. These properties make it particularly beneficial for managing the symptoms associated with UC.

HLD has demonstrated significant therapeutic effects on DSS-induced UC in mouse models. Studies indicate that HLD exerts anti-inflammatory effects by modulating key signaling pathways, including NF-κB, IL-6/signal transducer and activator of transcription 3 (STAT3), and the IL-23/IL-17 inflammatory axis (He et al., 2019; He et al., 2020; Cheng et al., 2022). In vitro experiments with drug serum containing HLD (HLD-DS) showed that it reduces inflammatory cytokine levels while increasing IL-10 levels in NCM460 cells. HLD-DS also decreased the expression of p-NF-κB p65, LC3II/I, and Beclin 1, suggesting that HLD alleviates colitis by inhibiting the NF-κB pathway and autophagy (Cheng et al., 2022). Clinically, HLD is used for treating mild to moderate E1 and E2 type UC via enema alone. In contrast, severe or E3-type UC is treated with HLD enemas and oral medications (He et al., 2019). Clinical studies have shown that modified HLD, when used alongside corticosteroids, can effectively improve gut microbiota and exhibit significant anti-inflammatory effects, aiding in managing IBD (He et al., 2023). Additionally, the retention enema method of HLD has been found to inhibit the intestinal mucosal inflammatory response in UC patients and reduce mucosal damage (Yang et al., 2023).

6.4 Huangkui Siwu Formula

Huangkui Siwu Formula (HKSWF) is a traditional Chinese medicinal formulation comprised of four key herbs: A. manihot (Huang Shu Kui), Astragalus mongholicus (Huang Qi), Polygonum cuspidatum (Hu Zhang), and Curcuma longa L (Jiang Huang) (Lu T. et al., 2020). The formula contains eleven identified components, including polydatin, hyperoside, isoquercitrin, hibifolin, myricetin, resveratrol, quercetin, didemethoxycurcumin, demethoxycurcumin, curcumin, and emodin (Lu T. et al., 2020). The herbal combination in HKSWF clears heat, promotes blood circulation, facilitates urination, and reduces swelling, effectively addressing the symptoms of CKD.

Research on HKSWF has shown promising therapeutic effects in kidney health, particularly in an anti-Thy-1 nephritis model. One study indicates that HKSWF can alleviate glomerular injury by attenuating pyruvate dehydrogenase activity, contributing to its protective effects on renal function (Lu T. et al., 2020). Further investigations by Lu et al. revealed that HKSWF does not alter the expression of organic anion transporters in the kidneys or the transport of p-cresyl sulfate (PCS) from blood to kidneys. Instead, it regulates the synthesis pathway of PCS within host cells, inhibiting its endogenous production. This action helps reduce the accumulation of uremic toxins and slows the progression of CKD (Lu et al., 2021). Moreover, HKSWF modulates uremic toxin metabolism pathways within the gut microbiota, inhibiting the formation of uremic toxin precursors at various stages. This modulation alleviates the symptoms associated with uremic toxin accumulation and further delays CKD progression, highlighting the multifaceted benefits of HKSWF for managing kidney health (Lu J. et al., 2020).

6.5 Yu Kui Qing

Yu Kui Qing (YKQ) is composed of A. manihot (Huang Shu Kui), Astragalus membranaceus (Huang Qi), and Polygonum multiflorum Thunb. (Zhi Shou Wu) (30:1.5:1) (Chen and Yu, 2008; Chen and Yu, 2009). YKQ clears heat, detoxifies, promotes diuresis, tonifies Qi, strengthens the spleen, activates blood circulation, and nourishes Yin and kidneys. Modern pharmacological studies have demonstrated that YKQ can reduce the expression and chemotactic effects of chemokines in human renal mesangial cells (HRMC) induced by advanced glycation end-products bound to bovine serum albumin (AGE-BSA). Additionally, YKQ intervenes in the expression of connective tissue growth factor (CTGF) mRNA and protein in HRMC, which may contribute to reducing renal inflammation associated with DN (Yang et al., 2010; Sun et al., 2014). Clinical studies have shown that YKQ effectively treats microalbuminuria in patients with type 2 DN, reduces urinary microalbumin levels, and improves symptoms (such as fatigue and lower back pain) in early-stage disease. These findings underscore the potential of YKQ as a valuable therapeutic option for managing diabetes-related complications (Chen and Yu, 2009).

6.6 Qikui Granules

Qikui Granules is composed with A. membranaceus (Huang Qi), A. manihot (Huang Shu Kui), and processed P. multiflorum (Zhi Shou Wu) (Wang L. et al., 2023). Specifically, they help to benefit Qi, nourish Yin, and clear heat. Clinically, Qikui Granules have been utilized to treat early to mid-stage DN (Yang et al., 2016).

The study by Lou et al. shows that Qikui Granules provide renal protection in DN by lowering blood glucose, reducing inflammatory markers like IL-6, monocyte chemoattractant protein-1 (MCP-1), and TGF-β1, and inhibiting the p38 MAPK signaling pathway (Yang et al., 2016; Shao et al., 2017). In addition to renal benefits, Qikui Granules were observed to improve bone density, likely linked to improved blood glucose regulation (Lou et al., 2022). In vitro experiments revealed that these granules enhance the proliferation of mesenchymal stem cells (MSCs) and promote their osteogenic differentiation while simultaneously reducing their potential for adipogenic differentiation (Lou et al., 2022). Clinically, Qikui Granules have been shown to reduce microalbuminuria in patients with early DN. It slows disease progression and alleviates symptoms such as fatigue, weakness, lower back and knee soreness, and facial and limb edema (Yan et al., 2018). Observations indicate a marked reduction in urine protein levels, UACR, urinary albumin excretion rate (UAER), and urinary MCP-1/creatinine (uMCP-1/Cr) levels in patients with early DN (Yan et al., 2018). The underlying mechanisms of action for Qikui Granules may involve inhibiting CTGF expression and soluble intercellular adhesion molecule-1 (sICAM-1) in urine and serum (Xie et al., 2017b; Zhang et al., 2021). Overall, the findings suggest that Qikui Granules could be a valuable therapeutic approach for managing complications associated with diabetes, particularly DN, by addressing metabolic and inflammatory pathways.

6.7 Huangshu Kuihua paste

The Huangshu Kuihua paste, which combines 0.3–10 parts of A. manihot (Huang Shu Kui) with 0.1–10 parts of propolis extract and 0.1-5 parts of borneol, is an innovative formulation widely used at the First Affiliated Hospital of Anhui Medical University (Han and Situ, 1997; Chen et al., 2017). Its strong analgesic properties make it particularly effective for managing pain associated with oral ulcers. Notably, the formulation is characterized by minimal tissue irritation and does not cause local numbness or discomfort, which enhances patient comfort during treatment. Moreover, the paste exhibits excellent adhesion to mucous membranes, facilitating prolonged contact and promoting the healing process of oral ulcers without any toxic side effects. In clinical trials involving 82 patients with oral ulcers, the formulation achieved an impressive cure rate of 97.5%, underscoring its efficacy and safety in treating this condition (Han et al., 1997). These findings make Huangshu Kuihua paste a valuable option in managing oral ulcer pain and healing.

6.8 Er Huang ointment

Er Huang Ointment, formulated with A. manihot (Huang Shu Kui), Scutellaria baicalensis (Huang qin), Phellodendron amurense (Huang bai), Gardenia jasminoides (Zhi zi), and Ampelopsis japonica (Bai lian) (5:5:5:3:3), has garnered attention for its therapeutic effects on burns and wounds (Yang, 2016). Clinical studies have affirmed that the overall efficacy of Er Huang Ointment in treating burns and scalds and reducing wound healing time is comparable to that of Moist Burn Ointment (Yang et al., 2016; Guo and Wang, 2017). Furthermore, Er Huang Ointment has notable antibacterial activity against common pathogens such as S. aureus, Pseudomonas aeruginosa, and E. coli, suggesting its potential in preventing infections associated with burns and wounds (Li, 1993). These findings position Er Huang Ointment as a promising clinical practice option for managing burns and enhancing wound healing.

7 Research challenges and future perspectives

The traditional Chinese medicinal herb AM features pale yellow flowers with a delicate fragrance and holds significant ornamental, medicinal, and edible value. Modernizing AM faces two core challenges: degree of development and utilization, and gaps in translation from laboratory to clinic. Jiangsu Suzhong Pharmaceutical Co., Ltd. in Taizhou (Jiangsu, China) has successfully developed and commercially produced HKC—a Category III new TCM—after years of research. These capsules are widely used clinically to treat conditions such as nephritis and rheumatoid arthritis, serving as an adjunctive therapy for glomerulonephritis and demonstrating considerable value in preventing gadolinium-based contrast agent-induced nephrogenic systemic fibrosis. Utilizing AM flowers as the primary raw material, the proven efficacy and substantial market potential of these capsules have driven high demand, consequently stimulating the flourishing cultivation industry across Taizhou, Jiangsu, surrounding regions, and nationwide. However, other AM parts—including leaves, roots, stems, and seeds—are typically discarded, resulting in resource wastage and environmental pollution. Literatures indicate that the entire AM plant possesses medicinal properties, suggesting that non-capsule components also hold therapeutic value. To enable more scientific, comprehensive, and rational utilization of this medicinal resource, intensified research on its other bioactive parts is essential. This will maximize economic and social benefits while accelerating the development of the AM industry.

Transitioning to evidence-based medicine is hampered by significant clinical evidence gaps, including small randomized controlled trials with fewer than 300 cases, short follow-up periods of 6 months or less, reliance on surrogate endpoints like proteinuria instead of hard endpoints such as end-stage renal disease incidence, and insufficient long-term safety data on aspects like reproductive toxicity. Currently, only HKC has gained broad clinical acceptance, primarily for treating nephropathy. This is due to its robust clinical data, characterized by rigorous record-keeping, standardized patient grouping, sufficient sample sizes, and sustained post-treatment follow-up. Other AM-containing TCM formulations suffer from significant clinical evidence gaps: their studies often involve small, non-systematic patient cohorts and lack post-administration observation. This evidence deficit severely limits the broader clinical adoption and justification for using AM. Therefore, building upon the systematically compiled data on AM-containing TCM formulations presented in this study, it is recommended to prioritize 1-2 promising prescriptions for development. Conducting standardized clinical research on these selected formulations is crucial. This focused approach will enhance the understanding of AM’s therapeutic potential and ultimately expand its clinical applications.

8 Conclusion

Based on the current body of evidence derived from both basic research and clinical practice, AM has demonstrated significant therapeutic potential. Its pharmacological activities, including the improvement of liver and kidney functions, regulation of material metabolism, and anti-fibrotic effects, have been scientifically validated, providing a rationale for its application in conditions such as CKD and IBD (Miao et al., 2024a; Wang Y. et al., 2024; Zhao H. et al., 2024). However, the predominant clinical application remains limited to the single-component preparation HKC (Geng et al., 2023), underscoring the need to broaden the development and utilization of AM-derived formulations.

Notwithstanding this promise, current research faces notable limitations that must be addressed in future studies. These include a narrow focus on the flowers and total flavonoids, neglecting other plant parts and individual bioactive compounds; the use of animal models that may not accurately replicate human diseases; insufficient mechanistic insights at cellular and molecular levels; and a lack of integrated pharmacokinetic-pharmacodynamic (PK-PD) studies to represent the whole herb’s in vivo behavior. Consequently, future efforts should prioritize expanding phytochemical investigations, pinpointing specific bioactive compounds and their mechanisms, establishing integrated PK-PD models, and developing improved formulations through rigorous clinical trials. Overcoming these challenges via a multidisciplinary approach is essential to fully realize the clinical potential of AM.

References

• 1

  Abdou H. M. Elmageed G. M. A. Hussein H. K. Yamari I. Chtita S. El-Samad L. M. et al (2025). Antidiabetic effects of quercetin and silk sericin in attenuating dysregulation of hepatic gluconeogenesis in diabetic rats through potential modulation of PI3K/Akt/FOXO1 signaling: in vivo and in silico studies. J. Xenobiot.15, 16–24. 10.3390/jox15010016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 2

  Ai G. Liu Q. Hua W. Huang Z. Wang D. (2013). Hepatoprotective evaluation of the total flavonoids extracted from flowers of abelmoschus manihot (L.) medic: in vitro and in vivo studies. J. Ethnopharmacol.146, 794–802. 10.1016/j.jep.2013.02.005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 3

  An Y. Zhang Y. Li C. Qian Q. He W. Wang T. (2011). Inhibitory effects of flavonoids from Abelmoschus manihot flowers on triglyceride accumulation in 3T3-L1 adipocytes. Fitoterapia82, 595–600. 10.1016/j.fitote.2011.01.010

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 4

  An W. Huang Y. Chen S. Teng T. Liu J. Xu Y. (2021). Efficacy and safety of Huangkui capsule for diabetic nephropathy: a protocol for systematic review and meta-analysis. Medicine100. 10.1097/MD.0000000000027569

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 5

  Besendorf L. Mueller T. M. Geppert C.-I. Schneider I. Muehl L. Atreya I. et al (2022). Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis. Ther. Adv. Gastroenterol.15, 175–186. 10.1177/17562848221098899

  • CrossRef
  • Google Scholar

• 6

  Bu F. Ding Y. Chen T. Wang Q. Wang R. Zhou J.-y. et al (2021). Total flavone of Abelmoschus Manihot improves colitis by promoting the growth of Akkermansia in mice. Sci. Rep.11, 20787–20796. 10.1038/s41598-021-00070-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 7

  Cai H. Su S. Guo S. Zhu Y. Qian D. Tao W. et al (2016). Effect of flavonoids from Abelmoschus manihot on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance. China J. Chin. Mater Med.41, 4635–4641. 10.4268/cjcmm20162424

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 8

  Cai H. Su S. Qian D. Guo S. Tao W. Cong X. et al (2017a). Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids. J. Ethnopharmacol.206, 152–159. 10.1016/j.jep.2017.02.046

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 9

  Cai H. Tao W. Su S. Guo S. Zhu Y. Guo J. et al (2017b). Antidepressant activity of flavonoid ethanol extract of Abelmoschus manihot corolla with BDNF up-regulation in the hippocampus. Acta Pharm. Sin.52, 222–228. 10.16438/j.0513-4870.2016-0764

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 10

  Cao L. Yin C. Zhou Q. Hu W. Zhou Y. (2014). Observation on curative effect of chuangling fluid and skul lcap ointment used for postoperative dressing in patients with low simple anal fistula patients. Nurs. Res.28, 3127–3129. 10.3969/j.issn.1009-6493.2014.25.022

  • CrossRef
  • Google Scholar

• 11

  Cao H. Xu H. Zhu G. Liu S. (2017). Isoquercetin ameliorated hypoxia/reoxygenation-induced H9C2 cardiomyocyte apoptosis via a mitochondrial-dependent pathway. Biomed. Pharmacother.95, 938–943. 10.1016/j.biopha.2017.08.128

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 12

  Cha M. Sun H. Zhang S. Ye L. Huang L. Chen S. et al (2020). Effect of Jiahua Tablets as adjuvant treatment on serum inflammatory factors levels and renal function in patients with early diabetic nephropathy. Guangxi Med. J.42, 2059–2061.

  • Google Scholar

• 13

  Chang C. Houng J. Peng W. Yeh T. Wang Y. Chen Y. et al (2022). Effects of abelmoschus manihot flower extract on enhancing sexual arousal and reproductive performance in zebrafish. Molecules27, 2218–2229. 10.3390/molecules27072218

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 14

  Chen X. Yu J. (2008). Clinical Study on the intervention treatment of early type 2 diabetic nephropathy with Yu Kui qing. Jiangsu J.TCM, 48–49. 10.3969/j.issn.1672-397X.2008.07.028

  • CrossRef
  • Google Scholar

• 15

  Chen X. Yu J. (2009). Clinical Study of yukuiqing on early Type-2 diabetic kidney cell factors. Zhejiang J. Trad. Chin. Med.33, 56–57. 10.16466/j.issn1005-5509.2009.01.038

  • CrossRef
  • Google Scholar

• 16

  Chen L. Su C. Liu Q. Xu X. Yu S. Li R. et al (2012a). Protective effect of F-6 from abelmoschus manihot on acute liver injury of mice induced by CCl4. Pharm. J. Chin. PLA.28, 214–217. 10.3969/j.issn.1008-9926.2012.03.07

  • CrossRef
  • Google Scholar

• 17

  Chen P. Wan Y. Wang Z. Zhao Q. Wei Q. Tu Y. et al (2012b). Mechanisms and effects of Abelmoschus manihot preparations in treating chronic kidney disease. China J. Chin. Mater Med.37, 2252–2256. 10.4268/cjcmm20121514

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 18

  Chen Y. Cai G. Sun X. Chen X. (2016). Treatment of chronic kidney disease using a traditional Chinese medicine, flos Abelmoschus manihot (Linnaeus) Medicus (Malvaceae). Clin. Exp. Pharmacol. Physiol.43, 145–148. 10.1111/1440-1681.12528

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 19

  Chen S. Chai C. Ge H. (2017). Research progress of the topical preparations containing abelmoschus coroll. Shanghai Yiyao38, 75–78. 10.3969/j.issn.1006-1533.2017.05.025

  • CrossRef
  • Google Scholar

• 20

  Chen X. Li H. Wang Z. Zhou Q. Chen S. Yang B. et al (2020). Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway. Eur. J. Pharmacol.868, 172885–172893. 10.1016/j.ejphar.2019.172885

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 21

  Chen J. Lin R. Jiang C. Chen F. Li W. Wang L. et al (2025). Brain endothelial HIF-1α exacerbates diabetes-associated cognitive impairment by accelerating glycolysis-driven lactate production. Acta Pharm. Sin. B15, 5772–5788. 10.1016/j.apsb.2025.09.028

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 22

  Cheng L. Hu K. Chen X. Huang Z. (2010). The flavonoid components of abelmoschus manihot flowers-experimental study on the treatment of non-alcoholic fatty liver in rats using F-6. Pharm. J. Chin.7–12.

  • Google Scholar

• 23

  Cheng X. Qin S. Dong L. Zhou J. (2006). Inhibitory effect of total flavone of abelmoschus manihot L. medic on NMDA receptor-mediated current in cultured rat hippocampal neurons. Neurosci. Res.55, 142–145. 10.1016/j.neures.2006.02.011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 24

  Cheng Y. Chen Y. Zhou J. Qu D. Zhou Z. Yang B. et al (2015). Effects of abelmoschi corolla extracts on IBD treatment in mice and expression of TNF-α and IFN-γ. J. Nanjing Univ. Tradit. Chin. Med.31, 32–34. 10.14148/j.issn.1672-0482.2015.0032

  • CrossRef
  • Google Scholar

• 25

  Cheng X. Du J. Zhou Q. Wu B. Wang H. Xu Z. et al (2022). Huangkui lianchang decoction attenuates experimental colitis by inhibiting the NF-κB pathway and autophagy. Front. Pharmacol.13, 951558. 10.3389/fphar.2022.951558

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 26

  Dai Y. Zhang H. Zhang J. Yan M. (2018). Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. Chem. Biol. Interact.284, 32–40. 10.1016/j.cbi.2018.02.017

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 27

  Deng J. He Z. Li X. Chen W. Yu Z. Qi T. et al (2021). Huangkui capsule attenuates lipopolysaccharide-induced acute lung injury and macrophage activation by suppressing inflammation and oxidative stress in mice. Evid. Based Complement. Altern. Med.2021, 6626483–6626505. 10.1155/2021/6626483

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 28

  Diao Z. Yu H. Wu Y. Sun Y. Tang H. Wang M. et al (2024). Identification of the main flavonoids of Abelmoschus manihot (L.) medik and their metabolites in the treatment of diabetic nephropathy. Front. Pharmacol.14, 1290868. 10.3389/fphar.2023.1290868

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 29

  Ding L. Li S. Jiang Q. Guo Y. Chen Z. Dong L. (2013). Effects of total flavone of Abelmoschus manihot (L.) Medic on hemodynamics and myocardial oxygen consumption in anesthetized dogs. Chin. J. Pharmacol. Clin.29, 79–82. 10.13412/j.cnki.zyyl.2013.03.032

  • CrossRef
  • Google Scholar

• 30

  Du L.-y. Tao J.-h. Jiang S. Qian D.-w. Guo J.-m. Duan J.-a. (2017). Metabolic profiles of the Flos Abelmoschus manihot extract by intestinal bacteria from the normal and CKD model rats based on UPLC‐Q‐TOF/MS. Biomed. Chromatogr.31, e3795. 10.1002/bmc.3795

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 31

  Fan L. Dong L. Jiang Q. Cen D. Chen Z. Ma C. (2003a). Analgesic effect of Total Flavone of Abelmoschl manihot L medic. Chin. J. Tradit. Med., 12–14. 10.13412/j.cnki.zyyl.2003.01.007

  • CrossRef
  • Google Scholar

• 32

  Fan L. Dong L. Jiang Q. Cen D. Chen Z. Ma C. (2003b). Anti inflammatory and antipyretic effects of TFA. J Anhui Med Univ.25–27. 10.19405/j.cnki.issn1000-1492.2003.01.009

  • CrossRef
  • Google Scholar

• 33

  Fernando P. D. S. M. Piao M. J. Herath H. M. U. L. Kang K. A. Hyun C. L. Kim E. T. et al (2024). Hyperoside reduced particulate matter 2.5-induced endoplasmic reticulum stress and senescence in skin cells. Toxicol. Vitro99, 105870. 10.1016/j.tiv.2024.105870

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 34

  Gao S. Fan L. Dong L. Zhao W. Chen Z. (2003). Effect of TFA on cell apoptosis in MCAO rats. Chin. Pharmacol. Bull., 704–707. 10.3321/j.issn:1001-1978.2003.06.029

  • CrossRef
  • Google Scholar

• 35

  Gao Y. Liang Z. Lv N. Shan J. Zhou H. Zhang J. et al (2022). Exploring the total flavones of Abelmoschus manihot against IAV-induced lung inflammation by network pharmacology. BMC Complement. Med. Ther.22, 36–45. 10.1186/s12906-022-03509-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 36

  Gao R.-J. Aikeremu N. Cao N. Chen C. Ma K.-T. Li L. et al (2024). Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-β1-Smad2/3 pathway. BMC Cardiovasc Disord.24, 535. 10.1186/s12872-024-04192-4

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 37

  Gao T. Wang C. Yang X. He Z. Wang Y. Mi W. (2025). Hyperoside ameliorates neuropathic pain by modulating the astroglial reactivity in the vlPAG. Neuropharmacology.266, 110276. 10.1016/j.neuropharm.2024.110276

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 38

  Ge J. Miao J. Sun X. Yu J. (2016). Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator–activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. J. Ethnopharmacol.189, 238–249. 10.1016/j.jep.2016.05.033

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 39

  Geng Y. Dong Z. Wang Y. Zhang P. Tang J. Li P. et al (2023). Efficacy of huangkui capsules in the treatment of diabetic kidney disease: a systematic review and using network pharmacology. Integr. Med. Nephrol. Androl.10, 1–8. 10.1097/IMNA-D-22-00020

  • CrossRef
  • Google Scholar

• 40

  Gu L. Ge H. Zhao L. Wang Y. Zhang F. Tang H. et al (2020). Huangkui capsule ameliorates renal fibrosis in a unilateral ureteral obstruction mouse model through TRPC6 dependent signaling pathways. Front. Pharmacol.11, 996–1005. 10.3389/fphar.2020.00996

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 41

  Gu L. Yun S. Tang H. Xu Z. (2021). Huangkui capsule in combination with metformin ameliorates diabetic nephropathy via the Klotho/TGF-β1/p38MAPK signaling pathway. J. Ethnopharmacol.281, 113548–113561. 10.1016/j.jep.2020.113548

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 42

  Guo Y. Chen Z. (2002). Protective effect of abelmischl manihot medic against cerebral ischemia-reperfusion injury. Chin. Pharmacol. Bull., 692–695. 10.3321/j.issn:1001-1978.2002.06.026

  • CrossRef
  • Google Scholar

• 43

  Guo Y. Wang S. (2017). Clinical Study of Erhuang Ointment combined with recombinant human granulocyte-macrophage colony stimulating factor gel in the treatment of superficial second-degree burns. J. Tradit. Chin. Med. Pharm.23, 90–92. 10.13862/j.cnki.cn43-1446/r.2017.14.030

  • CrossRef
  • Google Scholar

• 44

  Guo J. Xue C. Duan J. Qian D. Tang Y. You Y. (2011). Anticonvulsant, antidepressant-like activity of abelmoschus manihot ethanol extract and its potential active components in vivo. Phytomedicine18, 1250–1254. 10.1016/j.phymed.2011.06.012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 45

  Guo X. Liu Y. Zhang Q. Shang L. (2021). Comparative study on contents of flavonoids indifferent parts of Abelmoschi Corolla. Food Drug23, 514–520.

  • Google Scholar

• 46

  Han X. Situ M. (1997). 82 cases of oral mucosal ulcer treated with abelmoschus manihot paste. Anhui J. Clin.TCM, 308–309.

  • Google Scholar

• 47

  Han X. Si T. Man L. (1997). The treatment of oral mucosal ulcers with Huang Shukui Paste: a Study of 82 cases. Anhui Clin. J. Tradit. Chin. Med., 308–310. 10.16448/j.cjtcm.1997.06.024

  • CrossRef
  • Google Scholar

• 48

  Hao J. Zhou L. (2009). Effects of total flavone of Abelmoschus Manihot L. Medic on the expression of corticotropin releasing factor in rats with post stroke depression. Anhui Med. Pharm. J.13, 1025–1027. 10.3969/j.issn.1009-6469.2009.09.008

  • CrossRef
  • Google Scholar

• 49

  Hao J. Zhou L. Si L. Jiang Q. Ma Y. Yan H. (2007). Effects of total flavone of abelmoschus manihot on pos-stroke depression in rats. China Pharm., 885–887. 10.3969/j.issn.1001-0408.2007.12.002

  • CrossRef
  • Google Scholar

• 50

  He Z. Zhou Q. Wen K. Wu B. Sun X. Wang X. et al (2019). Huangkui Lianchang Decoction ameliorates DSS-Induced ulcerative colitis in mice by inhibiting the NF-kappaB signaling pathway. Evid. Based Complement. Altern. Med.2019. 10.1155/2019/1040847

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 51

  He Z. Zhou Q. Wu B. Wen K. Wang X. Chen Y. (2020). Huangkui Lianchang decoction improving inflammatory effect of DSS-Induced UC mice by regulating IL-6/STAT3 Pathway and IL-23/IL-17 inflammatory axis. China J. Chin. Med.35, 821–826. 10.16368/j.issn.1674-8999.2020.04.183

  • CrossRef
  • Google Scholar

• 52

  He X. Wei X. Wang Q. Xi Z. (2023). Curative effect of Huangkui Lianchang Decoction and Western medicine in treatment of inflammatory bowel disease. Liaoning J. Tradit. Chin. Med.50, 90–93. 10.13192/j.issn.1000-1719.2023.05.025

  • CrossRef
  • Google Scholar

• 53

  Hong G. Quan H. Yu K. Quan X. (2021). The relationship between the size of abelmoschus manihot buds and pollen development stages. Mod. Hortic.44, 4–5. 10.14051/j.cnki.xdyy.2021.19.002

  • CrossRef
  • Google Scholar

• 54

  Hou J. Qian J. Li Z. Gong A. Zhong S. Qiao L. et al (2020). Bioactive compounds from abelmoschus manihot L. alleviate the progression of multiple myeloma in mouse model and improve bone marrow microenvironment. Onco Targets Ther.13, 959–973. 10.2147/OTT.S235944

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 55

  Hsuan C. Tsai I. T. Fang L. Chang T. Chen Y. Houng H. et al (2024). Aibika flower Flavonoid extract exhibits antiulcer activity in a murine model of ethanol-induced Acute Gastric injury. J. Med. Food27, 615–626. 10.1089/jmf.2024.k.0015

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 56

  Hu Y. (2016). Application of chuangling liquid in skin damage caused by Winter disease treatment in summer with pasting therapy. Chin. J. Emerg. Tradit. Chin. Med.25, 2008–2010. 10.3969/j.issn.1004-745X.2016.10.060

  • CrossRef
  • Google Scholar

• 57

  Hu C. Dai M. Chen J. Xuan Z. (2011). Therapeutic effects of total flavones of abelmoschus Manihot (L.) medic on chronic nephritis of heat-dampness type and its influence on immune adherence ability of red blood cell. J. Anhui TCM Coll.30, 57–61. 10.3969/j.issn.1000-2219.2011.01.021

  • CrossRef
  • Google Scholar

• 58

  Huang Z. Chen J. (2012). Efficacy analysis of treating 28 cases of ulcer stage bedsores by the Chuangling liquid plus Shengji Yuhong ointment. J. TCM Clin. Res.4, 108–110. 10.3969/j.issn.1674-7860.2012.18.066

  • CrossRef
  • Google Scholar

• 59

  Jain P. S. Todarwal A. A. Bari S. B. Surana S. J. (2011). Analgesic Activity of Abelmoschus manihot extracts. Int. J. Pharmacol.7, 716–720. 10.3923/ijp.2011.716.720

  • CrossRef
  • Google Scholar

• 60

  Jayachandran M. Wu Z. Ganesan K. Khalid S. Chung S. M. Xu B. (2019). Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines and regulates AMPK pathway in streptozotocin-induced diabetic rats. Chem. Biol. Interact.303, 62–69. 10.1016/j.cbi.2019.02.017

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 61

  Jayachandran M. Zhang T. Wu Z. Liu Y. Xu B. (2020). Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ-induced diabetic rats. Mol. Biol. Rep.47, 593–602. 10.1007/s11033-019-05166-y

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 62

  Jiang Q. Dong L. Fang M. Li J. Chen Z. Ma C. (2006). Antiviral action of total flavone of abelmoschus Manihot L medic in vitro. Anhui Med. J., 93–94. 10.3969/j.issn.1009-6469.2006.02.005

  • CrossRef
  • Google Scholar

• 63

  Karadeniz F. Oh J. H. Jo H. J. Seo Y. Kong C. S. (2021). Myricetin 3-O-β-D-Galactopyranoside exhibits potential anti-osteoporotic properties in human bone marrow-derived mesenchymal stromal cells via stimulation of osteoblastogenesis and suppression of adipogenesis. Cells10, 1–12. 10.3390/cells10102690

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 64

  Kim H. Dusabimana T. Kim S. R. Je J. Jeong K. Kang M. C. et al (2018). Supplementation of abelmoschus manihot ameliorates diabetic nephropathy and hepatic steatosis by activating autophagy in mice. Nutrients10, 1703. 10.3390/nu10111703

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 65

  Li D. (2016). Observation on the effect and nursing of chuangling liquid combined with Zhilou Fumigationand wash lotion on postoperative wound of mixed hemorrhoids. Mod. Distance Educ. Chin. Med.14, 116–117. 10.3969/j.issn.1672-2779.2016.09.050

  • CrossRef
  • Google Scholar

• 66

  Li D. (2017). Observation on the curative effect and nursing of chuangling solution combined with Photon therapeutic instrument on postoperative mixed hemorrhoids. China J. TCMDE15, 121–123. 10.3969/j.issn.1672-2779.2017.10.053

  • CrossRef
  • Google Scholar

• 67

  Li J. (1993). Erhuangointment for the treatment of erosive hand-foottinea (Athlete’s foot). Jiangxi Univ. Tradit. Chin. Med.62.

  • Google Scholar

• 68

  Li J. Yu R. Lin X. Wang K. (2006). Pharmacological Study of abelmoschus manihot flower extract on oral mucosal ulcers in rabbits. J. Shandong Univ. Tradit. Chin. Med., 497–498. 10.16294/j.cnki.1007-659x.2006.06.028

  • CrossRef
  • Google Scholar

• 69

  Li J. Zhang J. Wang M. (2016a). Extraction of flavonoids from the flowers of abelmoschus manihot (L.) medic by modified supercritical CO2 extraction and determination of antioxidant and anti-adipogenic activity. Molecules21, 1–9. 10.3390/molecules21070810

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 70

  Li Z. Wu S. Quan X. Jin M. (2016b). Study on flowering and seed setling biology of abelmoschus manihot. Seed35, 25–28. 10.16590/j.cnki.1001-4705.2016.02.025

  • CrossRef
  • Google Scholar

• 71

  Li P. Chen Y. Lin H. Ni Z. Zhan Y. Wang R. et al (2017). Abelmoschus manihot – a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial. Trials18, 170–173. 10.1186/s13063-016-1774-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 72

  Li M. Song C. Wang S. Xue Y. Ma Y. (2018). Effects of total flavone of Abelmoschl manihot combined with glipizide on model rats of diabetic nephropathy. Chin. J. Pharmacol. Vigil.15, 12–15. 10.3969/j.issn.1672-8629.2018.01.003

  • CrossRef
  • Google Scholar

• 73

  Li W. He W. Xia P. Sun W. Shi M. Zhou Y. et al (2019). Total extracts of abelmoschus manihot L. Attenuates Adriamycin-Induced renal tubule injury via suppression of ROS-ERK1/2-Mediated NLRP3 inflammasome activation. Front. Pharmacol.10, 567–578. 10.3389/fphar.2019.00567

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 74

  Li D. Chang J. Wang Y. Du X. Xu J. Cui J. et al (2024a). Hyperoside mitigates photoreceptor degeneration in part by targeting cGAS and suppressing DNA-induced microglial activation. Acta Neuropathol. Commun.12, 76–88. 10.1186/s40478-024-01793-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 75

  Li Y. Wu C. Song C. Liu S. Nan Z. (2024b). Efficacy and safety of Huangkui capsule for diabetic nephropathy: a systematic review and meta-analysis. Medicine103, e38417–e38417. 10.1097/MD.0000000000038417

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 76

  Li Q. Zhang H. He Y. Zhang H. Han C. (2025). Inhibition of colorectal cancer metastasis by total flavones of abelmoschus manihot via LncRNA AL137782-mediated STAT3/EMT pathway regulation. Curr. Pharm. Des.31, 219–232. 10.2174/0113816128298998240828060306

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 77

  Lin X. Gao K. Miao X. Wu Q. (2020a). Study on prevention and treatment effect of Jiahua Tablets on postoperative AKI in patients with coronary intervention. Chongqing Med.49, 4055–4057. 10.3969/j.issn.1671-8348.2020.24.003

  • CrossRef
  • Google Scholar

• 78

  Lin X. Wang Y. Miao X. Gao K. Wu Q. (2020b). Clinical study on Jiahua tablet in preventing and treating contrast-medium nephropathy in patients undergoing coronary intervention. Mod. J. Integr. Tradit. West Med.29, 3882–3885. 10.3969/j.issn.1008-8849.2020.35.002

  • CrossRef
  • Google Scholar

• 79

  Liu Y. (2019). Research on the application value of photon therapeutic apparatus irradiation combined with chuangling liquid wet compression in the nursing of lung cancer patients with diabetic foot. Chin. J. Feet Health28, 49–50. 10.19589/j.cnki.issn1004-6569.2019.13.049

  • CrossRef
  • Google Scholar

• 80

  Liu M. Jiang Q. Rao J. Zhou L. (2009). Protective effect of total flavones of Abelmoschus manihot L. medic against poststroke depression injury in mice and its action mechanism. Anat. Rec. Hob.292, 412–422. 10.1002/ar.20864

  • CrossRef
  • Google Scholar

• 81

  Liu S. Jiang W. Wu B. (2010). Research progress on the chemical composition and pharmacological activity of abelmoschus manihot Mod Chin med. 12, 5–9. 10.13313/j.issn.1673-4890.2010.08.006

  • CrossRef
  • Google Scholar

• 82

  Liu Z. Li Y. Zhou Y. Yong T. Xu J. Lu Y. (2012). The progress of research on the chemical composition and pharmacokinetics of abelmoschus manihot. Cent. South Pharm.10, 839–841. 10.3969/j.issn.1672.2981.2012.11.012

  • CrossRef
  • Google Scholar

• 83

  Liu J. Guo S. Duan J. Yan H. Qian D. Tang H. et al (2016). Analysis and utilization value discussion of multiple chemical composition in different tissues of Abelmoschus manihot. Zhongguo Zhong Yao Za Zhi41, 3782–3791. 10.4268/cjcmm20162013

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 84

  Liu S. Ye L. Tao J. Ge C. Huang L. Yu J. (2017). Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats. Pharm. Biol.56, 1–11. 10.1080/13880209.2017.1412467

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 85

  Liu L. Duan P. Yan S. Wang H. Wang Z. Huo X. (2018). Antibacterial effeet of Chuanglingye in vitro and its effeet on rat skin and external diseases model withsensitive bacteria infection. Jiangsu Med.44, 1370–1372. 10.19460/j.cnki.0253-3685.2018.12.004

  • CrossRef
  • Google Scholar

• 86

  Liu B. Tu Y. Ni G. Yan J. Yue L. Li Z. et al (2021a). Total flavones of abelmoschus manihot ameliorates podocyte pyroptosis and injury in high glucose conditions by targeting METTL3-Dependent m6A modification-mediated NLRP3-Inflammasome activation and PTEN/PI3K/Akt signaling. Front. Pharmacol.12, 667644–667673. 10.3389/fphar.2021.667644

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 87

  Liu C. Jia Y. Qiu Y. (2021b). Ethyl acetate fraction of Abelmoschus manihot (L.) medic flowers exerts inhibitory effects against oxidative stress in H2O2-Induced HepG2 cells and D-Galactose-Induced aging mice. J. Med. Food24, 997–1009.

  • Pubmed Abstract
  • Google Scholar

• 88

  Liu C. Jia Y. Qiu Y. (2021c). Ethyl acetate fraction of Abelmoschus manihot (L.) medic flowers exerts inhibitory effects against oxidative stress in H2O2-Induced HepG2 cells and D-Galactose-Induced aging mice. J. Med. Food24, 997–1009. 10.1089/jmf.2021.K.0053

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 89

  Liu H.-J. Miao H. Yang J.-Z. Liu F. Cao G. Zhao Y.-Y. (2023). Deciphering the role of lipoproteins and lipid metabolic alterations in ageing and ageing-associated renal fibrosis. Ageing Res. Rev.85, 101861. 10.1016/j.arr.2023.101861

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 90

  Lou Y. Yu X. Sun X. Miao Y. Xu W. Zha M. (2022). Experimental Study on the intervention effects of qikui granules on type 2 diabetes rats with osteoporosis. J. West Chin. Med.35, 25–28. 10.12174/j.issn.2096-9600.2022.06.07

  • CrossRef
  • Google Scholar

• 91

  Lu J. Wang Y. Zhang S. Li J. Li C. Xu X. et al (2020a). Huang-Kui-Si-Wu Formula decreases uremic toxin production by modulating intestinal microbial metabolic pathways. Acta Pharm. Sin.55, 1229–1236. 10.16438/j.0513-4870.2019-0852

  • CrossRef
  • Google Scholar

• 92

  Lu T. Bian Y. Zhu Y. Guo M. Yang Y. Guo J. et al (2020b). HUANGKUISIWUFANG inhibits pyruvate dehydrogenase to improve glomerular injury in anti-Thy1 nephritis model. J. Ethnopharmacol.253, 112682. 10.1016/j.jep.2020.112682

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 93

  Lu J. Wang Y. Peng Y. Xu X. Chen C. Duan J. et al (2021). Effect of Huangkui Siwu Formula on metabolism and transportation pathway of urotoxin p-cresyl sulfate in vivo. Zhong Cao Yao52, 176–185. 10.7501/j.issn.0253-2670.2021.01.021

  • CrossRef
  • Google Scholar

• 94

  Luan F. Wu Q. Yang Y. Lv H. Liu D. Gan Z. et al (2020). Traditional uses, chemical constituents, biological properties, clinical settings, and toxicities of abelmoschus manihot L.: a comprehensive review. Front. Pharmacol.11, 1068. 10.3389/fphar.2020.01068

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 95

  Luo M. Liu Z. Hu Z. He Q. (2022). Quercetin improves contrast-induced acute kidney injury through the HIF-1α/lncRNA NEAT1/HMGB1 pathway. Pharm. Biol.60, 889–898. 10.1080/13880209.2022.2058558

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 96

  Lv D. Cheng X. Tang L. Jiang M. (2017). The cardioprotective effect of total flavonoids on myocardial ischemia/reperfusion in rats. Biomed. and Pharmacother.88, 277–284. 10.1016/j.biopha.2017.01.060

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 97

  Mao Z. Shen S. Wan Y. Sun W. Chen H. Huang M. et al (2015). Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid. J. Ethnopharmacol.173, 256–265. 10.1016/j.jep.2015.07.036

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 98

  Miao H. (2013). Observation on the efficacy of wet compression with chuangling liquid combined with heat-sensitive moxibustion in the treatment of stage Ⅲ - Ⅳ Pressure Ulcers in Elderpy StrokeuPatients.eJ. Nurs. sci.20p 68–70. 10.16460/j.issn1008-9969.2013.22.005

  • CrossRef
  • Google Scholar

• 99

  Miao H. Liu F. Wang Y.-N. Yu X.-Y. Zhuang S. Guo Y. et al (2024a). Targeting Lactobacillus johnsonii to reverse chronic kidney disease. Signal Transduct. Target. Ther.9, 195. 10.1038/s41392-024-01913-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 100

  Miao H. Wang Y.-N. Yu X.-Y. Zou L. Guo Y. Su W. et al (2024b). Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites. Br. J. Pharmacol.181, 162–179. 10.1111/bph.16219

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 101

  Neurath M. F. (2014). New targets for mucosal healing and therapy in inflammatory bowel diseases. Mucosal Immunol.7, 6–19. 10.1038/mi.2013.73

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 102

  Niu R. Lin X. Xu Z. Liu J. Wang Y. Miao X. et al (2023). Efficacy observation of Jiahua tablet on contrast agent-induced kidney injury based on KIM-1 and MCP-1. Shanxi J. TCM39, 18–20. 10.20002/j.issn.1000-7156.2023.04.007

  • CrossRef
  • Google Scholar

• 103

  Ogunro O. B. Olasehinde O. R. (2024). Neuroinflammatory response and redox-regulation activity of hyperoside in manganese-induced neurotoxicity model of Wistar rats. Curr. Aging Sci.17, 220–236. 10.2174/0118746098277166231204103616

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 104

  Oh J. H. Karadeniz F. Lee J. I. Park S. Y. Seo Y. Kong C. S. (2020). Anticatabolic and anti-inflammatory effects of myricetin 3-O-β-d-Galactopyranoside in UVA-Irradiated dermal cells via repression of MAPK/AP-1 and activation of TGFβ/Smad. Molecules25, 1331–1345. 10.3390/molecules25061331

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 105

  Page M. J. McKenzie J. E. Bossuyt P. M. Boutron I. Hoffmann T. C. Mulrow C. D. et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ372, 71–88. 10.1136/bmj.n71

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 106

  Pan X. Tao J. Jiang S. Zhu Y. Qian D. Duan J. (2018). Characterization and immunomodulatory activity of polysaccharides from the stems and leaves of Abelmoschus manihot and a sulfated derivative. Int. J. Biol. Macromol.107, 9–16. 10.1016/j.ijbiomac.2017.08.130

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 107

  Park Y. I. Cha Y. E. Jang M. Park R. Namkoong S. Kwak J. et al (2020). The flower extract of abelmoschus manihot (Linn.) increases cyclin D1 expression and activates cell proliferation. J. Microbiol. Biotechnol.30, 1044–1050. 10.4014/jmb.2002.02024

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 108

  Pei W. (2018). Observation on the efficacy of chuangling liquid combined with traditional Chinese medicine fumigation and washing in the treatment of diabetic foot. Prac. J. Clin. Nurs.3, 73–74. 10.3969/j.issn.2096-2479.2018.39.059

  • CrossRef
  • Google Scholar

• 109

  Pei S. Li Y. (2021). Huangkui capsule in combination with leflunomide improves immunoglobulin A nephropathy by inhibiting the TGF-β1/Smad3 signaling pathway. Clinics76, 2904–2911. 10.6061/clinics/2021/e2904

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 110

  Puel C. Mathey J. Kati-Coulibaly S. Davicco M. J. Lebecque P. Chanteranne B. et al (2005). Preventive effect of Abelmoschus manihot (L.) medik. On bone loss in the ovariectomised rats. J. Ethnopharmacol.99, 55–60. 10.1016/j.jep.2005.01.047

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 111

  Qian Q. Zhou Y. An X. (2023). Research progress of treating diabetic kidney disease with abelmoschus manihot. Henan J. Tradit. Chin. Med.43, 1257–1264. 10.16367/j.issn.1003-5028.2023.08.0249

  • CrossRef
  • Google Scholar

• 112

  Qiao L. Fang L. Zhu J. Xiang Y. Xu H. Sun X. et al (2021). Total flavone of abelmoschus manihot ameliorates TNBS-induced colonic fibrosis by regulating Th17/Treg balance and reducing extracellular matrix. Front. Pharmacol.12, 769793. 10.3389/fphar.2021.769793

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 113

  Qin G. Ma J. Huang Q. Yin H. Han J. Li M. et al (2018). Isoquercetin improves hepatic lipid accumulation by activating AMPK pathway and suppressing TGF-β signaling on an HFD-Induced nonalcoholic Fatty Liver Disease rat model. Int. J. Mol. Sci.19, 4126–4154. 10.3390/ijms19124126

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 114

  Qiu Y. Ai P. Song J. Liu C. Li Z. (2017). Total flavonoid extract from Abelmoschus manihot (L.) medic flowers attenuates D-Galactose-Induced oxidative stress in mouse liver through the Nrf2 pathway. J. Med. Food20, 557–567. 10.1089/jmf.2016.3870

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 115

  Rey D. Fernandes T. A. Sulis P. M. Goncalves R. Sepulveda R M. Silva Frederico M. J. et al (2020). Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle. Chem. Biol. Interact.330, 109198. 10.1016/j.cbi.2020.109198

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 116

  Riemschneider S. Hoffmann M. Slanina U. Weber K. Hauschildt S. Lehmann J. (2021). Indol-3-Carbinol and Quercetin Ameliorate chronic DSS-Induced colitis in C57BL/6 mice by AhR-Mediated anti-inflammatory mechanisms. Int. J. Environ. Res. Public Health18, 2262. 10.3390/ijerph18052262

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 117

  Shao G. (2012). The characteristics and cultivation techniques of abelmoschus manihot. Mod. Agric. Sci. Technol., 110–119. 10.3969/j.issn.1007-5739.2012.23.069

  • CrossRef
  • Google Scholar

• 118

  Shao X. Yu J. Ni W. (2017). The Study of the renal protective effects and mechanisms of qikui granules on STZ-Induced diabetic nephropathy in rats. Zhong Yao Cai40, 2437–2440. 10.13863/j.issn1001-4454.2017.10.045

  • CrossRef
  • Google Scholar

• 119

  Sheng J. (2014). Treatment and nursing experience of chuangling liquid in 20 patients with oral pressure ulcers caused by tracheal intubation. Hunan J. TCM30, 102–103. 10.16808/j.cnki.issn1003-7705.2014.12.057

  • CrossRef
  • Google Scholar

• 120

  Shi R. Tao Y. Tang H. Wu C. Fei J. Ge H. et al (2023). Abelmoschus Manihot ameliorates the levels of circulating metabolites in diabetic nephropathy by modulating gut microbiota in Non-obese diabetes mice. Microb. Biotechnol.16, 813–826. 10.1111/1751-7915.14200

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 121

  Shu X. Chen H. Zhou H. Jiang Y. Zou J. Liu Z. (2016). HPLC determination of 9 components in chuanglingye. Cent. South Pharm.14, 1354–1358. 10.7539/j.issn.1672-2981.2016.12.017

  • CrossRef
  • Google Scholar

• 122

  Silva D. d.C. Orfali G. D. C. Santana M. G. Palma J. K. Y. Assuncao I. R. d.O. Marchesi I. M. et al (2022). Antitumor effect of isoquercetin on tissue vasohibin expression and colon cancer vasculature. Oncotarget13, 307–318. 10.18632/oncotarget.28181

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 123

  Song Y. Fu Z. Zhu X. Zhang J. Bai W. Song B. (2024). The flower of Abelmoschus manihot (L.) medik exerts antioxidant effects by regulating the Nrf2 signalling pathway in scald injury. Wound Repair Regen.32, 123–134. 10.1111/wrr.13146

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 124

  Su J. Yang F. Kang X. Liu J. Tao Y. Diao Q. et al (2022). Chalcone derivatives from abelmoschus manihot seeds restrain NLRP3 inflammasome assembly by inhibiting ASC oligomerization. Front. Pharmacol.13, 932198. 10.3389/fphar.2022.932198

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 125

  Sun H. Yuan Y. Zhou L. Yu J. Sun Z. (2014). Effeet of YuKuiOing on the expression of monoeyte chemoattractant protein-1 and fractalkine induced by AGEs. Chin. J. Diabetes22, 942–946. 10.3969/j.issn.1006-6187.2014.10.017

  • CrossRef
  • Google Scholar

• 126

  Sun J. Wen C. Zhang B. Bao X. (2019). The protective effect of quercetin on vascular endothelial progenitor cells by regulating PI3K/Akt signaling pathway and its mechanisms. Chin. Pharmacol. Bull.35, 85–90. 10.3969/j.issn.1001-1978.2019.01.017

  • CrossRef
  • Google Scholar

• 127

  Sun Z. Liu W. Zhang S. Tian S. Aikemu A. (2024). Optimization of flavonoid extraction from abelmoschus manihot flowers using ultrasonic techniques: predictive modeling through response surface methodology and deep neural network and biological activity assessment. Molecules29, 2610. 10.3390/molecules29112610

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 128

  Tang L. Pan W. Zhu G. Liu Z. Lv D. Jiang M. (2017). Total flavones of abelmoschus manihot enhances angiogenic ability both in vitro and in vivo. Oncotarget8, 69768–69778. 10.18632/oncotarget.19264

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 129

  Tao P. Huo J. Chen L. (2024a). Bibliometric analysis of the relationship between Gut Microbiota and chronic kidney disease from 2001–2022. Integr. Med. Nephrol. Androl.11. 10.1097/IMNA-D-23-00017

  • CrossRef
  • Google Scholar

• 130

  Tao Y. Liu J. Li M. Wang H. Fan G. Xie X. et al (2024b). Abelmoschus manihot (L.) medik. seeds alleviate rheumatoid arthritis by modulating JAK2/STAT3 signaling pathway. J. Ethnopharmacol.325, 117641. 10.1016/j.jep.2023.117641

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 131

  Teng D. Ji C. (2016). Clinical observation of 30 cases of stage II pressure ulcers treated with the combination of chuangling liquid and mepilex. Jiangsu J. TCM.48, 33–34.

  • Google Scholar

• 132

  Todarwal A. Jain P. Bari S. (2011). Abelmoschus manihot Linn: ethnobotany, phytochemistry and pharmacology. Asian J. Tradit. Med.6, 114–129.

  • Google Scholar

• 133

  Topcu-Tarladacalisir Y. Sapmaz-Metin M. Mercan Z. Ercetin D. (2024). Quercetin Attenuates endoplasmic Reticulum stress and apoptosis in TNBS-Induced colitis by inhibiting the glucose regulatory protein 78 activation. Balk. Med. J.41, 30–37. 10.4274/balkanmedj.galenos.2023.2023-10-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 134

  Tu Y. Fang Q. Sun W. Liu B. Liu Y. Wu W. et al (2020). Total flavones of abelmoschus manihot remodels Gut Microbiota and inhibits microinflammation in chronic renal failure progression by targeting autophagy-mediated macrophage polarization. Front. Pharmacol.11, 566611. 10.3389/fphar.2020.566611

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 135

  Wang C. Feng Z. Xu Y. Yao C. Shi Y. (2016). Clinical Study on the treatment of 20 cases of chronic lower extremity ulcers with chuangling liquid-loaded collagen. Jiangsu J. TCM48, 37–40.

  • Google Scholar

• 136

  Wang C. Shi Y. Tang M. Zhang X. Gu Y. Liang X. et al (2017). Isoquercetin ameliorates cerebral impairment in focal ischemia through Anti-Oxidative, Anti-Inflammatory, and anti-apoptotic effects in primary culture of rat hippocampal neurons and hippocampal CA1 Region of rats. Mol. Neurobiol.54, 2126–2142. 10.1007/s12035-016-9806-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 137

  Wang Q. Wei Y. Dong Y. (2020). Clinical effect between chuangling solution wet-compressing and povid one iodine-diluent wet-compressing in thetreatment of puncture site infection afterperipherally inserted central catheter placement. Int J Nurs Integr Med (Chin and Eng).6, 61–64. 10.11997/nitcwm.202001014

  • CrossRef
  • Google Scholar

• 138

  Wang R. Chen T. Wang Q. Yuan X. Duan Z. Feng Z. et al (2021). Total flavone of abelmoschus manihot ameliorates stress-induced microbial alterations drive intestinal barrier injury in DSS colitis. Drug Des. Devel Ther.15, 2999–3016. 10.2147/dddt.s313150

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 139

  Wang K. Lu C. Wang T. Qiao C. Lu L. Wu D. et al (2022a). Hyperoside suppresses NLRP3 inflammasome in Parkinson's disease via Pituitary Adenylate Cyclase-Activating Polypeptide. Neurochem. Int.152, 105–121. 10.1016/j.neuint.2021.105254

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 140

  Wang S. W. Chang C. C. Hsuan C. F. Chang T. H. Chen Y. L. Wang Y. Y. et al (2022c). Neuroprotective effect of abelmoschus manihot flower extracts against the H2O2-Induced cytotoxicity, oxidative stress and inflammation in PC12 cells. Bioeng. (Basel)9, 596–611. 10.3390/bioengineering9100596

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 141

  Wang L. Feng F. Zhou J. Ruan Y. Zha M. Pu Q. et al (2023a). Short-term effect of Qi-Kui granules combined with dulaglutide in the treatment of clinical stage of diabetic kidney disease in the elderly. Pract. J. Geriatr. Med.37, 348–351. 10.3969/j.issn.1003-9198.2023.04.007

  • CrossRef
  • Google Scholar

• 142

  Wang M. Cai Y. Fang Q. Liu Y. Wang J. Chen J. et al (2023b). Inhibition of ferroptosis of renal tubular cells with total flavones of Abelmoschus manihot alleviates diabetic tubulopathy. Anat. Rec. Hob.306, 3199–3213. 10.1002/ar.25123

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 143

  Wang J. Liao E. Ren Z. Wang Q. Xu Z. Wu S. et al (2024a). Extraction and in vitro skincare effect assessment of polysaccharides extract from the roots of abelmoschus manihot (L.). Molecules29, 2109. 10.3390/molecules29092109

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 144

  Wang S. W. Lee T. L. Chang T. H. Chen Y. L. Houng H. Y. Chang N. et al (2024b). Antidiabetic potential of abelmoschus manihot flower extract: in vitro and intracellular studies. Medicina60, 1211–1212. 10.3390/medicina60081211

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 145

  Wang T. Hu L. Li R. Ren H. Li S. Sun Q. et al (2024c). Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways. J. Virol.98, 159–174. 10.1128/jvi.00159-24

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 146

  Wang Y. Li C. Li J. Zhang S. Zhang Q. Duan J. et al (2024d). Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance. Acta Pharm. Sin. B14, 3901–3915. 10.1016/j.apsb.2024.06.002

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 147

  Wang Y.-n. Wu X. Shan Q.-y. Yang Q. Yu X.-y. Yang J.-h. et al (2025). Acteoside-containing caffeic acid is bioactive functional group of antifibrotic effect by suppressing inflammation via inhibiting AHR nuclear translocation in chronic kidney disease. Acta Pharmacol. Sin.46, 2975–2988. 10.1038/s41401-025-01598-4

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 148

  Wei C. Wang C. Li R. Bai Y. Wang X. Fang Q. et al (2023). The pharmacological mechanism of Abelmoschus manihot in the treatment of chronic kidney disease. Heliyon9, 22017. 10.1016/j.heliyon.2023.e22017

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 149

  Weingarden A. R. Vaughn B. P. (2017). Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease. Gut Microbes8, 238–252. 10.1080/19490976.2017.1290757

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 150

  Wen J. Chen Z. (2006). Protective effect of pharmacological preconditioning of total flavone of abelmoschl Manihot on cerebral ischemicre perfusion injury in rats. J Anhui Med Univ.667–669. 10.19405/j.cnki.issn1000-1492.2006.06.018

  • CrossRef
  • Google Scholar

• 151

  Wen J. Feng Z. Xu Y. Yao C. Shi Y. (2017). Protective effect of total flavones of abelmoschl manihot on hippocampal neurons subjected to anoxia-reoxygenation injury. Chin. J. Clin. Pharmacol. Ther.22, 367–372.

  • Google Scholar

• 152

  Wen R. Xie G. Li X. Qin M. (2015). Advance research on chemical constituents and pharmacological activities of abelmoschus manihot (L.) medic. Chin. Wild Plant Res.34, 37–44. 10.3969/j.issn.1006-9690.2015.02.010

  • CrossRef
  • Google Scholar

• 153

  Wu Z. (2011). The effects of unsaturated fatty acids from Jin Hua Kui seeds on blood lipids and liver function in experimental hyperlipidemic rats. Zhong Cheng Yao33, 1245–1247. 10.3969/j.issn.1001-1528.2011.07.045

  • CrossRef
  • Google Scholar

• 154

  Wu Q. Lin X. Miao X. Liu F. (2020). Effects of Jiahua Tablet on renal injury index of patients with nephropathy after coronary angiography or PCI. Nanjing J. TCM36, 189–192. 10.14148/j.issn.1672-0482.2020.0189

  • CrossRef
  • Google Scholar

• 155

  Wu B. Zhou Q. He Z. Wang X. Sun X. Chen Y. (2021). Protective effect of the Abelmoschus manihot flower extract on DSS-Induced ulcerative colitis in mice. Evid. Based Complement. Altern. Med.2021, 7422792–7427431. 10.1155/2021/7422792

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 156

  Wu C. Tang H. Cui X. Li N. Fei J. Ge H. et al (2024). A single-cell profile reveals the transcriptional regulation responded for Abelmoschus manihot (L.) treatment in diabetic kidney disease. Phytomedicine130, 155642–155655. 10.1016/j.phymed.2024.155642

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 157

  Xia J. Wan Y. Wu J.-j. Yang Y. Xu J.-F. Zhang L. et al (2024). Therapeutic potential of dietary flavonoid hyperoside against non-communicable diseases: targeting underlying properties of diseases. Crit. Rev. Food Sci. Nutr.64, 1340–1370. 10.1080/10408398.2022.2115457

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 158

  Xie S. Cao W. Hu Y. Chu X. Zhu B. Yu J. et al (2017a). Effects of Qi Kui granules on urine protein and inflammatory markers in patients with type 2 diabetic nephropathy. World Sci-Tech J. TCM Mod.19, 149–153.

  • Google Scholar

• 159

  Xie S. Cao W. Hu Y. Chu X. Zhu B. Yu J. et al (2017b). Effects of Qi Kui granules on urine protein and inflammatory markers in patients with type 2 diabetic nephropathy. World Sci. Technol. - Mod. Tradit. Chin. Med.19, 149–153. 10.11842/wst.2017.01.022

  • CrossRef
  • Google Scholar

• 160

  Xu Z. (2010). Clinical observation of chuangling liquid in the treatment of 16 cases of stage Ⅳ Pressure Ulcprs. Jiangsu J. TCM42, 47–49. 10.3969/j.issn.1672-397X.2010.11.033

  • CrossRef
  • Google Scholar

• 161

  Xu F. (2017). Influence of chuangling lotion on wound-surface healing after operation of anal fistula and abscess. China J. Coloproctol.37, 65–66. 10.3969/j.issn.1000-1174.2017.08.029

  • CrossRef
  • Google Scholar

• 162

  Xu Z. Cai H. (2010). Treatment of stage Ⅳ Pressure Ulcprs with uhe Combination cf Chuangling Lcquid and Ildophor WetiCompresswon.cJ. Nurs. Sci.25, 56–57. 10.3870/hlxzz.2010.21.056

  • CrossRef
  • Google Scholar

• 163

  Xu Z. Qian L. Niu R. Wang Y. Yang Y. Liu C. et al (2022). Mechanism of abelmoschus manihot L. in the treatment of contrast-induced nephropathy on the basis of network pharmacology analysis. Front. Nephrol.2, 834513–834515. 10.3389/fneph.2022.834513

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 164

  Xu Z. Wang Y. Yang W. Han W. Ma B. Zhao Y. et al (2024). Total extracts from Abelmoschus manihot (L.) alleviate radiation-induced cardiomyocyte ferroptosis via regulating redox imbalances mediated by the NOX4/xCT/GPX4 axis. J. Ethnopharmacol.334, 1185–1198. 10.1016/j.jep.2024.118582

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 165

  Xue J. Cao S. Tang T. Wen Y. Ye B. (2020). External use of chuangling liquid for reducing mass caused by plasma cell mastitis. Chin. J. Integr. Med.40, 418–421. 10.7661/j.cjim.20200119.135

  • CrossRef
  • Google Scholar

• 166

  Xue C. Zhang X. Ge H. Tang Q. Jeon J. Zhao F. et al (2023). Total flavone of flowers of Abelmoschus manihot (L.) Medic inhibits the expression of adhesion molecules in primary mesenteric arterial endothelial cells and ameliorates dextran sodium sulphate-induced ulcerative colitis in mice. Phytomedicine112, 154713–154722. 10.1016/j.phymed.2023.154713

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 167

  Yan J. Y. Ai G. Zhang X. J. Xu H. J. Huang Z. M. (2015). Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats. J. Ethnopharmacol.172, 202–213. 10.1016/j.jep.2015.06.044

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 168

  Yan Q. Sheng M. Yu J. Huang L. Gu L. Zhang S. et al (2018). Effect of Qikui granule on microalbuminuria and progress in patients with early diabetic nephropathy. Chin. J. Integr. Tradit. West Med.38, 430–434. 10.7661/j.cjim.20180326.080

  • CrossRef
  • Google Scholar

• 169

  Yang N. (1997). Treatment of 38 Cases of Ischemic Ulcers with Chuangling Liquid. Nanjing J TCM Univ.310–311. 10.14148/j.issn.1672-0482.1997.05.035

  • CrossRef
  • Google Scholar

• 170

  Yang J. (2016). Erhuang ointment for the treatment of superficial second-degree burns. Jilin Univ. Tradit. Chin. Med.36, 905–908. 10.13463/j.cnki.jlzyy.2016.09.012

  • CrossRef
  • Google Scholar

• 171

  Yang B. Sun Z. Yu J. Gao F. Liu S. (2010). Effect of yukuiqing on expression of connective tissue growth factor in human real mesangial cells incubated with AGEs. China J. Tradit. Chin. Med. Pharm.25, 1102–1105.

  • Google Scholar

• 172

  Yang C. Zhu X. Yu J. Zhang D. (2016). Effect of Qikui Granules on the expression of TGF -β1 and MCP -1 in kidney of rats with diabetic nephropathy. Chin. J. Med. Guid13, 8–11.

  • Google Scholar

• 173

  Yang B. L. Zhu P. Li Y. R. Xu M. M. Wang H. Qiao L. C. et al (2018). Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis. World J. Gastroenterol.24, 3414–3425. 10.3748/wjg.v24.i30.3414

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 174

  Yang W. Cai L. He N. Meng H. (2023). Clinical Study of retention enema of Huangkui Lianchang Decoction in the treatment of ulcerative colitis with internal accumulation of damp - heat syndrome. Chin. Pharm.32, 100–103. 10.3969/j.issn.1006-4931.2023.15.022

  • CrossRef
  • Google Scholar

• 175

  Ye B. Xue J. Feng Z. Tang T. Yao C. (2021). Study on the effect of Chuangling Liquid on wound inflammation of non-actating mastitis. Mod. J. Integr. Med.30, 1825–1829. 10.3969/j.issn.1008-8849.2021.17.001

  • CrossRef
  • Google Scholar

• 176

  Yin C. Zhou Q. Hu W. Zhou Y. (2013). Application of Chuangling fluid in postoperative wound healing in patients with anal fistula or perianal abscess. Nurs. Res.27, 1491–1492. 10.3969/j.issn.1009-6493.2013.15.041

  • CrossRef
  • Google Scholar

• 177

  Yin S. Mei Y. Wei L. Zou L. Cai Z. Wu N. et al (2021). Comparison of multiple bioactive constituents in the corolla and other parts of Abelmoschus manihot. Molecules26, 1864. 10.3390/molecules26071864

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 178

  Yu H. Tang H. Wang M. Xu Q. Yu J. Ge H. et al (2023a). Effects of total flavones of Abelmoschus manihot (L.) on the treatment of diabetic nephropathy via the activation of solute carriers in renal tubular epithelial cells. Biomed. Pharmacother.169, 115899. 10.1016/j.biopha.2023.115899

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 179

  Yu H. Wang M. Yu J. Tang H. Xu Q. Cheng N. et al (2023b). Evaluation of the efficacy of Abelmoschus manihot (L.) on diabetic nephropathy by analyzing biomarkers in the glomeruli and proximal and distal convoluted tubules of the kidneys. Front. Pharmacol.14, 1215996–1216012. 10.3389/fphar.2023.1215996

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 180

  Zha M. Sun H. Zhang S. Ye L. Huang L. Chen S. et al (2020). Effect of Jiahua Tablets as adjuvant treatment on serum inflammatory factors levels and renal function in patients with early diabetic nephropathy. Guangxi Med.42, 2059–2061. 10.11675/j.issn.0253-4304.2020.16.01

  • CrossRef
  • Google Scholar

• 181

  Zhang Y. Zhou Q. (2012). Granulation process and prescription for Jiahua Tablet. Chin. Pharm.23, 2519–2521. 10.6039/j.issn.1001-0408.2012.27.08

  • CrossRef
  • Google Scholar

• 182

  Zhang A. Lu Y. Xu H. Chen B. Xue P. (1997). Pharmacology Study of chuamgningyie. Jiangsu Pharm. Clin. Res., 14–18. 10.13664/j.cnki.pcr.1997.04.006

  • CrossRef
  • Google Scholar

• 183

  Zhang H. Dong L. Jiang Q. Fang M. Li J. Chen Z. et al (2006). Effect of anti-infection oral mucosa ulcers of guinea-pig and antibacterial in vitro of total flavone of abelmoschus Manihot L medic. Anhui Med. J., 810–811. 10.3969/j.issn.1009-6469.2006.11.005

  • CrossRef
  • Google Scholar

• 184

  Zhang L. Li P. Xing C. Zhao J. He Y. Wang J. et al (2014). Efficacy and safety of abelmoschus manihot for primary glomerular disease: a prospective, Multicenter randomized controlled clinical trial. Am. J. Kidney Dis.64, 57–65. 10.1053/j.ajkd.2014.01.431

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 185

  Zhang D. Qian H. Yang B. Chen Y. (2017). The effect of total flavonoids from abelmoschus manihot on intestinal fibrosis in TNBS-Induced crohn’s disease mice. Jiangsu J. Tradit. Chin. Med.49, 76–79. 10.3969/j.issn.1672-397X.2017.03.029

  • CrossRef
  • Google Scholar

• 186

  Zhang D. Zhu P. Liu Y. Shu Y. Zhou J. Y. Jiang F. et al (2019a). Total flavone of Abelmoschus manihot ameliorates Crohn's disease by regulating the NF-B and MAPK signaling pathways. Int. J. Mol. Med.44, 324–334. 10.3892/ijmm.2019.4180

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 187

  Zhang W. Cheng C. Han Q. Chen Y. Guo J. Wu Q. et al (2019b). Flos Abelmoschus manihot extract attenuates DSS-induced colitis by regulating gut microbiota and Th17/Treg balance. Biomed. Pharmacother.117, 109162. 10.1016/j.biopha.2019.109162

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 188

  Zhang J. Fu Z. L. Chu Z. X. Song B. W. (2020). Gastroprotective activity of the total flavones from Abelmoschus manihot (L.) medic flowers. Evid. Based Complement. Altern. Med.2020, 6584945. 10.1155/2020/6584945

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 189

  Zhang S. Ruan Y. Zhou J. Ye L. Jia J. Yu J. et al (2021). Effect of Qikui particles on diabetic kidney disease and its influence on urinary CTGF and serum sICAM-1. Shaanxi J. Tradit. Chin. Med.42, 308–311. 10.3969/j.issn.1000-7369.2021.03.009

  • CrossRef
  • Google Scholar

• 190

  Zhang H.-X. Li Y.-Y. Liu Z.-J. Wang J.-F. (2022a). Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathwa in vivo and in vitro. Food Nutr. Res.66, 1–23. 10.29219/fnr.v66.8948

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 191

  Zhang H. Zhang D. Qian H. Wang Y. Zeng L. (2022b). TFA regulating autophagy through activation of AMPK/mTOR pathway to improve intestinal fibrosis of CD. Inf. TCM39, 1–10. 10.19656/j.cnki.1002-2406.20220701

  • CrossRef
  • Google Scholar

• 192

  Zhang D. Liu J. Lv L. Chen X. Qian Y. Zhao P. et al (2024). Total flavone of Abelmoschus manihot regulates autophagy through the AMPK/mTOR signaling pathway to treat intestinal fibrosis in Crohn's disease. J. Gastroenterol. Hepatol.39, 1586–1596. 10.1111/jgh.16560

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 193

  Zhao H. Zhu Y. (2013). Study on the promotion of wound healing by Collagen modified with chuangling liquid. World J. Integr. Tradit. West Med.8, 417–418. 10.13935/j.cnki.sjzx.2013.04.018

  • CrossRef
  • Google Scholar

• 194

  Zhao H. Zhao T. Li P. (2024a). Gut Microbiota-derived metabolites: a new perspective of traditional Chinese medicine against diabetic kidney disease. Integr. Med. Nephrol. Androl.11, 1–11. 10.1097/IMNA-D-23-00024

  • CrossRef
  • Google Scholar

• 195

  Zhao X. Wang S. He X. Wei W. Huang K. (2024b). Quercetin prevents the USP22-Snail1 signaling pathway to ameliorate diabetic tubulointerstitial fibrosis. Food Funct.15, 11990–12006. 10.1039/d4fo03564j

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 196

  Zhao K. Zhou F. Lu Y. Gao T. Wang R. Xie M. et al (2025). Hyperoside alleviates depressive-like behavior in social defeat mice by mediating microglial polarization and neuroinflammation via TRX1/NLRP1/Caspase-1 signal pathway. Int. Immunopharmacol.145, 113731. 10.1016/j.intimp.2024.113731

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 197

  Zheng X. Liu Z. Li S. Wang L. Lv J. Li J. et al (2016). Identification and characterization of a cytotoxic polysaccharide from the flower of Abelmoschus manihot. Int. J. Biol. Macromol.82, 284–290. 10.1016/j.ijbiomac.2015.10.004

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 198

  Zhong X. Jia J. Tan R. Wang L. (2024). Hederagenin improves Adriamycin-induced nephropathy by inhibiting the JAK/STAT signaling pathway. Integr. Med. Nephrol. Androl.11, 1–6. 10.1097/IMNA-D-22-00016

  • CrossRef
  • Google Scholar

• 199

  Zhou L. An X. F. Teng S. C. Liu J. S. Shang W. B. Zhang A. H. et al (2012). Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in Streptozotocin-Induced diabetic nephropathy. J. Med. Food15, 461–468. 10.1089/jmf.2011.1921

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 200

  Zhou L. Peng W. Zhou M. Jiang J. Xu P. Tan C. (2019). Effect of chuangling liquid on melanogenesis of rat immortalized melanocytes. Acta Chin. Med. Pharmacol.47, 19–23. 10.19664/j.cnki.1002-2392.190039

  • CrossRef
  • Google Scholar

• 201

  Zhou S. Fan K. K. Gu L. F. Yu B. Y. Chai C. Z. (2022). Anti-inflammatory effects of Abelmoschus manihot (L.) Medik. on LPS-induced cystitis in mice: potential candidate for cystitis treatment based on classic use. Chin. J. Nat. Med.20, 321–331. 10.1016/s1875-5364(22)60140-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 202

  Zhou Q. Tang H. Wang Y. Hua Y. Ouyang X. Li L. (2025). Hyperoside mitigates PCOS-associated adipogenesis and insulin resistance by regulating NCOA2-mediated PPAR-γ ubiquitination and degradation. Life Sci.364, 123417–123431. 10.1016/j.lfs.2025.123417

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 203

  Zhou X. Chen Z. (2016). Effects of total flavones of abelmoschl manihotonrats with experimental hyperglycemia. Chin. J. Clin. Pharmacol. Ther.21, 617–620.

  • Google Scholar

• 204

  Zhu G. S. Tang L. Y. Lv D. L. Jiang M. (2018). Total flavones of abelmoschus manihot exhibits pro-angiogenic activity by activating the VEGF-A/VEGFR2-PI3K/Akt signaling axis. Am. J. Chin. Med.46, 567–583. 10.1142/s0192415x18500295

  • Pubmed Abstract
  • CrossRef
  • Google Scholar