Ekom Monday Etukudo1
Ibe Michael Usman1*
Augustine Oviosun1
Vivian Onyinye Ojiakor1
Isxaq Abdi Jama1Wusa Makena1
Danladi Makeri2Elna Owembabazi1
Patrick Maduabuchi Aja3
Josiah Ifie3
Ilemobayo Victor Fasogbon3
Victor Bassey Archibong4Emeka Anyanwu1- 1Human Anatomy Department, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda
- 2Department of Microbiology, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda
- 3Biochemistry Department, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda
- 4Human Anatomy Department, School of Medicine and Pharmacy, University of Rwanda, Kigali, Rwanda
Medicinal plants have garnered significant attention for their potential in treating various human diseases. Many of these plants exhibit antioxidant and anti-inflammatory properties, which are crucial for mitigating the impact of oxidative stress and inflammation implicated in numerous clinical conditions. This review investigated the antioxidant and anti-inflammatory properties of medicinal plants, particularly Bidens pilosa, and their potential applications in disease management. A structured systematic approach was employed for this analysis. Scopus, PubMed, and Web of Science were searched using the following search algorithm: (“Bidens pilosa”) AND (“antioxidant”) AND (“anti-inflammatory” OR “anti-inflammatory”) on the second of April 2025 without any filters. At the end of the title, abstract and full text screening, only 50 articles met the inclusion criteria and hence included in the study. Most (35/50, 70%) were published within the years 2014–2024. Of the 50 studies, 23 (46%) were done in Africa, 14 (28%) in Asia, and 11 (22%) in South America. Most studies were done in a laboratory dish (29/50, 58%), with a smaller number done in animals (12/50, 24%). Fourteen percent (14%) of the studies used both in vivo and in vitro methods, and 4% were carried out on people. Out of the 50 studies, leaves were looked at most often (23 or 46%), followed by the whole plant (19 or 38%). Bidens pilosa lowered the tissue levels of tumor necrosis factor (TNF) and interleukin (IL)-6, IL-1β, and IL-8. It also improved the tissue levels of antioxidants glutathione while reducing lipid peroxidation via malondialdehyde (MDA). In conclusion, all the studies examined in the present study reported that Bidens pilosa possess antioxidant and anti-inflammatory potential, hence holding great promise in the management of oxidative stress and inflammation-related conditions.
1 Introduction
Oxidative stress is implicated in the pathogenesis of various diseases, including Alzheimer’s disease, chronic obstructive pulmonary disease, cancer and atherosclerosis (Forman and Zhang, 2021). It is usually a consequence of an imbalance in the pro-oxidant and antioxidant ratio (Panfoli et al., 2018). Pro-oxidants are pro-biotics or xenobiotics that result in oxidative stress and its related damage; and could include free radicals or reactive oxygen species. Free radicals are associated with radical chain reaction, hence are referred to as oxidants (Tchekalarova and Tzoneva, 2023). Free radicals can be generated exogenously or endogenously; exogenous free radical generation can be through exposure to heavy metal, radiation exposure, alcohol consumption, and cigarette smoking (Ozsurekci and Aykac, 2016). On the other hand, the exogenous free radical generation can be triggered by stress, cancer, excessive exercise, immune cell activation, aging, ischemia, infection, and inflammation (Ozsurekci and Aykac, 2016).
Based on the fact that oxidative stress has been implicated negatively in various diseases, both natural and synthetic antioxidants have been increasingly recognized as promising therapeutic options (Daglia et al., 2014; Selamoglu-Talaz et al., 2013; Selamoglu et al., 2008; Sureda et al., 2023). Gallic acid and curcumin are examples of polyphenols that lessen the risk of multi-faceted mechanistic clinical conditions by reducing neuroinflammation and oxidative stress, consequently protecting against neurotoxicity (Daglia et al., 2014; Sureda et al., 2023). Phytomedicine has highlighted the antioxidant properties of plants such as propolis and synthetic organoselenium compounds (Selamoglu-Talaz et al., 2013; Selamoglu et al., 2008). Furthermore, through antioxidant and cholinesterase-inhibiting qualities, Octaviania asterosperma, Scrophularia amplexicaulis, and Neurada procumbens promote nerve regeneration and cognition (Hamedi et al., 2020; Rasul et al., 2019; Sevindik et al., 2021).
Inflammation is a complex biological response crucial for tissue repair and defense against pathogens. It involves distinct phases: an initial pro-inflammatory response mediated by the innate immune system, followed by a resolution phase characterized by a macrophage phenotypic switch and a return to tissue homeostasis through inflammatory cell apoptosis (Kulkarni et al., 2016). However, when dysregulated, inflammation can contribute to the pathogenesis of various pathologies (Kulkarni et al., 2016; Rauf et al., 2022; Teleanu et al., 2022). Natural and synthetic anti-inflammatory agents have been effective in preventing neuroinflammation, which is heightened in these pathologic conditions (Hamsalakshmi et al., 2022; Kalra et al., 2022; Kaur and Singh, 2022; Yousaf et al., 2022).
Most of these effective antioxidant and anti-inflammatory agents are derived from easily accessible and cultivable plants. This makes medicinal plants to gain significant global attention as therapeutic alternatives (Ayuba et al., 2022; Onohuean et al., 2021; Onohuean et al., 2024; Salihu et al., 2022; Usman et al., 2016; Usman et al., 2022; Yusuf et al., 2023).
Bidens pilosa, a plant native to South America but widely distributed worldwide, including Africa, China, Japan and the Americas, has emerged as a promising candidate due to its rich phytochemical profile (Bartolome et al., 2013). Bidens pilosa is rich in phytocompounds such as saponins, alkaloids, polyacetylenes, flavonoids, and diterpenes (Abdel-ghany et al., 2016). Studies have reported that Bidens pilosa possess anti-hyperglycemic, antiulcerogenic, antihypertensive, hepatoprotective, antipyretic, anti-malarial, anti-leukemic, anti-bacterial, anticancer, antioxidant, immunosuppressive and anti-inflammatory (Silva et al., 2011). In some parts of Uganda, the plant is used for wound healing; however, there is limited information or studies on specific phytochemicals to enable the development of useful products for the treatment and management of neurodegenerative diseases. Hence, the present review examined the antioxidant and anti-inflammatory potential of Biden Pilosa, highlighting this plant’s promising therapeutic potential for variable yet related disease conditions heightened by oxidative stress and inflammation.
2 Methodology
2.1 Search strategy
The antioxidant and anti-inflammatory potential of Bidens pilosa, was examined using a structured and systematic approach. Scopus, PubMed, and Web of Science were searched using the following search algorithm: (“Bidens pilosa”) AND (“antioxidant”) AND (“anti-inflammatory” OR “anti-inflammatory”) on the second of March 2024 without any filters.
2.2 Study selection criteria
The database (Scopus, PubMed, and Web of Science) search yielded 65 bibliographies and extracted as comma-separated value (CSV) files, saved, and merged. Duplicates were sorted and removed, the remaining documents were retrieved for title and abstract screening, followed by full-text screening and data extraction. Only peer-reviewed articles on the antioxidant and anti-inflammatory properties of Bidens pilosa published in English were included in the present review. At the end of the screening exercise, only 12 articles met the selection criteria, hence used for data extraction (Figure).
2.3 Quality assessment
The risk of bias assessment was done using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) Checklist for the invivo studies (Hooijmans et al., 2014); on the other hand, Science in Risk Assessment and Policy (SCIRAP tool) as modified and used by Almeida et al. (2021) was adapted to assess the reporting quality for invitro studies since we could not find another tool (Roth et al., 2021). The findings from the risk of bias assessment were presented using the ROBVIS tool.
2.4 Data extraction
The data was extracted and classified as the following information: Author, Country, Study Design, Animals Number, participants or animal gender and strain, invivo/invitro experiments, disease model or cells used, part of the plant, extract/molecule, phytochemical analysis and key compounds identified, intervention on antioxidant and anti-inflammmatory potentials of B. Pilosa and study outcomes (Tables 1–3) and (Supplementary Tables S1–S3).
Table 1. Study characteristics and summarized data from articles reporting antioxidant and anti-inflammatory potentials of Bidens pilosa.
Table 2. Summarized data on intervention and dosages from included Studies.
Table 3. Antiinflammatory potentials of Bidens pilosa as reported in the included studies.
3 Result
3.1 Study selection
Our search of three database searches returned 414 bibliographies from which 175 duplicates were removed. The remaining 239 articles were used for title and abstract screening, at the end of which 168 articles were excluded. The report sorted for retrieval was 71, out of which we were unable to retrieved 4 articles despite all our efforts. The reports assessed for eligibility were 67, out of which 16 articles were excluded for been unrelated and 1 article for been written in Chinese. At the end of the entire screening process, 50 articles were included in the study for data extraction and synthesis (Figure 1).
Figure 1. Prisma flow chart.
3.2 Risk of bias assessment
The risk of bias assessment using SYRCLE Checklist for the in vivo studies based on the 10 domains revealed a general low risk of bias (Figure 2); however, 11 articles had no information about “D5 - Were the caregivers and/or investigators blinded from knowledge which intervention each animal received during the experiment?” and “D6 - Were animals selected at random for outcome assessment?”. Ten articles had no information on “D7 - Was the outcome assessor blinded?” (Figure 3).
Figure 2. Risk of bias for the 10 domains for the in vivo studies.
Figure 3. Risk of bias for the individual articles on the in vivo studies.
The SciRAP tool evaluation covered five key components: test compound and controls, test system, administration of the test compound, data collection, and analysis, encompassing a total of 23 topics. In assessing the test compound and controls, 36 studies were found to be partially fulfilled. For the test system and administration of the test compound, 20 studies met the criteria. Data collection and analysis were fulfilled in 37 studies. Regarding funding and competing interests, 13 articles met the criteria, while 19 did not (Figure 4).
Figure 4. The reporting quality for the in vitro studies.
3.3 Study characteristics
We reviewed 50 studies, and most (35/50, 70%) were published within the years 2014–2024. Of the 50 studies, 23 (46%) were done in Africa, 14 (28%) in Asia, and 11 (22%) in South America. Most studies were done in a laboratory dish (29/50, 58%), with a smaller number done in animals (12/50, 24%). Fourteen percent (14%) of the studies used both in vivo and in vitro methods, and 4% were carried out on people. Out of the 50 studies, leaves were looked at most often (23 or 46%), followed by the whole plant (19 or 38%). Most of the studies (44/50, 88%) concentrated on the roots, stems, or leaves, but the aerial parts were studied in just 4/50 (8%) of the studies (Table 1). To study antioxidant, anti-inflammatory, analgesic, anticancer and immunomodulatory effects, the researchers used both living and non-living models. For mucositis and oxidative stress, male Swiss mice (7–10 weeks) were used in vivo; for TNBS-induced colitis, carrageenan-induced edema and CCl4-induced toxicity, Wistar rats and BALB/c mice were used. Ovalbumin-induced airway inflammation was studied in female BALB/c mice, while transgenic G93A mice represented ALS. Chickens were used in Eimeria infection models and Drosophila were used to study the effects of paraquat on oxidative stress. RAW 264.7, THP-1, BV-2, SCC-4, HepG2, Vero, HeLa and KB-3-1 cell lines were used in in vitro systems to investigate leukemia, inflammation and several cancers. Both healthy volunteers and patients who had oral mucositis while receiving radio-chemotherapy were studied in this research. The antioxidant property and toxicity of the extracts were measured by DPPH, ABTS, FRAP, TBARS, SOD, GSH, catalase, β-carotene bleaching, phosphomolybdenum and MTT assays. They gave a complete understanding of oxidative stress, the immune system, inflammation and cancer development.
3.4 Summary of intervention and dosages of Bidens pilosa from the included studies
The included studies used different preparations of B. pilosa such as aqueous, methanolic, ethanolic and glycolic extracts, as well as isolated phytocompounds and essential oils. Most of the plants used were leaves, aerial parts and whole plants (Table 2). The amount and frequency of the extracts were different for each type of extract and model in the studies. In animals, researchers most often gave the compound via gavage or feed and doses varied from 15 mg/kg to 2 g/kg each day for up to 10 weeks (Bastos et al., 2016; Abiodun et al., 2020; Yang et al., 2018). In a few studies, intraperitoneal injection was used, with a 10 mg/kg butanol fraction given for 35 days (Chang et al., 2005). The plant was given to patients in human clinical trials either as a gargle (15 mL for 10 days) or in the form of a mucoadhesive (at 100 mg/kg by mouth) (Santos Filho et al., 2018; de Ávila et al., 2015) (Table 2). In vitro studies most often used Bidens pilosa phytocompounds at concentrations between 1 μg/mL and 1000 μg/mL and left the cells in contact with them for 24–72 h (Xin et al., 2021; Pereira et al., 1999; Chang et al., 2005). Interestingly, some research used mixtures of phytochemicals, for example, glucopyranosylated polyacetylenes (Yan et al., 2022) and essential oils (Deba et al., 2007), but did not always mention how much or for how long the compounds were given. Plant extracts were also used in foods or as ingredients in teas, much like they have been used in the past (Pegoraro et al., 2018). Less specific detail on how the botanical drugs were given was observed in some studies (Akula and Odhav, 2008; Yuniastri et al., 2022).
3.5 Phytochemical analysis of Bidens pilosa extracts and key phytocompounds identified
A variety of methods have been used to study the phytochemical content of Bidens Pilosa (Supplementary Table S1). Ultraviolet-Visible spectrophotometry (UV-Vis Spec.) was widely used to measure the total phenolic and flavonoid content, as shown by Mohamed et al. (2024), Akula and Odhav (2008) and Phiri et al. (2024). Specific phenolic acids and flavonoids were identified and quantified using HPLC, as was done by Nguyen et al. (2023), Yang et al. (2018) and Singh et al. (2017) (Supplementary Table S1). Using LC-MS/MS and LC-HR-MS, researchers were able to identify a wider range of secondary metabolites such as coumarins, ellagitannins and hydroxybenzoic acids (Angelini et al., 2021; Idris et al., 2023; Nxumalo et al., 2023). GC-MS was found to be the best method for detecting fatty acids and terpenoids among volatile and lipophilic compounds (Goudoum et al., 2016; Abiodun et al., 2020; Falowo et al., 2017) (Supplementary Table S1).
The included studies found that B. pilosa contains many bioactive compounds, suggesting it may be useful in medicine. The phytocompounds are shown in Supplementary Table S2. Quercetin, isookanin, rutin, and glucuronylated quercetin were found in every extraction method studied by Fotso et al. (2014), Xin et al. (2021), and Santos Filho et al. (2018). Ethyl acetate and n-butanol extracts from the plant were commonly found to contain 4-O-β-D-glucopyranosyloxy-1-hydroxy-6-(E)-tetradecene-8,10,12-triyne (Yan et al., 2022; Chang et al., 2005) (Supplementary Table S2). Caffeic acid, gallic acid, and chlorogenic acid were other phenolic acids that were commonly found, according to Horiuchi and Seyama (2008) and Nguyen et al. (2023). GC-MS tests also found that the main fatty acids and volatile oils in these oils are palmitic acid, oleic acid, α-pinene, and phytol (Quaglio et al., 2020; Goudoum et al., 2016) (Supplementary Table S2). They highlight the plant’s rich chemical makeup and its ability to help with diseases linked to oxidative stress, lipid peroxidation, and inflammation.
3.6 Bidens pilosa antioxidant mechanisms and outcome as reported in the included studies
It was shown that Bidens pilosa acts as a powerful antioxidant by removing free radicals and helping the body produce its own antioxidants (Supplementary Table S3). Methanolic, aqueous, ethanolic and ethyl acetate extracts from the plant showed strong DPPH, ABTS and FRAP scavenging abilities, similar to those of ascorbic acid and BHT (Chipurura et al., 2013; Adeolu Adedapo and AuthorAnonymous, 2011; Cortés-Rojas et al., 2011; Wu et al., 2012). There was a strong relationship between these activities and the total phenolic and flavonoid contents. In addition to neutralizing radicals, B. pilosa changed the activity of SOD, GSH and GSH-Px which resulted in a decrease in lipid peroxidation and MDA levels in both hepatic and erythrocyte models (Yuan et al., 2008; Yang et al., 2006). The gastric models showed that its formulations greatly reduced thiobarbituric acid reactive substances (TBARS) which indicated that it helped protect the stomach by reducing oxidative stress (Horiuchi et al., 2010) (Supplementary Table S3). In therapeutic terms, these antioxidant properties resulted in protecting cells from damage, including the liver, stomach and colon cancer cells (Wu et al., 2012). In general, the powerful ability to scavenge radicals, alter enzymes and provide protection make B. pilosa a promising natural antioxidant for disease prevention and management. All the studies included in this review have shown that Bidens Pilosa has beneficial antioxidant properties (Supplementary Table S3). A formulation of B. pilosa (MMPB) minimized oxidative markers such as MDA and TBARS, improved antioxidant enzymes (SOD, GSH, GSH-Px) and reduced tissue damage in models of liver, stomach and erythrocyte injury (Horiuchi et al., 2010; Yuan et al., 2008; Yang et al., 2006). Radical scavenging tests revealed that methanolic, ethanolic and ethyl acetate extracts have potential for treating conditions related to oxidative stress (Chipurura et al., 2013; Adeolu Adedapo and AuthorAnonymous, 2011; Wu et al., 2012). The ethyl acetate fraction caused cancer cells to die which suggests it may be useful in treating colorectal cancer. These reports reveal that B. pilosa can be used in various ways as an antioxidant and has many therapeutic benefits.
3.7 Bidens pilosa anti-inflammatory mechanisms and outcome as reported in included studies
Anti-inflammatory activity in Bidens pilosa has been shown in many studies using different plant materials and types of extracts (Table 3). Bastos et al. (2016), Quaglio et al. (2020), Pegoraro et al. (2018), and de Ávila et al. (2015) found that B. pilosa affects cytokines, boosting IL-10 and lessening IL-1β, IL-6, and TNF-α in tissues affected by inflammation. The anti-inflammatory and immunosuppressive effects of leaves and whole plants from this plant were confirmed by reducing paw edema, lymphocyte proliferation, and histamine release in animal experiments (Fotso et al., 2014; Chih et al., 1995; Pereira et al., 1999; Horiuchi and Seyama, 2008). Experiments done in a laboratory have found that it is effective. Yan et al. (2022) and Yang et al. (2018) found that ethanolic extracts of B. pilosa reduced IL-6, NO, and TNF-α in macrophages, while isookanin flavonoids from the plant blocked COX-2 and iNOS enzymes (Xin et al., 2021) (Table 3). According to Tsuruta et al. (2023), they discovered that pro-inflammatory cytokines in the spinal cord were selectively blocked in G93A mice. Meanwhile, Santos Filho et al. (2018) reported no changes in human inflammation, which suggests that clinical application varies. The reports show that B. Pilosa, helps reduce inflammation by controlling cytokines, limiting inflammatory mediators, and regulating the immune system.
Experiments across multiple models showed that B. pilosa has anti-inflammatory effects. The outcome revealed that extracts help reduce edema in acute inflammation, decrease inflammatory cytokine levels in both the intestine and kidney, and decrease the number of leukocytes and MPO activity in colitis models (Fotso et al., 2014; Chih et al., 1995; Yang et al., 2018; Mohammed et al., 2024; Abiodun et al., 2020) (Table 3). The treatment decreased IL-8 release in oral carcinoma (Arantes et al., 2021a). Specifically, the plant’s ability to fight colitis was linked to higher IL-10, lower IL-6, and lower TNF-α levels (Quaglio et al., 2020). Mucoadhesive gels showed advantages for certain tissues while still keeping the overall cytokine profile unchanged (as shown by Santos Filho et al., 2018) (Table 3).
4 Discussion
4.1 Study characteristics and scientific methodological overview
This review looks at fifty studies on Bidens Pilosa (B. pilosa), mainly focusing on its antioxidant, anti-inflammatory, and immunomodulatory effects. Most of the studies, 70%, were published during 2014–2024, which points to a growing interest worldwide in using this plant as a botanical drug because of its important metabolites and many medical uses. Significantly, studies from Africa, Asia, and South America confirm that people from different regions recognize how bioactive this plant and its metabolites can be.
This data shows studies ranging from in vitro designs to in vivo experiments, while some studies combined the two approaches. Although currently in an early translational phase, the few human clinical trials (Arantes et al., 2021a; Santos Filho et al., 2018) form a solid base for future studies. These results agree with previous studies (Abiodun et al., 2020; Rodríguez Mesa et al., 2023), highlighting the importance of bringing preclinical results into clinical use.
Although preclinical studies prove that B. pilosa has antioxidant and anti-inflammatory properties, very few clinical trials have been done. The lack of translation may be caused by problems in the way this plant is extracted, the variation in doses, and the different active compound concentrations found in studies, making it hard to standardize how cannabis should be used in humans. In addition, the information from preclinical studies is usually not robust enough in pharmacokinetics and toxicity to get ethical approval for clinical trials. Limits on regulations, money, and the belief that herbal remedies are not scientifically proven hold back progress to human studies. Future work should focus on standardizing B. pilosa extracts to guarantee that results from different studies are the same. Immense pharmacological and toxicological evaluations can strengthen the drug design and safety, thereby helping it gain approval from regulators.
In this current review, tests using Swiss mice for intestinal mucositis, oxidative stress, and inflammatory bowel models in BALB/c and Wistar rats, as well as transgenic mouse models of ALS, show the wide range of conditions studied with B. pilosa. Furthermore, the choice of RAW 264.7 (macrophages), THP-1 (monocytes), BV-2 (microglia) and SCC-4 (oral cancer) cell lines demonstrates how the plant relates to immunological, oxidative, and oncogenic pathways.
The results also highlight that B. pilosa is a multi-purpose botanical drug. In particular, leaves and whole plant extracts were most studied, pointing to their high content of bioactive substances. This matches earlier research that found the leaves’ extracts in water and methanol could scavenge radicals (Akula and Odhav, 2008; Fotso et al., 2014) and whole plant extracts helped treat inflammation and oxidative damage in colitis and hepatic toxicity (Abiodun et al., 2020; Mashinini et al., 2023). Despite this, phytochemical analysis of the aerial parts (8%) and roots/flowers has yet to be done, and these plant parts should be studied further.
In all these experiments, DPPH, ABTS, TBARS, and FRAP were chosen to evaluate radical scavenging activity. MTT, catalase, and GSH assays were used to measure how the compounds affected cells and enzymes. Together, these assays measure the plant’s capacity to clear free radicals, control redox balance, and reduce the release of inflammatory cytokines, all of which are important for many diseases (Rodríguez Mesa et al., 2023; Santos Filho et al., 2018).
These findings have important consequences. Since B. pilosa can affect many biological systems and diseases, it is a good candidate for making multi-targeted phytotherapeutics. Because it works well in both immune and oxidative models, it is well suited to be a dual-action agent, which is important when diseases negatively impact multiple biological pathways. As a result, we require botanical drugs that treat the main condition and its linked problems, such as oxidative stress, which is found in many chronic inflammatory and neurodegenerative diseases.
4.2 Intervention strategies and dosage patterns in Bidens pilosa administration
The results from this review show a lot of variation in how B. pilosa was studied and given to participants. Such variety demonstrates the plant’s many uses and the absence of a set way to use it in preclinical and clinical research.
Different extracts of B. pilosa were used in the studies. For example, aqueous, methanolic, ethanolic, glycolic, and butanolic fractions, isolated phytocompounds, and essential oils. Most studies used leaves, aerial parts, or the whole plant to make interventions, reflecting the multiple therapeutic components in B. pilosa (Bastos et al., 2016; Abiodun et al., 2020; Chang et al., 2005; Deba et al., 2007). The results add to earlier studies showing that B. pilosa contains many metabolites, especially polyacetylenes, flavonoids, and phenolic compounds, which have been found to have various biological activities (Yan et al., 2022; Xin et al., 2021).
In animal experiments, the majority of researchers gave B. pilosa by gavage or mixed it into the feed, using amounts from 15 mg/kg to 2 g/kg each day for periods of 6 days–10 weeks (Yang et al., 2018; Abiodun et al., 2020). Since the best dose is not feasible, the broad range of doses used in research makes it challenging to see how effective the treatment is in various models. Significant outcomes were obtained by Chang et al. (2005) when they treated mice with a butanol fraction at 10 mg/kg daily for 35 days by injection into the abdomen. Since drugs are delivered and stay in the body differently, pharmacokinetic research is done to determine the best doses and improve outcomes.
The majority of in vitro studies used extracts at concentrations from 1 to 1000 μg/mL for 24–72 h (Pereira et al., 1999; Chang et al., 2005; Xin et al., 2021). Even so, the findings indicate that B. pilosa metabolites affect cells in a way that depends on both the dose and the time, even though a lack of standard endpoints prevents direct comparison between studies. Furthermore, research with complex mixtures, like glucopyranosylated polyacetylenes (Yan et al., 2022) and essential oils (Deba et al., 2007), often failed to clearly state the amounts and lengths of exposure, which weakens their reproducibility and usefulness for translation.
Fortunately, research on humans, while limited, has shown that clinical use is possible. Santos Filho et al. (2018) showed that a B. pilosa gargle (15 mL/day for 10 days) could be therapeutic, and de Ávila et al. (2015) gave 100 mg/kg orally in the form of a mucoadhesive preparation. They are especially important because they look at how these approaches are delivered and whether people will accept them in practice. Even so, the limited number of patients, short follow-up, and lack of pharmacokinetic data weaken these results and suggest that further studies are needed.
Our results are consistent with earlier reviews and analyses, which confirm that B. pilosa has broad bioactivity and may be developed as phytopharmaceutical agents (Pegoraro et al., 2018; Pereira et al., 1999). Still, the differences found and the challenges in methods suggest that we need strong standardization and better ways to move from research to clinical use.
4.3 Bidens pilosa phytochemical analysis, composition, and pharmacological importance
The phytochemical analysis of Bidens pilosa presented in this review confirms the plant’s status as a chemically diverse medicinal herb with high therapeutic potential. Through various analytical platforms and extraction methodologies, researchers have consistently identified a spectrum of secondary metabolites, including flavonoids, phenolic acids, polyacetylenes, fatty acids, and terpenoids. These findings provide a robust chemical foundation to support B. pilosa’s ethnomedicinal applications in managing oxidative stress, lipid peroxidation, inflammation, and metabolic disorders.
The repeated use of UV-visible spectrophotometry across studies, such as those by Mohamed et al. (2024), Akula and Odhav (2008), and Phiri et al. (2024), has facilitated rapid quantification of total phenolic and flavonoid content, which are important classes of antioxidants. These bulk metrics serve as initial indicators of pharmacological relevance, given the well-established role of flavonoids and phenolics in neutralizing free radicals and mitigating oxidative damage.
More targeted profiling was achieved by High-Performance Liquid Chromatography (HPLC), which allowed the specific identification and quantification of key compounds such as caffeic acid, chlorogenic acid, and quercetin derivatives (Nguyen et al., 2023; Yang et al., 2018; Singh et al., 2017). These phenolic acids and flavonoids are recognized for their antioxidant, anti-inflammatory, and vasoprotective activities, suggesting that B. pilosa could exert multifaceted biological effects relevant to chronic inflammatory diseases.
Advanced metabolomic platforms like Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) and Liquid Chromatography–High-Resolution Mass Spectrometry (LC-HR-MS) revealed an even broader spectrum of bioactive constituents, including coumarins, ellagitannins, and hydroxybenzoic acids (Angelini et al., 2021; Idris et al., 2023; Nxumalo et al., 2023). The identification of such structurally diverse molecules underscores the plant’s chemotypic complexity and supports its potential utility in drug discovery pipelines. Notably, polyacetylenic glucosides, especially 4-O-β-D-glucopyranosyloxy-1-hydroxy-6-(E)-tetradecene-8,10,12-triyne, were consistently isolated in ethyl acetate and n-butanol extracts (Yan et al., 2022; Chang et al., 2005). These compounds are known for their immunomodulatory and cytotoxic properties, and their recurrent detection suggests they may serve as chemotaxonomic markers or lead molecules for pharmaceutical development.
In parallel, Gas Chromatography–Mass Spectrometry (GC-MS) analyses were pivotal in identifying lipophilic and volatile compounds, including palmitic acid, oleic acid, α-pinene, phytol, and other terpenoids (Goudoum et al., 2016; Abiodun et al., 2020; Falowo et al., 2017; Quaglio et al., 2020). These molecules, often associated with anti-inflammatory and antimicrobial effects, are key to understanding the broader pharmacological effects of B. pilosa, especially in topical and nutraceutical applications.
The consistency in identification of certain compounds across studies, such as quercetin, rutin, isookanin, and glucuronylated quercetin (Fotso et al., 2014; Xin et al., 2021; Santos Filho et al., 2018), adds to the credibility of these findings. These flavonoids are among the most pharmacologically relevant, with a wide range of reported activities including enzyme inhibition, reactive oxygen species scavenging, and modulation of intracellular signaling pathways. Their ubiquity in B. pilosa across various extraction methods and geographic sources strengthens the case for their use as quality control markers in future standardization protocols.
Specifically, we identified 35 key metabolites with proven pharmacological relevance in B. Pilosa. These compounds were relevant particularly in modulating oxidative stress, lipid peroxidation, and inflammation, which are drivers of various diseases, including neurodegenerative and non-communicable diseases. Key phenolic acids like caffeic acid, gallic acid, ferulic acid, and chlorogenic acid (for example, 1-caffeoylquinic acid and 5Z-caffeoylquinic acid) exhibit antioxidant and anti-inflammatory properties by suppressing ROS generation, NF-κB activation, and pro-inflammatory cytokines such as TNF-α and IL-6. Flavonoids, including quercetin, kaempferol, rutin, isoquercetin, catechin, and luteolin derivatives, enhance cellular defenses through Nrf2 pathway activation, PI3K/Akt signaling, and membrane stabilization, mitigating neuroinflammation and mitochondrial dysfunction. Fatty acids like oleic acid, palmitic acid, and linoleic acid, with their esters (such as ethyl linoleate), support membrane integrity and exhibit anti-inflammatory and hypolipidemic effects. Terpenoids such as phytol, beta-caryophyllene, limonene, alpha-pinene, cadinene, and delta-cadinene contribute to antimicrobial, analgesic, and anti-inflammatory actions. Phytosterols like stigmasterol and beta-sitosterol have cholesterol-lowering and anti-diabetic properties, while tannic acid and vanillin exert broad-spectrum antioxidant and neuroprotective roles. Notably, paclitaxel, though rare in plants outside the Taxus genus, suggests a possible antitumor synergy within B. pilosa. Collectively, the phytocompounds in B. pilosa demonstrate a strong potential for integrative therapeutic strategies targeting oxidative damage, inflammation, and chronic degenerative diseases.
The presence of these diverse and bioactive metabolites aligns with findings from previous phytochemical reviews of B. pilosa and related Asteraceae species (Pegoraro et al., 2018; Pereira et al., 1999). The current synthesis, however, benefits from recent technological advancements in mass spectrometry and chromatography, allowing for a more comprehensive phytochemical fingerprint. Furthermore, the correlation between specific compounds (e.g., chlorogenic acid, rutin, phytol) and pharmacological outcomes such as antioxidant and anti-inflammatory effects reinforces the mechanistic plausibility of B. pilosa’s traditional uses in managing inflammatory and oxidative stress-related conditions.
4.4 Combined antioxidant and lipid peroxidation reducing potential of Bidens pilosa
According to the studies included, Bidens pilosa possesses a strong and varied antioxidant ability, working by both trapping radicals and influencing the body’s methods of protection. A number of extracts from B. pilosa, for example methanolic, aqueous and tea, have been shown to have strong free radical-scavenging effects in tests such as DPPH, ABTS and FRAP, proving that they can block reactive oxygen species and protect against oxidative damage (Akula and Odhav, 2008; Mohamed et al., 2024; Nxumalo et al., 2023; Phiri et al., 2024). Significant decreases in malondialdehyde (MDA) levels which indicate lipid peroxidation, are also observed in both laboratory and animal experiments (Abiodun et al., 2020; de Ávila et al., 2015; Bastos et al., 2016; Santos Filho et al., 2018). Lipid peroxidation plays a significant role in systemic inflammatory diseases, cardiovascular conditions, and metabolic disorders (Moretti et al., 2024; Wazir et al., 2023). Damage to cell membranes caused by oxidative stress can trigger immune responses, contribute to chronic inflammation, and exacerbate conditions such as atherosclerosis, diabetes, and autoimmune diseases (Bhol et al., 2024; Sadiq, 2021). Studies suggest that Bidens pilosa, a plant rich in flavonoids and phenolic acids, may offer protective benefits by reducing oxidative stress and inflammation (Varadhan et al., 2022). Through its antioxidant and anti-inflammatory properties, Bidens pilosa may help maintain cellular integrity, protect against membrane destabilization, and support overall physiological function (Aborode et al., 2022; Alqahtani et al., 2023; Tchekalarova and Tzoneva, 2023; Teleanu et al., 2022). The ability of B. pilosa to reduce MDA is important because lipid peroxidation is a main cause of cell membrane damage in diseases such as colitis and mucositis.
As well as direct radical removal, B. pilosa also activates the body’s internal antioxidant systems. Several studies show that in rodents and plants, extracts can boost the activity of SOD, CAT, POD and GSH (Tesfay et al., 2016; Mohamed et al., 2024; Abiodun et al., 2020). Because these enzymes are the first line of defense against oxidative stress, their increased levels by B. pilosa suggest both quick and lasting protection against redox imbalances. Removing radicals and supporting the body’s defense system makes the therapeutic potential of this plant more promising.
Importantly, these antioxidant activities are strongly associated with the phytochemical richness of B. pilosa, particularly its high total phenolic and flavonoid contents. Studies have consistently reported that flavonoids such as quercetin and phenolic acids like chlorogenic and caffeic acids contribute to its antioxidant effects by donating hydrogen atoms, chelating pro-oxidant metal ions, and modulating redox-sensitive signaling pathways (Yuniastri et al., 2022; Goudoum et al., 2016; Shandukani et al., 2018; Phiri et al., 2024). Through metal ion chelation, flavonoids including quercetin and kaempferol neutralize free radicals and prevent oxidative damage (Gulcin and Alwasel, 2022). By contributing hydrogen atoms to combat reactive oxygen species (ROS), phenolic acids, such as caffeic acid and chlorogenic acid, demonstrate strong radical-scavenging action (Mashinini et al., 2023). Additionally, by modulating oxidative stress signaling pathways, terpenoids like β-sitosterol strengthen cellular antioxidant defenses (Dwivedi et al., 2023; Liu et al., 2013)
These mechanisms collectively contribute to its broad-spectrum cytoprotective benefits, especially in inflammatory and oxidative-stress-related conditions.
The therapeutic utility of B. pilosa is further validated by in vivo models. Notably, formulations such as FITOPROT and Ecobidens® significantly attenuated oxidative stress and inflammatory markers in models of 5-fluorouracil-induced oral and intestinal mucositis, respectively (Bastos et al., 2016; de Ávila et al., 2015; Santos Filho et al., 2018). These findings highlight the practical relevance of B. pilosa-based formulations in mitigating chemotherapy-induced toxicity. Moreover, studies on B. pilosa tea demonstrated its effectiveness in reversing oxidative damage in rats fed a high-oxalate diet, including restoration of GSH levels and reduction in MDA concentrations (Mohamed et al., 2024).
Another noteworthy observation is that methanolic and acetonic extracts of B. pilosa have shown antioxidant activities comparable to, or even surpassing, those of synthetic antioxidants such as butylated hydroxytoluene (BHT) (Goudoum et al., 2016). This not only positions B. pilosa as a promising candidate for inclusion in nutraceutical and pharmaceutical formulations but also aligns with current trends favoring natural over synthetic antioxidant sources due to safety concerns.
Collectively, these findings affirm that B. pilosa possesses strong antioxidant potential mediated by both its phytochemical constituents and its ability to modulate oxidative stress pathways. Its versatile applications across disease models, dietary supplementation, and food preservation further underscore its therapeutic and preventive promise.
4.5 Anti-inflammatory potential of Bidens pilosa
Our review confirms that Bidens pilosa possesses potent anti-inflammatory properties, mediated by a broad range of bioactive compounds that influence multiple immunological and molecular pathways. The findings reported across diverse studies highlight the plant’s capacity to downregulate pro-inflammatory mediators while promoting anti-inflammatory responses, indicating its promising therapeutic potential in managing inflammatory conditions.
Notably, B. pilosa inhibits major pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8, while concurrently upregulating IL-10, a critical anti-inflammatory cytokine (Bastos et al., 2016; Quaglio et al., 2020). These effects suggest that the plant may restore immune homeostasis, particularly in pathological states marked by cytokine imbalances. The suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by isookanin, leading to decreased nitric oxide and prostaglandin E2 levels, further affirms the mechanistic depth of B. pilosa’s anti-inflammatory action (Xin et al., 2021). These outcomes are consistent with those of Caporali et al. (2022) and Chiang et al. (2004), who previously demonstrated that flavonoids in medicinal plants inhibit these same enzymes, key drivers of inflammation.
Additionally, B. pilosa modulates non-cytokine pathways involved in inflammation. It reduces histamine release from mast cells (Horiuchi and Seyama, 2008), inhibits the 5-lipoxygenase pathway (Akula and Odhav, 2008), and suppresses lymphocyte proliferation (Pereira et al., 1999), suggesting both early-phase and chronic inflammatory processes are targeted. These findings resonate with those by Tahya et al. (2023), who identified flavonoid glycosides in B. pilosa capable of regulating early immunologic responses.
Evidence from cellular models further strengthens these conclusions. Extracts from B. pilosa significantly inhibited IL-6 and nitric oxide production, downregulated NF-κB activation, and reduced myeloperoxidase (MPO) activity in macrophages and colon cell lines (Yan et al., 2022; Abiodun et al., 2020; Mohammed et al., 2024). These molecular effects suggest interference with canonical inflammatory signaling pathways such as NF-κB and MAPK, which are known to orchestrate a cascade of pro-inflammatory gene transcription (Wang et al., 2023; Detka et al., 2024). Importantly, the reduction in MPO activity and leukocyte infiltration in colitis models aligns with the anti-colitic effects previously reported by Abiodun et al. (2020) and Quaglio et al. (2020).
Animal studies provided compelling in vivo validation of these cellular findings. For instance, ethanol and aqueous extracts of B. pilosa significantly reduced paw edema and tissue inflammation in acute and chronic models (Fotso et al., 2014; Chih et al., 1995), while also mitigating cytokine expression in intestinal and renal tissues (Yang et al., 2018; Mohammed et al., 2024). These observations parallel those of Rodríguez Mesa et al. (2023), who reported that stigmasterol and friedelan-3-one in B. pilosa effectively attenuate inflammation through both COX-2 inhibition and antioxidant mechanisms.
Interestingly, the anti-inflammatory outcomes appear to be tissue-specific in certain delivery systems. For instance, FITOPROT-based mucoadhesive gels provided localized anti-inflammatory benefits without altering systemic cytokine profiles (Santos Filho et al., 2018). This property may be advantageous in the targeted treatment of oral and mucosal inflammations, as further demonstrated by Arantes et al. (2021b) in oral carcinoma and salivary epithelial models.
Despite these encouraging findings, the immunological effects of B. pilosa are not universally anti-inflammatory. Chang et al. (2005) reported that in certain conditions, the plant promotes a Th2-skewed immune response with elevated IgE levels, implying potential allergenic or pro-inflammatory consequences under specific immunological contexts. This duality underscores the importance of dosage, route of administration, and the physiological state of the host in mediating B. pilosa’s outcomes.
Collectively, these findings present B. pilosa as a multi-targeted anti-inflammatory agent with broad therapeutic applications. Its ability to modulate cytokine profiles, inflammatory enzymes, immune cell activity, and signaling pathways positions it as a strong candidate for managing inflammatory disorders such as colitis, arthritis, and mucosal inflammations. Given the increasing burden of chronic inflammatory diseases worldwide, especially in resource-limited settings, B. pilosa could be a cost-effective, plant-based therapeutic option.
Furthermore, its actions on oxidative and inflammatory pathways suggest potential for use in neuroinflammatory and metabolic conditions where similar mechanisms are implicated (Iqbal et al., 2025; Schreiner and Popescu, 2022). These findings also justify a deeper investigation into its role in modulating inflammasome activation, especially in diseases like Alzheimer’s and diabetes, where NLRP3 and oxidative stress play central roles (Qin et al., 2024; Alqahtani et al., 2023).
4.6 Limitations and future perspective
Although Bidens pilosa has many pharmacological uses, several obstacles prevent it from being used in clinical practice. Since there is a wide variety in what parts of plants are used, the solvents chosen, and the methods applied, it is difficult to compare results between studies. Due to the inconsistency in phytochemical analysis and no standard ways to dose herbal products, it is difficult to connect a dose with a specific effect and to pinpoint the active compounds. Also, because information on how these drugs are processed in the body and tested in humans is limited, it is difficult to apply findings to real clinical practice. The way phytochemicals work together to produce health benefits is not well understood. Despite these problems, the positive results from our systematic review highlight that more research is needed on Bidens pilosa to include it in health-promoting programs dealing with tissue toxicity, oxidative stress, lipid peroxidation, and inflammation.
To enhance a better use of B. pilosa, future studies should standardize how it is extracted and should test and measure all important active compounds in the plant. Bioassay-guided fractionation and using omics methods (metabolomics, transcriptomics and network pharmacology) can help find the targets and explain how they work. Evaluating the pharmacokinetics and toxicology of polyacetylenes and quercetin derivatives in major metabolites is essential. In particular, clinical trials that compare a treatment to a placebo and use standardized formulations should be given priority for conditions linked to oxidative stress and inflammation. Advanced computer models and systems biology methods should be used to study how various treatments work together and how to improve their results.
5 Conclusion
The review shows that Bidens pilosa is a medicinal plant with strong antioxidant and anti-inflammatory properties, confirmed by several in vitro and in vivo studies. The multiple metabolites in it, such as flavonoids, phenolic acids, polyacetylenes, and fatty acids, affect various biological functions and seem safe in animal studies. To make the most of its therapeutic benefits, people from different fields should collaborate to create standard ways, explore how it works, and confirm its safety and effectiveness in important clinical studies. With all these discoveries, B. pilosa has a strong chance to help develop useful plant-based treatments for diseases caused by oxidative stress, lipid peroxidation, and inflammation.
According to the findings of this systematic review, the following recommendations are presented to help direct future studies and the development of Bidens pilosa as a standardized phytotherapeutic agent:
i) Standardization of Extracts and Fractions of B. pilosa plant parts: Creating standard, detailed procedures for extracting metabolites and active components, their proportions, the temperature, the time involved, and the quantity of phytochemicals yielded will enable easy comparison of outcomes and ensure reproducibility.
ii) Separating the most active metabolites: Working on isolating and structurally defining the main bioactive compounds such as flavonoids, phenolic acids, and polyacetylenes, by using HPLC, LC-MS/MS, and NMR will allow better targeting of pharmacological experiments and improvement of compounds.
iii) Performing in silico pharmacokinetic (ADME) and toxicological predictions: Predicting whether key metabolites are bioavailable, safe, and can be properly formulated using Lipinski’s Rule of Five and SwissADME will facilitate the drug discovery and design process.
iv) Employing Molecular Docking and Molecular Dynamic Simulation Approaches: Molecular docking can be used to predict how B. pilosa compounds interact with proteins related to oxidative stress, inflammation, and metabolic disorders (such as COX-2, TNF-α, Nrf2, MAPKs). In addition, molecular dynamics simulations should be carried out to understand how strongly the ligand binds, how its structure is affected, and how the interaction with the protein changes over time.
v) Performing long-term and disease-specific research: By carrying out long-term in vivo experiments with tested animal models, the long-term effects of B. pilosa’s metabolites can be revealed. These studies should target inflammation using LPS-induced systemic inflammation and not only carrageenan-induced paw edema models. Models of metabolic disorders, diabetes, neurodegeneration, and cancer should also be used, along with testing antiproliferative and cytotoxic effects on both human tumor xenografts and cancer cell cultures, in vitro.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Author contributions
EE: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing. IU: Conceptualization, Investigation, Methodology, Supervision, Validation, Visualization, Writing – original draft, Writing – review and editing. AO: Conceptualization, Data curation, Investigation, Methodology, Project administration, Supervision, Writing – review and editing. VO: Conceptualization, Investigation, Methodology, Project administration, Visualization, Writing – review and editing. IJ: Formal Analysis, Investigation, Methodology, Project administration, Visualization, Writing – review and editing. WM: Conceptualization, Data curation, Methodology, Project administration, Visualization, Writing – review and editing. MD: Data curation, Formal Analysis, Investigation, Methodology, Resources, Writing – review and editing. EO: Investigation, Methodology, Project administration, Visualization, Writing – review and editing. AP: Data curation, Investigation, Methodology, Project administration, Visualization, Writing – review and editing. JI: Conceptualization, Data curation, Methodology, Project administration, Visualization, Writing – review and editing. IF: Conceptualization, Investigation, Methodology, Project administration, Visualization, Writing – review and editing. VA: Conceptualization, Investigation, Methodology, Project administration, Resources, Writing – review and editing. EA: Conceptualization, Methodology, Project administration, Supervision, Visualization, Writing – review and editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2025.1569527/full#supplementary-material
Abbreviations
Bidens pilosa, Bidens pilosa; SYRCLE, Systematic Review Centre for Laboratory Animal Experimentation; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RoB, – Risk of Bias; SciRAP, Science in Risk Assessment and Policy; TPC, Total Phenolic Content; TFC, Total Flavonoid Content; TTC, Total Tannin Content; TSC, Total Saponin Content; UV Spec, Ultraviolet Spectrophotometry; GC-MS, Gas Chromatography-Mass Spectrometry; HPLC, High-Performance Liquid Chromatography; LC-MS/MS, Liquid Chromatography-Tandem Mass Spectrometry; LC-HR-MS, Liquid Chromatography-High-Resolution Mass Spectrometry; NA, Not Applicable; CID, Compound Identifier.
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Keywords: Bidens pilosa, cytoprotection, antioxidant properties, anti-inflammatory properties, systematic review
Citation: Etukudo EM, Usman IM, Oviosun A, Ojiakor VO, Jama IA, Makena W, Makeri D, Owembabazi E, Aja PM, Ifie J, Fasogbon IV, Archibong VB and Anyanwu E (2025) Exploring the phytochemical profile, antioxidant and anti-inflammatory potential of Bidens pilosa: A Systematic Review. Front. Pharmacol. 16:1569527. doi: 10.3389/fphar.2025.1569527
Received: 01 February 2025; Accepted: 30 June 2025;
Published: 01 August 2025.
Edited by:
Michael Heinrich, University College London, United KingdomReviewed by:
Zeliha Selamoglu, Niğde Ömer Halisdemir University, TürkiyeTshepo Mashela, University of Limpopo, South Africa
Cica Vissiennon, Leipzig University, Germany
Copyright © 2025 Etukudo, Usman, Oviosun, Ojiakor, Jama, Makena, Makeri, Owembabazi, Aja, Ifie, Fasogbon, Archibong and Anyanwu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ibe Michael Usman, Z29wYW1hMTNAZ21haWwuY29t