Shuibin Cen
Jianping Li
James Reilly3
Hui-Rong Jiang
Xinhua Shu- 1School of Materials, Guangdong Industry Polytechnic University, Guangzhou, Guangdong, China
- 2College of Basic Medicine, Guangdong Jiangmen Chinese Medicine College, Jiangmen, Guangdong, China
- 3Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
- 4Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Introduction
Age-related macular degeneration (AMD) is a progressive retinal disease considered to be the leading cause of irreversible vision loss among older adults globally (1). AMD is classified into non-exudative (dry) AMD and neovascular (wet) AMD (Figure 1). Dry AMD is the commonest type, accounting for approximately 90% of cases and is characterized by atrophy of retinal pigment epithelial (RPE) cells and sub-RPE deposits (drusen); wet AMD is the most severe form and is characterized by the growth of abnormal choroidal vessels and leakage of blood and fluid (2, 3). Current treatments approved by the Food and Drug Administration (FDA) of the United States include anti-vascular endothelial growth factor (VEGF) treatment for wet AMD and anti-complement treatment for dry AMD, respectively (4, 5). These lifelong intravitreal treatments can cause adverse complications, including ocular hemorrhage, retinal inflammation, retinal detachment, and cataract (4, 5). Therefore, development of alternative treatments is urgently needed.
Figure 1. Age-related macular degeneration (AMD) is of two types: dry AMD (presence of geographic atrophy and drusen) and wet AMD (presence of choroidal neovascularization). Oxidative stress, inflammation, and gut dysbiosis are proposed to contribute to the pathogenesis and progression of AMD. Gypenosides (Gyps), a group of main active compounds in Gynostemma pentaphyllum, contain both the hydrophilic sugar part and the hydrophobic sapogenin part in the molecule (R1 and R2: glucose, rhamnose; R3: glucose, xylose). Gyps have been shown to suppress oxidative stress and inflammation and mitigate gut dysbiosis. Therefore, Gyps have the therapeutic potential for treating AMD.
Gypenosides (Gyps), the triterpenoid saponins derived from Gynostemma pentaphyllum (G. pentaphyllum, called Jiaogulan in Chinese) (Figure 1), have demonstrated pharmacological activities, including inhibition of oxidative stress and inflammation and regulation of metabolism and immune response. In preclinical studies, Gyps have been shown to have protective effects against cancer, cardiovascular disease, diabetes, liver diseases, and neurodegenerative and neuropsychiatric disorders (6–8). In clinical trials, Gyps-rich extract from G. pentaphyllum has a beneficial effect against obesity, diabetes, anxiety and fatigue (9–12). Based on current findings on pathological mechanisms of AMD and pharmacological functions of Gyps, in this opinion piece we discuss the therapeutic potential of Gyps in treatment of AMD patients.
Age-related macular degeneration (AMD)
Overview of AMD
AMD primarily affects the macula, the central region of the retina, which is responsible for high acuity vision. The prevalence of AMD is estimated to be 8.69% in the global population between 45–85 years of age, affecting approximately 200 million individuals in 2020, rising to more than 288 million people by 2040, due to population aging (1). AMD is classified into three distinct stages according to the clinical progression. Early AMD is defined by the presence of medium-sized drusen (63–125 μm) only, intermediate AMD by the presence of medium-size drusen and pigmentary abnormalities or by large drusen (>127 μm) with/without pigmentary abnormalities, and late AMD by the presence of geographic atrophy and/or choroidal neovascularization (13). AMD pathogenesis and progression is associated with both environmental and genetic risk factors. Age is the major non-modifiable environmental risk factor, while other risk factors include smoking, high-fat diet (HFD), elevated body mass index, high levels of serum cholesterol, hypertension, and cardiovascular disease (14). Two major susceptible genes contributing to AMD are Complement Factor H (CFH) and LOC387715/HTRA1. Genes involved in lipid metabolism, collagen synthesis, extracellular matrix organization, and receptor-mediated endocytosis are also associated with AMD (15).
Oxidative stress and inflammation are associated with AMD
It is proposed that the RPE plays a critical role in the pathogenesis of AMD. RPE cells have high metabolic activity and consume large amounts of oxygen, resulting in production of high levels of reactive oxygen species (ROS) (3, 16). ROS is also produced in RPE cells due to their role in the daily renewal of photoreceptor outer segments, as a result of which H2O2 is generated from β-oxidation of lipids in the shed outer segments and from the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagosome (16). Additionally, light processing for vision also produces photooxidative stress, as earlier studies have shown that sun exposure is a risk factor for AMD (3, 16). Excessive ROS causes RPE dysfunction or even death by damage to intracellular lipids, proteins and mitochondrial DNA. Further, excessive ROS can activate the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, resulting in production of proinflammatory cytokines, which exacerbate damage to RPE cells. Furthermore, excessive ROS or dyshomeostasis of antioxidant defense systems could stimulate VEGF production, resulting in formation of choroidal neovascularization, the hallmark of wet AMD (3, 16). Given RPE cells maintain photoreceptor function by supplying nutrition, secreting growth factors, phagocytosing the outer segments, recycling vitamin A, and forming the outer blood-retinal barrier, dysfunction/loss of RPE cells leads to progressive degeneration of photoreceptors.
Nutrition and gut microbiome are associated with AMD
Nutrition plays an important role in AMD management, as specific nutrients (e.g., carotenoids) and dietary patterns (e.g., the Mediterranean diet, enriched with ω-3 fatty acids) have been shown to reduce the risk of AMD development and slow its progression (2). Nutrition is one of the crucial regulators of gut microbiota and directly influences gut microbial homeostasis and host health. Dysbiosis of gut microbiota is associated with development of AMD (17). Zinkernagel et al. (18) reported that the relative abundance of genera Anaerotruncus and Oscillibacter together with species Ruminococcus torques and Eubacterium ventriosum was significantly increased in gut microbiota of Swiss AMD patients, whereas species Bacteroides eggerthii was enriched in heathy individuals. Another study demonstrated that genera Veillonella and Lactobacillus were enriched, while genera Faecalibacterium, Blautia, Anaerostipes, Anaerobutyricum, Massilistercora, Eggerthella, Megamonas, and Desulfovibrio were depleted, in Chinese AMD patients, compared to healthy controls (19). The authors also reported 14 species were positively associated with AMD pathological features (fovea thickness and lesion size). Additionally, activities of 24 metabolic pathways were also positively associated with lesion size in AMD patients (19). Further, Parekh et al. (20) reported that composition of gut microbiome and gut-derived metabolites were different among the heath controls, intermediate and advanced AMD patients; taxa associated with immunologic functions were enriched in advanced AMD, compared to that of intermediate AMD, and the levels of some protective short chain fatty acids and bile acids were significantly lowered in the advanced AMD cohort, compared to the intermediate group. In AMD animal models, HFD or high-glycemia diet induced altered composition, diversity, and metabolic functional pathways of gut microbiome and exacerbated AMD-like pathologies (21–23).
Pharmacological activities of gypenosides (Gyps)
Gyps inhibit oxidative stress and inflammation
Gyps are a group of triterpenoid saponins, enriched in G. pentaphyllum which is widely distributed in some provinces of China as well as other South and East Asia countries. Around 250 Gyps have been identified, demonstrating a wide range of functions (6). Many previous studies have shown the capacity of Gyps against oxidative stress and inflammation among in vitro cell lines and in vivo animal models. For example, Gyps inhibited production of ROS and malondialdehyde (MDA) and increased activities of antioxidant enzymes in H2O2 or oxidized low-density lipoprotein (ox-LDL) exposed cell lines. Similarly, Gyps also decreased production of proinflammatory cytokines in ox-LDL or lipopolysaccharide (LPS) treated cell lines. The antioxidative and anti-inflammation function of Gyps was further confirmed in animal models of disease, such as atherosclerosis, ischemia-reperfusion injury and Alzheimer's disease rodent models. It is proposed that NRF2 and NF-kB pathways are involved in these functions (6, 24).
Gyps regulate lipid metabolism
Gyps have also been demonstrated to regulate triglyceride and cholesterol metabolism (24). Gyp exposure can reduce cellular total triglycerides and cholesterol and increase lipid oxidation in cell lines (6). Treatment with Gyps reduced liver lipogenesis and enhanced lipid oxidation, resulting in a decrease in total blood triglycerides, cholesterol and LDL, and in liver lipid accumulation in HFD-fed mice (6). Clinical trials also showed Gyps' hypolipidemic effects. Individuals treated with Gyps had a significant decrease in total body weight, total fat mass, body mass index, and blood triglyceride levels. It is believed that Gyps regulate triglyceride homeostasis mainly via the PPAR/UCP1/PGC-1α/PRDM16 pathway (predominantly in fatty acid catabolism) and the SREBP-1c-ACC/FASN-CPT1 pathway (predominantly in triglyceride accumulation). Gyps regulate cholesterol homeostasis mainly via the SREBP2-HMGCR pathway (cholesterol biosynthesis), the PCSK9-LDLR pathway (degradation of LDL cholesterol), the LXRα/ABCA1/ABCG1 pathway (cholesterol transport), and the bile acid metabolism pathway (cholesterol excretion) (8).
Gyps modulate gut microbiome
Previous studies also demonstrate that Gyps regulate gut microbiome and related metabolites in rodents. Gyp treatment has been shown to lower serum total triglycerides and cholesterol, decrease the ratio of Firmicutes/Bacteroidetes (a biomarker for metabolic disorders) and restore gut dysbiosis by increasing the abundance of health-beneficial bacteria and lowering the abundance of metabolic disorder-associated bacteria in HFD or high fat and high cholesterol (HFHC) fed mice (25–27). Similarly, Gyps was also shown to decrease total serum triglycerides and cholesterol, reduce the ratio of Firmicutes/Bacteroidetes, increase production of short-chain fatty acids, and alleviate bile acid metabolism in ApoE knockout mice fed with a high fat choline diet and in mice fed with HFD along with a single injection of streptozotocin (28, 29).
Discussion
Our previous studies demonstrated that Gyps decreased the production of ROS and MDA, increased glutathione generation, and upregulated expression of antioxidant enzymes in H2O2-exposed human RPE cells. Gyps suppressed H2O2-induced production of proinflammatory cytokines at protein and mRNA levels in human RPE cells. Further experiments showed that Gyps' capacity against H2O2-induced oxidative stress, and inflammation was, respectively, through activation of the NRF2 signaling pathway and inactivation of the NF-kB pathways. Additionally, treatment with Gyps significantly reduced H2O2-induced apoptosis by inhibiting caspase activities (30). Our work in a zebrafish retinal disorder model also found that Gyps inhibited oxidative stress, endoplasmic reticulum stress and inflammation, and slowed down photoreceptor degeneration in disease zebrafish (31, 32). These data suggest that Gyps can restore RPE function under stress conditions and can promote photoreceptor survival, of significance in the treatment of AMD.
Gyps may also have therapeutic potential with respect to its effect on cholesterol metabolism. Dysregulation of cholesterol homeostasis is associated with a wide range of disorders, including cardiovascular diseases and Alzheimer's disease, and has been implicated in AMD (33). High-cholesterol diet increases the risk for the development of AMD (2) while animals fed with high-cholesterol diet display pathological characteristics of AMD (34). Abnormal accumulation of cholesterol and oxysterols has been detected beneath the RPE layer of AMD patients, suggesting dysregulation of cholesterol metabolism contributes to AMD pathogenesis (35). Genes related to cholesterol homeostasis, including APOE, ABCA1, LIPC, and CETP, are associated with AMD (15); knockout of certain cholesterol-related genes (e.g., Abca1 and ApoE) in rodents causes retinal degeneration and recapitulates AMD pathological features (35). It is therefore reasonable to hypothesize that inhibition of cholesterol biosynthesis or enhancement of cholesterol metabolism or reverse cholesterol transport in RPE cells will benefit AMD patients. We have shown that Gyps upregulate expression of cholesterol trafficking and metabolism genes, promote cholesterol efflux and decrease lipogenesis of cholesterol, triglyceride and phospholipids in human RPE cells. Gyps also suppress uptake of ox-LDL and decrease intracellular ox-LDL level and ox-LDL-induced inflammation (36).
The therapeutic potential of Gyps against AMD needs to be further validated in AMD models. There are various mouse models that have been used to characterize the disease mechanism and evaluate the protective effects of drug candidates for AMD (37). To validate the therapeutic potential of Gyps, we would suggest choosing two mouse models: high fat high glucose (HFHG) diet induced model and Sod1−/− model, as both models demonstrate key pathological features of AMD. Guided by previous publications (21, 23), study groups including the control, Gyp-treated, and untreated animals can be assessed for electroretinogram, retinal pathologies, oxidative stress, inflammation, abnormal accumulation of cholesterol and triglyceride, and lesion size of laser-induced choroidal neovascularization. Besides, neovascularization, and photoreceptor cell death in the retinal samples can be examined using biochemical and immunohistochemical approaches. Additionally, retinal metabolic and transcriptomic changes can be investigated by, respectively, liquid chromatography mass spectrometry (LC-MS) and RNA sequencing. Furthermore, the alteration of gut microbiome can be analyzed by 16 rRNA gene sequencing; changes in gut bacterial metabolites can be identified by LC-MS. Data from these experiments can provide further evidence of Gyps' therapeutic potential for AMD.
Conclusion
This opinion article described the progress in the pathogenesis and treatment of AMD, summarized the pharmacological activities of Gyps, and discussed the therapeutic potential of Gyps for AMD (Figure 1). Preclinical studies in AMD animal models and clinical trials are warranted for confirmation of Gyps' beneficial effects against AMD.
Author contributions
SC: Writing – original draft. JL: Writing – original draft. JR: Writing – review & editing. JC: Writing – review & editing. H-RJ: Writing – review & editing. XS: Writing – original draft, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This work was partially supported by Tenovus Scotland (XS), the Scottish Neurological Research Fund (XS), the RS MacDonald Facility Access fund (XS), Guangdong Provincial Department of Education Accreditation projects of Ordinary Higher University of Guangdong Province (No. 2024KTSCX385 to JL), Natural Science Foundation of Guangdong province, Guangdong, China (No. 2022A1515110258 to JC) and Guangdong Provincial Department of Education Key Project (No. 2022ZDZX3049 to JC).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author H-RJ declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
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.
References
1. Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for (2020) and (2040): a systematic review and meta-analysis. Lancet Glob Health. (2014) 2:e106–16. doi: 10.1016/S2214-109X(13)70145-1
2. Cao Y, Li Y, Gkerdi A, Reilly J, Tan Z, Shu X. Association of nutrients, specific dietary patterns, and probiotics with age-related macular degeneration. Curr Med Chem. (2022) 29:6141–58. doi: 10.2174/0929867329666220511142817
3. Toma C, De Cillà S, Palumbo A, Garhwal DP, Grossini E. Oxidative and nitrosative stress in age-related macular degeneration: A review of their role in different stages of disease. Antioxidants. (2021) 10:653. doi: 10.3390/antiox10050653
4. Fleckenstein M, Schmitz-Valckenberg S, Chakravarthy U. Age-related macular degeneration: a review. Jama. (2024) 331:147–57. doi: 10.1001/jama.2023.26074
5. Vienne-Jumeau A, Bousquet E, Behar-Cohen F. Complement system modulation in age-related macular degeneration: navigating failures, building future successes. Curr Opin Immunol. (2025) 96:102616. doi: 10.1016/j.coi.2025.102616
6. Su C, Li N, Ren R, Wang Y, Su X, Lu F, et al. Progress in the medicinal value, bioactive compounds, and pharmacological activities of Gynostemma pentaphyllum. Molecules. (2021) 26:6249. doi: 10.3390/molecules26206249
7. Liang G, Lee YZ, Kow ASF, Lee QL, Lim LWC, Yusof R, et al. Neuroprotective effects of gypenosides: a review on preclinical studies in neuropsychiatric disorders. Eur J Pharmacol. (2024) 978:176766. doi: 10.1016/j.ejphar.2024.176766
8. Xie P, Luo HT, Pei WJ, Xiao MY, Li FF, Gu YL, et al. Saponins derived from Gynostemma pentaphyllum regulate triglyceride and cholesterol metabolism and the mechanisms: a review. J Ethnopharmacol. (2024) 319:117186. doi: 10.1016/j.jep.2023.117186
9. Huyen VTT, Phan DV, Thang P, Hoa NK, Östenson CG. Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients. Hormone Metab Res. (2010) 42:353–7. doi: 10.1055/s-0030-1248298
10. Park SH, Huh TL, Kim SY, Oh MR, Tirupathi Pichiah PB, Chae SW, et al. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial. Obesity. (2014) 22:63–71. doi: 10.1002/oby.20539
11. Choi EK, Won YH, Kim SY, Noh SO, Park SH, Jung SJ, et al. Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: a randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. (2019) 52:198–205. doi: 10.1016/j.phymed.2018.05.002
12. Ahn Y, Lee HS, Lee SH, Joa KL, Lim CY, Ahn YJ, et al. Effects of gypenoside L-containing Gynostemma pentaphyllum extract on fatigue and physical performance: a double-blind, placebo-controlled, randomized trial. Phytother Res. (2023) 37:3069–82. doi: 10.1002/ptr.7801
13. Ferris III FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. (2013) 120:844–51. doi: 10.1016/j.ophtha.2012.10.036
14. Salimiaghdam N, Riazi-Esfahani M, Fukuhara PS, Schneider K, Kenney MC. Age-related macular degeneration (AMD): a review on its epidemiology and risk factors. Open Ophthalmol J. (2019) 13:147. doi: 10.2174/1874364101913010090
15. Fritsche LG, Igl W, Bailey JNC, Grassmann F, Sengupta S, Bragg-Gresham JL, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. (2016) 48:134–43. doi: 10.1038/ng.3448
16. Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res. (2017) 60:201–18. doi: 10.1016/j.preteyeres.2017.03.002
17. Xiao J, Zhang JY, Luo W, He PC, Skondra D. The emerging role of gut microbiota in age-related macular degeneration. Am J Pathol. (2023) 193:1627–37. doi: 10.1016/j.ajpath.2023.04.006
18. Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, et al. (2017). Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep. 7:40826. doi: 10.1038/srep40826
19. Xue W, Peng P, Wen X, Meng H, Qin Y, Deng T, et al. Metagenomic sequencing analysis identifies cross-cohort gut microbial signatures associated with age-related macular degeneration. Invest Ophthalmol Vis Sci. (2023) 64:11. doi: 10.1167/iovs.64.5.11
20. Parekh Z, Xiao J, Mani A, Evans Q, Phung C, Barba HA, et al. Fecal microbial profiles and short-chain fatty acid/bile acid metabolomics in patients with age-related macular degeneration: a pilot study. Investig Ophthalmol Vis Sci. (2025) 66:21. doi: 10.1167/iovs.66.4.21
21. Andriessen EM, Wilson AM, Mawambo G, Dejda A, Miloudi K, Sennlaub F, et al. Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization. EMBO Mol Med. (2016) 8:1366–79. doi: 10.15252/emmm.201606531
22. Biswas L, Ibrahim KS, Li X, Zhou X, Zeng Z, Craft J, et al. Effect of a TSPO ligand on retinal pigment epithelial cholesterol homeostasis in high-fat fed mice, implication for age-related macular degeneration. Exp Eye Res. (2021) 208:108625. doi: 10.1016/j.exer.2021.108625
23. Rowan S, Jiang S, Korem T, Szymanski J, Chang ML, Szelog J, et al. Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci. (2017) 114:E4472–81. doi: 10.1073/pnas.1702302114
24. Li X, Chen Y, Wang R, Cao B, Deng T, Han J, et al. Gypenosides, a promising phytochemical triterpenoid: research progress on its pharmacological activity and mechanism. Front Pharmacol. (2025) 16:1705946. doi: 10.3389/fphar.2025.1705946
25. Huang X, Chen W, Yan C, Yang R, Chen Q, Xu H, et al. Gypenosides improve the intestinal microbiota of non-alcoholic fatty liver in mice and alleviate its progression. Biomed Pharmacother. (2019) 118:109258. doi: 10.1016/j.biopha.2019.109258
26. Liu J, Li Y, Yang P, Wan J, Chang Q, Wang TT, et al. Gypenosides reduced the risk of overweight and insulin resistance in C57BL/6J mice through modulating adipose thermogenesis and gut microbiota. J Agric Food Chem. (2017) 65:9237–92. doi: 10.1021/acs.jafc.7b03382
27. Shu X, Chen R, Yang M, Xu J, Gao R, Hu Y, et al. Gynostemma pentaphyllum and Gypenoside-IV ameliorate metabolic disorder and gut microbiota in diet-induced-obese mice. Plant Foods Hum Nutr. (2022) 77:367–72. doi: 10.1007/s11130-022-00982-3
28. Gao M, Heng X, Jin J, Chu W. Gypenoside XLIX ameliorate high-fat diet-induced atherosclerosis via regulating intestinal microbiota, alleviating inflammatory response and restraining oxidative stress in ApoE–/– mice. Pharmaceuticals. (2022) 15:1056. doi: 10.3390/ph15091056
29. Wang R, Liu XF, Yang K, Yu LL, Liu SJ, Wang NN, et al. Gypenosides alleviate hyperglycemia by regulating gut microbiota metabolites and intestinal permeability. Curr Issues Mol Biol. (2025) 47:515. doi: 10.3390/cimb47070515
30. Alhasani RH, Biswas L, Tohari AM, Zhou X, Reilly J, He JF, et al. Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 112:76–85. doi: 10.1016/j.fct.2017.12.037
31. Alhasani RH, Zhou X, Biswas L, Li X, Reilly J, Zeng Z, et al. Gypenosides attenuate retinal degeneration in a zebrafish retinitis pigmentosa model. Exp Eye Res. (2020) 201:108291. doi: 10.1016/j.exer.2020.108291
32. Li X, Alhasani RH, Cao Y, Zhou X, He Z, Zeng Z, et al. (2021). Gypenosides alleviate cone cell death in a zebrafish model of retinitis pigmentosa. Antioxidants. 10:1050. doi: 10.3390/antiox10071050
33. Lin JB, Halawa OA, Husain D, Miller JW, Vavvas DG. Dyslipidemia in age-related macular degeneration. Eye. (2022) 36:312–8. doi: 10.1038/s41433-021-01780-y
34. Dasari B, Prasanthi JR, Marwarha G, Singh BB, Ghribi O. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina. BMC Ophthalmol. (2011) 11:22. doi: 10.1186/1471-2415-11-22
35. Zhang X, Alhasani RH, Zhou X, Reilly J, Zeng Z, Strang N, et al. Oxysterols and retinal degeneration. Br J Pharmacol. (2021) 178:3205–19. doi: 10.1111/bph.15391
36. Biswas L, Zeng Z, Graham A, Shu X. Gypenosides mediate cholesterol efflux and suppress oxidized LDL induced inflammation in retinal pigment epithelium cells. Exp Eye Res. (2020) 191:31. doi: 10.1016/j.exer.2020.107931
Keywords: age-related macular degeneration, gut microbiome, gypenosides, inflammation, lipid metabolism, oxidative stress, therapeutic potential
Citation: Cen S, Li J, Reilly J, Chen J, Jiang H-R and Shu X (2026) The therapeutic potential of gypenosides for age-related macular degeneration. Front. Nutr. 13:1773391. doi: 10.3389/fnut.2026.1773391
Received: 22 December 2025; Revised: 16 January 2026;
Accepted: 21 January 2026; Published: 04 February 2026.
Edited by:
Chenghao Lv, Central South University, ChinaReviewed by:
David Pei-Cheng Lin, Chung Shan Medical University, TaiwanMohd Aizuddin Mohd Lazaldin, University Technology Malaysia, Malaysia
Copyright © 2026 Cen, Li, Reilly, Chen, Jiang and Shu. 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: Xinhua Shu, eGluaHVhLnNodUBnY3UuYWMudWs=; Jinwei Chen, MjAwNTEwMzA1MkBnZGlwLmVkdS5jbg==
†These authors share first authorship