Berberine in obesity therapy: from molecular mechanisms to clinical applications
DOI:
https://doi.org/10.12775/QS.2025.38.58195Keywords
berberine, obesity, insulin sensitivity, gut microbiota, bioavailabilityAbstract
Objective:
The study aimed to explore the therapeutic potential of berberine in obesity treatment, with a particular focus on its effects on key metabolic mechanisms, inflammatory processes, and gut microbiota composition.
Materials and Methods:
This review encompasses an analysis of preclinical and clinical studies examining berberine’s mechanisms of action, including AMPK pathway activation, lipid profile regulation, white adipose tissue browning, and gut microbiota modulation. Data on berberine’s bioavailability and advanced delivery systems were also included.
Main results:
Studies demonstrate that berberine improves anthropometric parameters (BMI, waist circumference), promotes adipose tissue remodeling, and supports glycemic control. It exhibits anti-inflammatory properties, reduces inflammatory markers, and modulates gut microbiota to enhance metabolic processes. Advanced delivery systems have improved its bioavailability, enhancing clinical efficacy.
Conclusions:
Berberine shows multifaceted potential as a complementary therapy for obesity, especially when combined with lifestyle interventions. It offers a safe and effective alternative for addressing this global health challenge.
References
1. Obesity and overweight. (n.d.). Retrieved December 21, 2024, from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
2. Lin, X., & Li, H. (2021). Obesity: Epidemiology, Pathophysiology, and Therapeutics. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.706978
3. Firouzi, S., Malekahmadi, M., Ghayour-Mobarhan, M., Ferns, G., & Rahimi, H. R. (2018). Barberry in the treatment of obesity and metabolic syndrome: possible mechanisms of action. Diabetes, Metabolic Syndrome and Obesity, 11, 699–705. https://doi.org/10.2147/DMSO.S181572
4. Berberine ameliorates obesity-induced chronic inflammation through suppression of ER stress and promotion of macrophage M2 polarization at least partly via downregulating lncRNA Gomafu - ScienceDirect. (n.d.). Retrieved December 21, 2024, from https://www.sciencedirect.com/science/article/abs/pii/S1567576920314958?via%3Dihub
5. Yazdanpanah, E., Dadfar, S., Shadab, A., Orooji, N., Nemati, M., Pazoki, A., … Haghmorad, D. (2024). Berberine: A natural modulator of immune cells in multiple sclerosis. Immunity, Inflammation and Disease, 12(3), e1213. https://doi.org/10.1002/iid3.1213
6. An, Y., Sun, Z., Zhang, Y., Liu, B., Guan, Y., & Lu, M. (2014). The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clinical Endocrinology, 80(3), 425–431. https://doi.org/10.1111/cen.12294
7. Berberine Improves Insulin Sensitivity by Inhibiting Fat Store and Adjusting Adipokines Profile in Human Preadipocytes and Metabolic Syndrome Patients - Yang - 2012 - Evidence-Based Complementary and Alternative Medicine - Wiley Online Library. (n.d.). Retrieved December 21, 2024, from https://onlinelibrary.wiley.com/doi/full/10.1155/2012/363845
8. Xiong, P., Niu, L., Talaei, S., Kord-Varkaneh, H., Clark, C. C. T., Găman, M.-A., … Zhang, J. (2020). The effect of berberine supplementation on obesity indices: A dose– response meta-analysis and systematic review of randomized controlled trials. Complementary Therapies in Clinical Practice, 39, 101113. https://doi.org/10.1016/j.ctcp.2020.101113
9. Yang, Y., Liu, F., Lu, R., & Jia, J. (2019). Berberine Inhibits Adipogenesis in Porcine Adipocytes via AMP-Activated Protein Kinase-Dependent and -Independent Mechanisms. Lipids, 54(11–12), 667–678. https://doi.org/10.1002/lipd.12200
10. Yao, S., Yuan, Y., Zhang, H., Meng, X., Jin, L., Yang, J., … Zhang, Z. (2020). Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle. Free Radical Biology and Medicine, 159, 66–75. https://doi.org/10.1016/j.freeradbiomed.2020.07.028
11. Xu, X., Yi, H., Wu, J., Kuang, T., Zhang, J., Li, Q., … Fan, G. (2021). Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 133, 110984. https://doi.org/10.1016/j.biopha.2020.110984
12. Payab, M., Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Hasani-Ranjbar, S., Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Baeeri, M., Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran, … Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. (2020). Development of a Novel Anti-Obesity Compound with Inhibiting Properties on the Lipid Accumulation in 3T3-L1 Adipocytes. Iranian Biomedical Journal, 24(3), 155–163. https://doi.org/10.29252/ibj.24.3.155
13. Yao, S., Yuan, Y., Zhang, H., Meng, X., Jin, L., Yang, J., … Zhang, Z. (2020). Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle. Free Radical Biology and Medicine, 159, 66–75. https://doi.org/10.1016/j.freeradbiomed.2020.07.028
14. Horvath C, Wolfrum C. Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight. Proc Nutr Soc. 2020 Aug;79(3):338-356. doi: 10.1017/S0029665120006928. Epub 2020 Apr 15. PMID: 32290888; PMCID: PMC7663322.
15. Ilyas, Z., Perna, S., Al-thawadi, S., Alalwan, T. A., Riva, A., Petrangolini, G., … Rondanelli, M. (2020). The effect of Berberine on weight loss in order to prevent obesity: A systematic review. Biomedicine & Pharmacotherapy, 127, 110137. https://doi.org/10.1016/j.biopha.2020.110137
16. Rondanelli, M., Infantino, V., Riva, A., Petrangolini, G., Faliva, M. A., Peroni, G., … Perna, S. (2020). Polycystic ovary syndrome management: a review of the possible amazing role of berberine. Archives of Gynecology and Obstetrics, 301(1), 53–60. https://doi.org/10.1007/s00404-020-05450-4
17. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans | Cell Death & Disease. (n.d.). Retrieved December 21, 2024, from https://www.nature.com/articles/s41419-019-1706-y
18. Hirai, T., Mitani, Y., Kurumisawa, K., Nomura, K., Wang, W., Nakashima, K., & Inoue, M. (2019). Berberine stimulates fibroblast growth factor 21 by modulating the molecular clock component brain and muscle Arnt-like 1 in brown adipose tissue. Biochemical Pharmacology, 164, 165–176. https://doi.org/10.1016/j.bcp.2019.04.017
19. Abdelrahman, R., Abdelmonsif, D., Farghaly, E., Abounazel, M., & Zaki, E. I. (2021). The effect of Berberine on obesity through browning of the inguinal white adipose tissue of male rats. Egyptian Journal of Histology. https://doi.org/10.21608/ejh.2021.78368.1494
20. Li, C., Leng, Q., Li, L., Hu, F., Xu, Y., Gong, S., … Li, X. (2023). Berberine Ameliorates Obesity by Inducing GDF15 Secretion by Brown Adipocytes. Endocrinology, 164(4), bqad035. https://doi.org/10.1210/endocr/bqad035
21. Full article: Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice. (n.d.). Retrieved December 21, 2024, from https://www.tandfonline.com/doi/full/10.1080/13880209.2020.1756349
22. Zhou, M., Deng, Y., Liu, M., Liao, L., Dai, X., Guo, C., … Li, Y. (2021). The pharmacological activity of berberine, a review for liver protection. European Journal of Pharmacology, 890, 173655. https://doi.org/10.1016/j.ejphar.2020.173655
23. Zhong, Y., Jin, J., Liu, P., Song, Y., Zhang, H., Sheng, L., … Jiang, B. (2020). Berberine Attenuates Hyperglycemia by Inhibiting the Hepatic Glucagon Pathway in Diabetic Mice. Oxidative Medicine and Cellular Longevity, 2020, 6210526. https://doi.org/10.1155/2020/6210526
24. Yue, S.-J., Liu, J., Wang, A.-T., Meng, X.-T., Yang, Z.-R., Peng, C., … Yan, D. (2019). Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids. American Journal of Physiology. Endocrinology and Metabolism, 316(1), E73–E85. https://doi.org/10.1152/ajpendo.00256.2018
25. Meng, Z., Yu, Y., Zhang, Y., Yang, X., Lv, X., Guan, F., … Chen, L. (2020). Highly bioavailable Berberine formulation improves Glucocorticoid Receptor-mediated Insulin Resistance via reduction in association of the Glucocorticoid Receptor with phosphatidylinositol-3-kinase. International Journal of Biological Sciences, 16(14), 2527–2541. https://doi.org/10.7150/ijbs.39508
26. Khvostov, M. V., Gladkova, E. D., Borisov, S. A., Zhukova, N. A., Marenina, M. K., Meshkova, Y. V., … Salakhutdinov, N. F. (2021). Discovery of the First in Class 9-N-Berberine Derivative as Hypoglycemic Agent with Extra-Strong Action. Pharmaceutics, 13(12), 2138. https://doi.org/10.3390/pharmaceutics13122138
27. Rondanelli, M., Gasparri, C., Petrangolini, G., Allegrini, P., Avenoso, D., Fazia, T., … Riva, A. (2023). Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial. European Review for Medical and Pharmacological Sciences, 27(14), 6718–6727. https://doi.org/10.26355/eurrev_202307_33142
28. Bandala, C., Carro-Rodríguez, J., Cárdenas-Rodríguez, N., Peña-Montero, I., Gómez-López, M., Hernández-Roldán, A. P., … Lara-Padilla, E. (2024). Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study. Nutrients, 16(14), 2284. https://doi.org/10.3390/nu16142284
29. Kim, D.-G., Choi, J.-W., Jo, I.-J., Kim, M.-J., Lee, H.-S., Hong, S.-H., … Park, S.-J. (2020). Berberine ameliorates lipopolysaccharide-induced inflammatory responses in mouse inner medullary collecting duct-3 cells by downregulation of NF-κB pathway. Molecular Medicine Reports, 21(1), 258–266. https://doi.org/10.3892/mmr.2019.10823
30. Noh, J.-W., Jun, M.-S., Yang, H.-K., & Lee, B.-C. (2022). Cellular and Molecular Mechanisms and Effects of Berberine on Obesity-Induced Inflammation. Biomedicines, 10(7), 1739. https://doi.org/10.3390/biomedicines10071739
31. Li, J., Li, J., Ni, J., Zhang, C., Jia, J., Wu, G., … Wang, S. (2022). Berberine Relieves Metabolic Syndrome in Mice by Inhibiting Liver Inflammation Caused by a High-Fat Diet and Potential Association With Gut Microbiota. Frontiers in Microbiology, 12. https://doi.org/10.3389/fmicb.2021.752512
32. Li, D., Yang, C., Zhu, J., Lopez, E., Zhang, T., Tong, Q., … Lin, L. (2022). Berberine remodels adipose tissue to attenuate metabolic disorders by activating sirtuin 3. Acta Pharmacologica Sinica, 43(5), 1285–1298. https://doi.org/10.1038/s41401-021-00736-y
33. Neyrinck, A. M., Sánchez, C. R., Rodriguez, J., Cani, P. D., Bindels, L. B., & Delzenne, N. M. (2021). Prebiotic Effect of Berberine and Curcumin Is Associated with the Improvement of Obesity in Mice. Nutrients, 13(5), 1436. https://doi.org/10.3390/nu13051436
34. Vahedi-Mazdabadi, Y., Shahinfar, H., Toushih, M., & Shidfar, F. (2023). Effects of berberine and barberry on selected inflammatory biomarkers in adults: A systematic review and dose–response meta-analysis of randomized clinical trials. Phytotherapy Research, 37(12), 5541–5557. https://doi.org/10.1002/ptr.7998
35. Lin, J., Cai, Q., Liang, B., Wu, L., Zhuang, Y., He, Y., & Lin, W. (2019). Berberine, a Traditional Chinese Medicine, Reduces Inflammation in Adipose Tissue, Polarizes M2 Macrophages, and Increases Energy Expenditure in Mice Fed a High-Fat Diet. Medical Science Monitor, 25, 87–97. https://doi.org/10.12659/MSM.911849
36. Asbaghi, O., Ghanbari, N., Shekari, M., Reiner, Ž., Amirani, E., Hallajzadeh, J., … Asemi, Z. (2020). The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN, 38, 43–49. https://doi.org/10.1016/j.clnesp.2020.04.010
37. Zhang, L., Wu, X., Yang, R., Chen, F., Liao, Y., Zhu, Z., … Wang, L. (2021). Effects of Berberine on the Gastrointestinal Microbiota. Frontiers in Cellular and Infection Microbiology, 10. https://doi.org/10.3389/fcimb.2020.588517
38. Chen, Y., Hao, Z., Zhao, H., Duan, X., Jia, D., Li, K., … Zhao, D. (2023). Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut-microbiota-related tryptophan metabolites. Journal of the Science of Food and Agriculture, 103(3), 1464–1473. https://doi.org/10.1002/jsfa.12242
39. Guo, H.-H., Ma, C., Zheng, W.-S., Luo, Y., Li, C., Li, X.-L., … Jiang, J.-D. (2019). Dual-Stimuli-Responsive Gut Microbiota-Targeting Berberine-CS/PT-NPs Improved Metabolic Status in Obese Hamsters. Advanced Functional Materials, 29(14), 1808197. https://doi.org/10.1002/adfm.201808197
40. Wu, C., Zhao, Y., Zhang, Y., Yang, Y., Su, W., Yang, Y., … Wu, S. (2022). Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR’s cholesterol-decreasing efficacy in patients. Journal of Advanced Research, 37, 197–208. https://doi.org/10.1016/j.jare.2021.07.011
41. Amini, M. R., Sheikhhossein, F., Naghshi, S., Djafari, F., Askari, M., Shahinfar, H., … Shab-Bidar, S. (2020). Effects of berberine and barberry on anthropometric measures: A systematic review and meta-analysis of randomized controlled trials. Complementary Therapies in Medicine, 49, 102337. https://doi.org/10.1016/j.ctim.2020.102337
42. Yan, H.-M., Xia, M.-F., Wang, Y., Chang, X.-X., Yao, X.-Z., Rao, S.-X., … Gao, X. (2015). Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS ONE, 10(8), e0134172. https://doi.org/10.1371/journal.pone.0134172
43. Asha, T., Seema, K., Sanjeevani, D., Lata, K., & Sohan, C. (2021). Bioavailability of berberine: challenges and solutions. İstanbul Journal of Pharmacy, 51(1), 141–153. https://doi.org/10.26650/IstanbulJPharm.2020.0056
44. Murakami, T., Bodor, E., & Bodor, N. (2023). Approaching strategy to increase the oral bioavailability of berberine, a quaternary ammonium isoquinoline alkaloid: Part 1. Physicochemical and pharmacokinetic properties. Expert Opinion on Drug Metabolism & Toxicology, 19(3), 129–137. https://doi.org/10.1080/17425255.2023.2203857
45. Alsabeelah, N., & Kumar, V. (2022). Quality by design-based optimization of formulation and process parameters for berberine nanosuspension for enhancing its dissolution rate, bioavailability, and cardioprotective activity. Journal of Food Biochemistry, 46(10), e14361. https://doi.org/10.1111/jfbc.14361
46. Solnier, J., Zhang, Y., Kuo, Y. C., Du, M., Roh, K., Gahler, R., … Chang, C. (2023). Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers. Pharmaceutics, 15(11), 2567. https://doi.org/10.3390/pharmaceutics15112567
47. Chen, X., Yang, H., Shi, L., Mao, Y., Niu, L., Wang, J., … Zheng, Y. (2024). Self-Microemulsifying Drug Delivery System to Enhance Oral Bioavailability of Berberine Hydrochloride in Rats. Pharmaceutics, 16(9), 1116. https://doi.org/10.3390/pharmaceutics16091116
48. Mori, N., Oda, K., Takakura, H., Tanaka, Y., Yokooji, T., & Murakami, T. (2023). Comparison of Berberine Bioavailability between Oral and Rectal Administrations in Rats. Biological & Pharmaceutical Bulletin, 46(11), 1639–1642. https://doi.org/10.1248/bpb.b23-00444
49. Wang, A., Yang, W., Yang, X., Mei, X., Hu, T., Liang, R., … Yan, D. (2020). MgAl monolayer hydrotalcite increases the hypoglycemic effect of berberine by enhancing its oral bioavailability. Biomedicine & Pharmacotherapy, 127, 110140. https://doi.org/10.1016/j.biopha.2020.110140
50. Kutbi, H. I., Asfour, H. Z., Kammoun, A. K., Sirwi, A., Cavalu, S., & Gad, H. A. (2021). Optimization of Hyaluronate-Based Liposomes to Augment the Oral Delivery and the Bioavailability of Berberine. Materials, 14(19), 5759. https://doi.org/10.3390/ma14195759
51. Li, Z., Wang, Y., Xu, Q., Ma, J., Li, X., Yan, J., … Chen, T. (2023). Berberine and health outcomes: An umbrella review. Phytotherapy research: PTR, 37(5), 2051–2066. https://doi.org/10.1002/ptr.7806
52. Imenshahidi, M., & Hosseinzadeh, H. (2019). Berberine and barberry (Berberis vulgaris): A clinical review. Phytotherapy research: PTR, 33(3), 504–523. https://doi.org/10.1002/ptr.6252
53. Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., … Chen, R. (2022). Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.1015045
54. El-sawy, A. E.-S. F., El-Maddawy, Z. K., Demellawy, M. E., & Khedr, S. M. (2019). Some Toxicological, Hematological, Biochemical, and Reproductive Effects of Berberine In Male Rats. Alexandria Journal of Veterinary Sciences, 63(1), 59–59. https://doi.org/10.5455/ajvs.46154
55. Song, D., Hao, J., & Fan, D. (2020). Biological properties and clinical applications of berberine. Frontiers of Medicine, 14(5), 564–582. https://doi.org/10.1007/s11684-019-0724-6
56. Moon, J. M., Ratliff, K. M., Hagele, A. M., Stecker, R. A., Mumford, P. W., & Kerksick, C. M. (2022). Absorption Kinetics of Berberine and Dihydroberberine and Their Impact on Glycemia: A Randomized, Controlled, Crossover Pilot Trial. Nutrients, 14(1), 124. https://doi.org/10.3390/nu14010124
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Katarzyna Kamińska-Omasta, Bartosz Omasta, Kuba Borys Romańczuk, Olga Krupa, Paulina Dorota Pietrukaniec, Zofia Martyna Wójcik, Kinga Furtak, Szymon Przemysław Stolarczyk, Magdalena Agata Czerska, Daria Rybak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 17
Number of citations: 0
