Authors : Anita Devi; Akshit Sharma; Rajneesh Kaur; Brij Bhushan; Amandeep Kaur; Shruti Jaswal; Sarbjot Singh; Anuneet Kaur

Volume/Issue : Volume 10 - 2025, Issue 11 - November

Google Scholar : https://tinyurl.com/58ebfyyj

Scribd : https://tinyurl.com/yzupu9rd

DOI : https://doi.org/10.38124/ijisrt/25nov940

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Note : Google Scholar may take 30 to 40 days to display the article.

Abstract : Berberine chloride, an isoquinoline alkaloid derived from several medicinal plants, has gained significant scientific attention for its broad pharmacological profile. Traditionally used in Asian medicine, it is now widely investigated for its metabolic, cardiovascular, antimicrobial, and anti-inflammatory activities. This review synthesizes current evidence on the pharmacology, therapeutic potential, mechanisms of action, and safety profile of berberine chloride, with emphasis on its relevance to modern pharmacotherapy. berberine chloride demonstrates multitarget actions involving modulation of AMP- activated protein kinase (AMPK), regulation of gut microbiota, inhibition of inflammatory pathways, and improvement of glucose and lipid metabolism. Clinical studies suggest beneficial effects in conditions such as type 2 diabetes, dyslipidaemia, metabolic syndrome, and certain infectious diseases. Advances in nano formulation and delivery systems show promise for overcoming limitations in oral bioavailability. Overall, the compound exhibits a favourable safety profile, though gastrointestinal intolerance and drug–drug interactions have been reported.

Keywords : Berberine Chloride, Pharmacotherapy, Clinical Safety, Regulation.

References :

1. Furrianca MC, Alvear M et al., 2015. Medicinal value of the Berberis genus as hypoglycaemic agent. Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas, 14(5): 423-441.
2. Firouzi S, Malekahmadi M et al., 2018. Barberry in the treatment of obesity and metabolic syndrome: possible mechanisms of action. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 11: 699-705. DOI:10.2147/DMSO.S181572
3. Guo Y, Li F et al., 2017. CYP2D plays a major role in berberine metabolism in liver of mice and humans. Xenobiotica, 41(11): 996-1005. DOI:10.3109/00498254.2011.597456
4. Imenshahidi M, Hosseinzadeh H et al., 2016. Berberis Vulgaris and Berberine: An update review. Phytotherapy Research, 30: 1745-1764. DOI: 10.1002/ptr.5693
5. Imenshahidi M, Hosseinzadeh H et al., 2019. Berberine and Barberry (Berberis Vulgaris): A clinical review. Phytotherapy Research, 33: 504 523. www.ejbps.com DOI: 10.1002/ptr.6252
6. Jang J, Jung Y et al., 2017. Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Molecular Medicine Reports, 15(6): 4139-4147. DOI: 10.3892/mmr.2017.6513
7. James MA, Fu H et al., 2011. Dietary administration of berberine of Phellodendrone amurense extracts inhibits cell cycle progression and lung tumorigenesis. Molecular carcinogenesis, 50(1): 1-7. DOI:10.1002%2Fmc.20690
8. Jing Y, Weijia K et al., 2015. Learning from berberine: Treating chronic diseases through multiple targets. Science China Life Sciences, 58: 854-859. DOI: 10.1007/s11427-013-4568-z
9. Kaneda Y, Tanaka T et al., 1990. Effects of berberine, a plant alkaloid, on the growth of anaerobic protozoa in axenic culture. Tokai Journal of Experimental and Clinical Medicine, 15(6): 417 423.
10. Kattiyar D, Singh V et al., 2014. Isolation and characterization of stigmast-5-en-3β-ol from heartwood of Berberis aristata. International Journal of Drug Development & Research, 6(1): 92-98.
11. Khan I, Najeebullah S et al., 2016. Phytopharmacological and Ethnomedicinal uses of the genus Berberis (Berberidaceae): A review. Tropical Journal of Pharmaceutical Research, 15(9): 2047-2057. DOI: 10.4314/tjpr.v15i9.33
12. Kong LD, Cheng CH et al., 2001. Monoamine oxidase inhibitors from rhizoma of Coptis Chinensis. Planta Medica, 67: 74-76. DOI:10.1055/s-2001-10874
13. Kostalova D, Brazdovicova B et al., 1981. Isolation of quaternary alkaloids from Mahonia aquifolium. Chemicke Zvesti, 35(2): 279-283.
14. Kulkarni SK, Dhir A et al., 2008. On the mechanism of antidepressant-like action of berberine chloride. European Journal of Pharmacology, 589: 163-172.
15. Lee YS, Kim WS et al., 2006. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin resistant states. Diabetes, 55(8): 2256 64. DOI: 10.2337/db06-0006
16. Li H, Miyahara T et al., 2003. Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model. Biological and Pharmaceutical Bulletin, 26(1), 110-111. DOI: 10.1248/bpb.26.110
17. Deepak P, Gopal GV et al., 2014. Phytochemical profile of Berberis tinctoriaLesch. Bark using GC MS analysis. European Journal of Experimental Biology, 4(2): 419-425.
18. Domadia PN, Bhunia A et al., 2008. Berberine targets assembly of Escherichia coli cell division protein FtsZ. Biochemistry, 47(10): 3225-3234. DOI: 10.1021/bi7018546
19. Dong H, Wang N et al., 2012. Berberine in the treatment of type 2 diabetes mellitus: A systemic review and meta-analysis. Evidence Based Complementary and Alternative Medicine, 591654: 1-12. DOI:10.1155/2012/591654
20. Chavez ENA, Coy-barrera ED et al., 2014. Evaluation of the Leishmani activity of Rutaceae and Lauraceae ethanol extracts on Golden Syrian Hamster (Mesocricetus auratus) Peritoneal Macrophages. Indian Journal of Pharmaceutical Sciences, 76(3): 188-197.
21. Chen YY, Chang FR et al., 1996. Isoquinoline alkaloids and lignans from Rollinia mucosa. Journal of Natural Products, 59(9): 904-906. DOI: 10.1021/np960414z
22. Chen C, Yu Z et al., 2014. Effects of Berberine in the Gastrointestinal Tract-A review of actions and therapeutic implications. The American Journal of Chinese Medicine, 42(5): 1053-1070. DOI: 10.1142/S0192415X14500669
23. Al Rifai M., Mahtta D., Kherallah R., Kianoush S., Liu J., Rodriguez F., et al. (2021). Prevalence and Determinants of Difficulty in Accessing Medical Care in U.S. Adults. Am. J. Prev. Med. 61 (4), 492–500. 10.1016/j.amepre.2021.03.026 [DOI] [PubMed] [Google Scholar]
24. Allijn I. E., Czarny B. M. S., Wang X., Chong S. Y., Weiler M., da Silva A. E., et al. (2017). Liposome Encapsulated Berberine Treatment Attenuates Cardiac Dysfunction after Myocardial Infarction. J. Control Release. 247, 127–133. 10.1016/j.jconrel.2016.12.042 [DOI] [PubMed] [Google Scholar]
25. Altoé L. S., Alves R. S., Miranda L. L., Sarandy M. M., Bastos D. S. S., Gonçalves-Santos E., et al. (2021). Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats. Oxid. Med. Cel. Longev. 2021, 4681041. 10.1155/2021/4681041 [DOI] [PMC free article] [PubMed] [Google Scholar]
26. Li W, Hua B et al., 2015. Berberine regulates AMP activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice. Molecular Carcinogenesis, 54(10): 1096-1109. DOI:10.1002/mc.22179.
27. . Lin K, Liu S et al., 2013. Berberine attenuates Cigarette smoke-induced acute lung inflammation. Inflammation, 36(5): 1079-1086.
28. Liu Y, Zhang L et al., 2013. Update on Berberine in Nonalcoholic Fatty Liver Disease. Evidence Based Complementary and Alternative Medicine, 308134: 1-8. DOI: 10.1155%2F2013%2F308134
29. Mat A, Sariyar G et al., 2000. Alkaloids and bioactivity of Papaver dubiam Subsp. Dubium and P. Dubium Subsp. Laevigatum. Natural Product Research, 14(3): 205-210. DOI: 10.1080/10575630008041232
30. Mohammadzadeh N, Mehri S et al., 2017. Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities. Iranian Journal of Basic Medical Sciences, 20(5): 538-551. DOI:10.22038%2FIJBMS.2017.8678
31. Aggarwal S., Banerjee S. K., Talukdar N. C., Yadav A. K. (2020). Post-translational Modification Crosstalk and Hotspots in Sirtuin Interactors Implicated in Cardiovascular Diseases. Front. Genet. 11, 356. 10.3389/fgene.2020.00356 [DOI] [PMC free article] [PubMed] [Google Scholar]
32. Agrawal S., Zaritsky J. J., Fornoni A., Smoyer W. E. (2018). Dyslipidaemia in Nephrotic Syndrome: Mechanisms and Treatment. Nat. Rev. Nephrol. 14 (1), 57–70. 10.1038/nrneph.2017.155 [DOI] [PMC free article] [PubMed] [Google Scholar]
33. Ai X., Hou Y., Wang X., Wang X., Liang Y., Zhu Z., et al. (2019). Amelioration of Dry Eye Syndrome in Db/db Mice with Diabetes Mellitus by Treatment with Tibetan Medicine Formula Jikan Mingmu Drops. J. Ethnopharmacol. 241, 111992. 10.1016/j.jep.2019.111992 [DOI] [PubMed] [Google Scholar]
34. Ai X., Yu P., Hou Y., Song X., Luo J., Li N., et al. (2020). A Review of Traditional Chinese Medicine on Treatment of Diabetic Retinopathy and Involved Mechanisms. Biomed. Pharmacother. 132, 110852. 10.1016/j.biopha.2020.110852 [DOI] [PubMed] [Google Scholar]
35. Ajjan R. A., Kietsiriroje N., Badimon L., Vilahur G., Gorog D. A., Angiolillo D. J., et al. (2021). Antithrombotic Therapy in Diabetes: Which, when, and for How Long? Eur. Heart J. 42 (23), 2235–2259. 10.1093/eurheartj/ehab128 [DOI] [PMC free article] [PubMed] [Google Scholar].
36. Akhmedov A., Sawamura T., Chen C. H., Kraler S., Vdovenko D., Lüscher T. F. (2021). Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1): A Crucial Driver of Atherosclerotic Cardiovascular Disease. Eur. Heart J. 42 (18), 1797–1807.
37. Dai W., Lopez O. L., Carmichael O. T., Becker J. T., Kuller L. H., Gach H. M. (2009). Mild Cognitive Impairment and Alzheimer Disease: Patterns of Altered Cerebral Blood Flow at MR Imaging. Radiology 250 (3), 856–866. 10.1148/radiol.2503080751 [DOI] [PMC free article] [PubMed] [Google Scholar].
38. Detillieux K. A., Sheikh F., Kardami E., Cattini P. A. (2003). Biological Activities of Fibroblast Growth Factor-2 in the Adult Myocardium. Cardiovasc. Res. 57 (1), 8–19. 10.1016/s0008-6363(02)00708-3 [DOI] [PubMed] [Google Scholar]
39. Detillieux K. A., Sheikh F., Kardami E., Cattini P. A. (2003). Biological Activities of Fibroblast Growth Factor-2 in the Adult Myocardium. Cardiovasc. Res. 57 (1), 8–19. 10.1016/s0008-6363(02)00708-3 [DOI] [PubMed] [Google Scholar]
40. Dewanjee S., Chakraborty P., Mukherjee B., De Feo V. (2020). Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy. Int. J. Mol. Sci. 21 (6), 2217. 10.3390/ijms21062217 [DOI] [PMC free article] [PubMed] [Google Scholar]
41. Doña I., Pérez‐Sánchez N., Eguiluz‐Gracia I., Muñoz-Cano R., Bartra J., Torres M. J., et al. (2020). Progress in Understanding Hypersensitivity Reactions to Nonsteroidal Anti‐inflammatory Drugs. Allergy 75 (3), 561–575. 10.1111/all.14032 [DOI] [PubMed] [Google Scholar]
42. Durairajan S. S., Liu L. F., Lu J. H., Chen L. L., Yuan Q., Chung S. K., et al. (2012). Berberine Ameliorates β-amyloid Pathology, Gliosis, and Cognitive Impairment in an Alzheimer's Disease Transgenic Mouse Model. Neurobiol. Aging 33 (12), 2903–2919. 10.1016/j.neurobiolaging.2012.02.016 [DOI] [PubMed] [Google Scholar]
43. Fang C., Xie L., Liu C., Fu C., Ye W., Liu H., et al. (2018). Berberine Ameliorates Neonatal Necrotizing Enterocolitis by Activating the Phosphoinositide 3-kinase/protein Kinase B Signaling Pathway. Exp. Ther. Med. 15 (4), 3530–3536. 10.3892/etm.2018.5858 [DOI] [PMC free article] [PubMed] [Google Scholar]
44. Fang C., Dai L., Wang C., Fan C., Yu Y., Yang L., et al. (2021). Secretogranin II Impairs Tumor Growth and Angiogenesis by Promoting Degradation of Hypoxia‐inducible Factor‐1α in Colorectal Cancer. Mol. Oncol. 23, 1. 10.1002/1878-0261.13044 [DOI] [PMC free article] [PubMed] [Google Scholar]
45. Feng M., Zou Z., Zhou X., Hu Y., Ma H., Xiao Y., et al. (2017). Comparative Effect of Berberine and its Derivative 8-Cetylberberine on Attenuating Atherosclerosis in ApoE-/- Mice. Int. Immunopharmacol. 43, 195–202. 10.1016/j.intimp.2016.12.001 [DOI] [PubMed] [Google Scholar]
46. Feng R., Shou J. W., Zhao Z. X., He C. Y., Ma C., Huang M., et al. (2015). Transforming Berberine into its Intestine-Absorbable Form by the Gut Microbiota. Sci. Rep. 5, 12155. 10.1038/srep12155 [DOI] [PMC free article] [PubMed] [Google Scholar]
47. Feng X., Sureda A., Jafari S., Memariani Z., Tewari D., Annunziata G., et al. (2019). Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics. Theranostics 9 (7), 1923–1951. 10.7150/thno.30787 [DOI] [PMC free article] [PubMed] [Google Scholar]
48. Feng X., Wang K., Cao S., Ding L., Qiu F. (2021). Pharmacokinetics and Excretion of Berberine and its Nine Metabolites in Rats. Front. Pharmacol. 11, 594852. 10.3389/fphar.2020.594852 [DOI] [PMC free article] [PubMed] [Google Scholar]
49. Feng X., Zhang L., Xu S., Shen A. Z. (2020). ATP-citrate Lyase (ACLY) in Lipid Metabolism and Atherosclerosis: An Updated Review. Prog. Lipid. Res. 77, 101006. 10.1016/j.plipres.2019.101006 [DOI] [PubMed] [Google Scholar]
50. Ference B. A., Ginsberg H. N., Graham I., Ray K. K., Packard C. J., Bruckert E., et al. (2017). Low-density Lipoproteins Cause Atherosclerotic Cardiovascular Disease. 1. Evidence from Genetic, Epidemiologic, and Clinical Studies. A Consensus Statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 38 (32), 2459–2472. 10.1093/eurheartj/ehx144 [DOI] [PMC free article] [PubMed] [Google Scholar]
51. Ferron L., Ruchon Y., Renaud J. F., Capuano V. (2011). T-type Ca²+ Signalling Regulates Aldosterone-Induced CREB Activation and Cell Death through PP2A Activation in Neonatal Cardiomyocytes. Cardiovasc. Res. 90 (1), 105–112. 10.1093/cvr/cvq379 [DOI] [PMC free article] [PubMed] [Google Scholar]
52. Fatima M. T., Hasan M., Abdelsalam S. S., Sivaraman S. K., El-Gamal H., Zahid M. A. (2021). Sestrin2 Suppression Aggravates Oxidative Stress and Apoptosis in Endothelial Cells Subjected to Pharmacologically Induced Endoplasmic Reticulum Stress. Eur. J. Pharmacol. 907, 17424. 10.1016/j.ejphar.2021.174247 [DOI] [PubMed] [Google Scholar].