The effect(s) of berberine from Berberis vulgaris L. (Berberidaceae) on treating type 1 diabetes mellitus in streptozotocin-induced diabetic rats

Document Type : Original Article

Authors

1 Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

2 Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

10.22038/ijbms.2026.90772.19575

Abstract

Objective(s): Berberis vulgaris (B. vulgaris) L. (Berberidaceae), deeply rooted in Iranian traditional medicine, exhibits significant antidiabetic potential attributed to its berberine content. This plant has been historically used for its glucose-lowering, anti-oxidant, and anti-inflammatory properties. This research investigated berberine’s capacity to regenerate pancreatic β-cells in type 1 diabetic rats, specifically examining its dose-dependent effects on metabolic recovery, histopathological restoration, and molecular mechanisms underlying β-cell regeneration. 
Materials and Methods: Two groups of streptozotocin-induced diabetic rats received daily oral berberine (50 and 100 mg/kg) for 60 days. We measured berberine half-life and gamma aminobutyric acid (GABA) levels using high-performance liquid chromatography (HPLC) with ultraviolet-visible (Uv/Vis) and fluorescence detection (FD). Fasting blood sugar (FBS), lipid profiles, liver enzymes, insulin, and gastrin were assessed. Pancreatic histopathology (islet damage) and pancreatic and duodenal homeobox 1 (Pdx1) expression were analyzed.
Results: Berberine exhibited a 60-min half-life, with blood concentration declining to 0.63 and 0.95 µmol/l within 90 min. Treatment significantly elevated GABA levels (3.0 and 3.8 mg/dl vs diabetic group: 0.44 mg/dl) and reduced FBS by 50% (327 and 296 mg/dl vs diabetic group: 616 mg/dl). Gastrin levels increased to 8.70 and 8.93 pg/ml (vs diabetic group: 5.96 pg/ml). Histopathology revealed reduced islet shrinkage and vacuolization. Pdx1 expression was increased in the treated groups compared with diabetic controls. 
Conclusion: Berberine from B. vulgaris effectively stimulates pancreatic β-cell regeneration, as evidenced by restored histoarchitecture, up-regulated Pdx1, and sustained glycemic control despite rapid clearance. This validates its traditional antidiabetic use and positions berberine as a promising disease-modifying agent.

Keywords

Main Subjects


1. Paschou SA, Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. On type 1 diabetes mellitus pathogenesis. Endocr Connect 2018; 7:R38-R46.
2. DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet 2018; 391:2449-2462.
3. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 2014; 383:69-82.
4. Polychronakos C, Li Q. Understanding type 1 diabetes through genetics: advances and prospects. Nat Rev Genet 2011; 12:781-792.
5. Katsarou A, Gudbjornsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017; 3:17016.
6. van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol Rev 2011; 91:79-118.
7. Singh A, Afshan N, Singh A, Singh SK, Yadav S, Kumar M, et al. Recent trends and advances in type 1 diabetes therapeutics: A comprehensive review. Eur J Cell Biol 2023; 102:151329.
8. Fujimoto K, Polonsky KS. Pdx1 and other factors that regulate pancreatic beta-cell survival. Diabetes Obes Metab 2009; 11(Suppl 4):30-37.
9. Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, et al. Pdx1 maintains β cell identity and function by repressing an α cell program. Cell Metab 2014; 19:259-271.
10. 10. Zhang Y, Fang X, Wei J, Miao R, Wu H, Ma K, et al. PDX-1: A promising therapeutic target to reverse diabetes. Biomolecules 2022; 12:1785.
11. Yang YP, Thorel F, Boyer DF, Herrera PL, Wright CV. Context-specific α- to β-cell reprogramming by forced Pdx1 expression. Genes Dev 2011; 25:1680-1685.
12. Jewett BE, Sharma S. Physiology, GABA. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
13. Jin Z, Korol SV. GABA signalling in human pancreatic islets. Front Endocrinol (Lausanne) 2023; 14:1059110.
14. Rahimi-Madiseh M, Lorigoini Z, Zamani-Gharaghoshi H, Rafieian-Kopaei M. Berberis vulgaris: Specifications and traditional uses. Iran J Basic Med Sci 2017; 20:569-587.
15. Suau R, Rico R, Lopez-Romero JM, Najera F, Cuevas A. Isoquinoline alkaloids from Berberis vulgaris subsp, Australis. Phytochemistry 1998; 49:2545–2549.
16. Salmanizadeh H, Sahi N. Determination of amino acid profile for argininosuccinic aciduria disorder using high-performance liquid chromatography with fluorescence detection. Acta Biochim Pol 2020; 67:347-351.
17. Rahimi-Madiseh M, Heidarian E, Rafieian-kopaei M. Biochemical components of Berberis lycium fruit and its effects on lipid profile in diabetic rats. J Herbmed Pharmacol. 2014; 3:15-19.
18. Tabeshpour J, Imenshahidi M, Hosseinzadeh H. A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci 2017; 20:557-568.
19. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004; 10:1344-1351.
20. Thomas A, Kamble S, Deshkar S, Kothapalli L, Chitlange S. Bioavailability of berberine: challenges and solutions. İstanbul J Pharm 2021; 51:141-153.
21. Wan Y, Wang Q, Prud’homme GJ. GABAergic system in the endocrine pancreas: A new target for diabetes treatment. Diabetes Metab Syndr Obes 2015; 8:79-87.
22. Narayan G, Sundaravadivelu PK, Agrawal A, Gogoi R, Nagotu S, Thummer RP. Soluble expression, purification, and secondary structure determination of human PDX1 transcription factor. Protein Expr Purif 2021; 180:105807.