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Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study

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Abstract

Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have less side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed for evaluating the development of the diabetic model. Echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis was analyzed. In vitro BBR had no impact on cell viability up to a concentration of 50 μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

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The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.

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Funding

This study was supported by the Indian Council of Medical Research, New Delhi India (Grant No. 45/67/2018-BMS/PHA/OL).

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Authors and Affiliations

  1. Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India

    Mrinal Gupta, Babita Singh, Abbas Ali Mahdi & Shivani Pandey

  2. Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India

    Mohammad Rumman

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  1. Mrinal Gupta
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  4. Abbas Ali Mahdi
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  5. Shivani Pandey
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Contributions

MG and SP conceived the presented idea and planned the experiments. SP verified the analytical methods and supervised the findings of this work. MG, MR, and BS designed the model, carried out the experiments, and analyzed the data. MG wrote the manuscript with input from all authors. MR contributed to sample preparation and the interpretation of the results. MG and MR contributed to implementation of the research, to the analysis of the results, and to the writing of the manuscript. MG, BS, SP, and MR drafted the manuscript and designed the figures. SP and AM were involved in planning and supervised the work. SP and AM were in charge of overall direction and planning. All authors provided critical feedback and helped shape the research, analysis, and manuscript preparation. All authors approved the manuscript for submission. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Shivani Pandey.

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Ethical approval

The study was approved by the Institutional Animal Ethics Committee of the King George’s Medical University (KGMU), Lucknow, India (No. 101/IAEC/2018).

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All authors have read and approved the manuscript for submission.

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The authors declare no competing interests.

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Gupta, M., Rumman, M., Singh, B. et al. Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1647–1658 (2024). https://doi.org/10.1007/s00210-023-02703-2

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