Mechanism of Action of Natural Dipeptidyl Peptidase-IV Inhibitors (Berberine and Mangiferin) in Experimentally Induced Diabetes with Metabolic Syndrome
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Background: Berberine (BER) and mangiferin are known natural dipeptidyl peptidase (DPP-IV) inhibitors. Hence, the study was designed to elucidate the mechanism of action of natural DPP-IV inhibitors (BER and MNG) in experimentally induced diabetes with metabolic syndrome. Aim: The aim of this study was to observe mechanism through which natural DPP-IV inhibitor works in diabetes with metabolic syndrome rat model. Materials and Methods: Wistar rats were fed high-fat diet for 10 weeks and challenged with streptozotocin (STZ) (40 mg/kg) at the 3 rd week (high-fat diabetic control [HF-DC] group). After the confirmation of metabolic syndrome in the setting of diabetes, monotherapy (metformin [MET], vildagliptin [VIL], BER, and MNG) and combination (MET + VIL, MET + BER, and MET + MNG) therapy was orally fed to these rats from the 4 th to 10 th weeks. Results: Insulin resistance (IR) was seen in the HF-DC group as indicated by raised homeostasis model assessment of IR (HOMA-IR) in HF-DC group as compared with normal control (NC) groups. The treatment groups reduced IR as shown by a decrease in HOMA-IR as compared with HF-DC group rats. The marked reduction ( P < 0.001) of beta-cell function was observed in the HF-DC group as a reduced level of HOMA for beta-cell function (HOMA-β) was found as compared with the NC group. Increases in HOMA-β as compared to the HFDC group were observed in the therapy groups. The treatment group significantly reduced cholesterol and atherogenic index. The treatment group showed significant preservation of beta-cell mass as per immunohistochemistry and significant anti-apoptotic activity as per Terminal Deoxyribonucleotidyl Transferase-Mediated dUTP Nick End Labeling assay report. The treated rats significantly ( P < 0.05) reduced high-sensitivity C-reactive protein. Lipid peroxidation (thiobarbituric acid reactive substances) marker ( P < 0.001) was significantly reduced in the treatment group. Conclusion: The natural DPP-IV inhibitors BER and MNG treatment showed beneficial effects on various components of metabolic syndrome.
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Repeated oral administration of MGF (30 or 90 mg/kg for 14 days) in partially pancreatectomized mice may promote islet regeneration through upregulation of cyclin D1, Ki-67, Pdx1 and Ngn3.
“Similarly, repeated oral administration of MGF (30 or 90 mg/kg for 14 days) in partially pancreatectomized mice may promote islet regeneration through the upregulation of key cell-cycle regulators (such as cyclin D1 and Ki-67) and pancreatic progenitor markers, including Pdx1 and Ngn3 (27).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [27]
The Discussion section on preservation of pancreatic beta-cell mass and function reports more insulin-positive cells and preserved beta-cell mass in mangiferin-treated rats, which supports the general possibility of an islet benefit. But the cited paper studies diabetic rats, not partially pancreatectomized mice; its Results list a mangiferin dose of 40 mg/kg, not 30 or 90 mg/kg. Our copy does not report a 14-day regimen or upregulation of cyclin D1, Ki-67, Pdx1, or Ngn3. (LLM, conf=0.88)
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- Authors
- Suman, R. K., Borde, M. K., Mohanty, I. R., & Singh, H. K.
- Affiliations
- Department of Pharmacology, Hind Institute of Medical Sciences, Sitapur, Uttar Pradesh, India
- Department of Pharmacology, MGM Medical College, Vashi, Navi Mumbai, Maharashtra, India
- Department of Pharmacology, MGM Medical College, Kamothe, Navi Mumbai, Maharashtra, India
- Corresponding author
- Suman, Rajesh Kumar
- Venue
- International Journal of Applied & Basic Medical Research
- Published
- 2023-07
- Volume
- 13
- Issue
- 3
- Pages
- 133-142
- ISSN
- 2229-516X (ISSN-L)
- 2248-9606
- PMC
- PMC10666829
- OpenAlex
- W4387225066
- Cited by
- 7
- References
- 26
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- International Journal of Applied and Basic Medical Research (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research (58/2/2014-BMS)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- berberine, mangiferin, DPP-4 inhibitors, metabolic syndrome, streptozotocin-induced diabetes, high-fat diet, insulin resistance, beta-cell function, beta-cell mass, apoptosis, atherogenic index, lipid peroxidation, C-reactive protein, metformin, vildagliptin, combination therapy, natural compounds
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