TY - JOUR

T1 - Protective Effect of Betulin on Streptozotocin–Nicotinamide-Induced Diabetes in Female Rats

AU - Adepoju, Feyisayo o.

AU - Sokolova, Ksenia V.

AU - Gette, Irina F.

AU - Danilova, Irina G.

AU - Tsurkan, Mikhail V.

AU - Mondragon, Alicia C.

AU - Kovaleva, Elena g.

AU - Miranda, Jose Manuel

N1 - This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Priority—2030 Program), state assignment No. 122020900136–4 of the Institute of Immunology and Physiology UB Russian Academy of Science (IIP UB RAS) (work with experimental animals) and the European Regional European Funds (ED431C2018/05). The work with experimental animals was performed using the equipment of the Shared Research Center of Scientific Equipment of the IIP UB RAS.

PY - 2024

Y1 - 2024

N2 - Type 2 diabetes is characterized by hyperglycemia and a relative loss of β–cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin–nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α–amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA–IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β–cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.

AB - Type 2 diabetes is characterized by hyperglycemia and a relative loss of β–cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin–nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α–amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA–IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β–cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.

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UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=001171953500001

U2 - 10.3390/ijms25042166

DO - 10.3390/ijms25042166

M3 - Article

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 4

M1 - 2166

ER -