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

Type 2 diabetes is characterized by hyperglycemia and a relative loss of ß-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 ß-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.

Isoflavones derived from plant raw materials: bioavailability, anti-cancer, anti-aging potentials, and microbiome modulation.

Isoflavones are secondary metabolites that represent the most abundant category of plant polyphenols. Dietary soy, kudzu, and red clover contain primarily genistein, daidzein, glycitein, puerarin, formononetin, and biochanin A. The structural similarity of these compounds to ß-estradiol has demonstrated protection against age-related and hormone-dependent diseases in both genders. Demonstrative shreds of evidence confirmed the fundamental health benefits of the consumption of these isoflavones. These relevant activities are complex and largely driven by the source, active ingredients, dose, and administration period of the bioactive compounds. However, the preclinical and clinical studies of these compounds are greatly variable, controversial, and still with no consensus due to the non-standardized research protocols. In addition, absorption, distribution, metabolism, and excretion studies, and the safety profile of isoflavones have been far limited. This highlights a major gap in understanding the potentially critical role of these isoflavones as prospective replacement therapy. Our general review exclusively focuses attention on the crucial role of isoflavones derived from these plant materials and critically highlights their bioavailability, possible anticancer, antiaging potentials, and microbiome modulation. Despite their fundamental health benefits, plant isoflavones reveal prospective therapeutic effects that worth further standardized analysis.

Accelerated Generation of Extra-Islet Insulin-Producing Cells in Diabetic Rats, Treated with Sodium Phthalhydrazide.

ß-cells dysfunction plays an important role in the pathogenesis of type 2 diabetes (T2D), partially may be compensated by the generation of extra-islet insulin-producing cells (IPCs) in pancreatic acini and ducts. Pdx1 expression and inflammatory level are suggested to be involved in the generation of extra-islet IPCs, but the exact reasons and mechanisms of it are unclear. Macrophages are key inflammatory mediators in T2D. We studied changes in mass and characteristics of extra-islet IPCs in rats with a streptozotocin-nicotinamide model of T2D and after i.m. administration of 20 daily doses of 2 mg/kg b.w. sodium aminophthalhydrazide (APH). Previously, we found that APH modulates macrophage production and increases the proliferative activity of pancreatic ß-cells. Expressions of insulin and Pdx1, as well as F4/80 (macrophage marker), were detected at the protein level by immunohistochemistry analysis, the concentration of pro- and anti-inflammatory cytokines in blood and pancreas-by ELISA. Diabetic rats treated with APH showed an increasing mass of extra-islet IPCs and the content of insulin in them. The presence of Pdx1+ cells in the exocrine pancreas also increased. F4/80+ cell reduction was accompanied by increasing TGF-ß1 content. Interestingly, during the development of diabetes, the mass of ß-cells decreased faster than the mass of extra-islet IPCs, and extra-islet IPCs reacted to experimental T2D differently depending on their acinar or ductal location.

Accelerated liver recovery after acute CCl4 poisoning in rats treated with sodium phthalhydrazide.

Pharmacotherapy of hepatobiliary disorders is an important issue due to the high prevalence of liver failure, toxic and viral hepatitis and cirrhosis. The number of stimuli that can potentially induce or accelerate liver recovery is limited; in our study we selected sodium phthalhydrazide, which has been found to promote liver regeneration after partial hepatectomy. We examined the effects of phthalhydrazide on liver morphometric, histological and biochemical parameters in rats intoxicated with CCl4. Accelerated liver recovery after CCl4 intoxication in phthalhydrazide-treated animals was evidenced by increased number of liver sinusoidal cells, reduced focal necrosis of hepatocytes and reduced perifocal leukocyte infiltration. Decreased plasma levels of pro-inflammatory cytokines TNF-α and IL-18 and decreased concentrations of IL-6 and IFN-γ in liver homogenates were associated with reduced severity of cholestasis and normalized hepatic protein synthesis in CCl4-intoxicated rats exposed to phthalhydrazide. Anti-inflammatory and immunomodulating properties of phthahlhydrazide can be an important factor contributing to accelerated liver recovery at early stages of acute CCl4-toxic liver impairment.

Partial recovery from alloxan-induced diabetes by sodium phthalhydrazide in rats.

In the commonly used experimental model of diabetes, a cytotoxic glucose analogue alloxan can selectively destruct pancreatic ß-cells, with characteristics similar to the type-1 diabetes (T1D) in humans. Treatment of diabetic rats with sodium phthalhydrazide partially reversed diabetogenic pathology in the alloxan-induced diabetes. The alloxan-treated rats with permanent hyperglycemia, which further received i.p. twenty daily doses 2mg/kg b.w. phthalhydrazide, showed at 60days of the experiment a significant amelioration of the diabetes status. Hyperglycemia was decreased by 52%, glycated haemoglobin HbA1c returned to control value, insulin concentration significantly increased from 45,4% (alloxan group) to 59,5% (alloxan+phthalhydrazide) of the control values. Importantly, phthalhydrazide treatment of alloxan-treated diabetic rats markedly decreased the concentrationof interleukin-6 (IL-6) and corticosterone level. Morphometric analysis revealed a marked increase in the number of pancreatic islets/mm2, and a number of cells/mm2 in the pancreatic islets. These changes, including 3-fold increase in the number of insulin-producing cells and 2-fold decrease in blood glucose levels, correlated with the increased proliferative activity of pancreatic ß-cells in the diabetic phthalhydrazide-treated animals. Interestingly, the number of CD68+ cells/macrophages in the pancreatic islets, which was relatively high in the alloxan group (63,9+- 16.4/mm2), markedly decreased after the phthalhydrazide treatment (23,6+-7,2/mm2). Taking together with the previous data on the phthalhydrazide-related macrophage silencing, restriction of macrophage quantity in the alloxan-affected pancreatic islets can be possibly one of important events leading to the partial recovery from the ß-cell disruption.