Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

BACKGROUND: Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. METHODS: The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. RESULTS: Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. CONCLUSION: In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.

Amelioration of 5-Fluorouracil Induced Nephrotoxicity by Acacia catechu through Overcoming Oxidative Damage and Inflammation in Wistar Rats.

AIM: The research intended to explore the possible nephroprotective potential of the ethyl acetate fraction derived from Acacia catechu leaves against nephrotoxicity brought about by 5-fluorouracil (5-FU) in Wistar rats. BACKGROUND: While possessing strong anticancer properties, 5-FU is hindered in its therapeutic application due to significant organ toxicity linked to elevated oxidative stress and inflammation. OBJECTIVE: The study is undertaken to conduct an analysis of the ethyl acetate fraction of A. catechu leaves both in terms of quality and quantity, examining its impact on different biochemical and histopathological parameters within the context of 5-FU-induced renal damage in rats and elucidation of the mechanism behind the observed outcomes. METHODOLOGY: Intraperitoneal injection of 5-FU at a dosage of 20 mg/kg/day over 5 days was given to induce nephrotoxicity in rats. The evaluation of nephrotoxicity involved quantifying serum creatinine, urea, uric acid, and electrolyte concentrations. Furthermore, superoxide dismutase, catalase antioxidant enzymes, and TNF-α concentration in serum were also measured. RESULTS: 5-FU injection led to the initiation of oxidative stress within the kidneys, leading to modifications in renal biomarkers (including serum creatinine, urea, uric acid, and Na+, K+ levels), and a reduction in antioxidant enzymes namely superoxide dismutase and catalase. Notably, the presence of the inflammatory cytokine TNF-α was significantly elevated due to 5-FU. Microscopic examination of renal tissue revealed tubular degeneration and congestion. However, treatment involving the ethyl acetate fraction derived from A. catechu leaves effectively and dose-dependently reversed the changes observed in renal biomarkers, renal antioxidant enzymes, inflammatory mediators, and histopathological features, bringing them closer to normal conditions. The observed recuperative impact was mainly attributed to the antioxidant and antiinflammatory properties of the fraction. CONCLUSION: The ethyl acetate fraction of A. catechu leaves exhibited a mitigating influence on the renal impairment caused by 5-FU, showcasing its potential as a nephroprotective agent capable of preventing and ameliorating 5-FU-induced nephrotoxicity.

Hepatoprotective Activity of Gentisic Acid on 5-Fluorouracil-induced Hepatotoxicity in Wistar Rats

Objectives: 5-Fluorouracil (5-FU) is a very potent and effective antineoplastic drug that has been widely used for the management of various types of cancer. However, the clinical use of 5-FU is often associated with severe toxicities including hepatotoxicity, which limit its therapeutic use as a potent anticancer agent. The present study aimed to evaluate the hepatoprotective activity of a plant phenolic acid, gentisic acid (GA) (2,5-dihyroxybenzoic acid), against hepatotoxicity induced by 5-FU administration in Wistar rats. Materials and Methods: The rats were randomly divided into six groups, with six rats per group. Among these, group I and II served as normal control and 5-FU control groups, respectively. The rats in these groups received distilled water (1 mL/kg) for 14 days by oral route. Groups III, IV, V, and VI served as test groups and received GA at doses of 3, 10, 30, and 100 mg/kg body weight, respectively, via oral route for 14 days. From Day 9 onwards, all the groups, except group I, received intraperitoneal dose of 5-FU (20 mg/kg body weight) for five days up to day 14. At the end of the study, the rats were sacrificed, blood was withdrawn for biochemical estimations, and hepatic tissues were excised for histopathological evaluations. Results: Administration of 5-FU at a dose of 20 mg/kg body weight resulted in a significant increase in the serum levels of hepatic biomarkers, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin. In comparison to these, 5-FU treatment resulted in a reduction in total protein content (TPC). This was accompanied by significant histopathological changes in the hepatic tissues of the rats, indicating severe hepatotoxicity. Pre- and co-administration of GA with 5-FU at doses of 30 and 100 mg/kg body weight for 14 days resulted in a dose-dependent amelioration of the 5-FU induced alterations in the biochemical and histopathological parameters. Conclusion: The results of the study highlighted the potential of GA as a hepatoprotective agent for the prevention of 5-FU-induced hepatotoxicity.

Hepatoprotective potential of Cassia auriculata roots on ethanol and antitubercular drug-induced hepatotoxicity in experimental models.

CONTEXT: Tarvada [Cassia auriculata Linn. (Caesalpiniaceae)] is used against liver ailments in Indian folk medicine, but there is a lack of scientific evidence for this traditional claim. OBJECTIVE: The present study investigated the protective effect of methanol extract of tarvada (MECA) roots on ethanol and antitubercular drug induced hepatotoxicity in rats. MATERIALS AND METHODS: In the therapeutic model, ethanol (40%, 4 g/kg b.w., p.o.) was administered to rats for 21 days and the intoxicated rats were treated with MECA (300 and 600 mg/kg, b.w.) and silymarin (100 mg/kg, b.w.) for next 7 days. In the prophylactic model, MECA and silymarin were administered simultaneously along with a combination of isoniazid (27 mg/kg, b.w.), rifampicin (54 mg/kg, b.w.) and pyrazinamide (135 mg/kg, b.w.) for 30 days. After the study duration, serum levels of AST, ALT, ALP, total bilirubin, total cholesterol, total protein, albumin were estimated along with hepatic catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and liver histopathology in each group. RESULTS: Administration of tarvada root extract significantly (p < 0.01 and p < 0.05) lowered the elevated levels of serum AST, ALT, ALP, total bilirubin, total cholesterol, total protein and restored the abnormal levels of enzymatic antioxidants and MDA in liver due to toxicant administration in a dose-dependent manner. These results were confirmed by histopathological analysis. DISCUSSION AND CONCLUSION: Results suggest that tarvada root extract possess potent hepatoprotective activity against ethanol and antitubercular drug-induced hepatotoxicity in rats, which could be due to an inhibition of hepatic metabolizing enzymes and antioxidant activity.