Title : Sphagnum cuspidatulum extract ameliorates kidney injury by glucose intolerance, lipid metabolism and antioxidant mechanism in obese-insulin resistant rats
Introduction: Obesity remains a global health problem. High-fat diet (HFD) consumption increases the risk of type 2 diabetes and initiates kidney injury. Sphagnum cuspidatulum (SC) provides anti-obesity effects through several mechanisms. However, the effects of SC on preventing obesity-related kidney injury in obese-insulin resistance have not been studied. SC contains high levels of phenolic compounds. A novel action of phenolic compound in activating antioxidant enzyme mechanism assembly was reported in in vitro via the nuclear factor erythroid 2-related factor 2 (Nrf2) activation. HFD-induced systemic oxidative stress and apoptosis. Therefore, Nrf2 activation might be a therapeutic target for preventing obesity-related complications. Here, we explored the protective effects of SC in obesity-induced kidney dysfunction and the involved molecular mechanisms. We hypothesized that SC might exert renoprotection against obesity-induced kidney injury through the increasing antioxidant enzymes.
Methods: Male Wistar rats were fed with HFD and injected nicotinamide follow by low-dose streptozotocin for 8 weeks to induce obese insulin resistance. Next, HFD rats were randomly divided into 4 groups: HFD, HFD treated with SC 50 or 100 mg/kg/day (SC50 or SC100), and HFD treated with metformin 100 mg/kg/day (MET). The interventions were orally treated for 4 weeks. At the end of the experiment, blood, urine, and renal tissue samples were collected for further investigation.
Results: After 8 weeks of high-fat diet feeding, obesity, and glucose intolerance were presented in HFD compared to normal diet (ND) rats, as indicated by the significant increases in body weight (BW), plasma cholesterol, and total area under the curve for glucose (TAUCg). Kidney injuries were observed at week 8, as shown by elevated kidney injury score and serum creatinine. Treatment with SC50 or SC100 significantly decreased BW, hypercholesterolemia, glucose intolerance, and kidney dysfunction. Interestingly, SC100 markedly decreased malondialdehyde (MDA) compared with HFD. In addition, renal Nrf2 and downstream mechanism expressions were downregulated in HFD which were upregulated by SC100 and MET. Moreover, renal apoptosis markers, Bcl-2-associated X protein (Bax), and cytochrome-C were increased, along with the suppression of anti-apoptotic B-cell lymphoma-2 (Bcl-2) in HFD. Treatment with SC100 or MET markedly alleviated renal oxidative and apoptosis.
Conclusion: SC exerted renoprotection through attenuating renal oxidative stress and apoptosis as a result of the antioxidant mechanism via Nrf2 activation in obese insulin resistance rats. Therefore, SC might be an effective new dietary supplement for treating obesity and its related complications in clinical use.