Role of Glycyrrhizin in the Reduction of Inflammation in Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes. Recent evidence suggests chronic inflammation to be one of the causal factors of DKD. The mechanisms entailed are not completely elucidated except that a variety of cytokines play a major role in this process. High mobility group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4 (TLR4)-binding cytokine that is involved in inflammation-associated gene expression. This investigation was designed to assess the involvement of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD and to evaluate that whether blocking HMGB1 by its natural inhibitor Glycyrrhizin (GLC) can reduce the progression of the disease. METHODS: Studies were carried out in 8-10-weeks old Zucker diabetic fatty (ZDF) and lean, age- and gender-matched rats. At 10 weeks of age, ZDF rats as compared to controls, showed hyperglycemia, without proteinuria. After 8-10 weeks of the development of diabetes, ZDF animals that showed proteinuria were treated with GLC for 4 weeks. In addition, normal rat kidney (NRK-52E) cells with epithelial-like morphology were comparatively treated with GLC under hyperglycemic condition in vitro. RESULTS: Substantial increase in the expression of HMGB1, TLR4, and NF-κB in vivo and in vitro under hyperglycemic conditions was observed as compared to normoglycemic conditions. The overexpression of HMGB1, TLR4, NF-κB, and glomerular injury marker nestin was significantly ameliorated by GLC administration. CONCLUSION: Our findings suggest that hyperglycemia-induced HMGB1 activation in ZDF rats may contribute to the progression of DKD.

Effect of exercise on neurogenic inflammation in spinal cord of Type 1 diabetic rats.

Neuropathy is a long-standing and hard to treat complication of diabetes that interferes almost 25-30% of diabetic patients and impacts the quality of life of the patients. Unforeseen side effects, dependency and addiction made the existing medical treatments comparatively ineffective. A number of studies indicate that moderate physical activity provides health-related advantages. However, existing data do not confirm whether regular physical activity would reduce the amount of inflammation in the nervous system of the subjects with Type 1 diabetes. This study reveals the significance of exercise to alleviate inflammation in the spinal cord of the nervous system and preserve sensory nerve function in animals with Type 1 diabetes after 6 weeks of exercise paradigm. Streptozotocin-diabetic animals were placed in motorized running wheels for sixty minutes per day, for five days a week for 6 weeks starting at one week after diabetes. Emerging evidence suggests that the increases in inflammatory mediators play an important role in the development of sensory neuropathy. This study shows that moderate exercise can reduce the release of a number of proinflammatory cytokines in the dorsal horn (DH) of spinal cord, subsequently delaying the development of neuropathy along with an increase in the anti-inflammatory mediator IL10 in the DH. In general, this study indicates that exercise may provide an alternative to the treatment for sensory neuropathy in Type 1 diabetic subjects via reducing the use of medication and providing an easier way to manage neuropathy.