The Effects of sKlotho on Osteoblast Metabolisms under High Glucose and its mechanisms

Abstract Background Studies have found that excessive reactive oxygen(ROS) productions could cause senile osteoporosis and diabetic osteoporosis(DOP). Silent information regulator 1 (Sirt1) has anti-oxidative and anti-aging effects on improving bone metabolism through P53/P21 and P16 pathways in senile osteoporosis. Klotho is a kind of anti-aging gene and Klotho-/- mice is characterized by osteoporosis. The secreted Klotho(sKlotho) proteins exert anti-oxidative stress effect in multiple systems. Our study is aimed to explore the effects of sKlotho on osteoblast metabolisms, Sirt1 expression and senescence pathway under high glucose. Results We found that sKlotho could improve MC3T3-E1 proliferation and differentiation, reduce cell apoptosis and ROS, increased Sirt1 expression, and inhibit P53/P21 and P16 activation under high glucose. While the improvement of MC3T3-E1 activity and anti-aging effect of sKlotho on MC3T3-E1 under high glucose disappeared after transfected with Sirt1-siRNA. Conclusions We concluded that sKlotho could significantly improve the activity of MC3T3-E1, alleviate oxidative stress and senescence under high glucose via increasing the expression of Sirt1 by reducing ROS production.</jats:p

Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome

Abstract Background The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). Methods To assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot. Results The expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells. Conclusions The NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease

Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction.

Naringin, a flavanone glycoside extracted from Citrus grandis Osbeck, has a wide range of pharmacological effects. In the present study we aimed at demonstrating the protective effect of naringin against diabetic kidney disease (DKD) and elucidating its possible molecular mechanism underlying. The beneficial effect of naringin was assessed in rats with streptozotocin (STZ)-induced diabetes and high glucose-induced HBZY-1 cells. According to our results, first we found that naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. Second, we confirmed that naringin restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF- κ B signaling pathway. Taken together, our results demonstrate that naringin effectively alleviates DKD, which provide theoretical basis for naringin clinically used to treatment of DKD