The Yi-Qi-Bu-Shen Recipe Attenuates High Glucose-Induced Podocyte Injury Via The Inhibition Of Ikk-I Kappa B Alpha-Nf Kappa B And Erk/P38 Mapk Signaling

The exact mechanisms underlying diabetic nephropathy (DN) remain unknown, but some studies suggest that structural and compositional changes of the slit diaphragms (SD) between podocytes may play an important role in this course. The Yi-Qi-Bu-Shen recipe (YB) is a traditional Chinese herbal formula that is commonly used for the treatment of diabetes mellitus and especially DN. This study investigated the effect of high glucose (HG) on expression of nephrin, podocin, and CD2AP in podocytes and the treatment effect of YB on these molecules. Conditionally immortalized human podocytes were exposed to medium containing normal glucose (NG) or HG for 24 hours. The podocytes cultured in a HG environment had relatively lower expression of nephrin, podocin, and CD2AP both in mRNA and protein synthesis levels compared to NG group. Nephrin, podocin, and CD2AP expression in the HG group was effectively restored by the treatment of YB. In addition, inflammatory cytokines such as IL-1 beta, IL-6, INF-alpha, and MCP-1 were significantly decreased in HG+YB group compared with the HG group. Moreover, YB suppressed HG-induced activation of IKK-I kappa B alpha-NF kappa B and ERK/P38 MAPK signaling pathways. NF kappa B, ERK, and P38 inhibitors attenuated HG-induced podocyte injury and increased nephrin, podocin, and CD2AP expression further revealed the healing mechanisms of YB. This study demonstrates that YB treatment attenuated HG-induced podocyte injury through suppressing activation of IKK-I kappa B alpha-NF kappa B and ERK/P38 MAPK signaling pathways and reducing IL-1 beta, IL-6, TNF-alpha, and MCP-1 levels, suggesting that YB is a potential therapeutic drug for DN.