Abstract
Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.
Highlights
Traditional Chinese herbal medications (TCHMs) are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries[1]
To investigate whether rhubarb can inhibit renal fibrosis and interfere with autophagic activity in rats with Ade-induced renal tubular injury, we examined the changes in immunohistochemical staining of the fibrotic markers collagen type I and fibronectin, as well as autophagic marker light chain 3 (LC3) in the kidney
We demonstrated that autophagic activation accompanied with renal fibrosis, and that rhubarb could ameliorate autophagy and attenuate renal fibrosis in rats with Ade-induced renal tubular injury
Summary
Traditional Chinese herbal medications (TCHMs) are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries[1]. Livingston et al reported that persistent activation of autophagy in renal proximal tubules could promote renal interstitial fibrosis[10] These results suggested that the beneficial effect of rhubarb and rhein on renal fibrosis in CKD might have a close relationship with autophagy in renal tubular cells. There are still some important issues unresolved in the role of autophagy in CKD treated by rhubarb and rhein, for example, whether rhubarb can ameliorate renal fibrosis through regulation of autophagy, and if yes, what are the underlying mechanisms involved To address these important issues, we designed a number of in vivo and in vitro experiments to examine the hypothesis that rhubarb may reduce renal fibrosis and autophagy in rats with Ade-induced renal tubular injury, and that rhein may affect autophagic pathways in NRK-52E cells.
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