Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses

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• 作者：Juan Chen^a ; ^b ; ^c ; ^e ; ¹ ; Xue-feng Hou^f ; ¹ ; Gang Wang^a ; Qing-xiang Zhong^a ; ^c ; Ying Liu^a ; Hui-hui Qiu^a ; ^c ; Nan Yang^a ; ^c ; Jun-fei Gu^a ; ^c ; Chun-fei Wang^a ; Li Zhang^a ; Jie Song^a ; ^c ; Lu-qi Huang^b ; Xiao-bin Jia^a ; ^c ; ^e ; ^{jxiaobin2005@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Ming-hua Zhang^d ; ^{jdyx0701.111@163.com" class="auth_mail" title="E-mail the corresponding author} ; Liang Feng^a ; ^e ; ^{wenmoxiushi@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TCM ; traditional Chinese Medicine ; MC ; Moutan Cortex ; TG ; terpene glycoside ; DN ; diabetic nephropathy ; STZ ; streptozotocin ; AGEs ; advanced glycation end-products ; ER ; endoplasmic reticulum ; 4-PBA ; 4-phenylbutyric acid ; AG ; amino guanidine ; TEM ; transmission electron microscopy ; WB ; western blotting ; ELISA ; enzyme-linked immunosorbent assay ; IHC ; immunohistochemistry ; IL-6 ; interleukin-6 ; MCP-1 ; monocyte chemoattractant protein-1 ; ICAM-1 ; intercellular cell adhesion molecule-1 ; GRP78/Bip ; glucose
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 December 2016
• 年：2016
• 卷：193
• 期：Complete
• 页码：433-444
• 全文大小：4572 K

文摘

Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN. However, the underlying mechanisms of MC-TG for treating DN are still unknown.

Aim of the study

To explore the role of ER stress-related inflammatory responses in the progression of DN, and to investigate the underlying protective mechanisms of MC-TG in kidney damage.

Materials and methods

DN rats and advanced glycation end-products (AGEs) induced HBZY-1 cell dysfunction were established to evaluate the protective effect of MC-TG on ameliorating renal injury. Evaluation of pathological lesions was performed by Masson staining and transmission electron microscopy (TEM). Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), glucose regulated protein 78 (GRP78/Bip), as well as spliced X box binding protein 1(XBP-1(s)) levels in rat serum were detected by an enzyme-linked immunosorbent assay (ELISA). Furthermore, western blotting (WB) was applied to detect the protein expressions including IL-6, MCP-1, intercellular cell adhesion molecule-1 (ICAM-1), GRP78/Bip, XBP-1 (s), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), and phosphorylated nuclear factor κB p65 (p-NF-κB p65) in vivo and in vitro. Immunohistochemistry (IHC) was carried out to determine the phosphorylation of IRE1α and NF-κB p65 in kidney tissues.

Results

Pretreatment with MC-TG could markedly improve renal insufficiency and pathologic changes. It could down-regulate ER stress-related factors GRP78/Bip, XBP-1(s) levels, and also reduce the pro-inflammatory molecules IL-6, MCP-1, and ICAM-1 expressions. Furthermore, a significant decrease in phosphorylation of IRE1α and NF-κB p65 by the treatment of MC-TG.

Conclusions

These findings indicated that MC-TG ameliorated ER stress-related inflammation in the pathogenesis of DN, wherein the protective mechanism might be associated with the inhibition of IRE1/NF-κB activation. Thus, MC-TG might be a potential therapeutic candidate for the prevention and treatment of DN.