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Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum
Juan Chen1, Xue-Feng Hou2, Gang Wang3
1Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; State Key Laboratory Breeding Base of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijng 100700, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China; Third School of Clinical Medical of Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
Ethnopharmacological Relevance:
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.
Insights
Moutan Cortex terpene glycoside (MC-TG) alleviates diabetic nephropathy (DN) by reducing endoplasmic reticulum (ER) stress and inflammation. MC-TG inhibits IRE1/NF-κB activation, offering a potential treatment for DN.
Area of Science:
- Pharmacology
- Nephrology
- Cell Biology
Background:
- Diabetic nephropathy (DN) pathogenesis involves endoplasmic reticulum (ER) stress and inflammation.
- Moutan Cortex (MC), a traditional Chinese medicine, has anti-inflammatory properties.
- Previous research indicated MC terpene glycosides (TG) show promise in treating DN, but mechanisms were unclear.
Purpose of the Study:
- Investigate the role of ER stress in DN progression.
- Elucidate the protective mechanisms of MC-TG in kidney damage.
Main Methods:
- Established DN rat and cell models to assess MC-TG's protective effects.
- Evaluated renal pathology using Masson staining and transmission electron microscopy.
- Measured serum and tissue levels of inflammatory markers (IL-6, MCP-1, ICAM-1) and ER stress markers (GRP78/Bip, XBP-1(s)) via ELISA, Western Blotting, and Immunohistochemistry.
Main Results:
- MC-TG treatment significantly improved renal function and pathology.
- MC-TG downregulated ER stress markers (GRP78/Bip, XBP-1(s)) and inflammatory molecules (IL-6, MCP-1, ICAM-1).
- MC-TG treatment reduced the phosphorylation of IRE1α and NF-κB p65.
Conclusions:
- MC-TG ameliorates ER stress-related inflammation in DN.
- The protective mechanism involves inhibiting IRE1/NF-κB activation.
- MC-TG shows potential as a therapeutic agent for DN prevention and treatment.
