PMID- 27664441 OWN - NLM STAT- MEDLINE DCOM- 20170417 LR - 20211204 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 193 DP - 2016 Dec 4 TI - Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. PG - 433-444 LID - S0378-8741(16)30933-3 [pii] LID - 10.1016/j.jep.2016.09.043 [doi] AB - 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-1alpha (p-IRE1alpha), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), and phosphorylated nuclear factor kappaB p65 (p-NF-kappaB p65) in vivo and in vitro. Immunohistochemistry (IHC) was carried out to determine the phosphorylation of IRE1alpha and NF-kappaB 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 IRE1alpha and NF-kappaB 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-kappaB activation. Thus, MC-TG might be a potential therapeutic candidate for the prevention and treatment of DN. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Chen, Juan AU - Chen J AD - Key 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. FAU - Hou, Xue-Feng AU - Hou XF AD - School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. FAU - Wang, Gang AU - Wang G AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Zhong, Qing-Xiang AU - Zhong QX AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China. FAU - Liu, Ying AU - Liu Y AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Qiu, Hui-Hui AU - Qiu HH AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China. FAU - Yang, Nan AU - Yang N AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China. FAU - Gu, Jun-Fei AU - Gu JF AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China. FAU - Wang, Chun-Fei AU - Wang CF AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Zhang, Li AU - Zhang L AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Song, Jie AU - Song J AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210023, PR China. FAU - Huang, Lu-Qi AU - Huang LQ AD - State Key Laboratory Breeding Base of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijng 100700, PR China. FAU - Jia, Xiao-Bin AU - Jia XB AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, 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. Electronic address: jxiaobin2005@hotmail.com. FAU - Zhang, Ming-Hua AU - Zhang MH AD - Department of Pharmacy, Wuxi Xishan People's Hospital, Jiangsu, Wuxi 214011, PR China. Electronic address: jdyx0701.111@163.com. FAU - Feng, Liang AU - Feng L AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; Third School of Clinical Medical of Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. Electronic address: wenmoxiushi@163.com. LA - eng PT - Journal Article DEP - 20160921 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Glycation End Products, Advanced) RN - 0 (Glycosides) RN - 0 (Inflammation Mediators) RN - 0 (Membrane Proteins) RN - 0 (Rela protein, rat) RN - 0 (Terpenes) RN - 0 (Transcription Factor RelA) RN - 0 (moutan cortex) RN - 5W494URQ81 (Streptozocin) RN - EC 2.7.1.- (Ern2 protein, rat) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemistry/isolation & purification/*pharmacology MH - Cell Line MH - Chromatography, High Pressure Liquid MH - Diabetes Mellitus, Experimental/chemically induced/*drug therapy/metabolism MH - Diabetic Nephropathies/etiology/metabolism/pathology/*prevention & control MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/chemistry/isolation & purification/*pharmacology MH - Endoplasmic Reticulum Stress/*drug effects MH - Glycation End Products, Advanced/metabolism MH - Glycosides/chemistry/isolation & purification/*pharmacology MH - Inflammation Mediators/metabolism MH - Male MH - Membrane Proteins/metabolism MH - Mesangial Cells/*drug effects/metabolism/ultrastructure MH - Paeonia/chemistry MH - Phosphorylation MH - Phytotherapy MH - Plants, Medicinal MH - Protein Serine-Threonine Kinases/metabolism MH - Rats, Sprague-Dawley MH - Renal Insufficiency/etiology/metabolism/pathology/*prevention & control MH - Signal Transduction/drug effects MH - Streptozocin MH - Terpenes/chemistry/isolation & purification/*pharmacology MH - Transcription Factor RelA/metabolism OTO - NOTNLM OT - 4-phenylbutyric acid (PubChem CID: 4775) OT - Anti-inflammation OT - Benzoylpaeoniflorin (PubChem CID: 102004405) OT - Diabetic nephropathy OT - Endoplasmic reticulum stress OT - Moutan Cortex OT - Oxypaeoniflorin (PubChem CID: 46882883) OT - Paeoniflorin (PubChem CID: 118701402) OT - Streptozotocin (PubChem CID: 45357367) OT - Terpene glycoside component EDAT- 2016/09/25 06:00 MHDA- 2017/04/18 06:00 CRDT- 2016/09/25 06:00 PHST- 2016/05/05 00:00 [received] PHST- 2016/09/16 00:00 [revised] PHST- 2016/09/20 00:00 [accepted] PHST- 2016/09/25 06:00 [pubmed] PHST- 2017/04/18 06:00 [medline] PHST- 2016/09/25 06:00 [entrez] AID - S0378-8741(16)30933-3 [pii] AID - 10.1016/j.jep.2016.09.043 [doi] PST - ppublish SO - J Ethnopharmacol. 2016 Dec 4;193:433-444. doi: 10.1016/j.jep.2016.09.043. Epub 2016 Sep 21.