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Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses.
J Ethnopharmacol. 2016 Dec 04; 193:433-444.JE

Abstract

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.

Authors+Show Affiliations

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.School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China.Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.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.Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.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.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.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.Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.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.State Key Laboratory Breeding Base of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijng 100700, PR China.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.Department of Pharmacy, Wuxi Xishan People's Hospital, Jiangsu, Wuxi 214011, PR China. Electronic address: jdyx0701.111@163.com.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27664441

Citation

Chen, Juan, et al. "Terpene Glycoside Component From Moutan Cortex Ameliorates Diabetic Nephropathy By Regulating Endoplasmic Reticulum Stress-related Inflammatory Responses." Journal of Ethnopharmacology, vol. 193, 2016, pp. 433-444.
Chen J, Hou XF, Wang G, et al. Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. J Ethnopharmacol. 2016;193:433-444.
Chen, J., Hou, X. F., Wang, G., Zhong, Q. X., Liu, Y., Qiu, H. H., Yang, N., Gu, J. F., Wang, C. F., Zhang, L., Song, J., Huang, L. Q., Jia, X. B., Zhang, M. H., & Feng, L. (2016). Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. Journal of Ethnopharmacology, 193, 433-444. https://doi.org/10.1016/j.jep.2016.09.043
Chen J, et al. Terpene Glycoside Component From Moutan Cortex Ameliorates Diabetic Nephropathy By Regulating Endoplasmic Reticulum Stress-related Inflammatory Responses. J Ethnopharmacol. 2016 Dec 4;193:433-444. PubMed PMID: 27664441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. AU - Chen,Juan, AU - Hou,Xue-Feng, AU - Wang,Gang, AU - Zhong,Qing-Xiang, AU - Liu,Ying, AU - Qiu,Hui-Hui, AU - Yang,Nan, AU - Gu,Jun-Fei, AU - Wang,Chun-Fei, AU - Zhang,Li, AU - Song,Jie, AU - Huang,Lu-Qi, AU - Jia,Xiao-Bin, AU - Zhang,Ming-Hua, AU - Feng,Liang, Y1 - 2016/09/21/ PY - 2016/05/05/received PY - 2016/09/16/revised PY - 2016/09/20/accepted PY - 2016/9/25/pubmed PY - 2017/4/18/medline PY - 2016/9/25/entrez KW - 4-phenylbutyric acid (PubChem CID: 4775) KW - Anti-inflammation KW - Benzoylpaeoniflorin (PubChem CID: 102004405) KW - Diabetic nephropathy KW - Endoplasmic reticulum stress KW - Moutan Cortex KW - Oxypaeoniflorin (PubChem CID: 46882883) KW - Paeoniflorin (PubChem CID: 118701402) KW - Streptozotocin (PubChem CID: 45357367) KW - Terpene glycoside component SP - 433 EP - 444 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 193 N2 - 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27664441/Terpene_glycoside_component_from_Moutan_Cortex_ameliorates_diabetic_nephropathy_by_regulating_endoplasmic_reticulum_stress_related_inflammatory_responses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30933-3 DB - PRIME DP - Unbound Medicine ER -