Protective effect of the ethanol extract from Ligusticum chuanxiong rhizome against streptozotocin–induced diabetic nephropathy in mice

• Published in: Journal of ethnopharmacology Vol. 227; pp. 166 - 175
• Main Authors: Yang, Wen-Jing, Li, Yan-Ru, Gao, Hui, Wu, Xue-Yi, Wang, Xiao-Ling, Wang, Xiao-Ning, Xiang, Lan, Ren, Dong-Mei, Lou, Hong-Xiang, Shen, Tao
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 05.12.2018
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cell Line; Cell Survival - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic nephropathy; Humans; Ligusticum; Ligusticum chuanxiong; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB; Nrf2; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Rhizome; ESRD; NO; COX-2; DI; DN; NF-κB; GFR; SF; Nrf2; STZ; iNOS; Diabetic nephropathy; NQO1; QR; IL; MQI; AEL; EEL; 8-oxo-dG; ARE; TNF-α; TMP; LC; ROS; LGT; Ligusticum chuanxiong; FA; GCLM; ELISA; TCM
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2018.08.037

Rhizome of Ligusticum chuanxiong Hort. (Abbreviated as LC) is a frequently prescribed component in plenty of traditional Chinese medicine (TCM) formulas which are used to treat diabetic nephropathy (DN). The aims of the present study are to investigate the protective effect of the ethanol extract of LC rhizome (EEL) against DN in vivo, evaluate its potential mechanism, and find the evidence supporting its enthopharmacological use as an anti-DN agent. Hepa 1c1c7 murine hepatoma cells, human breast carcinoma MDA-MB-231 cells, human renal glomerular endothelial cells (HRGEC), and RAW 264.7 murine macrophages were adopted to test the effects of EEL and its active constituents on inhibitions of oxidative stress and inflammation in vitro. A streptozotocin (STZ) -induced DN C57BL/6 mice model was established and used to investigate the preventive effect of EEL against DN in vivo. EEL demonstrated potential inhibitory effects against oxidative stress and inflammation in vitro. Using a STZ-induced DN mice model, it has been found that EEL treatment significantly prevented STZ-induced increases of urine production, urinary albumin excretion (UAE) and urine albumin-to-creatinine ratio (UACR), and markedly attenuated STZ-induced renal damages (e.g. glomerulosclerosis and fibrosis). The predominant bioactive constituents, Z-ligustilide (LGT), ferulic acid (FA), and tetramethylpyrazine (TMP), were inhibitors of oxidative stress and inflammation through acting with Nrf2 and NF-κB pathways. EEL attenuates structural and functional damages of kidney in STZ-induced DN model in vivo, which might be related to the functions of EEL on inhibitions of oxidative stress and inflammation. These finding definitely supports the ethnopharmacological use of LC as an anti-DN agent. [Display omitted]