Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo
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To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control (n = 6), (2) control + 200 mg/kg andrographolide (n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n = 6), (4) ANIT + 50 mg/kg andrographolide (n = 6), (5) ANIT + 100 mg/kg andrographolide (n = 6), and (6) ANIT + 200 mg/kg andrographolide (n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.
KeywordsAndrographolide Cholestatic liver injury Inflammation Oxidative stress
This study was partly supported by the National Natural Science Foundation of China (no. 81473504) and the China Scholarship Council (no. 201708080032).
PG and ZW carried out the research; LW, FC, LZ, PL and WL provided Figs. 1, 2 and 4; XD and YS provided Fig. 3; HB was responsible for the reagents and animals; LW and FC wrote the paper. All of the authors listed have revised and approved the manuscript.
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Conflict of interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
- 6.Wu JS, Li YF, Li YY, Dai Y, Li WK, Zheng M, Shi ZC, Shi R, Wang TM, Ma BL, Liu P, Ma YM (2017) Huangqi decoction alleviates alpha-naphthylisothiocyanate induced intrahepatic cholestasis by reversing disordered bile acid and glutathione homeostasis in mice. Front Pharmacol 8:938CrossRefGoogle Scholar
- 11.Li YF, Wu JS, Li YY, Dai Y, Zheng M, Zeng JK, Wang GF, Wang TM, Li WK, Zhang XY, Gu M, Huang C, Yang L, Wang ZT, Ma YM (2017) Chicken bile powder protects against alpha-naphthylisothiocyanate-induced cholestatic liver injury in mice. Oncotarget 8(57):97137–97152Google Scholar
- 15.Yao H, Xu Y, Yin L, Tao X, Xu L, Qi Y, Han X, Sun P, Liu K, Peng J (2017) Dioscin protects ANIT-induced intrahepatic cholestasis through regulating transporters, apoptosis and oxidative stress. Front Pharmacol 8:116Google Scholar
- 19.Cabrera D, Wree A, Povero D, Solis N, Hernandez A, Pizarro M, Moshage H, Torres J, Feldstein AE, Cabello-Verrugio C, Brandan E, Barrera F, Arab JP, Arrese M (2017) Andrographolide ameliorates inflammation and fibrogenesis and attenuates inflammasome activation in experimental non-alcoholic steatohepatitis. Sci Rep 7(1):3491CrossRefGoogle Scholar
- 21.Feng B, Zhang Q, Wang X, Sun X, Mu X, Dong H (2017) Effect of andrographolide on gene expression profile and intracellular calcium in primary rat myocardium microvascular endothelial cells. J Cardiovasc Pharmacol 70(6):369–381Google Scholar
- 22.Ambili R, Janam P, Saneesh Babu PS, Prasad M, Vinod D, Anil Kumar PR, Kumary TV, Asha Nair S, Radhakrishna Pillai M (2017) An ex vivo evaluation of the efficacy of andrographolide in modulating differential expression of transcription factors and target genes in periodontal cells and its potential role in treating periodontal diseases. J Ethnopharmacol 196:160–167CrossRefGoogle Scholar
- 23.Wu KC, McDonald PR, Liu J, Klaassen CD (2014) Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta Med 80(1):97–104Google Scholar
- 26.Ding Y, Shi C, Chen L, Ma P, Li K, Jin J, Zhang Q, Li A (2017) Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-kappaB/MAPK pathway. Oncol Lett 14(6):7367–7373Google Scholar