Effect of senkyunolide I on cholestatic liver injury via the STAT3 signaling pathway

JIANG Tingting; LIU Dongsheng; CHEN Ying

doi:10.12467/j.issn.2096-3882.20240683

Journal of Xuzhou Medical University > 2024 > 44(12): 876-881. > DOI: 10.12467/j.issn.2096-3882.20240683

JIANG Tingting, LIU Dongsheng, CHEN Ying. Effect of senkyunolide I on cholestatic liver injury via the STAT3 signaling pathway[J]. Journal of Xuzhou Medical University, 2024, 44(12): 876-881. DOI: 10.12467/j.issn.2096-3882.20240683

Citation:

PDF (14446 KB)

Effect of senkyunolide I on cholestatic liver injury via the STAT3 signaling pathway

1. Department of Clinical Examination, Suqian Hospital, Xuzhou Medical University, Suqian, Jiangsu 223800, China;
2. School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004

More Information

Received Date: September 11, 2024
Revised Date: December 09, 2024

Graphical Abstract

Abstract

Abstract

Objective To investigate the effect of senkyunolide I on cholestatic liver injury through the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods A total of 30 mice were divided into three groups: a normal group, a cholestatic liver injury model group, and a senkyunolide I treatment group. The model group was fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), while the senkyunolide I group was additionally administered with 100 mg/kg of senkyunolide I by gavage daily. The mice were treated four weeks. Then, blood samples were collected, and the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The mice were sacrificed and liver tissues were collected for hematoxylin-eosin (H-E) staining. The levels of related proteins and the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD) were detected by Western blot and RT-qPCR. Furthermore, HepG2 cells were divided into three groups: a normal group, a model group, and a senkyunolide I group. The senkyunolide I group was treated with 100 μmol/L senkyunolide I for 24 h for apoptosis assay. The levels of janus kinase 2 (JAK2) and STAT3, and their phosphorylated proteins and mRNA were measured. Results Compared with the normal group, the model group exhibited significantly elevated serum AST and ALT levels(P＜0.01). Compared with the model group, the senkyunolide I group showed significantly reduced AST and ALT levels(P＜0.01). Compared with the normal group, the model group presented decreases in liver SOD and catalase (CAT) activity, and increases in malondialdehyde (MDA) levels(P＜0.01). Compared with the model group, the senkyunolide I group showed increases in SOD and CAT activity and decreases in MDA levels(P＜0.01). Compared with the normal group, phosphorylated STAT3 levels were elevated in the model group(P＜0.05). Compared with the model group, phosphorylated STAT3 levels were reduced in the senkyunolide I group(P＜0.05). According to cellular experiment results, hepatocyte apoptosis increased in the model group compared with those in the normal group. Compared with the model group, the senkyunolide I group showed decreased cellular apoptotic rates, enhanced SOD and glutathione (GSH) activity, lowered MDA levels(P＜0.01), and upregulated mRNA expression of Nrf2, HO-1, and SOD(P＜0.05), with enhanced antioxidant capacity, reduced JAK2 and STAT3 phosphorylation(P＜0.05), and alleviated hepatocyte damage. Conclusions Senkyunolide I alleviates cholestatic liver injury through regulating the STAT3 signaling pathway, inhibiting oxidative stress, enhancing antioxidant enzyme activity, and reducing hepatocyte apoptosis.
- senkyunolide I,
- signal transducer and activator of transcription 3,
- cholestatic liver injury,
- apoptosis,
- oxidative stress

FullText(HTML)

References (17)

References

[1]	El-Agamy DS,Almaramhy HH,Ahmed N,et al.Anti-inflammatory effects of vardenafil against cholestatic liver damage in mice:a mechanistic study[J].Cell Physiol Biochem,2018,47(2):523-534.
[2]	Watanabe S,Tsuneyama K.Eicosapentaenoic acid attenuates hepatic accumulation of cholesterol esters but aggravates liver injury and inflammation in mice fed a cholate-supplemented high-fat diet[J].J Toxicol Sci,2013,38(3):379-390.
[3]	Colares JR,Hartmann RM,Schemitt EG,et al.Melatonin prevents oxidative stress,inflammatory activity,and DNA damage in cirrhotic rats[J].World J Gastroenterol,2022,28(3):348-364.
[4]	冯帅霞,徐莹,韩涵,等.龙胆苦苷调控PPAR-α改善胆汁淤积性肝损伤的药效机制研究[J].上海中医药杂志,2024,58(2):84-91.
[5]	Yang Q,Zhao ZZ,Xie J,et al.Senkyunolide I attenuates hepatic ischemia/reperfusion injury in mice via anti-oxidative,anti-inflammatory and anti-apoptotic pathways[J].Int Immunopharmacol,2021,97:107717.
[6]	Zhang LZ,Hu YH,Qi SL,et al.Astragalus saponins and its main constituents ameliorate ductular reaction and liver fibrosis in a mouse model of DDC-induced cholestatic liver disease[J].Front Pharmacol,2022,13:965914.
[7]	Hasegawa S,Yoneda M,Kurita Y,et al.Cholestatic liver disease:current treatment strategies and new therapeutic agents[J].Drugs,2021,81(10):1181-1192.
[8]	Brevini T,Tysoe OC,Sampaziotis F.Tissue engineering of the biliary tract and modelling of cholestatic disorders[J].J Hepatol,2020,73(4):918-932.
[9]	Tao WL,Yue X,Ye RL,et al.Hepatoprotective effect of the Penthorum chinense pursh extract against the CCl₄-induced acute liver injury via NF-κB and p38-MAPK PATHWAYS in dogs[J].Animals (Basel),2022,12(5):569.
[10]	Jones BE,Lo CR,Liu H,et al.Role of caspases and NF-kappaB signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis[J].Am J Physiol Gastrointest Liver Physiol,2000,278(5):G693-G699.
[11]	Cederbaum AI,Lu YK,Wu DF.Role of oxidative stress in alcohol-induced liver injury[J].Arch Toxicol,2009,83(6):519-548.
[12]	Kasembeli MM,Bharadwaj U,Robinson P,et al.Contribution of STAT3 to inflammatory and fibrotic diseases and prospects for its targeting for treatment[J].Int J Mol Sci,2018,19(8):2299.
[13]	Yu HM,Zhi JL,Cui Y,et al.Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells[J].Apoptosis,2006,11(6):931-941.
[14]	Butturini E,de Prati AC,Mariotto S.Redox regulation of STAT1 and STAT3 signaling[J].Int J Mol Sci,2020,21(19):7034.
[15]	Qu Y,Oyan AM,Liu RH,et al.Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling[J].Cancer Res,2013,73(23):7090-7100.
[16]	Waris G,Huh KW,Siddiqui A.Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress[J].Mol Cell Biol,2001,21(22):7721-7730.
[17]	Wang BE.Treatment of chronic liver diseases with traditional Chinesemedicine[J].J Gastroenterol Hepatol,2000,15 (Suppl):E67-E70.

Cited By

Get Citation

PDF

XML

Article views (93) PDF downloads (9)

Turn off MathJax

Article Contents

Abstract

References

Effect of senkyunolide I on cholestatic liver injury via the STAT3 signaling pathway

Abstract

References

Catalog

Export File

Citation

Format

Content