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Hepatoprotective effect and possible mechanism of phytoestrogen calycosin on carbon tetrachloride-induced liver fibrosis in mice.
Naunyn Schmiedebergs Arch Pharmacol. 2021 01; 394(1):189-204.NS

Abstract

The study was to explore the hepatoprotective effect and possible mechanism of calycosin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Hepatic fibrosis was induced by intraperitoneal injection of CCl4 in C57BL/6 male mice. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activity, superoxide dismutase (SOD) activity, and hydroxyproline (Hyp) and malondialdehyde (MDA) levels were determined by biochemical assays. Liver histopathology was assessed by H&E and Masson trichrome staining. The mRNA expressions of α-smooth muscle actin (α-SMA), collagen-I (Col-I), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined using qRT-PCR. The protein levels of α-SMA, Col-I, estrogen receptor α (ERα), estrogen receptor β (ERβ), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1 (MMP-1), JAK2, phospho-JAK2 (p-JAK2), STAT3, and phospho-STAT3 (p-STAT3) were detected by Western blotting. The levels of α-SMA and ERβ were measured by immunohistochemistry. Calycosin significantly reduced liver index, MDA level, and ALT and AST activity and increased SOD activity. The α-SMA, Col-I, and Hyp of the calycosin group were significantly lower than those of the model group. Calycosin increased MMP-1 and inhibited TIMP-1 expression resulting in the improvement of MMP-1/TIMP-1 ratio. Importantly, calycosin improved ERβ protein expression, JAK2 and STAT3 mRNA expressions, p-JAK2/JAK2, and p-STAT3/STAT3 relative protein expressions. However, ERα, JAK2, and STAT3 protein expressions were relatively unchanged. Calycosin significantly inhibits liver fibrosis in mice, and its mechanism may involve the following: calycosin inhibits oxidative stress; calycosin inhibits collagen synthesis and balances MMP-1/TIMP-1 system; calycosin increases ERβ expression and activates JAK2-STAT3 pathway.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China.Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China.Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China.Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China.Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China. wjj@ahmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32474674

Citation

Zhang, Mengmeng, et al. "Hepatoprotective Effect and Possible Mechanism of Phytoestrogen Calycosin On Carbon Tetrachloride-induced Liver Fibrosis in Mice." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 394, no. 1, 2021, pp. 189-204.
Zhang M, Wang Y, Zhu G, et al. Hepatoprotective effect and possible mechanism of phytoestrogen calycosin on carbon tetrachloride-induced liver fibrosis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(1):189-204.
Zhang, M., Wang, Y., Zhu, G., Sun, C., & Wang, J. (2021). Hepatoprotective effect and possible mechanism of phytoestrogen calycosin on carbon tetrachloride-induced liver fibrosis in mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 394(1), 189-204. https://doi.org/10.1007/s00210-020-01891-5
Zhang M, et al. Hepatoprotective Effect and Possible Mechanism of Phytoestrogen Calycosin On Carbon Tetrachloride-induced Liver Fibrosis in Mice. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(1):189-204. PubMed PMID: 32474674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatoprotective effect and possible mechanism of phytoestrogen calycosin on carbon tetrachloride-induced liver fibrosis in mice. AU - Zhang,Mengmeng, AU - Wang,Yaxin, AU - Zhu,Guannan, AU - Sun,Cheng, AU - Wang,Jiajia, Y1 - 2020/05/30/ PY - 2019/12/02/received PY - 2020/04/28/accepted PY - 2020/6/1/pubmed PY - 2020/6/1/medline PY - 2020/6/1/entrez KW - Calycosin KW - Estrogen receptor KW - Hepatoprotective KW - JAK-STAT pathway KW - Liver fibrosis KW - Matrix metalloproteinase SP - 189 EP - 204 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 394 IS - 1 N2 - The study was to explore the hepatoprotective effect and possible mechanism of calycosin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Hepatic fibrosis was induced by intraperitoneal injection of CCl4 in C57BL/6 male mice. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activity, superoxide dismutase (SOD) activity, and hydroxyproline (Hyp) and malondialdehyde (MDA) levels were determined by biochemical assays. Liver histopathology was assessed by H&E and Masson trichrome staining. The mRNA expressions of α-smooth muscle actin (α-SMA), collagen-I (Col-I), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined using qRT-PCR. The protein levels of α-SMA, Col-I, estrogen receptor α (ERα), estrogen receptor β (ERβ), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1 (MMP-1), JAK2, phospho-JAK2 (p-JAK2), STAT3, and phospho-STAT3 (p-STAT3) were detected by Western blotting. The levels of α-SMA and ERβ were measured by immunohistochemistry. Calycosin significantly reduced liver index, MDA level, and ALT and AST activity and increased SOD activity. The α-SMA, Col-I, and Hyp of the calycosin group were significantly lower than those of the model group. Calycosin increased MMP-1 and inhibited TIMP-1 expression resulting in the improvement of MMP-1/TIMP-1 ratio. Importantly, calycosin improved ERβ protein expression, JAK2 and STAT3 mRNA expressions, p-JAK2/JAK2, and p-STAT3/STAT3 relative protein expressions. However, ERα, JAK2, and STAT3 protein expressions were relatively unchanged. Calycosin significantly inhibits liver fibrosis in mice, and its mechanism may involve the following: calycosin inhibits oxidative stress; calycosin inhibits collagen synthesis and balances MMP-1/TIMP-1 system; calycosin increases ERβ expression and activates JAK2-STAT3 pathway. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/32474674/Hepatoprotective_effect_and_possible_mechanism_of_phytoestrogen_calycosin_on_carbon_tetrachloride_induced_liver_fibrosis_in_mice_ L2 - https://dx.doi.org/10.1007/s00210-020-01891-5 DB - PRIME DP - Unbound Medicine ER -