PMID- 36471937 OWN - NLM STAT- MEDLINE DCOM- 20221207 LR - 20221207 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 47 IP - 22 DP - 2022 Nov TI - [Therapeutic effect of Jingfang Granules on CCl_4-induced liver fibrosis in mice and its mechanism]. PG - 6127-6136 LID - 10.19540/j.cnki.cjcmm.20220530.402 [doi] AB - To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg.kg~(-1))+CCl_4, a Jingfang high-dose(16 g.kg~(-1)) group, a Jingfang high-dose(16 g.kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g.kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g.kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL.kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL.kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-alpha(TNF-alpha), interleukin-6(IL-6) and interleukin-1beta(IL-1beta) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-beta(TGF-beta), alpha-smooth muscle actin(alpha-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-alpha, IL-6, and IL-1beta in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-beta, alpha-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-beta/Smad4 signaling pathway. FAU - Li, Yu-Ru AU - Li YR AD - School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 100029,China. FAU - Zhao, Ya-Fang AU - Zhao YF AD - School of Traditional Chinese Medicine,Beijing University of Chinese Medicine Beijing 100029,China. FAU - Cheng, Guo-Liang AU - Cheng GL AD - School of Traditional Chinese Medicine,Beijing University of Chinese Medicine Beijing 100029,China. FAU - Wang, En-Li AU - Wang EL AD - State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd. Linyi 276000,China. FAU - Tan, Yu-Jun AU - Tan YJ AD - State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd. Linyi 276000,China. FAU - Yao, Jing-Chun AU - Yao JC AD - State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd. Linyi 276000,China. FAU - Zhao, Yan AU - Zhao Y AD - School of Traditional Chinese Medicine,Beijing University of Chinese Medicine Beijing 100029,China. FAU - Zhang, Gui-Min AU - Zhang GM AD - State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd. Linyi 276000,China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-6) RN - 0 (Olive Oil) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Mice MH - Male MH - Animals MH - *Tumor Necrosis Factor-alpha/metabolism MH - *Interleukin-6/metabolism MH - Olive Oil/metabolism/pharmacology/therapeutic use MH - Carbon Tetrachloride/adverse effects/metabolism MH - Liver Cirrhosis/chemically induced/drug therapy/metabolism MH - Liver MH - Superoxide Dismutase/metabolism MH - Transforming Growth Factor beta/metabolism OTO - NOTNLM OT - Jingfang Granules OT - TGF-beta/Smad4 signaling pathway OT - liver fibrosis OT - mechanism OT - mice OT - therapeutic effect EDAT- 2022/12/07 06:00 MHDA- 2023/02/25 06:00 CRDT- 2022/12/06 02:32 PHST- 2022/12/06 02:32 [entrez] PHST- 2022/12/07 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] AID - 10.19540/j.cnki.cjcmm.20220530.402 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2022 Nov;47(22):6127-6136. doi: 10.19540/j.cnki.cjcmm.20220530.402.