Your browser doesn't support javascript.
loading
Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss. Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathway / 中国结合医学杂志
Chinese journal of integrative medicine ; (12): 60-68, 2022.
Article in English | WPRIM | ID: wpr-928934
ABSTRACT
OBJECTIVE@#To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo.@*METHODS@#For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot.@*RESULTS@#EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05).@*CONCLUSIONS@#EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Carbon Tetrachloride / Signal Transduction / Phosphatidylinositol 3-Kinases / Ribosomal Protein S6 Kinases, 70-kDa / Proto-Oncogene Proteins c-akt / Hepatic Stellate Cells / TOR Serine-Threonine Kinases / Liver / Liver Cirrhosis Type of study: Prognostic study Limits: Animals Language: English Journal: Chinese journal of integrative medicine Year: 2022 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Carbon Tetrachloride / Signal Transduction / Phosphatidylinositol 3-Kinases / Ribosomal Protein S6 Kinases, 70-kDa / Proto-Oncogene Proteins c-akt / Hepatic Stellate Cells / TOR Serine-Threonine Kinases / Liver / Liver Cirrhosis Type of study: Prognostic study Limits: Animals Language: English Journal: Chinese journal of integrative medicine Year: 2022 Type: Article