Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss. Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathway.
10.1007/s11655-021-3298-5
- Author:
Yuan LIU
1
;
Yan-Meng BI
1
;
Ting PAN
2
;
Ting ZENG
2
;
Chan MO
2
;
Bing SUN
1
;
Lei GAO
2
;
Zhi-Ping LYU
3
Author Information
1. College of Integrated Traditional Chinese and Western Medicine, Jining Medical University, Jining, Shandong Province, 272000, China.
2. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
3. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. lzp48241@126.com.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
Dicliptera chinensis (L.) Juss.;
autophagy;
hepatic stellate cells;
liver fibrosis
- MeSH:
Acetates;
Animals;
Autophagy;
Carbon Tetrachloride;
Hepatic Stellate Cells;
Liver/pathology*;
Liver Cirrhosis/pathology*;
Male;
Mice;
Mice, Inbred C57BL;
Phosphatidylinositol 3-Kinases;
Proto-Oncogene Proteins c-akt/metabolism*;
Ribosomal Protein S6 Kinases, 70-kDa;
Signal Transduction;
TOR Serine-Threonine Kinases/metabolism*
- From:
Chinese journal of integrative medicine
2022;28(1):60-68
- CountryChina
- Language:English
-
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.
