AUTHOR=Yang Xulong , Wang Tiancheng , Tang Yiping , Shao Yawen , Gao Yaqin , Wu Peng 

TITLE=Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1193132

DOI=10.3389/fmed.2023.1193132

ISSN=2296-858X

ABSTRACT=Background: Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). 
Methods: The PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals and Wan Fang database were searched, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to investigate the mechanism of TCM in treating LF in HLD.
Results: The results of the meta-analysis revealed that adding Chinese herbal medicine (CHM) to the treatment of HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), p = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = -1.20, 95% CI (-1.70, -0.70), p < 0.00001; Aspartate aminotransferase: SMD = -1.41, 95% CI (-2.34, -0.49), p = 0.003; Total bilirubin: SMD = -1.70, 95% CI (-3.36, -0.03), p = 0.05], but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = -1.15, 95% CI (-1.76, -0.53), p = 0.0003; Procollagen peptide Ⅲ: SMD = -0.72, 95% CI (-1.29, -0.15), p = 0.01; Collagen IV: SMD = -0.69, 95% CI (-1.21, -0.18), p = 0.008; Laminin: SMD = -0.47, 95% CI (-0.95, 0.01), p = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = -1.06, 95% CI (-1.77, -0.36), p = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core target (AKT1, SRC, and JUN) via the core component (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathway), and play the role of anti-LF.
Conclusion: TCM is beneficial in treating HLD patients and improving LF. This study successfully predicts the effective components and potential targets and pathways involved in the treatment of LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.