■中药(TCM)被广泛用于肝豆状核变性(HLD)和肝纤维化(LF)的临床治疗。在本研究中,采用meta分析评价疗效.利用网络药理学和分子动力学模拟研究了中药抗HLD中LF的可能机制。
■对于文献收集,我们搜索了几个数据库,包括PubMed,Embase,科克伦图书馆,WebofScience,中国国家知识基础设施(CNKI),中国技术期刊VIP数据库(VIP)和万方数据库至2023年2月,并使用ReviewManager5.3进行数据分析。采用网络药理学和分子动力学模拟方法探讨中药治疗HLD中LF的作用机制。
■荟萃分析的结果表明,在治疗HLD中添加中草药(CHM)导致比单独使用西药更高的临床总有效率[RR1.25,95%CI(1.09,1.44),p=0.002]。它不仅对肝脏有更好的保护作用[丙氨酸转氨酶:SMD=-1.20,95%CI(-1.70,-0.70),p<0.00001;天冬氨酸转氨酶:SMD=-1.41,95%CI(-2.34,-0.49),p=0.003;总胆红素:SMD=-1.70,95%CI(-3.36,-0.03),p=0.05]但通过四个指标对LF也有出色的治疗效果[透明质酸:SMD=-1.15,95%CI(-1.76,-0.53),p=0.0003;前胶原肽III:SMD=-0.72,95%CI(-1.29,-0.15),p=0.01;胶原IV:SMD=-0.69,95%CI(-1.21,-0.18),p=0.008;层粘连蛋白:SMD=-0.47,95%CI(-0.95,0.01),p=0.06]。同时,肝脏硬度测量值显著下降[SMD=-1.06,95%CI(-1.77,-0.36),p=0.003]。网络药理实验和分子动力学模拟结果表明,三种高频中药(大黄-黄连-姜黄,DH-HL-JH)主要作用于核心靶标(AKT1、SRC、和JUN)通过核心组分(大黄酸,槲皮素,豆甾醇,和姜黄素),调节信号通路(PI3K-Akt,MAPK,EGFR,和VEGF信号通路),发挥抗LF的作用。
■Meta分析显示中药对治疗HLD患者和改善LF有益。本研究成功预测了DH-HL-JH的三种高频CHM治疗LF的有效成分,潜在靶标和途径。本研究结果希望为临床治疗提供一些证据支持。
■https://www.crd.约克。AC.英国/PROSPERO,标识符:CRD42022302374。
UNASSIGNED: Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.
UNASSIGNED: For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the
Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.
UNASSIGNED: The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating 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 targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.
UNASSIGNED: Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating 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.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.