Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

Abstract

Background Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) indicated for the treatment of hepatocellular carcinoma (HCC). Its potential targets and molecular mechanisms are not clear. Therefore, this study intends to explore the molecular mechanism of YFJP based on network pharmacology analysis and in vitro validation. Methods and results Through univariate and multivariate analyses and survival analysis in HCC patients with or without YFJP treatment we found that drinking alcohol, alfafeto protein ≥ 400 ng/l, baseline portal vein tumor thrombus and total bilirubin level ≥ 18.8 μM) were independent risk factors for poor prognosis, while red blood cell count ≥ 4 × 109/l and TCM treatment were independent protective factors. Besides, YFJP prolonged the cumulative survival of HCC patients. Using online pharmacological methods, we obtained 58 relevant compounds and molecular 53 targets. By using scratch test, Transwell assay, EdU assay, and TUNEL staining, we found that YFJP-containing serum repressed the migration, invasion and proliferation of HCC cells in vitro, and induced cell apoptosis. Moreover, YFJP diminished the gene expression of TP53, CCND1, p-EGFR, EGF, VEGFA, JUN, IL6, COX-2, AKT1, and MAPK1 in HCC cells, but elevated the expression of ESR1 and CASP3. Conclusions Taken together, results showed that YFJP attenuated HCC progression through mediating effects on HCC-related genes.

Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma

“…It is well known that flavonoids have a protective effect on HCC, and different flavonoids can play a role in the treatment of HCC by inhibiting tumor growth and exerting anti‐metastasis, anti‐angiogenesis, and anti‐inflammatory effects 41 . This result is consistent with our previous studies, in which HMM and RB in YFJP were found to improve the suppression of the TME 42 . To obtain HCC‐related targets, five databases were used.…”

“…With the recognition of the importance of remodeling the immune microenvironment for the treatment of HCC, the immunomodulatory effects of TCM have increasingly received attention in recent years. Previous studies by our team have shown that YFJP acts on multiple HCC‐related genes to inhibit tumor progression 42 . In vivo experiments have also confirmed that the mechanism of the antitumor effect of YFJP involves alleviating CD8 + T cell exhaustion and improving the immunosuppressive HCC microenvironment 14 .…”

“…Previous studies by our team have shown that YFJP acts on multiple HCC‐related genes to inhibit tumor progression. 42 In vivo experiments have also confirmed that the mechanism of the antitumor effect of YFJP involves alleviating CD8 + T cell exhaustion and improving the immunosuppressive HCC microenvironment. 14 In the present study, the whole prescription was disassembled into three decoctions to screen the key drugs of YFJP, explore their potential mechanism, and elucidate the therapeutic effects of the disassembled prescriptions on H22 tumor‐bearing mice.…”

“… 41 This result is consistent with our previous studies, in which HMM and RB in YFJP were found to improve the suppression of the TME. 42 To obtain HCC‐related targets, five databases were used. As a result, we obtained 5725 targets from DisGeNet, 35 targets from Drugbank, 40 targets from GAD, 566 targets from onco.DB.HCC, and 42 targets from TTD.…”

Preclinical In Silico Evidence Indicates the Pharmacological Targets and Mechanisms of Mogroside V in Patients With Ovarian Cancer and Coronavirus Disease 2019

“…In addition, suppression of VEGFA activation may enhance the therapeutic effectiveness of ovarian tumour chemotherapy through inhibition of autophagy related to VEGFA ( 38 ). It has been shown preclinically that targeting VEGFA activity or its signalling pathway is one of the pharmacological mechanisms of action of traditional Chinese medicines in cancers ( 39 , 40 ). However, the biological mechanisms of anti-ovarian cancer effects of mogroside V associated with VEGFA remain unreported.…”