Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology

Abstract

Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan–Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

“…DU145 cells were seeded into 96-well plates at a density of 1x10 4 cells/well and cultured with complete medium containing various concentrations of ursolic acid (0, 10, 20, 40 and 80 µM) for 24, 48 and 72 h. Following ursolic acid treatment, CCK-8 reagent was added to the cells and incubated for 4 h at 37˚C in an atmosphere of 5% CO 2 . Subsequently, the absorbance of each well was detected at 450 nm using a microplate reader (Bio-Rad Laboratories, Inc., Hercules, CA, USA).…”

“…According to previous studies, the use of Chinese herbs to treat tumors is achieving increasing recognition (4)(5)(6). Previous studies have reported that Traditional Chinese Medicine (TCM) has effects on androgen-dependent and -independent prostate carcinoma (7)(8)(9).…”

Traditional Chinese medicine combined with other therapies for treatment of hepatocellular carcinoma in clinical trials

“…Further, TCM has a good analgesic effect, and can promote the restoration of bowel peristalsis and minimize abdominal distension and urinary retention [30,31]. A series of statistical analyses showed that 8 herbs are closely associated with tumor proliferation, metastasis, angiogenesis and apoptosis [32]. These analyses also demonstrated that the products containing Ginseng, Astragalus and Mylabris have the greater significant therapeutic effects on HCC [33].…”

Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

“…Network pharmacology, proposed by Andrew L. Hopkins, clarifies the synergistic effects and the underlying mechanisms of multi-component and multi-target agents by analyzing various networks of complex and multilevel interactions [15,16]. This method has been widely applied in systematic understanding of the mechanisms of herbal formula [7,17,18]. For example, it was used to identify 1327 targets of 673 compounds from nine herbs involved in Fc epsilon RI signaling pathway and regulation of immunoglobulin production from a Chinese herb formula on rheumatoid arthritis [7].…”

“…For example, it was used to identify 1327 targets of 673 compounds from nine herbs involved in Fc epsilon RI signaling pathway and regulation of immunoglobulin production from a Chinese herb formula on rheumatoid arthritis [7]. Gao et al ascertained molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on this method [18]. …”