Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active “constituent–target–pathway” networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense.

Molecular Docking and Simulation-Binding Analysis of Plant Phytochemicals with the Hepatocellular Carcinoma Targets Epidermal Growth Factor Receptor and Caspase-9

“…Khalid et al [28] represented a multitarget network pharmacology approach to explore the mechanisms of S. surattense to target HCC. A molecular docking analysis revealed the potential of quercetin to inhibit the target proteins involved in the pathogenesis of HCC.…”

Exploring the mechanism of bioactive components of Prunella vulgaris L. in treating hepatocellular carcinoma based on network pharmacology

“…PPI analysis showed that AKT1, EGFR, SRC, ESR1, PPARG, PTGS2, MAPK3, GSK3B, MMP9, and PARP1 were key targets for PVL treatment of HCC. These key targets were mainly involved in biological processes such as HCC cell proliferation, apoptosis, cell cycle regulation, epithelial mesenchymal transition, tumor metastasis, and drug resistance (Khalid et al., 2022; Wang et al., 2017; Weng et al., 2023; Yun et al., 2022). KEGG analysis showed that PVL may block HCC progression via multiple pathways and biological processes including PI3K/Akt signaling.…”