A Network Pharmacology Perspective Investigation of the Pharmacological Mechanisms of the Herbal Drug FDY003 in Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most common and deadly malignant tumors worldwide. While the application of herbal drugs for GC treatment is increasing, the multicompound–multitarget pharmacological mechanisms involved are yet to be elucidated. By adopting a network pharmacology strategy, we investigated the properties of the anticancer herbal drug FDY003 against GC. We found that FDY003 reduced the viability of human GC cells and enhanced their chemosensitivity. We also identified 8 active phytochemical compounds in FDY003 that target 70 GC-associated genes and proteins. Gene ontology (GO) enrichment analysis suggested that the targets of FDY003 are involved in various cellular processes, such as cellular proliferation, survival, and death. We further identified various major FDY003 target GC-associated pathways, including PIK3-Akt, MAPK, Ras, HIF-1, ErbB, and p53 pathways. Taken together, the overall analysis presents insight at the systems level into the pharmacological activity of FDY003 against GC.

A Study on the Mechanism of Herbal Drug FDY003 for Colorectal Cancer Treatment by Employing Network Pharmacology

“…42,43 We defined hubs to be the nodes with degrees possessing a number of connections ≥ 2 × average degree value per node (6.17). 7–13 DC analysis indicated that the following nodes, AKT1 (DC = 17), CYP1A1 (DC = 13), CYP3A4 (DC = 14), EGFR (DC = 13), ESR1 (DC = 15), JUN (DC = 15), PIK3R1 (DC = 17), PIK3R1 (DC = 17), SRC (DC = 20), TP53 (DC = 21), and VEGFA (DC = 14), satisfied the inclusion criteria for being considered a hub (Figure 3), suggesting the core targets for the anti-CRC activity of FDY003.…”

“…7–13 Additionally, FDY003 acts as a chemosensitizer that can increase the effectiveness of anticancer chemotherapeutics. 7–13 To date, no study has been conducted to establish the mechanisms of FDY003 against CRC, focusing on its multiple-compound-multiple-target network perspective. 8…”

A Network Pharmacological Elucidation of the Systematic Treatment Activities and Mechanisms of the Herbal Drug FDY003 Against Esophageal Cancer

“…11,14 Oral bioavailability ≥30% is a general criterion for screening chemicals with effective delivery in the human body. 5,11,15 Druglikeness determines whether a chemical possesses pharmacologically suitable properties in terms of structures and physicochemical and molecular activities. 5,11,15 Druglikeness ≥0.18 is a general criterion for screening chemicals with strong potential as drug candidates.…”

“…5,11,15 Druglikeness ≥0.18 is a general criterion for screening chemicals with strong potential as drug candidates. 5,11,15 Caco-2 permeability determines whether a chemical shows reasonable permeability in the human intestinal systems. 11 Caco-2 permeability ≥−0.4 is a typical criterion for screening chemicals that may permeate the intestines to exert pharmacological action.…”

“…5,11,15 Druglikeness determines whether a chemical possesses pharmacologically suitable properties in terms of structures and physicochemical and molecular activities. 5,11,15 Druglikeness ≥0.18 is a general criterion for screening chemicals with strong potential as drug candidates. 5,11,15 Caco-2 permeability determines whether a chemical shows reasonable permeability in the human intestinal systems.…”