Background: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. Methods: Cytoscape was used to construct a network of compound–disease targets and protein–protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. Results: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Conclusions: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA’s significant potential as a prospective agent for the therapy of cancer.

Background: Madecassoside is widely utilized in wound healing due to its multiple physiological activities. However, its limited bioavailability and solubility hinder its clinical application. Enzymatic hydrolysis has been employed to enhance the bioavailability and bioactivity of natural products, but its potential for modifying madecassoside remains unexplored. Methods: In this study, we prepared MA1G and MA2G through enzymatic hydrolysis, inspired by the metabolic processes of madecassoside. Network pharmacology was employed to investigate the mechanisms of these madecassoside derivatives (MDs) in wound healing, and molecular docking was performed to evaluate their binding affinities. Transdermal permeation studies, scratch assays, and antioxidant and anti-inflammatory tests were conducted to characterize the biological properties and activities of MDs. Results: Network pharmacology identified TLR4, NF-κB, and STAT3 as key targets for wound healing, and the MDs inhibited the expression of these proteins in vitro. Additionally, the results demonstrated that MDs exhibited robust reactive oxygen species (ROS) scavenging activity (43.05–147.50% reduction) and significantly enhanced cell migration (36.76–77.28% increase). Notably, the biomodified MA2G showed superior transdermal permeability and biological activities. Conclusions: This paper represents the first report directly comparing the biological activities of the parent compound (madecassoside) and its metabolites while simultaneously proposing a novel therapeutic strategy for wound healing.