Multiple Targets Directed Multiple Ligands: An In Silico and In Vitro Approach to Evaluating the Effect of Triphala on Angiogenesis

Abstract

Angiogenesis is critical in both physiological and pathological conditions and targeting angiogenesis is a promising strategy for the development of therapies against cancer; however, cells develop resistance to anti-angiogenic therapy, necessitating a more effective strategy. Natural medicines have been used in anti-cancer therapy for many years, but the mechanisms behind these have not generally been explored. Triphala churna (THL), an Indian ayurvedic herbal formulation made from the dried fruits of three medicinal plants, is used as a herbal drug for the treatment of various diseases, including cancer. THL contains over fifteen phytochemicals with different pharmacological effects, especially inhibition of tumor progression. In this study, we examined the effect of these compounds against different targets using docking and in vitro studies. Results showed that THL has a prediction efficacy of (−)436.7, and it inhibited angiogenesis by blocking multiple components of the VEGF/VEGFR2 signaling pathway. The anti-angiogenic effect was mediated by the combined effect of the two top ranked phytochemicals, punicalagin (−424.8) and chebulagic acid (−414.8). The new approach developed in this study to determine the potential efficacy of herbal formulation could be a useful strategy to assess the efficacy of different herbal formulations.

Identification of Hub Genes and Key Pathways Associated with Anti-VEGF Resistant Glioblastoma Using Gene Expression Data Analysis

“…The possible role of these hub genes in the development of anti VEGF resistance in GBM was suggested from the data showing interaction of 18 of these hub genes with 58 genes of different network modules in the VEGF - mediated angiogenesis signaling pathway [ 6 , 67 ]. In this context, our previous report on multiple phytochemicals of a poly-herbal formulation targeting multiple components of VEGF - VEGFR2 pathway and inhibiting angiogenesis is particularly significant [ 68 ].…”

Methamphetamine exposure increases cardiac microvascular permeability by activating the VEGF-PI3K-Akt-eNOS signaling pathway, reversed by Bevacizumab

“…15 It’s worth noting that VEGF, also known as “vascular permeability factor”, promotes microvascular permeability. 16 Following METH treatment, neurotrophic factors such as VEGF increased expression, according to recent studies. 17,18 eNOS, on the other hand, is a cardiovascular guardian angel.…”

Pharmacology of Triphala With Special Focus on Their Chemical Constituents

“…Over 130 compounds were evaluated, out of which 10, linked to more than three genes. The anti-angiogenic effect was mediated by the combined effect of punicalagin and chebulagic acid [52]. Triphala bioactives target 39 proteins which are expressed in 45 different tissues that come under 11 tissue types.…”