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

Biomolecules. 2020 Jan 23;10(2):177. doi: 10.3390/biom10020177.

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.

Keywords: angiogenesis; molecular docking; polyherbal formulation; triphala churna.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Benzopyrans / pharmacology
  • Cell Movement
  • Computer Simulation
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Glucosides / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrolyzable Tannins / pharmacology
  • Ligands
  • Medicine, Ayurvedic
  • Molecular Docking Simulation
  • Neoplasms / drug therapy
  • Neovascularization, Pathologic / drug therapy*
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Benzopyrans
  • Glucosides
  • Hydrolyzable Tannins
  • Ligands
  • Plant Extracts
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • triphala
  • chebulagic acid
  • punicalagin
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2