Integrated computational biology revealed ellagic acid exerts antioxidant and anticancer activities through inhibition of ROS-induced JNK/p38 MAPK kinase pathway

Ellagic acid (EA) is a naturally occurring plant polyphenol, largely present in pomegranate and different types of berries. The pharmacokinetic, pharmacological, and biological properties of EA have also never been studied. Herein, we have employed an integrated and systematic approach to elucidate these properties using machine learning and neural networking-based computational tools. The pharmacokinetic properties of EA have been elucidated to establish EA as a drug-like molecule with appreciable GI absorption and no blood-brain permeation. In-silico ADME analysis showed EA obeys the Lipinski rule-5 without any violation. The modulation of gene activity by EA has also been studied using DIGEP-Pred. We have reported genes that were upregulated ( TCF12, IGFBP2, EP300, BLM, CEP72, ITGA6 ) and downregulated ( NOP56, TFAM and UGP2 ) by EA. Altogether, the predicted result showed high corroboration with the involvement of the EA in the modulation of cellular oxidative stress through inhibition of ROS-induced JNK/p38 MAPK pathway via inhibition of the receptor tyrosine kinases (RTKs) and thereby negatively regulate the downstream cascade of cell signalling pathways related to the proliferation, survival, invasion, and migration of cell. Altogether, our results have unveiled the molecular and cellular level mechanistic of the mode of action of EA as an antioxidant drug with anti-cancer activities. Our results are novel and the first documented evidence of inhibition of the RTKs and JNK/p38 MAPK-mediated cancer signalling in the EA. We envisage that EA-based nutritional therapy can be used as adjuvant therapy for various cancer treatments and other chronic ailments.