Eclipta prostrata の活性植物化学物質のスクリーニングとヒト悪性腫瘍に対する分子メカニズムの解明

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemotherapeutic activities against around 15 different human malignancies. In vitro and preclinical models support that the chemotherapeutic properties of phytochemicals derived from Eclipta prostrata are believed to be regulated by many pathways, including targeting signaling pathways, for example, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), tumor necrosis factor-alpha (TNF-α), nuclear Factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK); regulated cell death such as Fas cell surface death receptor (FAS), Bid, apoptosis-inducing factor (AIF), Bcl2, Bax, Bak, Bad, caspase, and Poly (ADP-ribose) Polymerase (PARP); metastasis and angiogenesis such as matrix metalloproteinases (MMPs) (2&9), wingless/integrated (Wnt)/beta-catenin, angiogenesis (E-cCadherin & N-cadherin, vimentin), cell proliferation (cyclins-A, B1, D1, E1, and cyclin-dependent kinases (CDKs) 1, 2,4), inflammatory molecules (programmed death-ligand 1 (PD-L1), TNF-α, NF-κB, Interleukin-1 (IL-1), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1 beta (IL-1β)), regulating tumor suppressor genes (p21, p27, p38, p51, p53), microRNA (miRNA) regulation, and some nonspecific pathways like DNA fragmentation damage and repair, autophagy (light chain 3-II (LC3-II) and mTOR), and many other pathways. Some selective phytochemicals exert synergistic activities with standard chemotherapeutic drugs and reverse drug resistance through several mechanisms. Nano-based phytochemicals target numerous cancer cells, resulting in drug accumulation and improved drug efficacy, making phytochemicals more potent chemotherapeutic agents in cancer treatment. Additionally, an in-silico pharmacokinetics study reveals that phytoestrogen possesses suitable pharmacokinetic characteristics with minor toxicity in the human body. So, direct consumption of different parts of Eclipta prostrata or specific phytochemicals from this plant can be a potential candidate drug against human malignancies.