Reverse Screening and Network Pharmacology to Model the Anticancer Action of Momordica Charantia L.
Date of Award
8-2021
Document Type
Thesis
Degree Name
Master of Science in Chemistry
First Advisor
Nina Rosario L. Rojas, PhD,Fabian Antonio M. Dayrit, PhD, Armando Jerome H. de Jesus, PhD, Alexander T. Young, PhD
Abstract
Whole extracts and isolated phytochemicals in bitter gourd (Momordica charantia L.) have shown anticancer activity in vitro and in vivo. However, the cellular action of bitter gourd is not fully understood. To address this, we combined reverse screening and network pharma- cology into an in-silico workflow to model the action of bitter gourd against colorectal can- cer. The workflow consists of (1) phytochemical compilation, (2) reverse screening, and (3) network analysis. Reverse screening results were evaluated by molecular docking. We used two chemotherapy drugs, vemurafenib and sorafenib, as positive controls. Through this work- flow, we built a phytochemical-protein interaction (PCPI) network that shows protein targets, cellular location, phytochemical class, and pharmacokinetics. The network can be viewed at https://yumibriones.github.io/network/.
Our findings suggested that flavonoids, phenolics, and triterpenoid aglycones are key players in the PCPI network. Molecular docking found that flavonoids and phenolics in bitter gourd are able to block the ATP-binding site of kinases, inhibiting the EGFR/MAPK and PI3K/AKT pathways. Meanwhile, triterpenoids are poor inhibitors of the ATP-binding site, but they may bind more strongly to other sites in the protein. We used high confidence docking results to construct a simplified PCPI network that summarizes the anticancer effects of bitter gourd. In general, this workflow can also be used to visualize the action of other medicinal plants against diseases of interest. Resulting PCPI networks can be easily interpreted and used to inform future in vitro or in vivo experiments.
Keywords: reverse screening, network pharmacology, Momordica charantia L. (bitter gourd), colorectal cancer, medicinal plants, phytochemicals, network visualization, interaction network
Recommended Citation
Yumi, Briones L., (2021). Reverse Screening and Network Pharmacology to Model the Anticancer Action of Momordica Charantia L.. Archīum.ATENEO.
https://archium.ateneo.edu/theses-dissertations/735
