In silico study of potential inhibitors of the proinflammatory marker p50 NF-κB subunit from new and novel Philippine plant constituents and the evaluation of the pharmacognosy of the leading genus through chemical characterization, in vitro assays and network pharmacology

• Main Author: Ting, Jasmine U.
• Format: text
• Language: English
• Published: Animo Repository 2023
• Subjects: Plants > Philippines; Lecythidaceae > Analysis; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/etdd_chem/5; https://animorepository.dlsu.edu.ph/context/etdd_chem/article/1006/viewcontent/2023_Ting_In_silico_Study_of_Potential_Inhibitors_of_the_Proinflammatory_Full_text.pdf
• Institution: De La Salle University

The current trend in natural products research is to elaborate and develop plant-derived compounds and its analogues as lead compounds for target-based approach drug discovery. As such, the Philippines, a mega-biodiverse country which is rich in both terrestrial and marine resources have been exploited by international scientists especially concerning the physio-chemical exploration of endemic plants. Internationally renowned and Filipino natural products chemist, the late Professor Dr. Consolacion Y. Ragasa, reported 61 new and novel compounds from introduced and locally found Philippine plants. Though these constituents were investigated through extensive NMR spectroscopic techniques, other modes of chemical characterization, their respective bioactivity evaluation, and the probable applications of these compounds are relatively limited. Since the majority of the compounds are terpenes which are known to have immunomodulatory capabilities, molecular simulations were utilized to identify potential anti-inflammatory agents acting as p50 subunit inhibitor. Based on the results of the molecular simulation, the Genus of the best-performing plant (Barringtonia species) was selected for further chemical deconvolution using colorimetric assays (e.g., Folin Ciocalteu Assay), spectroscopic (e.g., NMR) and chromatographic (e.g., GC-EI-MS) analytical tools. In order to ascertain the potential of botanical drugs as immunomodulator anti-cancer agents, the total antioxidant capacity of plant extracts was assessed using DPPH and cyclic voltammetry techniques. Thirteen plant extracts have shown promising antioxidant properties which most of these extracts were derived from the dichloromethane extract of leaf, stalk and stem bark from the Barringtonia spp. Furthermore, these thirteen extracts exhibited particular cytotoxic effects against different human cancer cell lines in the cell viability assay. Additionally, the best performing extracts: B.racemosa stalk (IC50 = 16.18 ppm for HT-29) B. macrocarpa stalk (IC50 = 16.39 ppm for BxPC3), B. acutangula leaf(IC50 = 19.36 ppm for MCF-7) B. asiatica leaf (IC50 = 19.36 ppm for HepG2) and stalk (IC50 = 14.63ppm for H69PR) were found to induce genotoxicity against the respective cancer cell line in their IC50 concentration. Interestingly, these extracts were also found to down regulate pro-inflammatory cytokines (TNF-α and IL-1β) in the LPS-induced THP-1 monocyte. Based on network pharmacology investigation, the observed phenomena can be attributed to the metabolites found in the extract, which have the ability to induce effect on the common macromolecular targets (EGFR, ERBB2, ESR1, MTOR, and PTGS2) associated with cancer, inflammation, and oxidative stress by affecting COX-2, PI3k-Akt-mTOR and ERBB signaling pathways. Keywords: Philippine plant, Barringtonia, molecular simulation, p50 subunit, anti-oxidant, anti-inflammatory, anti-cancer, cytotoxicity, genotoxicity, network pharmacology