New mechanistic insights on Justicia vahlii Roth: UPLC-Q-TOF-MS and GC-MS based metabolomics, in-vivo, in-silico toxicological, antioxidant based anti-inflammatory and enzyme inhibition evaluation

Justicia vahlii Roth. (acanthaceae) is an important medicinal food plant used in pain relief and topical inflammation. The present study aimed to evaluate phytochemical composition, toxicity, anti-inflammatory, antioxidant and enzyme inhibition potential of n-butanol extract of J. vahlii (BEJv). The extract prepared through maceration was found rich in total phenolic contents (TPC) 196.08 +/- 6.01 mg of Gallic acid equivalent (mg GAE/g DE) and total flavonoid contents (TFC) 59.08 +/- 1.32 mg of Rutin equivalent (mg RE/g DE). The UPLC-Q-TOF-MS analysis of BEJv showed tentative identification of 87 compounds and 19 compounds were detected in GC-MS analysis. The HPLC-PDA quantification showed the presence of 14 polyphenols amongst which kaempferol (3.45 +/- 0.21 mg/ mL DE) and ferulic acid (2.31 +/- 1.30 mg/ mL DE) were found in highest quantity. The acute oral toxicity study revealed the safety and biocompatibility of the extract up to 3000 mg/kg in mice. There was no effect of BEJv on human normal liver cells (HL 7702) and very low cytotoxic effect on liver cancer cells (HepG2) and breast cancer cells (MCF-7). In anti-inflammatory evaluation, the BEJv treated groups showed significant inhibition (p < 0.001) of late phase carrageenan induced paw edema at 400 mg/kg and increased the levels of oxidative stress markers; catalase, superoxide dismutase (SOD) and glutathione (GSH) while decreased the inflammatory markers; interleukin-1beta (IL-beta) and tumor necrosis factor alpha (TNF-alpha) in paw tissue of mice. BEJv displayed highest results in Ferric reducing antioxidant power (FRAP) assay 97. 21 +/- 2.34 mg TE (trolox equivalent)/g DE, and highest activity 3.32 +/- 0.31 mmol ACAE (acarbose equivalent)/g D.E against alpha-glucosidase. Docking study showed good docking score by the tested compounds against the various clinically significant enzymes. Conclusively the current study unveiled J. vahlii as novel non-toxic source with good antioxidant-mediated anti-inflammatory potential which strongly back the traditional use of the species in pain and inflammation. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.