New Triterpenoids and Anti-Inflammatory Constituents from Glinus oppositifolius.

Three new triterpenoids-spergulagenin B (1), spergulagenin C (2), and spergulagenin D (3)-were isolated from the aerial part of Glinus oppositifolius, along with 17 known compounds (4-20). The structures of these new compounds were identified by spectroscopic and MS analyses. Compounds 3, 5, 19, and 20 were evaluated for inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells with IC50 values of 17.03, 18.21, 16.30, and 12.64 µM, respectively. Compounds 3, 5, and 20 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 cells with IC50 values of 18.35 ± 1.34, 17.56 ± 1.41, and 14.27 ± 1.29 µM, respectively.

Chemometric profiling and anti-arthritic activity of aerial parts of Glinus oppositifolius (L.) Aug. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.