Metabolomics and anti-inflammatory activity of Commiphora madagascariensis jacq. leaves extract using in vitro and in vivo models

[Display omitted] •Identification and quantification of 116 diverse metabolites using NMR and GC–MS based non-targeted metabolite profiling for the first time from Commiphora madagascariensis.•A novel phytocompound, trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI) along with four known bio-actives were isolated for the first time from C. madagascariensis.•An extraction process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves.•In vitro and in vivo anti-inflammatory potential of TTDI and processed extracts were evaluated.•In silico molecular docking study of TTDI against anti-inflammatory enzyme Cyclooxygenase-2 (COX-2), phospholipase 2 (PLA-2) and 5β reductase was also performed. C. madagascariensis, an unexplored species of Burseraceae is used by local population for the management of inflammation and throat pain. The disease alleviation by this plant could be due to the presence of rich repository of active compounds with various pharmacological importances. In this study, therefore, the profiling of metabolites and isolation of active compounds of C. madagascariensis was performed. Furthermore, the ethanol, ethyl acetate extracts and a selected active compound was subjected for in vitro and in vivo anti-inflammatory activities. Metabolomic analysis identified and quantified 116 metabolites from leaves, young stem and gum-resins of C. madagascariensis (Burseraceae) followed by multivariate PCA analysis. NMR, GC–MS and HPLC were used to analyze primary and secondary metabolites. Subsequently, five main isolated compounds were identified as trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI), butyl phenol, butyl propionate phenol, germacrone and β-elemenone. Amongst them, TTDI was found to be a novel compound. Hence, a process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves. Furthermore, TTDI and extracts were subjected for their in vitro anti-inflammatory activity in LPS sensitized murine splenocytes. The results showed that TTDI and both extracts significantly suppressed the levels of pro-inflammatorycytokines (TNF-α, IFN-γ). Interestingly, the suppression of pro-inflammatory cytokines was evenmore significant by the similar concentration of TTDI when compared with colchicine. However, the level of anti-inflammatory cytokine (IL-10) was found to be unchanged. Additionally, in vivo anti-inflammatory study revealed a significant reduction in car