Anti-inflammatory actions of Caesalpinin M2 in experimental colitis as a selective glucocoricoid receptor modulator.

In this study, we found that Caesalpinin M2 (C-M2), a cassane furanoditerpene isolated from a Chinese medical plant, exerts an anti-inflammatory potential both in vitro and in vivo. C-M2 inhibited the expression of proinflammatory cytokine IL-1β and IL-6 in LPS-activated bone marrow-derived macrophages. Meanwhile, C-M2 treatment attenuated DSS-induced experimental acute colitis in mice and did not cause side effects, such as spleen involution, like dexamethasone treatment. Molecular docking and cellular thermal shift assay demonstrated that C-M2 could bind to GR in the ligand binding site. We showed that C-M2 mediates gene-inhibitory effects by activating GR. More importantly, C-M2 failed to induce GR binding to glucocoricoid response element-dependent genes and in turn activate their transcription. But it did repress NF-κB-dependent transcription by facilitating the interaction between GR and p65. Taken together, this non-steroidal compund of plant origin may exert anti-inflammatory actions as a selective GR modulator and might hold great potential for therapeutic use in inflammatory diseases. PMID: 29427627 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research