Monoterpenoid indole alkaloids from Melodinus axillaris W.T.Wang exhibit anti-inflammatory activities by inhibiting the NF-κB signaling pathways

• Published in: Journal of ethnopharmacology Vol. 324; p. 117771
• Main Authors: Du, Kaicheng, Liang, Yanan, Song, Zihao, Zheng, Changwei, Lai, Lantao, Zong, Kunqi, Wang, Yumeng, Meng, Dali
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 24.04.2024
• Subjects: Alkaloids; Animals; Anti-Inflammatory Agents - pharmacology; Apocynaceae; Cyclooxygenase 2 - metabolism; Ethanol - pharmacology; Inflammatory; Lipopolysaccharides - pharmacology; Melodinus axillaris; Mice; NF-kappa B - metabolism; NF-κB signaling pathways; Plant Extracts - pharmacology; RAW 264.7 Cells; Secologanin Tryptamine Alkaloids - pharmacology; Signal Transduction; DMSO; MIAs; br s; LPS; Comp; Apocynaceae; Alkaloids; MA; HRESIMS; 13C-NMR; m/z; NF-κB signaling pathways; CH2Cl2; ODS; EtOAc; CUR; d; HMBC; ECD; Fr; m; s; 1H-NMR; t; MeOH; Inflammatory; Melodinus axillaris; HSQC
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2024.117771

Melodinus axillaris W.T.Wang has been widely used as an important medicine in China. In the folk of China, its whole plant has been used for fractures, rheumatic heart disease, testitis, hernia, abdominal pain, and dyspepsia, etc. Despite its extensive use, there is a shortage of literature investigating the specific bioactive compounds and underlying mechanisms responsible for their anti-inflammatory effects. This knowledge gap serves as the primary impetus for conducting this study, which aims to shed light on the previously unexplored therapeutic potential of M. axillaris. This study aims to investigate the material basis and potential mechanism of anti-inflammatory activity of M. axillaris. Compounds were isolated from the 95% ethanol extract of M. axillaris using a systematic phytochemical method. The structures were established by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD calculation, and DP4+ analysis. The anti-inflammatory activities of ethanol extract and compounds from M. axillaris were tested by an inflammation model of LPS-stimulated RAW264.7 cells in vitro. Western blot analysis was employed to evaluate the expressions of COX-2, iNOS, and NF-κB signaling pathways, aiming to elucidate the underlying mechanisms. Eleven undescribed monoterpenoid indole alkaloids (MIAs), axillines A−K (1–11), along with thirteen known analogs were isolated from M. axillaris. Compound 1 was the first representative of vincadine alkaloid with unprecedented 6/5/9/6/6 skeletons. Compounds 1–11 and ethanol extract showed significant anti-inflammatory effects in vitro. Among them, compound 2 had the best activity of inhibiting NO release (IC50 = 3.7 ± 0.9 μM). Additionally, subsequent Western blot analysis revealed that 2 could significantly inhibit the up-regulation of NF-κB signaling pathways, iNOS, and COX-2 in LPS-stimulated RAW264.7 cells, thereby demonstrating its anti-inflammatory activity. This study provides support for the traditional use of M. axillaris in terms of its anti-inflammatory properties and highlights the potential of MIAs as promising candidates for further development as anti-inflammatory drugs. [Display omitted] •Eleven undescribed monoterpenoid indole alkaloids (MIAs) were isolated from M. axillaris.•Compound 1 was the first representative of vincadine alkaloid with 6/5/9/6/6 skeletons.•These MIAs were isolated exhibited significant anti-inflammation activity.•Compound 2 inhibited inflammation by NF-κB signaling pathway.