Gelsevirine

Gelsevirine is an oxindole alkaloid that has been found in G. elegans and has anti-inflammatory activity.^1,2 It binds to stimulator of interferon genes (STING; K_d = 27.6 µM) and prevents 2'3'-cGAMP-induced Sting dimerization in RAW 264.7 macrophages when used at a concentration of 5 µM.² Gelsevirine (10 µM) inhibits 2'3'-cGAMP-, poly(dA:dT) dsDNA-, or IFN-stimulatory DNA-induced increases in the levels of mRNA encoding chemokine (C-X-C motif) ligand 10 (CXCL10) and IL-6 in THP-1 monocytes and RAW 264.7 cells. It inhibits 2'3'-cGAMP-induced increases in the levels of Sting and phosphorylated IFN regulatory factor 3 (IRF3), p65, and TANK-binding kinase 1 (TBK1) in RAW 264.7 cells when used at a concentration of 5 µM. In vivo, gelsevirine (20 mg/kg) increases animal survival time, reduces lung injury and total protein levels in bronchoalveolar lavage fluid (BALF), and decreases serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine, IL-6, TNF-α, and blood urea nitrogen (BUN) levels in wild-type, but not Sting1^-/-, mice in a model of sepsis induced by cecal ligation and puncture (CLP).

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1. Su, Y.P., Shen, J., Xu, Y., et al. Preparative separation of alkaloids from Gelsemium elegans Benth. using pH-zone-refining counter-current chromatography. J. Chromatogr. A 1218(23), 3695-3698 (2011).

2. Chen, Y., Bian, H., Lv, J., et al. Gelsevirine is a novel STING-specific inhibitor and mitigates STING-related inflammation in sepsis. Front. Immunol. 14, 1190707 (2023).