Cynaropicrin is a sesquiterpene lactone containing an α-methylene-γ-butyrolactone active group, isolated from the Ranunculaceae plant Saussurea lappa. Cynaropicrin has an inhibitory effect on tumor necrosis factor (TNF-α) production and cytokine-induced neutrophil chemokine-1. Cynaropicrin also inhibits the upregulation of the cartilage degradation factor MMP13 and can suppress the NF-κB signaling pathway[1][2].
In vitro, Cynaropicrin (0-40µM; 6h) exhibited no cytotoxicity in RAW264.7 and U937 cells. Cynaropicrin (0-40µM; 24h) inhibited macrophage proliferation in a dose-dependent manner, with IC₅₀ values of 16.3µM in RAW264.7 cells and 17.2µM in U937 cells. Cynaropicrin (0-40µM) inhibited the proliferation of Sup-T1 cells after 24h and 48h of treatment, with IC₅₀ values of 27.5µM and 14.1µM, respectively. Cynaropicrin (0-40µM; 6h) strongly inhibited lipopolysaccharide-induced TNF-α release from both murine and human macrophage cells in a dose-dependent manner with the IC50 values of 8.24 and 3.18µM[1]. Cynaropicrin (1–4µM; 1h) dose-dependently inhibited TNF-α-induced upregulation of MMP13, HIF-2α, and ADAMTS4 mRNA expression and reversed the downregulation of Sox9 mRNA expression in OUMS-27 cells[2].
In vivo, Cynaropicrin (2.5 and 5mg/kg; i.p.; every 2 days for 14 days) decreased tumor volume and weight in mice bearing HCT116 xenografts with minimal toxicity[3].
References:
[1] Cho, J Y et al. “In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa.” European journal of pharmacology vol. 398,3 (2000): 399-407.
[2] Masutani, Teruaki et al. “Cynaropicrin is dual regulator for both degradation factors and synthesis factors in the cartilage metabolism.” Life sciences vol. 158 (2016): 70-7.
[3] Zheng, Dandan et al. “Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis.” Frontiers in cell and developmental biology vol. 8 605184. 11 Jan. 2021.