Ent-kauranes and ent-atisanes from Euphorbia wallichii and their anti-inflammatory activity

Phytochemical investigation on the whole plant of Euphorbia wallichii led to the identification of twelve diter-penoids, including nine undescribed ones, in which wallkauranes A-E (1-5) were classified as ent-kaurane diterpenoids and wallatisanes A-D (6-9) were assigned as ent-atisane diterpenoids. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model, resulting in the identification of a series of potent NO inhibitors, with the most active wallkaurane A showing an IC50 value of 4.21 mu M. The mechanistic study disclosed that wallkaurane A could inhibit pro-inflammatory cy-tokines generation such as TNF-alpha, IL-1 beta, and IL-6, and decrease the expression of iNOS and COX-2. Wallkaurane A could regulate the NF-kappa B signaling pathways and the JAK2/STAT3 signaling pathway to suppress the in-flammatory reaction in LPS-induced RAW264.7 cells. Meanwhile, wallkaurane A could also inhibit the JAK2/ STAT3 signaling pathway, thereby suppressing apoptosis in LPS-induced RAW264.7 cells.

Automated summary

Phytochemical investigation on Euphorbia wallichii led to the discovery of twelve diterpenoids, including nine previously undescribed compounds. These compounds showed potent inhibitory effects on NO production in LPS-induced RAW264.7 cells, with wallkaurane A being the most active (IC50 = 4.21 mu M). Mechanistic studies revealed that wallkaurane A could suppress the generation of pro-inflammatory cytokines, decrease the expression of iNOS and COX-2, and regulate the NF-kappa B and JAK2/STAT3 signaling pathways to suppress inflammation and apoptosis.