Saleucanes A-J, structurally diverse neo-clerodane diterpenoids from Salvia leucantha with anti-neuroinflammatory activity via TLR4/MYD88/NF-κB pathway.

Saleucanes A-J (1-10), ten unprecedented neo-clerodane diterpenoids, and twenty-two knowns were isolated from the whole plant of Salvia leucantha. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single-crystal X-ray crystallographic and ECD calculation. Compound 7 possesses an unusual 6/5/6/4/6/5-hexacyclic fused ring skeleton, with a rare oxetane unit. All compounds were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 cells. The results showed that five compounds exhibited significant NO inhibitory effects, with IC50 values ranging from 3.29 to 6.65 μM, which were better than the positive control minocycline hydrochloride (IC50 = 18.81 μM). Among them, compound 5 showed significant inhibitory effect, which significantly suppressed the production of IL-6, IL-1β, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigation results showed that compound 5 exerts anti-inflammatory effect via the TLR4/MYD88/NF-κB signaling pathway. To summarize, these findings supported the great hope of compound 5 as a potential novel inhibitor of neuroinflammation.