Abietane diterpenoid with diverse structures and multi-functional neuroprotective effects from Salvia castanea

Fitoterapia. 2025 Jun 22:185:106691. doi: 10.1016/j.fitote.2025.106691. Online ahead of print.

Abstract

Twelve diterpenoids involving five carbon skeletons were isolated from the aerial parts of Salvia castanea, an alternation of Danshen in Tibetan medicine. Their structures were established by 1H and 13C NMR data analysis. Biological evaluation revealed that methyl tanshinonate (1) exhibited anti-neuroinflammatory activity through restraining the expression of iNOS and COX-2, and down-regulating the phosphorylation levels of NF-κB p65, which was further confirmed by immunocytochemical analysis. Moreover, compounds 1, 2, 4, and 6 could delay Aβ-induced paralysis, and 1 as well as 2 also reduced ROS accumulation in AD Caenorhabditis elegans CL4176. Notably, compounds 1 and 2 obviously promoted NGF-induced neurite growth in PC-12 cells, and the neurite growth promotion rate of 2 (22.76 ± 1.03 %) displayed approximately 3-fold higher than NGF (7.98 ± 0.03 %) at 10 μM. These results provide new potential neuroprotective agents for the prevention and treatment of neurodegenerative diseases.

Keywords: Abietane diterpenoids; Aβ-induced paralysis; Neurite outgrowth; Neuroprotective effect; Salvia castanea.