Clerodane diterpenoids and acetophenones from Solidago canadensis L. with anti-neuroinflammation activity via regulating the expressions of NLRP3 and IL-1β

Abstract

Neuroinflammation is a key pathogenic factor in neurodegenerative diseases, while the anti-neuroinflammatory effects of Solidago canadensis L. have not been reported to date. This study aimed to identify the anti-neuroinflammatory active components of S. canadensis and elucidate their regulatory effects on neuroinflammation-related protein expression. A total of 20 compounds, including 17 clerodane diterpenoids (1-7 and 10-19) and 3 acetophenone derivatives (8, 9, and 20) were isolated from S. canadensis. Seven clerodane diterpenoids (1-7) and two acetophenone compounds (8 and 9) are previously unreported, and their structures were were elucidated via a comprehensive approach integrating spectroscopic data analysis, empirical stereochemical rules, DP4+ probability analysis using GFN2NMR, and ECD calculations. Compounds 1-5 are novel 1,2-seco-(3 → 1)-abeo-clerodane diterpenoids, which expand the chemical diversities of the genus Solidago. The anti-neuroinflammatory activity of all isolated compounds was evaluated in LPS-stimulated BV2 microglial cells. The results revealed that compounds 3, 10, 11, 12, 17, and 18 exhibited potent activity, yielding ICvalues of 14.54, 12.35, 14.32, 16.42, 13.86, and 15.64 μM, respectively. Western Blot analysis demonstrated that these compounds decreased NLRP3 and IL-1β protein expressions to display anti-neuroprotective effects. These results support the potential of clerodane diterpenoids from S. canadensis as anti-neuroinflammatory agents for treating neurodegenerative diseases.