Genkwalathins A and B, new lathyrane-type diterpenes from <i>Daphne genkwa</i>

Screening for new natural anti-neuroinflammatory compounds was performed with the traditional folk medicine Genkwa Flos, which potently inhibited nitric oxide (NO) production by LPS-activated microglial BV-2 cells. Two new lathyrane-type diterpenes, genkwalathins A (<b>1</b>) and B (<b>2</b>), and 14 known daphnane-type diterpenes (<b>3</b>–<b>16</b>) were isolated. The lathyrane-type diterpenes were isolated for the first time from the Thymelaeaceae family in this study. Compounds <b>1</b> and <b>2</b> moderately inhibited LPS-induced NO production in BV-2 cells without affecting cell viability, while six daphnane-type diterpenes (<b>3</b>, <b>4</b>, <b>6</b>, <b>7</b>, <b>9</b> and <b>10</b>) potently reduced NO production with IC₅₀ values less than 1 μM, although they did display weak cytotoxicity. A structure–activity relationship study on the daphnane-type diterpenes indicated that the stereochemistry at C-19, the benzoate group at C-20, and the epoxide moiety could be important for their anti-neuroinflammatory effects.