Two new clerodane diterpenoids with analgesic activity from the roots of <i>Paratinospora sagittata</i> (Oliv.) Wei Wang

As a Yi medicine for relieving pain, the roots of <i>Paratinospora sagittata</i> (Oliv.) Wei Wang are widely used to treat pain-related diseases. However, investigation of its effective analgesic constituents is very poor. In this study, two new clerodane diterpenoids, tinophyllol A (<b>1</b>) and tinophyllol B (<b>2</b>), as well as eight known ones, were isolated from the roots of <i>P. sagittata</i> and identified using the HRESIMS, IR, and NMR data. Meanwhile, their analgesic activities were evaluated using the acetic acid-induced nociception model. The isolated compounds (<b>1</b> and <b>4</b>-<b>10</b>) demonstrated effective antinociceptive activity. <b>1</b> exhibits the best antinociceptive activity, inhibiting 59.2%, with an ED₅₀ of 26.3 ± 3.2 mg/kg. It also demonstrates clear antinociceptive effects in the other two nociception models induced by hot plate and formalin. Mechanism investigation showed that <b>1</b> could exhibit central and peripheral analgesic activity, possibly by modulating the glutamatergic and vanilloid systems (TRPV1).