Structurally diverse sesquiterpenes from the roots of Isotrema yunnanense and their analgesic and anti-inflammatory activity.

Five undescribed sesquiterpenes, including a dimeric sesquiterpene lactone with an unreported rare framework, neoversicolactone (1), and four sesquiterpenes, yunnadolins A-D (3-6), and a reidentified dimeric sesquiterpene lactone, versicolactone D (2), were obtained from the roots of Isotrema yunnanense, together with twelve known compounds. Their structures were established by spectroscopic analysis, single-crystal X-ray diffraction, and calculated electronic circular dichroism. Moreover, their analgesic and anti-inflammatory activities were evaluated in vivo and in vitro. All compounds exhibited significant anti-nociceptive activity, up to 59.5 % inhibition, except compounds 1 and 2. Meanwhile, compounds 6 and 15-17 showed better NO inhibition effects with IC50 values of 17.4 ± 2.9, 14.1 ± 2.0, 18.4 ± 0.3, and 12.8 ± 3.0 μM, respectively. Further investigation of the anti-inflammatory effect and mechanism shows that 6 exhibits a distinct anti-inflammatory effect by inhibiting the activation of MAPK/NF-κB pathways. Additionally, it also demonstrated effective anti-rheumatoid arthritis activity.