Ca(v)2.2 and Ca(v)3.1 calcium channel inhibitors from Valeriana jatamansi Jones

摘要

In China, the roots and rhizomes of Valeriana jatamansi Jones are traditionally used to treat gastrointestinal and rheumatic pain. Small molecule inhibitors of N-type (Ca(v)2.2) and T-type (Ca(v)3.1-3.3) calcium channels have become attractive resources in analgesic drug development. Therefore, in the present study, the isolated compounds (1-13) from V. jatamansi, including three new valepotriates (1-3), were initially evaluated on Ca(v)2.2 and Ca(v)3.1. As a result, compounds 1-12 showed weak to potent inhibition on Ca(v)2.2 peak currents at 30 mu M. Among them, compounds 1, 6, 7, 11 and 12 exhibited significant antagonistic effects, with EC50 values of 4.33, 2.18, 1.13, 2.70 and 7.8 mu M, respectively. Meanwhile, the aforementioned compounds exhibited 18.2 +/- 2.5% to 49.2 +/- 7.1% peak current inhibition on Ca(v)3.1 at 30 mu M. In addition, they also exhibited noticeable specificity against Ca(v)1.2, Ca(v)2.1, and KCNH2 (hERG) channels.