Cav2.2 and Cav3.1 calcium channel inhibitors from Valeriana jatamansi Jones

Abstract

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_v2.2) and T-type (Ca_v3.1–3.3) 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_v2.2 and Ca_v3.1. As a result, compounds 1–12 showed weak to potent inhibition on Ca_v2.2 peak currents at 30 μM. 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 μM, respectively. Meanwhile, the aforementioned compounds exhibited 18.2 ± 2.5% to 49.2 ± 7.1% peak current inhibition on Ca_v3.1 at 30 μM. In addition, they also exhibited noticeable specificity against Ca_v1.2, Ca_v2.1, and KCNH2 (hERG) channels.