Iridoids isolated from Viticis Fructus inhibit paclitaxel-induced mechanical allodynia in mice.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic. Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified 1 has not been evaluated due to its low content in Plantaginis Semen. In the present study, 1 was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated 1, 2, and 3 were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative 1H-NMR, using DSS-d6 as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of 1, 2, and 3. This study provides confirmatory evidence for the anti-allodynic activity of purified 1 and also reveals two additional active iridoids from Viticis Fructus. These three iridoids could be potential candidates for the treatment of CIPN.