TRPV1 Activation BY KAMPO Extract Formulations for Prescription

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel activated by capsaicin and heat. Capsaicin has various effects such as pain relief, rubefacient, weight loss, and gastrointestinal protection. Some compounds in Kampo (a traditional Japanese medicine) formulas, such as evodiamine of Evodia fruit, are known to activate TRPV1. But, it is not clear whether TRPV1 is activated by taking Kampo prescriptions. Therefore, the effects of 128 Kampo extract formulations for prescription on the HEK293 cells with/without human TRPV1 expression were examined. The specific increase of intracellular Ca²⁺ was used as the index of TRPV1 activation. The samples with specific TRPV1 activation were further examined whether they have capsaicin-like contractile effects in mice isolated ileum. In this study, the final concentrations of samples were adjusted to be 1 – 2% of the normal Kampo decoctions. The Daikenchuto which TRPV1 activating ability was already known was served as a positive control. Capsazepine, a TRPV1 antagonist, was used to check the site of action. As a result, 12 Kampo prescriptions have shown stronger TRPV1 activation than Daikenchuto in HEK293 cells with hTRPV1. In the mice isolated ileum, Daiokanzoto, Tokakujokito, Tokishigyakukagoshuyushokyoto and Goshuyuto showed strong contractile effects which was suppressed by the pretreatment of capsazepine. Rubarb and Evodia fruit were suggested to be the main contributing crude drugs for TRPV1 activation. Sennoside B, a main constituent of Rubarb, was found to be a TRPV1 activator. In conclusion, some Kampo prescriptions showed strong TRPV1 activation at the concentrations lower than those in decoction, suggesting the TRPV1 stimulation might play an important part in their pharmacological actions.