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Activation of transient receptor potential vanilloid 3 by the methanolic extract of <em>Schisandra chinensis</em> fruit and its chemical constituent γ-schisandrin

Activation of transient receptor potential vanilloid 3 by the methanolic extract of <em>Schisandra chinensis</em> fruit and its chemical constituent γ-schisandrin

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plantderived natural compounds such as camphor and eugenol. <em>Schisandra chinensis</em> (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, antiinflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that γ-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of 30 μM. In addition, γ-schisandrin (~100 μM) increased cytoplasmic Ca<sup>2+</sup> concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and γ-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which γ-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

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