4.2 Pharmacodynamics and pharmacokinetics of isorhamnetin
Isorhamnetin, a natural flavonoid, is commonly found in various plants and plant-delivered foods, such as wine, nuts, and olive oil. Quercetin, another plant flavanol, has been shown to have various beneficial health (Cogolludo et al., 2007; Heiss et al., 2010; Serban et al., 2016). According to reports on the bioavailability of quercetin, most absorbed quercetin is methylated and converted to isorhamnetin (Li et al., 2012; Zhang et al., 2010). Isorhamnetin has also been shown to have cardioprotective effects induced by doxorubicin hydrochloride, myocardial ischemia-reperfusion, aortic binding, and AngII infusion by suppressing cardiac oxidation, hypertrophy, and fibrosis (Aonuma et al., 2020; Gong et al., 2020; Sun et al., 2012; Sun et al., 2013; Xu et al., 2020). Additionally, previous reports have suggested the possible effects of isorhamnetin on Ca2+ channels and currents (Saponara et al., 2011; Zhu et al., 2005). Based on these findings, in the current study, we explored whether isorhamnetin could possibly inhibit AF vulnerability by improving morphological abnormalities and regulating Ca2+-handling. In the present study, we found that AngII increased the AF induction rate, prolonged AF duration, and decreased AERP. However, these effects were reversed with isorhamnetin (Fig. 1B-D).