In this study, we investigated the effects of Perilla frutescens var. acuta aqueous extract (PFA) on eyestrain using in vitro, ex vivo, and clinical tests. We confirmed the antioxidant activity of compounds present in the extract by using high-performance liquid chromatography. PFA contains antioxidant compounds such as rosmarinic acid, luteolin-7-O-glucuronide, and apigenin-7-O-glucuronide, and has been shown to inhibit reactive oxygen species generation in C2C12 muscle cells. In an ex vivo study, PFA inhibited the carbachol (100 μM)-induced contraction of ciliary muscle from rabbit eyeball. We then investigated the mechanism by which PFA caused muscle relaxation and found that it effectively increased cyclic GMP production and inhibited PDE5A activity, but did not affect the cyclic AMP pathway, in cultured human aortic smooth muscle cells. In addition, PFA (50, 100, and 200 µg/mL) dose-dependently decreased basal intracellular calcium in smooth muscle cells and attenuated the endothelin-1-stimulated increase in intracellular calcium. Finally, we performed a clinical study to evaluate the effects of PFA on the near point of accommodation (NPA) after visual display terminal (VDT) work. Thirty participants were randomized to either PFA (500 mg/day) or placebo, and intake for one consecutive week. NPA was evaluated before and after 2 h of VDT work, and was found to be improved in the PFA-treated group. Thus, our findings show that PFA may ameliorate visual fatigue.

This study was conducted to evaluate the effects of Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz., and Angelica gigas Nakai extract (CPAE) on the reduction of tail skin temperature (TST) in ovariectomized (OVX) rats. To evaluate TST reduction in ovariectomized rats, 125, 250, and 1000 mg/kg CPAE was administered to rats for 1 week. The measurement of TST after the induction of artificial stress revealed a significant temperature reduction effect in the CPAE administration group (p<0.05). The TST induced by the injection of yohimbine, to induce hot flashes, was found to decrease as the administered dose of CPAE increased from 10 min to 20min (125 and 250 mg/kg/day, p<0.05; 1000 mg/kg/day, p<0.01). In addition, in a drug interaction test between tamoxifen, an anti-estrogen drug, and CPAE, no significant difference was found between the pharmacokinetic (PK) profiles after the administration of tamoxifen only and the combination of tamoxifen and CPAE. We also found that CPAE did not affect CYP2d4 and CYP3a2, which affect tamoxifen metabolism, in a subsequent experiment on liver tissues extracted during the drug interaction test. In this study, we found that CPAE inhibited temperature increase on the tail skin of OVX rats, and therefore is effective in the improvement of hot flashes. CPAE may be potentially used for the improvement of hot flashes induced by the administration of tamoxifen.