黄蓮解毒湯はTNF-α誘発性大動脈弁間質細胞石灰化を抑制する

抄録

Although calcific aortic valve stenosis (CAVS) is the most common heart valve disease in aging society, there is no effective medical treatment. Although orengedokuto (OGT), a herbal medicine, was used for treating inflammatory symptoms, the effect of OGT on aortic valve calcification (AVC) is unknown. So, we aimed to discover whether OGT inhibits AVC. Calcified AV were obtained from CAVS patients. Human aortic valve interstitial cells (HAVICs) were isolated from AV by collagenase treatment and cultured in α-MEM with 10% FBS. The medium containing TNF-α (30 ng/mL) was replenished every 3-4 days. We acknowledged that TNF-α strongly accelerated HAVICs calcification. We found that OGT (10-30 μg/mL) inhibited TNF-α-induced HAVIC calcification, significantly, which maintained cell viability. The elevation of alkaline phosphatase activity and gene expression of bone morphogenetic protein 2 induced by TNF-α was significantly inhibited by OGT (10 μg/mL). OGT also inhibited the acceleration of AVC in spontaneously hypertensive rat caused by aging and hypertension confirmed in vivo. These data showed that OGT inhibited AVC both in vitro and in vivo. The molecular mechanism of OGT inhibiting AVC needs to be further clarified for establishing medical therapy of CAVS.