Ye Byeong Hyeok, Kim Eun Jung, Baek Seung Eun, Choi Young Whan, Park So Youn, Kim Chi Dae
Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Yangsan 50612, Korea.
Korean J Physiol Pharmacol. 2018 Jul;22(4):437-445. doi: 10.4196/kjpp.2018.22.4.437. Epub 2018 Jun 25.
α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms, but the mechanism responsible for this activity has not been determined. To determine the role played by ICB on the regulation of vascular tone, we investigated the inhibitory effects of ICB on vascular contractile responses by adrenergic α-receptor agonists. In addition, we investigated the role on myosin light chain (MLC) phosphorylation and cytosolic calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl (60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused marked relaxation of aortic rings with or without endothelium, suggesting a direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC phosphorylation and increased cytosolic calcium levels. Both of these effects were significantly suppressed by ICB. In conclusion, our results showed that ICB regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic potential for cardiovascular disorders related to vascular hypertension.
α-异古巴烯（ICB）是一种存在于著名药用植物石南科植物（SC）中的二苯并环辛二烯木质素，该植物可改善心血管症状，但其作用机制尚未明确。为了确定ICB在血管张力调节中所起的作用，我们研究了ICB对肾上腺素能α受体激动剂引起的血管收缩反应的抑制作用。此外，我们还研究了其对血管平滑肌细胞（VSMC）中肌球蛋白轻链（MLC）磷酸化和胞浆钙浓度的影响。在从C57BL/6J小鼠分离的主动脉环中，ICB显著减弱了去氧肾上腺素（PE）和去甲肾上腺素（NE）诱导的收缩，而ICB对氯化钾（60 mM）诱导的收缩无影响。在用PE预收缩的血管中，ICB使有或无内皮的主动脉环明显舒张，表明其对VSMC有直接作用。在培养的大鼠VSMC中，PE或NE增加了MLC磷酸化并提高了胞浆钙水平。这两种作用均被ICB显著抑制。总之，我们的结果表明，ICB通过抑制MLC磷酸化和钙流入VSMC来调节血管张力，并表明ICB具有抗高血压特性以及对与血管高血压相关的心血管疾病的治疗潜力。
