Nobiletin, A Citrus Flavonoid, Suppresses SPC-induced Abnormal Vascular Contraction

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  • MIYANARI Kenji
    Department of Molecular and Cellular Physiology（PhysiologyⅠ.），Yamaguchi University Graduate School of Medicine

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  • Sphingosylphosphorylcholine（SPC）によって引き起こされる血管平滑筋異常収縮に対するノビレチンの抑制作用
  • Sphingosylphosphorylcholine SPC ニ ヨッテ ヒキオコサレル ケッカン ヘイカツキン イジョウ シュウシュク ニ タイスル ノビレチン ノ ヨクセイ サヨウ

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<p> In contrast to Ca2+-dependent contraction of vascular smooth muscle（VSM），sphingosylphosphorylcholine（SPC）/ Rho-kinase（ROK）pathway, which induces Ca2+-independent VSM contraction, contributed to abnormal VSM hypercontraction such as vasospasm. After extensive screening of various food-derived components, we found that nobiletin, a citrus flavonoid, which suppressed the SPC-induced </p><p>Ca2+-sensitization of VSM contraction with little inhibitory effect on depolarization-induced Ca2+-dependent contraction by 40 mM K+. </p><p>Furthermore, in the simultaneous measurement of［Ca2+］i and force, nobiletin inhibited the SPC-induced Ca2+-sensitization of VSM contraction without change of ［Ca2+］i, but had slight effects on 40 mM K+-induced Ca2+-dependent contraction and［Ca2+］i. We previously reported that SPC induced ROK translocation from cytoplasm to cell membrane, and activation of ROK led to the increase in phosphorylation levels of myosin phosphatase target subunit1（MYPT1）and myosin light chain（MLC），suggesting that activation of ROK plays an important role in vasospasm. Nobiletin significantly inhibited the SPC-induced phosphorylation levels of MYPT1 </p><p>and MLC. These results suggest that nobiletin is </p><p>a promising candidate for novel therapeutic drug target for abnormal VSM contraction leading to vasospasm.</p>

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