Yoon Hyuk-Jun, Kang Dae Hong, Jin Fanxue, Bang Joon Seok, Sohn Uy Dong, Je Hyun Dong
Department of Pharmacology, College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea.
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
Biomol Ther (Seoul). 2023 Mar 1;31(2):193-199. doi: 10.4062/biomolther.2022.087. Epub 2022 Sep 6.
In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited increase in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.
在本研究中，我们研究了木犀草素（一种存在于蔬菜、草药和水果等植物中的类黄酮）对血管收缩性的作用，并阐明其舒张作用的潜在机制。记录去内皮肌肉的等长收缩，并结合蛋白质免疫印迹分析，以评估肌球蛋白磷酸酶靶向亚基1（MYPT1）和肌球蛋白磷酸酶磷酸化依赖性抑制蛋白（CPI-17）的磷酸化情况，并研究木犀草素对RhoA/ROCK/CPI-17信号通路的影响。无论内皮一氧化氮合成情况如何，木犀草素均能显著减轻佛波酯、氟化物和血栓素类似物引起的收缩，这表明其对平滑肌有直接作用。它还能显著减轻氟化物引起的pCPI-17和pMYPT1水平升高以及佛波醇12,13-二丁酸酯引起的pERK1/2水平升高，提示其对ROCK和PKC/MEK活性有抑制作用，进而导致MYPT1、CPI-17和ERK1/2的磷酸化。综上所述，这些结果表明，木犀草素引起的舒张包括肌球蛋白磷酸酶的重新激活和钙脱敏，这似乎是通过抑制ROCK/PKC使CPI-17去磷酸化来介导的。
