Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation

• Published in: Biomolecules & therapeutics Vol. 32; no. 3; pp. 361 - 367
• Main Authors: Yoon, Hyuk-Jun, Moon, Heui Woong, Min, Young Sil, Jin, Fanxue, Bang, Joon Seok, Sohn, Uy Dong, Je, Hyun Dong
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.05.2024; 한국응용약물학회
• Subjects: Original; 약학; PKC; CPI-17; Fluoride; Kaempferol; Phorbol ester; MYPT1
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2023.186

In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.