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Published on: April 21, 2023
Hesperetin Inhibits Sphingosylphosphorylcholine-Induced Vascular Smooth Muscle Contraction by Regulating the
Qian Lu1, Hiroko Kishi1, Ying Zhang1
1Department of Molecular and Cellular Physiology, Yamaguchi University Graduate School of Medicine, Ube, Japan ; and.
Hesperetin effectively inhibits sphingosylphosphorylcholine (SPC)-induced vasospasm by blocking the Fyn/Rho-kinase pathway. This suggests hesperetin as a potential therapeutic agent for preventing and treating vasospasm.
Area of Science:
- Cardiovascular research
- Pharmacology
- Molecular biology
Background:
- Cardiovascular diseases are a major global health concern.
- Sphingosylphosphorylcholine (SPC) is identified as a key mediator of vasospasm.
- The SPC/Src family tyrosine kinase Fyn/Rho-kinase (ROK) pathway is a novel signaling pathway for vascular smooth muscle contraction.
Purpose of the Study:
- To investigate hesperetin's inhibitory effect on SPC-induced vascular contraction.
- To determine if hesperetin affects K+-induced contraction.
- To elucidate the underlying molecular mechanisms of hesperetin's action.
Main Methods:
- Utilized porcine coronary artery smooth muscle strips and human coronary artery smooth muscle cells (HCASMCs).
- Assessed muscle contraction in response to SPC and high potassium (K+).
- Examined the translocation and phosphorylation of Fyn and ROK, and myosin light chain (MLC) phosphorylation.
Main Results:
- Hesperetin significantly inhibited SPC-induced contraction but not K+-induced contraction.
- Hesperetin blocked SPC-induced translocation of Fyn and ROK in HCASMCs.
- Hesperetin suppressed SPC-induced alterations in Fyn, myosin phosphatase target subunit 1, and MLC phosphorylation.
Conclusions:
- Hesperetin inhibits SPC-induced vasospasm by suppressing the Fyn/ROK pathway.
- Hesperetin demonstrates potential as a novel therapeutic for vasospasm prevention and treatment.
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