ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1651847
Luteolin improves the systolic and diastolic functions of the thoracic aortic vessels in type 2 diabetic rats through the Kv7.1 channel
Provisionally accepted
- 1Fenyang College, Shanxi Medical University, Fenyang, China
- 2Chengdu University of Traditional Chinese Medicine, Chengdu, China
- 3Shanxi University of Chinese Medicine, Jinzhong, China
- 4Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China
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Objective: This study aimed to evaluate the therapeutic effects of luteolin (Lut) on vascular dysfunction in type 2 diabetic rats and explore its underlying mechanisms, particularly its regulation of the myogenic response in thoracic aortic vessels via the Kv7.1 (KCNQ1) channel. Methods: Type 2 diabetes mellitus (T2DM) was induced in rats via high-fat/high-glucose diet combined with intraperitoneal streptozotocin (30 mg/kg). Animals were assigned to four groups: normal control (NC), NC+Lut (80 mg/kg), diabetic (DM), and DM+Lut. Fasting blood glucose, body weight, lipid profile, and blood pressure were monitored. Myogenic response of the thoracic aorta was assessed using vascular ring tension assays. Expression of KCNQ1 was evaluated via qRT-PCR. In vitro, A7r5 cells were cultured under normal (5.5 mM) or high glucose (30 mM) conditions, with or without the addition of chromanol 293B (Kv7.1 inhibitor) or PDBu (PKC agonist), the effects of Lut on the expression of KCNQ1 and Kv7.1 were observed by qRT-PCR and cellular immunofluorescence assay. Results: Luteolin significantly reduced fasting blood glucose, lowered blood pressure, and improved lipid parameters in diabetic rats. It attenuated the enhanced vasoconstriction and impaired vasodilation observed in DM rats. KCNQ1 expression was downregulated in DM rats but restored by Lut treatment. In A7r5 cells, Lut increased KCNQ1 and Kv7.1 expression, which was inhibited by high glucose or PKC activation. Conclusions: Luteolin improves vascular tone and function in diabetic rats by restoring Kv7.1/KCNQ1 expression, possibly through inhibition of PKC signaling. These findings highlight Kv7.1 as a potential therapeutic target for diabetic vascular complications.
Keywords: Luteolin, Type 2 Diabetic Rats, Thoracic aorta, vasomotion, Kv7.1
Received: 22 Jun 2025; Accepted: 03 Sep 2025.
Copyright: © 2025 Li, Yang, Wang, Guo, Wu, Wang, Lyu, Xu and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weiping Li, Fenyang College, Shanxi Medical University, Fenyang, China
Xiaojia Xu, Shanxi University of Chinese Medicine, Jinzhong, China
Haijie Ji, Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China
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