Medicinal plant rosemary relaxes blood vessels by activating vascular smooth muscle KCNQ channels
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The evergreen plant rosemary (Salvia rosmarinus) has been employed medicinally for centuries as a memory aid, analgesic, spasmolytic, vasorelaxant and antihypertensive, with recent preclinical and clinical evidence rationalizing some applications. Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. KCNQ4 and KCNQ5 regulate vascular smooth muscle excitability and contractility and are implicated as antihypertensive drug targets. Here, we found that rosemary extract potentiates homomeric and heteromeric KCNQ4 and KCNQ5 activity, resulting in membrane hyperpolarization. Two rosemary diterpenes, carnosol and carnosic acid, underlie the effects and, like rosemary, are efficacious KCNQ-dependent vasorelaxants, quantified by myography in rat mesenteric arteries. Sex- and estrous cycle stage-dependence of the vasorelaxation matches sex- and estrous cycle stage-dependent KCNQ expression. The results uncover a molecular mechanism underlying rosemary vasorelaxant effects and identify new chemical spaces for KCNQ-dependent vasorelaxants.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e23125 |
| Tidsskrift | FASEB Journal |
| Vol/bind | 37 |
| Udgave nummer | 9 |
| Sider (fra-til) | 1-15 |
| ISSN | 0892-6638 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This study was supported by the National Institutes of Health, National Institute of General Medical Sciences (GM130377) to GWA and a Susan Samueli Integrative Health Institute, Samueli Scholarship to GWA; Lundbeck Foundation (R323-2018-3674) to TAJ. We are grateful to Dr. Ryan Yoshimura for technical assistance and advice, Dr. Derk Hogenkamp for carnosol synthesis, and to George Abbott and Victoria Abbott for collecting Salvia rosmarinus samples.
Funding Information:
This study was supported by the National Institutes of Health, National Institute of General Medical Sciences (GM130377) to GWA and a Susan Samueli Integrative Health Institute, Samueli Scholarship to GWA; Lundbeck Foundation (R323‐2018‐3674) to TAJ. We are grateful to Dr. Ryan Yoshimura for technical assistance and advice, Dr. Derk Hogenkamp for carnosol synthesis, and to George Abbott and Victoria Abbott for collecting samples. Salvia rosmarinus
Publisher Copyright:
© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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