Carnosic acid, a novel food-source AT1R antagonist and its anti-hypertension mechanism.
Int J Biol Macromol
; 278(Pt 3): 135012, 2024 Oct.
Article
de En
| MEDLINE
| ID: mdl-39181360
ABSTRACT
Hypertension is the most prevalent non-communicable disease, affecting billions of people worldwide. Discovery and development of natural antihypertensive lead compounds or drugs are important to resolve the limitations of existing antihypertensive drug safety and resistance. This investigation verified that carnosic acid (CA), an important active ingredient of rosemary, an edible spice plant, indicates a significant anti-hypertensive activity in spontaneous hypertension rats by targeting AT1R. Moreover, our research indicated that CA shared a comparable antagonistic mechanism with established synthetic angiotensin II receptor blockers (ARBs), as it occupies the binding sites of Angiotensin II (AngII) at His6 and Pro7 within the AT1R's ligand-binding pocket. Notably, CA exerted better anti-hypertensive activity since it could not break the Asn1113.35-Asn2957.46 hydrogen bond to stabilize the AT1R inactive state. As the first potent AT1R antagonist identified in a natural food source, CA is poised to become a novel anti-hypertensive lead compound, distinguished by its unique skeleton structure different from conventional ARBs. This research lays a valuable theoretical groundwork for the future exploration of CA and rosemary extract in both fundamental studies and clinical applications.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Abiétanes
/
Hypertension artérielle
/
Antihypertenseurs
Limites:
Animals
Langue:
En
Journal:
Int J Biol Macromol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Pays-Bas