Endothelium-dependent and adrenergic involvement in the biphasic vascular effects of a phenolic-rich ethanolic fraction from male Cannabis sativa inflorescences

Abstract

Male Cannabis sativa plants are known to contain fewer cannabinoids compared to their female counterparts, with most research focused on cannabinoids like THC and CBD. However, the phenolic compounds in male plants, especially regarding their cardiovascular effects, remain underexplored. This study aimed to evaluate the effects of a phenolic-rich ethanolic fraction from male C. sativa inflorescences (EMCS) on isolated rat thoracic aorta and to elucidate the underlying mechanisms. HPLC-DAD analysis identified eight phenolic compounds in EMCS. EMCS exhibited a biphasic concentration-dependent effect, inducing significant vasorelaxation at low concentrations (10–300 µg/mL), with maximal relaxation of approximately 60–70 %, and vasoconstriction at higher concentrations (≥300 µg/mL), reaching a maximum of 109 ± 7.8 % relative to the basal tone. The vasorelaxant effect was endothelium-dependent and was inhibited by atropine, L-NAME, ODQ, and potassium channel blockers, indicating the involvement of endothelial muscarinic receptors, nitric oxide, and potassium channels. The marked reduction of the vasoconstrictor effect following preincubation with yohimbine and prazosin suggests that α-adrenergic receptors mediate this response. Therefore, while EMCS may have components with antihypertensive potential, its overall effect on vascular health requires careful consideration of dose-dependent responses.