Cardioprotective and antispasmodic effects of Humulus lupulus (Hops) in an oral subacute treatment in rats

• Published in: Journal of biologically active products from nature 2024-07, Vol.14 (4), p.463-480
• Main Authors: Colareda, Germán A., Díaz, Romina G., Lojano-Gutierrez, Lucía C., Matera, Soledad I., Córdoba, Osvaldo L., Flores, María L., Consolini, Alicia E.
• Format: Article
• Language: English
• Subjects: Cannabaceae; Cardiac stunning; Humulus lupulus; Intestine,Bladder; Uterus
• ISSN: 2231-1866; 2231-1874
• DOI: 10.1080/22311866.2024.2393662

Hops (Humulus lupulus) was used to treat menopausal symptoms because it contains phytoestrogens. Since these compounds prevent cardiac ischemic diseases, it was evaluated whether oral administration of an ethanol extract (Hops-T) to rats during a week could reduce cardiac post-ischemic dysfunction. Moreover, its effects on visceral peristaltism and the mechanisms of action were studied. Rat isolated hearts were perfused inside a calorimeter, left intraventricular pressure and calorimetrical signals were recorded during ischemia/reperfusion. The NO-synthases and mKATP channels roles were evaluated by respectively blocking them with L-NAME and 5-HD before ischemia. After the experiment, western-blots for cellular pathways (p-AKT, p-PKCϵ, GSK3b and BCL-2) were done. In isolated intestinal, bladder and uterine rat tissues, contractile carbachol concentration-response curves (CCh-CRCs) were performed. The HPLC-DAD mainly showed prenylated flavonoids, beta acids and isoflavones. Hops-T increased contractile and energetic recoveries more significantly in the male rat hearts compared to females, due to beneficial NO production and mitochondrial mKATP channels activation. However, the p-AKT, p-PKCϵ, GSK3b or BCL-2 expressions were not affected after reperfusion. Hops-T inhibited CCh-CRCs in intestinal, bladder and uterine tissues through a non-competitive mechanism. Additionally, it showed a non-competitive antagonism of the Ca 2+ -CRCs in bladder tissues, similar to the effects observed with verapamil. In conclusion, oral Hops-T prevented cardiac mitochondrial and contractile ischemic dysfunction, and it was a good visceral antispasmodic medicine by interfering with Ca 2+ influx. This is a significant finding since it pre-clinically supports the use of hops extract for prevention of visceral spasms and cardiac diseases associated with coronary insufficiency.