Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Research & Development Department, Xinjiang Ailexin Pharmaceutical. Co., Ltd., the Xinjiang Uygur Autonomous Region 830011, China.
Biomed Pharmacother. 2020 Aug;128:110240. doi: 10.1016/j.biopha.2020.110240. Epub 2020 May 29.
Allicin, the principle active constituent in garlic, has been reported to have antihypertensive effects on drug-induced hypertension or renal hypertension in rats, but reports on spontaneously hypertensive rats (SHRs) are rare. Allicin is comprised of a variety of sulfur-containing compounds, and hydrogen sulfide (HS) has been shown to have specific vasomotor effects. We therefore hypothesize that allicin may exert a vasorelaxant activity by inducing HS production, and this eventually result in a reduction in blood pressure in SHRs.
The in vivo antihypertensive effect of allicin was assessed using a tail-cuff method on SHRs. The in vitro vasorelaxant effect and in-depth mechanisms of allicin were explored on rat mesenteric arterial rings (RMARs) isolated from SD rats.
In the in vivo study, administration of allicin (7 mg/kg and 14 mg/kg, 4 weeks, i.g) dramatically decreased the blood pressure in SHRs, which was also shown to be attenuated by HS synthase inhibitor (PAG, 32 mg/kg, i.g). In in vitro studies, allicin (2.50-15.77 mM) produced a concentration-dependent vasorelaxation on RMARs, which was obviously reduced by preincubation with PAG. The removal of endothelium led to a decline in allicin's vasorelaxation, which was almost completely mitigated when treatment was followed with PAG. Inhibitors of nitric oxide (NO) and prostaglandin (PGI) pathways separately suppressed the vasorelaxation induced by allicin to a certain degree. When the RMARs incubated with PAG were treated with or without the above inhibitors in separate groups, the relaxations caused by allicin were almost identical under both these conditions. Moreover, allicin treatment increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) levels (downstream products of NO and PGI pathways), which was decreased by PAG. Additionally, allicin increased the acetylcholine-induced endothelium-derived hyperpolarizing factor (EDHF) -mediated relaxation, which was unaffected by PAG.
Allicin exhibits a potent antihypertensive effect through vasodilatory properties and HS mechanisms. Moreover, the vasodilation of allicin is partially dependent on endothelium. The endothelium-dependent vasodilation of allicin is mediated by the NO-sGC-cGMP, PGI-AC-cAMP and EDHF pathways, of which HS participates in the first two but not the third one. The endothelium independent vasodilation can be predominantly attributed to HS production.
大蒜中的主要活性成分蒜素已被报道具有抗高血压作用，可降低药物诱导的高血压或大鼠肾性高血压，但关于自发性高血压大鼠（SHR）的报道很少。蒜素由多种含硫化合物组成，已有研究表明硫化氢（HS）具有特定的血管舒张作用。因此，我们假设蒜素可能通过诱导 HS 产生发挥血管舒张活性，从而降低 SHR 的血压。
采用尾套法检测蒜素对 SHR 的体内降压作用。采用分离的 SD 大鼠肠系膜动脉环（RMAR）研究蒜素的体外血管舒张作用及其深入机制。
在体内研究中，给予蒜素（7 mg/kg 和 14 mg/kg，4 周，ig）可显著降低 SHR 的血压，而 HS 合酶抑制剂（PAG，32 mg/kg，ig）可减弱这种作用。在体外研究中，蒜素（2.50-15.77 mM）对 RMAR 产生浓度依赖性血管舒张作用，预孵育 PAG 可明显减弱这种作用。去除血管内皮导致蒜素的血管舒张作用下降，而在用 PAG 处理后几乎完全消除。一氧化氮（NO）和前列环素（PGI）途径的抑制剂分别在一定程度上抑制了蒜素诱导的血管舒张作用。当用 PAG 孵育 RMAR 并在不同组中分别用或不用上述抑制剂处理时，在这两种情况下，蒜素引起的舒张作用几乎相同。此外，蒜素处理增加了环鸟苷单磷酸（cGMP）和环腺苷单磷酸（cAMP）水平（NO 和 PGI 途径的下游产物），而 PAG 降低了这些水平。此外，蒜素增加了乙酰胆碱诱导的内皮衍生超极化因子（EDHF）介导的舒张作用，而 PAG 对此无影响。
蒜素通过血管舒张作用和 HS 机制发挥强大的降压作用。此外，蒜素的血管舒张作用部分依赖于内皮。蒜素的内皮依赖性血管舒张作用通过 NO-sGC-cGMP、PGI-AC-cAMP 和 EDHF 途径介导，其中 HS 参与前两个途径，但不参与第三个途径。内皮非依赖性血管舒张主要归因于 HS 的产生。
