Laboratory of Engineering Pedagogy and Sciences Didactics, Department of Life Sciences, Regional Center of Education and Training Careers (CRMEF), Fez, Morocco; R.N.E Laboratory, Multidisciplinary Faculty of Taza, University Sidi Mohamed Ben Abdellah, Fez, Morocco; Louvain Drug Research Institute, Pharmacognosy Research Group, Université catholique de Louvain, UCLouvain, Brussels, Belgium.
R.N.E Laboratory, Multidisciplinary Faculty of Taza, University Sidi Mohamed Ben Abdellah, Fez, Morocco.
J Ethnopharmacol. 2021 Apr 24;270:113791. doi: 10.1016/j.jep.2021.113791. Epub 2021 Jan 11.
Ajuga iva (L.) Schreb. (Labiatae) (AI) is used in folk medicine for a variety of ailments, including diabetes mellitus and hypertension.
In this work, we aimed to investigate the antihypertensive and vasorelaxant effects of AI aqueous extract in stroke prone spontaneously hypertensive rats (SHR-SP).
Male SHR-SP rats were orally force-fed AI aqueous extract (500 mg/kg body weight) daily for one week. Systolic blood pressure and urine output were recorded in vivo by non-invasive methods. AI vasoactive effects on noradrenaline contractile response and acetylcholine-evoked relaxation were assessed ex vivo on aorta rings of treated and untreated SHR-SP rats. AI extract was then subjected to bio-guided fractionation using solvents of increasing polarity. For each fraction, in vitro vasorelaxation assay was performed on noradrenaline-precontracted aorta of Wistar rats, in the absence/presence of N-nitro-L-arginine (L-NNA). HPLC analysis of AI total extract, and the most in vitro active AI residual aqueous extract fraction (A1) was performed using naringin, naringenin, apigenin, apigenin 7-O-glucoside as marker compounds.
AI aqueous extract (500 mg/kg) significantly (P < 0.05) decreased systolic blood pressure (SBP) in SHR-SP rats, while not affecting the urine output. In ex vivo experiments, the total extract decreased contractile response to noradrenaline of aortic rings isolated from AI-treated SHR-SP rats with or without addition of N-nitro-L-arginine, but endothelium dependent relaxation evoked by acetylcholine in noradrenaline-contracted aortic rings was not affected by the extract treatment. In vitro experiments on AI aqueous extract fractions showed that its polar fraction was the only one affecting in vitro noradrenaline induced contractions, but only in an endothelium dependent manner. This fraction was shown by HPLC-UV to contain flavonoid glycosides among other polar compounds whose activity and mode of action may be modified in vivo by metabolization.
These results support the use of AI as antihypertensive treatment in folk medicine. The systolic blood pressure decrease may be attributed at least in part to vasorelaxant glycosylated/polar phenolic compounds as flavonoids and/or their metabolites.
Ajuga iva（L.）Schreb.（唇形科）（AI）在民间医学中用于治疗多种疾病，包括糖尿病和高血压。
在这项工作中，我们旨在研究 AI 水提物对易发生中风的自发性高血压大鼠（SHR-SP）的降压和血管舒张作用。
雄性 SHR-SP 大鼠每天经口灌胃 AI 水提物（500mg/kg 体重），持续一周。通过非侵入性方法在体内记录收缩压和尿排量。在未经处理和处理过的 SHR-SP 大鼠的主动脉环上，通过体外评估 AI 对去甲肾上腺素收缩反应和乙酰胆碱诱导的舒张反应的血管活性作用。然后，使用极性逐渐增加的溶剂对 AI 水提物进行基于生物导向的分段。对于每个部分，在 Wistar 大鼠去甲肾上腺素预收缩的主动脉上进行体外血管舒张测定，在存在/不存在 N-硝基-L-精氨酸（L-NNA）的情况下进行。使用柚皮苷、柚皮素、芹菜素、芹菜素 7-O-葡萄糖苷作为标记化合物对 AI 总提取物和体外最活跃的 AI 剩余水提物部分（A1）进行 HPLC 分析。
AI 水提物（500mg/kg）显著（P<0.05）降低了 SHR-SP 大鼠的收缩压（SBP），而不影响尿排量。在离体实验中，总提取物降低了来自 AI 处理的 SHR-SP 大鼠的主动脉环对去甲肾上腺素的收缩反应，无论是否添加 N-硝基-L-精氨酸，但对去甲肾上腺素收缩的乙酰胆碱诱导的内皮依赖性舒张不受提取物处理的影响。对 AI 水提物部分的体外实验表明，其极性部分是唯一影响体外去甲肾上腺素诱导收缩的部分，但仅以内皮依赖性方式。HPLC-UV 显示该部分含有黄酮苷等极性化合物，其活性和作用方式可能在体内通过代谢而改变。
这些结果支持将 AI 用作民间医学中的降压治疗。收缩压下降至少部分归因于血管舒张性糖基化/极性酚类化合物，如黄酮类化合物和/或其代谢物。
