Dib Ikram, Tits Monique, Angenot Luc, Wauters Jean Noel, Assaidi Asmae, Mekhfi Hassane, Aziz Mohammed, Bnouham Mohammed, Legssyer Abdelkhaleq, Frederich Michel, Ziyyat Abderrahim
Laboratoire de Physiologie, Génétique et Ethnopharmacologie URAC-40, Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda, Morocco.
Laboratoire de Pharmacognosie, Centre Interfacultaire de Recherche sur les Médicaments (CIRM), Université de Liège, Belgium.
J Ethnopharmacol. 2017 Jul 12;206:224-235. doi: 10.1016/j.jep.2017.05.036. Epub 2017 May 31.
Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension.
This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated.
the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice.
The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10-2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl did not alter this effect. The oral administration of AcAE (0-6g/kg) reveals no mortality or toxicity.
our study proved that AcAE possess an important antihypertensive, hypotensive and vasorelaxant effect, which is mediated via calmodulin-NO-cGC-PKG pathway, and via inhibition of calcium influx through voltage-operated calcium channels and activation of intracellular calcium mobilization into sarcoplasmic reticulum. Therefore, our findings give first evidence about the traditional use of A. campestris L. as antihypertensive plant.
野艾蒿(菊科)有许多传统用途,其中包括治疗糖尿病和高血压。
本研究旨在证实野艾蒿水提取物(AcAE)的降压和降血压作用,探讨其血管舒张作用的潜在作用机制以及急性毒性。此外,还对AcAE的化学成分进行了研究。
采用高效液相色谱(HPLC)和核磁共振(NMR)技术测定AcAE的化学成分。通过尾套法间接评估AcAE对L-NAME诱导的高血压大鼠的降压作用,通过侵入性方法静脉监测其对正常血压大鼠的降血压作用。在存在拮抗剂和阻滞剂的情况下,研究从正常血压大鼠分离的主动脉的血管舒张作用和血管作用机制。另一方面,通过给小鼠口服提取物研究急性毒性。
AcAE的整体植物化学图谱显示存在几种多酚作为主要成分。野艾蒿浸剂的特征在于单肉桂酰和二肉桂酰化合物,其中3,5-二咖啡酰奎尼酸(异绿原酸A)是主要化合物,其次是5-咖啡酰奎尼酸(绿原酸)。在黄酮类化合物中,异荭草苷(芹菜素6,8-二-C-葡萄糖苷)似乎是最丰富的化合物。以150mg/kg/天的剂量每日用AcAE治疗可预防L-NAME高血压大鼠发生高血压,并使收缩压从172mmHg降至144mmHg。在40mg/kg的剂量下,AcAE可引起收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)降低,而不影响心率。此外,AcAE(10-2mg/ml)可使预收缩的主动脉舒张95.8±1.3%。主动脉去内皮以及用阿托品、氯米帕明、L-NAME、甲钴胺、ODQ、8-RP-Br-PET-cGMP、毒胡萝卜素和维拉帕米预孵育可减弱血管舒张反应,而用4-AP、TEA、格列本脲和BaCl预处理不会改变这种作用。口服AcAE(0-6g/kg)未显示死亡率或毒性。
我们的研究证明,AcAE具有重要的降压、降血压和血管舒张作用,其通过钙调蛋白-NO-cGC-PKG途径介导,并通过抑制电压门控钙通道的钙内流和激活细胞内钙向肌浆网的动员来实现。因此,我们的研究结果首次为野艾蒿作为抗高血压植物的传统用途提供了证据。