[en] ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. AIM OF THE STUDY: 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. MATERIAL AND METHODS: 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. RESULTS: 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 (10-2-2mg/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 BaCl2 did not alter this effect. The oral administration of AcAE (0-6g/Kg) reveals no mortality or toxicity. CONCLUSIONS: 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Dib, Ikram
Tits, Monique ; Université de Liège > Département de pharmacie > Département de pharmacie
Angenot, Luc ; Université de Liège > Département de pharmacie > Département de pharmacie
Wauters, Jean Noel
Assaidi, Asmae
Mekhfi, Hassane
Aziz, Mohammed
Bnouham, Mohammed
Legssyer, Abdelkhaleq
Frederich, Michel ; Université de Liège > Département de pharmacie > Pharmacognosie
Ziyyat, Abderrahim
Language :
English
Title :
Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco.
Adeloye, D., Basquill, C., Estimating the prevalence and awareness rates of hypertension in Africa: a systematic analysis. PLoS One 9 (2014), e104300–e104316.
Akkari, H., Rtibi, K., B'chir, F., Rekik, M., Darghouth, M.A., Gharbi, M., In vitro evidence that the pastoral Artemisia campestris species exerts an anthelmintic effect on Haemonchus contortus from sheep. Vet. Res. Commun. 38 (2014), 249–255.
Ben-Nasr, H., Salama, M., Ksouda, K., Zeghal, K.M., Hammami, S., Hemodynamic effects of aqueous extract of Artemisia campestris in adult men. J. Appl. Pharm. Sci. 4 (2014), 38–42.
Ben Nasr, H., Hammami, T.S., Mahmoudi, L., Zeghal, K., Aqueous leaves extract of Artemisia campestris inhibition of the scorpion venom induced hypertension. J. Med. Plant Res. 8 (2014), 538–542.
Benchelah, A.-C., Bouziane, H., Maka, M., Fleurs du Sahara, arbres et arbustes, voyage au coeur de leurs usages avec les Touaregs du Tassili. Phytothérapie 2 (2004), 191–197.
Benítez, G., González-Tejero, M., Molero-Mesa, J., Pharmaceutical ethnobotany in the western part of Granada province (southern Spain): ethnopharmacological synthesis. J. Ethnopharmacol. 129 (2010), 87–105.
Berrada El Azizi, G., Ahid, S., Ghanname, I., Belaiche, A., Hassar, M., Cherrah, Y., Trends in antihypertensives use among Moroccan patients. Pharmacoepidemiol. Drug Saf. 21 (2012), 1067–1073.
Bnouham, M., Mekhfi, H., Legssyer, A., Ziyyat, A., Ethnopharmacology forum medicinal plants used in the treatment of diabetes in Morocco. Int. J. Diabetes Metab. 10 (2002), 33–50.
Boudjelal, A., Henchiri, C., Sari, M., Sarri, D., Hendel, N., Benkhaled, A., Ruberto, G., Herbalists and wild medicinal plants in M'Sila (North Algeria): an ethnopharmacology survey. J. Ethnopharmacol. 148 (2013), 395–402.
Buqui, G.A., Sy, S.K., Merino-Sanjuán, M., Gouvea, D.R., Nixdorf, S.L., Kimura, E., Derendorf, H., Lopes, N.P., Diniz, A., Characterization of intestinal absorption of C-glycoside flavonoid vicenin-2 from Lychnophora ericoides leafs in rats by nonlinear mixed effects modeling. Rev. Bras. De. Farmacogn. 25 (2015), 212–218.
De Pascual Teresa, J., Gonzalez, M., Muriel, M., Arcocha, A., Bellido, I., Flavonoids from Artemisia campestris ssp. glutinosa. J. Nat. Prod., 49, 1986 (177-177).
Dib, I., Angenot, L., Mihamou, A., Ziyyat, A., Tits, M., Artemisia campestris L.: ethnomedicinal, phytochemical and pharmacological review. J. Herbal. Med., 2016, 10.1016/j.hermed.2016.10.005.
Dib, I., Mihamou, A., Berrabah, M., Mekhf, i.H., Aziz, M., Legssyer, A., Bnouham, M., Ziyyat, A., Identification of Artemisia campestris L. subsp. glutinosa (Besser) Batt. from Oriental Morocco based on its morphological traits and essential oil profile. J. Mater. Environ. Sci. 8 (2017), 180–187.
Dib, I., Fauconnier, M.-L., Sindic, M., Belmekki, F., Assaidi, A., Berrabah, M., Mekhfi, H., Aziz, M., Legssyer, A., Bnouham, M., Ziyyat, A., Chemical composition, vasorelaxant, antioxidant and antiplatelet effects of essential oil of Artemisia campestris L. from Oriental Morocco. BMC Complement. Altern. Med., 17, 2017, 10.1186/s12906-017-1598-2.
Djeridane, A., Yousfi, M., Nadjemi, B., Vidal, N., Lesgards, J., Stocker, P., Screening of some Algerian medicinal plants for the phenolic compounds and their antioxidant activity. Eur. Food Res. Technol. 224 (2007), 801–809.
Djidel, S., Khennouf, S., Baghiani, A., Harzallah, D., Arrar, L., Medicinal plants used traditionally in the Algerian folk medicine for gastrointestinal disorders and hypertension: total polyphenols, flavonoids and antioxidant activity. Acta Hortic. 854 (2009), 59–65.
Eddouks, M., Maghrani, M., Lemhadri, A., Ouahidi, M.-L., Jouad, H., Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). J. Ethnopharmacol. 82 (2002), 97–103.
El Hassani, M., Douiri, E., Bammi, J., Zidane, L., Badoc, A., Douira, A., Plantes médicinales de la Moyenne Moulouya (Nord-Est du Maroc). Ethnopharmacologia 50 (2013), 39–53.
Fakchich, J., Elachouri, M., Ethnobotanical survey of medicinal plants used by people in Oriental Morocco to manage various ailments. J. Ethnopharmacol. 154 (2014), 76–87.
Félétou, M., Huang, Y., Vanhoutte, P.M., Endothelium‐mediated control of vascular tone: cox‐1 and COX‐2 products. Br. J. Pharmacol. 164 (2011), 894–912.
Ferchichi, L., Merza, J., Landreau, A., Le Ray, A.M., Legseir, B., Seraphin, D., Richomme, P., Occurrence of isocoumarinic and phenolic derivatives in Artemisia campestris L. subsp. campestris. Biochem. Syst. Ecol. 34 (2006), 829–832.
Furchgott, R.F., Role of endothelium in responses of vascular smooth muscle. Circ. Res. 53 (1983), 557–573.
Furchgott, R.F., Zawadzki, J.V., The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288 (1980), 373–376.
Guarino, C., De Simone, L., Santoro, S., Ethnobotanical study of the Sannio area, Campania, Southern Italy. Ethnobot. Res. Appl. 6 (2008), 255–317.
Hammiche, V., Maiza, K., Traditional medicine in Central Sahara: pharmacopoeia of Tassili N'ajjer. J. Ethnopharmacol. 105 (2006), 358–367.
Harvey, R.D., Muscarinic receptor agonists and antagonists: effects on cardiovascular function. Fryerl, A.D., Christopoulos, A., Nathanson, N.M., (eds.) Muscarinic Receptors, 2012, Springer, New York, 299–316.
Hofmann, F., Ammendola, A., Schlossmann, J., Rising behind NO: cGMP-dependent protein kinases. J. Cell Sci. 113 (2000), 1671–1676.
Hurabielle, M., Eberle, J., Paris, M., Etude des flavonoïdes d'Artemisia campestris sous-espèce glutinosa [Flavonoids of Artemisia campestris, ssp. glutinosa]. Planta Med. 46 (1982), 124–125.
Jouad, H., Haloui, M., Rhiouani, H., El Hilaly, J., Eddouks, M., Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez–Boulemane). J. Ethnopharmacol. 77 (2001), 175–182.
Karabegović, I., Nikolova, M., Veličković, D., Stojičević, S., Veljković, V., Lazić, M., Comparison of antioxidant and antimicrobial activities of methanolic extracts of the Artemisia sp. recovered by different extraction techniques. Chin. J. Chem. Eng. 19 (2011), 504–511.
Ko, E.A., Han, J., Jung, I.D., Park, W.S., Physiological roles of K+ channels in vascular smooth muscle cells. J. Smooth Muscle Res. 44 (2008), 65–81.
Laporte, R., Hui, A., Laher, I., Pharmacological modulation of sarcoplasmic reticulum function in smooth muscle. Pharmacol. Rev. 56 (2004), 439–513.
Ledoux, J., Werner, M.E., Brayden, J.E., Nelson, M.T., Calcium-activated potassium channels and the regulation of vascular tone. Physiology 21 (2006), 69–78.
Leporatti, M.L., Ghedira, K., Comparative analysis of medicinal plants used in traditional medicine in Italy and Tunisia. J. Ethnobiol. Ethnomed. 5 (2009), 1–8.
Megdiche-Ksouri, W., Trabelsi, N., Mkadmini, K., Bourgou, S., Noumi, A., Snoussi, M., Barbria, R., Tebourbi, O., Ksouri, R., Artemisia campestris phenolic compounds have antioxidant and antimicrobial activity. Ind. Crops Prod. 63 (2015), 104–113.
Parkington, H.C., Coleman, H.A., Tare, M., Prostacyclin and endothelium-dependent hyperpolarization. Pharmacol. Res. 49 (2004), 509–514.
Paulis, L., Zicha, J., Kunes, J., Hojna, S., Behuliak, M., Celec, P., Kojsova, S., Pechanova, O., Simko, F., Regression of L-NAME-induced hypertension: the role of nitric oxide and endothelium-derived constricting factor. Hypertens. Res., 31, 2008, 793.
Popović, Z., Smiljanić, M., Matić, R., Kostić, M., Nikić, P., Bojović, S., Phytotherapeutical plants from the Deliblato sands (Serbia): traditional pharmacopoeia and implications for conservation. Indian J. Tradit. Knowl. 11 (2012), 385–400.
Reagan-Shaw, S., Nihal, M., Ahmad, N., Dose translation from animal to human studies revisited. FASEB J. 22 (2008), 659–661.
Riedel, H., Cai, Z., Smetanska, I., Obtaining phenolic acids from cell cultures of various Artemisia species. Afr. J. Biotechnol. 9 (2010), 8805–8809.
Sandoo, A., van Zanten, J.J.V., Metsios, G.S., Carroll, D., Kitas, G.D., The endothelium and its role in regulating vascular tone. Open Cardiovasc. Med. J. 4 (2010), 302–312.
Sawabe, A., Matsubara, Y., Bioactive glycosides in citrus fruit peels. Chong-Ren, Y., Osamu, T., (eds.) Studies in Plant Science, 1999, Elsevier, 261–274.
Sawabe, A., Matsubara, Y., Iizuka, Y., Okamoto, K., Structures and hypotensive effect of flavonoid glycosides in young Citrus unshiu peelings. J. Jpn. Oil Chem. Soc. 38 (1989), 53–59.
Scifinder, 2016. American Chemical Society 〈www.cas.org/products/scifinder〉.
Sebai, H., Jabri, M.-A., Souli, A., Hosni, K., Selmi, S., Tounsi, H., Tebourbi, O., Boubaker, S., El-Benna, J., Sakly, M., Protective effect of Artemisia campestris extract against aspirin-induced gastric lesions and oxidative stress in rat. RSC Adv. 4 (2014), 49831–49841.
Sefi, M., Fetoui, H., Makni, M., Zeghal, N., Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats. Food Chem. Toxicol. 48 (2010), 1986–1993.
Sobey, C.G., Potassium channel function in vascular disease. Arterioscler., Thromb., Vasc. Biol. 21 (2001), 28–38.
Suzuki, A., Yamamoto, N., Jokura, H., Yamamoto, M., Fujii, A., Tokimitsu, I., Saito, I., Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J. Hypertens. 24 (2006), 1065–1073.
Tahraoui, A., El-Hilaly, J., Israili, Z., Lyoussi, B., Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province). J. Ethnopharmacol. 110 (2007), 105–117.
Tazi, M.A., Abir-Khalil, S., Chaouki, N., Cherqaoui, S., Lahmouz, F., Sraïri, J.E., Mahjour, J., Prevalence of the main cardiovascular risk factors in Morocco: results of a National Survey, 2000. J. Hypertens. 21 (2003), 897–903.
Valant-Vetschera, K.M., Fischer, R., Wollenweber, E., Exudate flavonoids in species of Artemisia (Asteraceae—Anthemideae): new results and chemosystematic interpretation. Biochem. Syst. Ecol. 31 (2003), 487–498.
Vasconcelos, J.M.J., Silva, A.M.S., Cavaleiro, J.A.S., Chromones and flavanones from Artemisia campestris subsp. maritima. Phytochemistry 49 (1998), 1421–1424.
Walford, G., Loscalzo, J., Nitric oxide in vascular biology. J. Thromb. Haemost. 1 (2003), 2112–2118.
Zhao, Y., Wang, J., Ballevre, O., Luo, H., Zhang, W., Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens. Res. 35 (2012), 370–374.
Ziyyat, A., Legssyer, A., Mekhfi, H., Dassouli, A., Serhrouchni, M., Benjelloun, W., Phytotherapy of hypertension and diabetes in oriental Morocco. J. Ethnopharmacol. 58 (1997), 45–54.
Ziyyat, A., Ramdani, N., Bouanani, N.E.H., Vanderpas, J., Hassani, B., Boutayeb, A., Aziz, M., Mekhfi, H., Bnouham, M., Legssyer, A., Epidemiology of hypertension and its relationship with type 2 diabetes and obesity in eastern Morocco. SpringerPlus 3 (2014), 644–650.
