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World Journal of Pharmaceutical Sciences Bidens Pilosa Attenuates World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Bidens pilosa attenuates monocrotaline-induced pulmonary arterial hypertension in rats Esther Ngo Lemba Tom1*, Frida Longo1, Celine Nguefeu Nkenfou1, Simeon Kouam Fogue2, Jean Pierre Savineau3, Theophile Dimo4 1Department of Biological Sciences, Higher Teachers’ Training College, University of Yaoundé I, P.O Box 47, Yaoundé, Cameroon 2Department of Chemistry, Higher Teachers’ Training College, University of Yaoundé I, P.O Box 47, Yaoundé, Cameroon 3Cardiothoraxic Research Center of Bordeaux (INSERM U 1045), University of Victor Segalen Bordeaux 2, 146, street Léo Saignat, 33076 Bordeaux cedex, France 4Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O Box 812, Yaoundé, Cameroon Received: 12-02-2017 / Revised: 27-05-2017 / Accepted: 28-05-2017 / Published: 28-05-2017 ABSTRACT Bidens pilosa is an Asteraceae plant commonly used as a herb and as an ingredient in teas or herbal medicines. In the present study, we investigated the effects of an ethyl acetate extract of Bidens pilosa leaves on pulmonary hypertension in rats induced by intraperitoneal injection of monocrotaline (50 mg/kg) in Wistar rats. One week later, the animals were treated orally with the extract (100 or 200 mg/kg) or sildenafil (1.7 mg/kg) used as control drug for fourteen days. Three weeks after monocrotaline injection, pulmonary arterial pressure and lung weight was significantly increased in the vehicle-treated group, whereas they were attenuated by the extract treatment at the highest dose studied (200 mg/kg). The Fulton index (ratios of right ventricle weight to left ventricle + septum weight) was increased (P<0.01) in monocrotaline-treated rats, suggesting the occurrence of right ventricular hypertrophy. Both the extract (200 mg/kg) and sildenafil significantly (P<0.01) reduced the Fulton index. Compared to the control group, monocrotaline induced thickening of lung vessel walls with luminal narrowing. The monocrotaline-induced morphologic change was attenuated by administration of the extract. These overall results suggest that the ethyl acetate extract of Bidens pilosa might have a promising therapeutic potential for pulmonary arterial hypertension. Keywords: Bidens pilosa, monocrotaline, pulmonary hypertension, cardiac hypertrophy, lung morphology INTRODUCTION [4]. Many known factors causing pulmonary hypertension are hyperendemic including human Pulmonary arterial hypertension (PAH) is a immunodeficiency virus (HIV) Acquired Immune progressive disease which causes an increase in Deficiency Syndrome (AIDS), chronic hepatitis B pulmonary vascular resistance and pulmonary and C, schistosomiasis and sickle cell disease [5]. arterial pressure and leads to right ventricular dysfunction, failure and ultimately death [1]. The The treatment of pulmonary hypertension includes right ventricle (RV) of the heart initially adapts by lifestyle modifications, conventional treatments hypertrophy to maintain cardiac output, but such as diuretics, warfarin anticoagulation, and eventually fails [2]. PAH is a chronic progressive disease-specific treatments such as calcium channel and devastating disease in which means pulmonary blockers, prostacyclins (intravenous epoprostenol, arterial pressure increases by more than 25 mmHg subcutaneous treprostinil, aerosolized iloprost and in the resting state and finally leads to right oral beraprost), endothelin (ET) receptor ventricular failure [3]. The epidemiology of antagonists (bosentan, sitaxsentan and ambrisentan) pulmonary hypertension in sub-Saharan Africa is and the known potent and highly specific not well-known, but the incidence could be higher phosphodiesterase type 5 inhibitor, sildenafil [6]. than that reported from developed countries, owing Although prostacyclin and endothelin receptor to the pattern of diseases prevalent in the region antagonists are suggested as first line of therapeutic *Corresponding Author Address: Dr. Ngo Lemba Tom Esther, Department of Biological Sciences, Higher Teachers’ Training College, University of Yaoundé I, P.O Box 47, Yaoundé, Cameroon; E-mail: [email protected] Tom et al., World J Pharm Sci 2017; 5(6): 286-293 strategy of PAH [7] there are still several potential MATERIALS AND METHODS limitations in these modalities, including side effects of drugs, complexity of administration Extract preparation: Fresh leaves of B. pilosa methods, high medical costs and the development were collected early in the morning from the fields of additional novel therapeutic approaches focusing at Messassi-Yaoundé (Center Region-Cameroon) on the components of multifactorial pulmonary in December 2012. They were identified at the vascular pathobiology is necessary [8,9]. Although National herbarium and compared to the voucher current therapies could improve the quality of life specimen deposited by Dr Longo Frida under the of PAH patients, PAH cannot be cured completely number 65112/HNC. Powdered leaves (1000 g) by the drugs used in current clinic therapy [10]. were extracted by maceration in 5 L of methylene Some reports have suggested increased oxidative chloride-methanol (1/1) at room temperature for 2 stress as a mediator in the pathogenesis and the days. The methylene chloride–methanol extract development of PH [11]. Accordingly, antioxidant were concentrated in rotavapor (HEIDOLPH therapy has been effective in the treatment of right W2000) to yield 60 g dried extract. 500 mL of ventricle (RV) dysfunction in PAH [12]. ethyl acetate was added to this extract and the Monocrotaline (MCT)-induced PH is widely fraction soluble in ethyl acetate was concentrated to recognized as an experimental model for studying yield 12.7 g of dried extract. This fraction soluble right ventricular (RV) hypertrophy [13]. in ethyl acetate was kept in refrigerator for all experiments. Monocrotaline injures the endothelial cells of the pulmonary blood vessels, causing pulmonary Animals: Male Wistar rats (200-240 g; 8 weeks hypertension and interstitial pulmonary fibrosis old) were used in this study. They were housed in [14]. This substance also induces the proliferation the Animal House of the Laboratory of Physiology of muscular intimal cells in arterioles and of the Higher Teachers’ Training College, fibroblasts in alveolar walls at the capillary level University of Yaoundé I at controlled ambient [15]. It is now believed that medicinal plants can be temperature of 23 ± 2 ° C with 12 h of light and 12 a valuable source of assistance for prescription h of darkness. The animals were given food and medicines and can be taken to aid recovery from water ad libitum. This study was performed in serious disease such as heart failure. accordance with the procedures approved by the Cameroon National Ethical Commitee (Reg. No. Bidens pilosa L. (Asteraceae) is a plant widely FWA-IRD 0001954). found in the tropical and subtropical regions of the world [16,17]. It is well known in African folk Study design: Animals were randomized into five medicinal practices, especially in the western groups of 10 rats in each. Group 1 (normal control) region of Cameroon and parts of Central America, received an intraperitoneal (i.p) injection of as a potent hypotensive agent. Previous studies physiological saline (0.5mL) and remained have shown that B. pilosa exerts a dose-dependent untreated for the whole period of the experiment (3 decrease in systolic blood pressure in hypertensive weeks). Groups 2 to 5 were injected (i.p) a single rats [18]. Its roots, leaves, and seeds are reported to dose of monocrotaline (MCT, 50 mg/kg) and one have antibacterial, anti-dysenteric, anti- week later they were given respectively inflammatory and antimicrobial, antimalarial, dimethylsulfoxide 1% (10 mL/kg), sildenafil citrate diuretic, hepatoprotective and hypotensive (1.7 mg/kg), 100 or 200 mg/kg of the extract of B. properties [17,19-22]. Although more and more pilosa, daily, continued for 2 weeks. The extract evidence suggests that B. pilosa shows a number of were suspended in dimethylsulfoxide (1%). At the beneficial cardiovascular actions in experimental end of the experiments, pulmonary arterial settings, its effect on PAH has not yet been pressure, blood pressure and heart rate were clarified. On this basis, the present study was measured. Then the animals were sacrificed under carried out to evaluate the efficacy of an anesthesia, and their hearts, lungs and liver were ethylacetate extract of B. pilosa leaves in an removed. experimental rat PAH model induced by monocrotaline. The study was undertaken to Assessment of hemodynamics: Pulmonary arterial determine the therapeutic effects of an ethyl acetate pressure (PAP) was used as the index for extract of B. pilosa (EAEBP) by measuring not pulmonary hypertension (PH). Measurement of Ppa only pulmonary arterial pressure and right and was carried out three weeks after the MCT or ventricular hypertrophy but also histopathological saline treatment. The animals were anaesthetized changes and transaminases activity in the lung and with urethane (1.5g/kg; i.p). After insertion of an liver. endotracheal cannula for artificial respiration, a saline-filled catheter was introduced into the right jugular vein and then advanced to the right atrium, 287 Tom et al., World J Pharm Sci 2017; 5(6): 286-293 right ventricle, and finally to the pulmonary artery.
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