Extract from Mimosa pigra attenuates chronic experimental pulmonary hypertension G. Rakotomalala a,b,c , C. Agard a,b,c , P. Tonnerre b,d , A. Tesse a,b , S. Derbré e , S. Michalet f , J. Hamzaoui f , M. Rio a,b , C. Cario-Toumaniantz a,b , P. Richomme e , B. Charreau b,d , G. Loirand a,b,c , P. Pacaud a,b,c,n a INSERM, UMR_S1087-CNRS UMR_C6291, Nantes, F-44000 France b Université de Nantes, Nantes, F-44000 France c CHU de Nantes, l'institut du thorax, Nantes, F-44000 France d INSERM, UMR_S1064, Nantes, F-44000 France e PRES LUNAM, Université d'Angers, SFR QUASAV 4207, EA 921 SONAS, UFR Sciences pharmaceutiques et ingénierie de la santé, Angers, F-49100 France f Université Lyon 1, CNRS, UMR5557, INRA, USC1193, Ecologie Microbienne, Centre d'Etude des Substances Naturelles (CESN), Villeurbanne, F-69622, France article info Article history: Received 13 November 2012 Received in revised form 21 March 2013 Accepted 26 March 2013 Available online 10 April 2013 Keywords: Artery Arterial pressure Endothelium Anti-oxidant Anti-inflammatory abstract Ethnopharmacological relevance: Different parts of Mimosa pigra (MPG) are used in traditional medicine in Madagascar, tropical Africa, South America and Indonesia for various troubles including cardiovascular disorders. Aim of the study: To investigate the mechanisms underlying the vascular effects of MPG by assessing in vitro its antioxidant and anti-inflammatory properties, and its vascular relaxing effects, and in vivo, its action on hypoxic pulmonary hypertension (PAH) in rats. Material and methods: The antioxidant activity of MPG leaf hydromethanolic extract was determined by using both the 1,1-diphenyl-2-picrylhydrazyl radical scavenging and the oxygen radical absorbance capacity in vitro assays. Anti-inflammatory properties were assayed on TNFα-induced VCAM-1 expres- sion in endothelial cells. The vasorelaxant effect of MPG extract was studied on rat arterial rings pre- contracted with phenylephrine (1 μM) in the presence or absence of the endothelium. In vivo MPG extract effects were analyzed in chronic hypoxic PAH, obtained by housing male Wistar rats, orally treated or not with MPG extract (400 mg/kg/d), in a hypobaric chamber for 21 days. Results: MPG leaf extract had antioxidant and anti-inflammatory properties. It induced endothelium- dependent, NO-mediated relaxation of rat aorta and pulmonary artery. In vivo, chronic MPG treatment reduced hypoxic PAH in rat by decreasing by 22.3% the pulmonary arterial pressure and by 20.0% and 23.9% the pulmonary artery and cardiac remodelling, respectively. This effect was associated with a restoration of endothelium function and a 2.3-fold increase in endothelial NO synthase phosphorylation. MPG leaf hydromethanolic extract contained tryptophan and flavonoids, including quercetin glycosides. Both compounds also efficiently limit hypoxia-induced PAH. Conclusions: Our results show endothelial protective action of MPG leaf hydromethanolic extract which is likely to be due to its antioxidant action. MPG successfully attenuated the development of PAH, thus demonstrating the protective effect of MPG on cardiovascular diseases. & 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Pulmonary arterial hypertension (PAH) is a complex and multi- factorial disease characterized by a progressive increase of pul- monary vascular resistance and pulmonary arterial pressure (PAP), leading to right ventricle hypertrophy and death (Humbert and Hoeper, 2008; Rubin, 2006). Idiopathic, familial and connective tissue disease-associated forms of PAH share similar features (Rabinovitch, 1997). Pathologic changes of pulmonary arteries, which involve endothelial dysfunction, endothelial and smooth muscle cell proliferation, and increased vasoconstriction, decrease the lumen area of the pulmonary microvasculature, causing fixed elevation of pulmonary resistance. Although major advances in the understanding of disease development and treatment have been achieved over the last 15 years, the pathogenesis of PAH remains not clearly understood and the mechanisms responsible for this abnormal pulmonary vascular remodelling are unknown. Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jep Journal of Ethnopharmacology 0378-8741/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2013.03.075 n Corresponding auhtor at: Inserm, UMR_S1087 IRT-UN, 8 Quai Moncousu, BP 70721, F-44007 Nantes, Cedex 1, France. Fax: +33 2 28 08 01 20. E-mail address: pierre.pacaud@univ-nantes.fr (P. Pacaud). Journal of Ethnopharmacology 148 (2013) 106–116