Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).
OBJECTIVE
The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays.


METHODS
The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis.


RESULTS
The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril.


CONCLUSIONS
Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting antihypertensive agent.
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Silas Nascimento
SN
Ronchi
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Girlandia Alexandre
GA
Brasil
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Andrews Marques
AM
do Nascimento
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Ewelyne Miranda
EM
de Lima
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Rodrigo
R
Scherer
Petroleomic and Forensic Laboratory, Department of Chemistry, Federal University of Espírito Santo, Vitória, ES, Brazil.
Helber B
HB
Costa
Petroleomic and Forensic Laboratory, Department of Chemistry, Federal University of Espírito Santo, Vitória, ES Brazil Federal Institute of Education, Science and Technology of the Espírito Santo - IFES, Vila Velha, ES, Brazil.
Wanderson
W
Romão
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Giovanna Assis Pereira
GA
Boëchat
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Dominik
D
Lenz
Department of Pharmacy, University Vila Velha, Vila Velha, ES, Brazil.
Marcio
M
Fronza
Department of Physiological Sciences, Federal University of Espírito Santo - UFES, Vitoria, ES, Brazil.
Nazaré Souza
NS
Bissoli
Department of Pharmacy, University Vila Velha - UVV, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, ES, 29102-920, Brazil tadeu.andrade@uvv.br denise.endringer@uvv.br.
Denise Coutinho
DC
Endringer
Department of Pharmacy, University Vila Velha - UVV, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, ES, 29102-920, Brazil tadeu.andrade@uvv.br denise.endringer@uvv.br.
Tadeu Uggere
TU
de Andrade
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017704:Baroreflex / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D002853:Chromatography, Liquid / Q000379:methods; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D031022:Mangifera / Q000737:chemistry*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D053719:Tandem Mass Spectrometry / Q000379:methods
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000975:Antioxidants; D010936:Plant Extracts; D009599:Nitroprusside; D010656:Phenylephrine; D004656:Enalapril
Mangifera indica L.; angiotensin-converting enzyme; antihypertensive activity; baroreflex