TY - JOUR
T1 - Mangiferin protect myocardial insults through modulation of MAPK/TGF-β pathways
AU - Suchal, Kapil
AU - Malik, Salma
AU - Gamad, Nanda
AU - Malhotra, Rajiv Kumar
AU - Goyal, Sameer N.
AU - Ojha, Shreesh
AU - Kumari, Santosh
AU - Bhatia, Jagriti
AU - Arya, Dharamvir Singh
N1 - Funding Information:
The authors are grateful to Mr. Deepak Sharma and Mr. B.M. Sharma for their technical assistance. The research work in part was supported by the research Grants from the United Arab Emirates University, United Arab Emirates (NP-13/36) , Al Ain, UAE.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/4/5
Y1 - 2016/4/5
N2 - Mangiferin, a xanthone glycoside isolated from leaves of Mangifera indica (Anacardiaceae) is known to modulate many biological targets in inflammation and oxidative stress. The present study was designed to investigate whether mangiferin exerts protection against myocardial ischemia-reperfusion (IR) injury and possible role of Mitogen Activated Protein Kinase (MAPKs) and Transforming Growth Factor-β (TGF-β) pathways in its cardioprotection. Male albino Wistar rats were treated with mangiferin (40 mg/kg, i.p.) for 15 days. At the end of the treatment protocol, rats were subjected to IR injury consisting of 45 min ischemia followed by 1 h reperfusion. IR-control rats caused significant cardiac dysfunction, increased serum cardiac injury markers, lipid peroxidation and a significant decrease in tissue antioxidants as compared to sham group. Histopathological examination of IR rats revealed myocardial necrosis, edema and infiltration of inflammatory cells. However, pretreatment with mangiferin significantly restored myocardial oxidant-antioxidant status, maintained membrane integrity, and attenuated the levels of proinflammatory cytokines, pro-apoptotic proteins and TGF-β. Furthermore, mangiferin significantly reduced the phosphorylation of p38, and JNK and enhanced phosphorylation of ERK1/2. These results suggest that mangiferin protects against myocardial IR injury by modulating MAPK mediated inflammation and apoptosis.
AB - Mangiferin, a xanthone glycoside isolated from leaves of Mangifera indica (Anacardiaceae) is known to modulate many biological targets in inflammation and oxidative stress. The present study was designed to investigate whether mangiferin exerts protection against myocardial ischemia-reperfusion (IR) injury and possible role of Mitogen Activated Protein Kinase (MAPKs) and Transforming Growth Factor-β (TGF-β) pathways in its cardioprotection. Male albino Wistar rats were treated with mangiferin (40 mg/kg, i.p.) for 15 days. At the end of the treatment protocol, rats were subjected to IR injury consisting of 45 min ischemia followed by 1 h reperfusion. IR-control rats caused significant cardiac dysfunction, increased serum cardiac injury markers, lipid peroxidation and a significant decrease in tissue antioxidants as compared to sham group. Histopathological examination of IR rats revealed myocardial necrosis, edema and infiltration of inflammatory cells. However, pretreatment with mangiferin significantly restored myocardial oxidant-antioxidant status, maintained membrane integrity, and attenuated the levels of proinflammatory cytokines, pro-apoptotic proteins and TGF-β. Furthermore, mangiferin significantly reduced the phosphorylation of p38, and JNK and enhanced phosphorylation of ERK1/2. These results suggest that mangiferin protects against myocardial IR injury by modulating MAPK mediated inflammation and apoptosis.
KW - Apoptosis
KW - Inflammation
KW - Ischemia-reperfusion injury
KW - MAPK
KW - Mangiferin
KW - Oxidative stress
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U2 - 10.1016/j.ejphar.2016.02.055
DO - 10.1016/j.ejphar.2016.02.055
M3 - Article
C2 - 26921754
AN - SCOPUS:85017165287
SN - 0014-2999
VL - 776
SP - 34
EP - 43
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -