Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis.

Published on Jun 27, 2014in Life Sciences
· DOI :10.1016/J.LFS.2014.04.035
Bidya Dhar Sahu16
Estimated H-index: 16
(Indian Institute of Chemical Technology),
Harika Anubolu1
Estimated H-index: 1
(Indian Institute of Chemical Technology)
+ 4 AuthorsRamakrishna Sistla32
Estimated H-index: 32
(Indian Institute of Chemical Technology)
Sources
Abstract
Abstract Aims Preventive and/or therapeutic interventions using natural products for ischemic heart disease have gained considerable attention worldwide. This study investigated the cardioprotective effect and possible mechanism of embelin, a major constituent of Embelia ribes Burm, using isoproterenol (ISO)-induced myocardial infarction model in rats. Materials and methods Rats were pretreated for three days with embelin (50 mg/kg, p.o) before inducing myocardial injury by administration of ISO (85 mg/kg) subcutaneously at an interval of 24 h for 2 consecutive days. Serum was analyzed for cardiac specific injury biomarkers, lipids and lipoprotein content. Heart tissues were isolated and were used for histopathology, antioxidant and mitochondrial respiratory enzyme activity assays and western blot analysis. Key findings Results showed that pretreatment with embelin significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB, LDH and AST), serum levels of lipids and lipoproteins and histopathological changes when compared to ISO-induced controls. Exploration of the underlying mechanisms of embelin action revealed that embelin pretreatment restored the myocardial mitochondrial respiratory enzyme activities (NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity), strengthened antioxidant status and attenuated ISO-induced myocardial lipid peroxidation. Immunoblot analysis revealed that embelin interrupted mitochondria dependent apoptotic damage by increasing the myocardial expression of Bcl-2 and downregulating the expression of Bax, cytochrome c, cleaved-caspase-3 & 9 and PARP. Histopathology findings further strengthened the cardioprotective findings of embelin. Significance Result suggested that embelin may have a potential benefit in preventing ischemic heart disease like myocardial infarction.
📖 Papers frequently viewed together
20.8k Citations
20k Citations
1,574 Citations
References35
Newest
#1Bidya Dhar Sahu (Indian Institute of Chemical Technology)H-Index: 16
#2Srujana TatireddyH-Index: 1
Last. Ramakrishna Sistla (Indian Institute of Chemical Technology)H-Index: 32
view all 9 authors...
Abstract Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced neph...
83 CitationsSource
#1Stefano Vendrame (UMaine: University of Maine)H-Index: 11
#2Allison Daugherty (UMaine: University of Maine)H-Index: 2
Last. Dorothy Klimis-Zacas (UMaine: University of Maine)H-Index: 24
view all 4 authors...
The present study investigated the potential of a wild blueberry (WB)-enriched diet to improve blood lipid profile and modulate the expression of genes related to lipid homeostasis in obese Zucker rats (OZR), a model of the metabolic syndrome with severe dyslipidaemia. For this purpose, twenty OZR and twenty lean Zucker rats (LZR; controls) were placed either on a control (C) or an 8 % WB diet for 8 weeks. Plasma total cholesterol (TC), HDL-cholesterol and TAG concentrations were determined. The...
51 CitationsSource
#1Danxia Yu (Vandy: Vanderbilt University)H-Index: 22
#2Xianglan Zhang (Vandy: Vanderbilt University)H-Index: 33
Last. Xiao-Ou Shu (Vandy: Vanderbilt University)H-Index: 136
view all 9 authors...
Protective associations of fruit and vegetables against coronary heart disease (CHD) have been suggested in many epidemiological studies among Western populations. However, prospective data are lacking for Asian populations. We examined the associations of fruit and vegetable intake with incidence of CHD among 67,211 women (40–70 years) and 55,474 men (40–74 years) living in Shanghai, China. Food intake was assessed using validated food-frequency questionnaires through in-person interviews. Coro...
36 CitationsSource
Abstract Cardiovascular disease may be induced or worsened by mitochondrion-toxic agents. Mitochondrion-toxic agents may be classified as those with or without a clinical effect, those which induce cardiac disease only in humans or animals or both, as prescribed drugs, illicit drugs, exotoxins, or nutritiants, as those which affect the heart exclusively or also other organs, as those which are effective only in patients with a mitochondrial disorder or cardiac disease or also in healthy subjects...
49 CitationsSource
#1Felicia Carotenuto (Link Campus University)H-Index: 14
#2Marilena MinieriH-Index: 18
Last. Paolo Di Nardo (Link Campus University)H-Index: 22
view all 9 authors...
n-3 polyunsaturated fatty acids (PUFAs) induce beneficial effects on the heart, but the mechanisms through which these effects are operated are not completely clarified yet. Among others, cardiac diseases are often associated with increased levels of cytokines, such as tumour necrosis factor-a (TNF), that cause degeneration and death of cardiomyocytes. The present study has been carried out to investigate (i) the potential anti-apoptotic effects induced by the n-3 polyunsatur- ated a-linolenic a...
23 CitationsSource
#1Yangzhen Shao (University of Gothenburg)H-Index: 17
#2Björn Redfors (University of Gothenburg)H-Index: 28
Last. Elmir Omerovic (University of Gothenburg)H-Index: 36
view all 7 authors...
Abstract Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine...
9 CitationsSource
#1P. Stanely Mainzen Prince (Annamalai University)H-Index: 41
#2Abhro Jyoti Roy (Annamalai University)H-Index: 3
Abstract Background Cardiac apoptosis plays an important role in the pathology of myocardial infarction. The protective effects of p -coumaric acid on cardiac apoptosis were evaluated in isoproterenol induced myocardial infarcted rats. Methods Rats were pretreated with p -coumaric acid (8mg/kg body weight) daily for a period of 7days. After pretreatment, isoproterenol (100mg/kg body weight) was injected subcutaneously into rats at an interval of 24h for 2days to induce myocardial infarction. Car...
38 CitationsSource
#1Anja M. Schaible (FSU: University of Jena)H-Index: 13
#2Heidi Traber (FSU: University of Jena)H-Index: 1
Last. Oliver Werz (FSU: University of Jena)H-Index: 34
view all 10 authors...
A B S T R A C T Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) possesses anti-inflammatory and anti-carcinogenic properties in vivo, and these features have been related to interference with multiple targets including XIAPs, NFkB, STAT-3, Akt and mTOR. However, interference with these proteins requires relatively high concentrations of embelin (IC50 > 4 mM) and cannot fully explain its bioactivity observed in several functional studies. Here we reveal human 5-lipoxygenase (5-LO) and microsom...
68 CitationsSource
#1Gabriela Azofeifa (UCR: University of Costa Rica)H-Index: 8
#2Silvia QuesadaH-Index: 12
Last. Alain MichelH-Index: 16
view all 8 authors...
This study evaluates the antioxidant and anti-inflammatory activities in a polyphenol extract from blackberries. The antioxidant activity measured via oxygen radical absorbance capacity (ORAC) was higher for the blackberry extract (4339 ± 144 μM TE/g) than for quercetin and ellagic acid. The blackberry phenolic compounds protected liposomes and liver homogenates against lipid peroxidation; in both models, the antioxidant activity (IC50 = 7.0 ± 0.5 and 20.3 ± 4.2 μg/mL, respectively) was greater ...
22 CitationsSource
#1Subhro Jyoti Roy (Annamalai University)H-Index: 2
#2P. Stanely Mainzen Prince (Annamalai University)H-Index: 41
Abstract Lipids and lipoproteins play a vital role in the pathogenesis of myocardial infarction. There are no studies reported on the protective effects of sinapic acid on changes in electrocardiogram, lipids and lipoproteins in myocardial infarction. This study aims to evaluate the protective effects of sinapic acid on cardiac hypertrophy, dyslipidaemia and alterations in lipoproteins and electrocardiogram in isoproterenol-induced myocardial infarcted rats. Rats were pre- and co-treated with si...
45 CitationsSource
Cited By39
Newest
#1M.F. Nagoor Meeran (United Arab Emirates University)H-Index: 4
#2Farah Laham (United Arab Emirates University)H-Index: 3
Last. Shreesh Ojha (United Arab Emirates University)H-Index: 30
view all 9 authors...
The downregulation of cannabinoid type-2 receptors (CB2R) have been reported in numerous diseases including cardiovascular diseases (CVDs). The activation of CB2R has been recently emerged as an important therapeutic target to mitigate myocardial injury. We examined whether CB2R activation can protect against isoproterenol (ISO)-induced myocardial injury (MI) in rats. In the present study, we investigated the cardioprotective effect of β-caryophyllene (BCP), a naturally occurring dietary cannabi...
1 CitationsSource
#1M.F. Nagoor Meeran (United Arab Emirates University)H-Index: 4
#2Sheikh Azimullah (United Arab Emirates University)H-Index: 17
Last. Shreesh K. Ojha (United Arab Emirates University)H-Index: 5
view all 4 authors...
Abstract Background : Myocardial infarction (MI) is a lethal manifestation of cardiovascular diseases. Oxidative stress, inflammation, and subsequent cell death are known to play crucial roles in the pathogenesis of MI. Despite tremendous developments in interventional cardiology, there is need for novel drugs for the prevention and treatment of MI. For the development of novel drugs, usage of natural products has gained attention as a therapeutic approach for ischemic myocardial injury. Among m...
Source
#1Jing Sun (CPU: China Pharmaceutical University)H-Index: 1
#2Lei ChenH-Index: 8
Last. Wei Qu (CPU: China Pharmaceutical University)H-Index: 16
view all 11 authors...
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa kwangtungensis Chun (C. kwangtungensis) is a very famous herbal medicine with the function of promoting blood circulation and removing blood stasis which is beneficial for cardiovascular disease (CVD). Phenylethanoid glycosides (PGs) are the major class of active ingredients in C. kwangtungensis and present significant anti-oxidative and anti-inflammatory property related to apoptosis. Therefore, this study aimed to investigate the effects of total phen...
4 CitationsSource
#1Nasiruddin Nalban (Indian Institute of Chemical Technology)H-Index: 3
#2Rajendra Sangaraju (Indian Institute of Chemical Technology)H-Index: 3
Last. Ramakrishna Sistla (Indian Institute of Chemical Technology)H-Index: 32
view all 6 authors...
Arbutin is a glycoside reported for its anti-oxidant, anti-inflammatory and anti-tumor properties. However, the cardioprotective effect of Arbutin is not well established. The study aims to understand the effect of arbutin on isoproterenol (ISO)-induced cardiac hypertrophy in mice. The animals were pretreated with Arbutin for a week and ISO was administered for 10 days and then sacrificed. Cardiac injury markers such as creatinine kinase and lactate dehydrogenase concentrations were measured in ...
5 CitationsSource
#1Francesco Caruso (Vassar College)H-Index: 10
#2Miriam Rossi (Vassar College)H-Index: 32
Last. Sandra IncerpiH-Index: 23
view all 10 authors...
Embelin, a plant natural product found in Lysimachia punctata (Primulaceae), and Embelia ribes Burm (Myrsinaceae) fruit, possesses interesting biological and pharmacological properties. It is a unique chemical species as it includes both quinone and hydroquinone functional groups plus a long hydrophobic tail. By using hydrodynamic voltammetry, which generates the superoxide radical in situ, we show an unusual scavenging capability by embelin. Embelin as a scavenger of superoxide is stronger than...
6 CitationsSource
#1Lili Sun (Peking Union Medical College)H-Index: 4
#1Lili Sun (Academy of Medical Sciences, United Kingdom)H-Index: 1
Last. Zhongmei Zou (Academy of Medical Sciences, United Kingdom)H-Index: 1
view all 8 authors...
Emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease. Here, we performed 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabolomics to investigate the gut microbiome and metabolomes of cecal contents in the isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rats. As expected, considerable gut microbiota alterations were observed in the AMI rats compared with the control rats, paralleling with intestinal inflammation and apop...
15 CitationsSource
#1Xuexiang QinH-Index: 1
#2Kakani MeghanaH-Index: 1
Last. Nagaraja Sreeharsha (King Faisal University)H-Index: 11
view all 11 authors...
: In kidneys, elevated levels of inflammatory cytokines and oxidative stress were observed in nephrotoxicity triggered by cisplatin. Embelin has the anti-inflammatory property. It also got anti-tumorigenic and antioxidant properties. In this research, we analyzed the actions of embelin on nephrotoxicity triggered by cisplatin and vital actions by which it increases antioxidant actions and corrects the inflammation after embelin administration during nephrotoxicity triggered by cisplatin. Kidney ...
8 CitationsSource
#1Yeh Peng Chen (PRC: China Medical University (PRC))H-Index: 5
#2Kalaiselvi Sivalingam (PRC: China Medical University (PRC))H-Index: 4
Last. Chih Yang HuangH-Index: 56
view all 11 authors...
Abstract Background: Fisetin, a polyphenolic compound, has drawn notable attention owing to its antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, the cardiac effects of fisetin are not clear yet. Hypothesis The aim of the present study is to examine the cardioprotective effect of fisetin against Ang-II induced apoptosis in H9c2 cells and in spontaneous hypertensive rats (SHR). Methods/study design The in vitro protective effect of fisetin was evaluated after the c...
12 CitationsSource
#1Naranjan S. DhallaH-Index: 77
#2Pallab K. Ganguly (Alfaisal University)H-Index: 5
Last. Paramjit S. TappiaH-Index: 22
view all 4 authors...
Although the sympathetic nervous system plays an important role in the regulation of cardiac function, the overactivation of the sympathetic nervous system under stressful conditions including diab...
6 CitationsSource
#1Zhen Li (Tianjin University of Traditional Chinese Medicine)H-Index: 2
#2Shujing Chen (Tianjin University of Traditional Chinese Medicine)H-Index: 2
Last. Yan-xu Chang (Tianjin University of Traditional Chinese Medicine)H-Index: 19
view all 7 authors...
Embelin exhibits the broad bioactivities such as antitumor, antifertility, antidiabetic, anti-inflammatory, antioxidant, anticonvulsant, anxiolytic, antimicrobial, and hepatoprotective activity. In order to further understand the pharmacokinetic characteristics and oral bioavailability of embelin in vivo, the concentration of embelin in rat plasma was determined by a sensitive high-performance liquid chromatography with diode array detector (HPLC-DAD). The preparation of samples was accomplished...
2 CitationsSource