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

Sahu, Bidya Dhar; Anubolu, Harika; Koneru, Meghana; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Rachamalla, Shyam Sunder; Sistla, Ramakrishna

doi:10.1016/j.lfs.2014.04.035

Cited by 47 publications

(24 citation statements)

References 29 publications

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“…This may determine that Nrf2, upon embelin treatment, isolates from Keap1 protein and consequently translocates to the nucleus. Parallel to our conclusion, earlier research works also established that embelin offers a protective effect against isoproterenol‐induced acute myocardial injury by stimulating the Nrf2 pathway .…”

Section: Discussionmentioning

confidence: 99%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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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 function markers including blood urea nitrogen; serum creatinine; the markers of oxidative stress like malondialdehyde (MDA), antioxidant systems like glutathione, superoxide dismutase, glutathione S-transferase, catalase, and glutathione reductase; inflammation markers like nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β); and the extent of nuclear factor-erythroid-2 p45-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were determined. Histopathology studies of kidneys were also used to analyze nephrotoxicity induced by cisplatin. Treatment with embelin (25 and 50 mg/kg) upgrades the function of kidneys, by elevating antioxidant levels and reducing the MDA level in cisplatin-administered rats. Embelin treatment demonstrated a significant curtailment of oxidative stress as well as increased the activities of antioxidant enzymes, endogenously. Cisplatin upregulates cytokines (i.e., TNF-α and IL-1β) and NF-κB, and downregulates Nrf2 and HO-1. Embelin treatment also reduced the infiltration of neutrophils in the renal tubules and thus reduced the level of histological impairment. The outcome of this study implements that the signaling pathway of Nrf2/HO-1 may be the principal mechanism of embelin for protection from nephrotoxicity triggered by cisplatin, and thus, embelin diminishes oxidative stress and inflammation by impeding NF-κB.

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Section: Discussionmentioning

confidence: 99%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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“…Rats were randomized into five groups ( n = 6): group (1), normal control rats received dd H 2 O by gavage for a month before subcutaneous injection of physiological saline for two successive days; group (2), ISO control rats received dd H 2 O by oral gavage for a month before subcutaneous injection of ISO (85 mg/kg/day) for two successive days; group (3): acrolein + ISO rats received dd H 2 O by gavage for 28 days, then the rats received acrolein (5 mg/kg/day) by gavage for two days before subcutaneous injection of ISO (85 mg/kg/day) for two successive days; group (4) and (5), rats received OLE at 200 mg/kg/day and 400 mg/kg/day for 28 days, then the rats received acrolein (5 mg/kg/day) by gavage for two days before subcutaneous injection of ISO (85 mg/kg/day) for two successive days. The animals were killed, and the blood and tissue samples were taken after injection of ISO for 48 h. Many studies reported that ISO (85 mg/kg/day) was used to induce MI [ 52 , 53 , 54 ]. Besides, ISO was detected at the different concentrations (5 mg/kg/day, 40 mg/kg/day, 85 mg/kg/day) to induce MI in our pilot experiment and the results indicated that ISO at 85 mg/kg/day presented the clearest effects on inducing MI.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway

Chen

et al. 2018

IJMS

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Many studies reported that air pollution particulate matter (PM) exposure was associated with myocardial infarction (MI). Acrolein representing the unsaturated aldehydes, the main component of PM, derives from the incomplete combustion of wood, plastic, fossil fuels and the main constitute of cigarette smoking. However, the effect of acrolein on MI remains not that clear. In the current study, the effect of acrolein-exacerbated MI was investigated. In vivo, male Sprague–Dawley rats received olive leaf extract (OLE) followed by acrolein, then isoprenaline (ISO) was received by subcutaneous injection to induce MI. Results showed that the expression levels of GRP78 and CHOP, two major components of endoplasmic reticulum (ER) stress were higher in the combination of acrolein and ISO than those in ISO treatment. The apoptosis marker, Bax, was also higher while the anti-apoptosis indicator, Bcl2 expression was lower both at protein and mRNA levels in the combination group. Also, the acrolein-protein adducts and myocardial pathological damage increased in the combination of acrolein and ISO relative to the ISO treatment. Besides, cardiac parameters, ejection fraction (EF) and fractional shortening (FS) were reduced more significantly when acrolein was added than in ISO treatment. Interestingly, all the changes were able to be ameliorated by OLE. Since hydroxytyrosol (HT) and oleuropein (OP) were the main components in OLE, we next investigated the effect of HT and OP on cardiomyocyte H9c2 cell apoptosis induced by acrolein through ER stress and Bax pathway. Results showed that GRP78, CHOP and Bax expression were upregulated, while Bcl2 expression was downregulated both at the protein and mRNA levels, when the H9c2 cells were treated with acrolein. In addition, pretreatment with HT can reverse the expression of GRP78, CHOP, Bax and Bcl2 on the protein and mRNA levels, while there was no effect of OP on the expression of GRP78 and CHOP on the mRNA levels. Overall, all these results demonstrated that OLE and the main components (HT and OP) could prevent the negative effects of acrolein on myocardium and cardiomyocytes.

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“…In addition, it reduced apoptosis by downregulating Bax, cytochrome c, caspase‐3, caspase‐9, poly ADP ribose polymerase (PARP), and enhanced the expression of Bcl‐2. Moreover, embelin pretreatment considerably decreased the pathological changes such as loss of myofibrillar alignment, myocardial degeneration, severe cytoplasmic vacuolization, and infiltration of inflammatory cells when compared with only ISP administered rats (Sahu et al, ). Kocak et al () reported similar cardioprotective effects of embelin and carnosic acid via modulation of NFκB‐Nrf‐2‐MAPK pathway.…”

Section: Natural Products and Their Pharmacological Potential In Allementioning

confidence: 99%

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Allawadhi

Khurana

Sayed

et al. 2018

Phytotherapy Research

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Heart is the most active and incumbent organ of the body, which maintains blood flow, but due to various pathological reasons, several acute and chronic cardiac complications arise out of which myocardial infarction is one of the teething problems. Isoproterenol (ISP)-induced myocardial ischemia is a classical model to screen the cardioprotective effects of various pharmacological interventions. Phytochemicals present a novel option for treating various human maladies including those of the heart. A large number of plant products and their active ingredients have been screened for efficacy in ameliorating ISP-induced myocardial ischemia including coriander, curcumin, Momordica, quercetin, and Withania somnifera. These phytochemicals constituents may play key role in preventing disease and help in cardiac remodeling. Reactive oxygen species scavenging, antiinflammatory, and modulation of various molecular pathways such as Nrf2, NFкB, p-21 activated kinase 1 (PAK1), and p-smad2/3 signaling modulation have been implicated behind the claimed protection. In this review, we have provided a focused overview on the utility of ISP-induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis for preclinical research. In addition, we have also surveyed molecular mechanism of various plant-based interventions screened for cardioprotective effect in ISP-induced cardiotoxicity, and their probable mechanistic profile is summarized.

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

Cited by 47 publications

References 29 publications

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

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