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Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats.

ABSTRACT: Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As Murraya koenigii leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardioprotective potential of Murraya leaf extract against doxorubicin-induced cardiotoxicity in rats. Rats were randomly divided into five groups with 10 animals in each group. Doxorubicin was administered intraperitonially at 18?mg/kg while lyophilized plant extract was administered orally at 2?g/kg. Dexrazoxane, at 180?mg/kg, was used as the positive control. Cardiac damage of doxorubicin control was evident with a significant increase (p < 0.05) in cardiac troponin I, NT-pro BNP, AST, and LDH compared to the normal control. Plant-treated group showed cardioprotective effect by significantly reducing (p < 0.05) all of the above parameters compared to doxorubicin control (p < 0.05). Increased oxidative stress in doxorubicin control was evident with a significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity and a significant increase in lipid peroxidation compared to the control. Interestingly, treatment with Murraya leaf extract showed a significant increase in all of the above antioxidant parameters and a significant reduction in lipid peroxidation by showing an antioxidant effect. A significant increase in myeloperoxidase activity confirmed the increased inflammatory activity in doxorubicin control group whereas plant-treated group showed a significant reduction (p < 0.05) which expressed the anti-inflammatory effect of Murraya leaf extract. Doxorubicin-treated group showed histological evidence of extensive damage to the myocardium while plant-treated group showed a preserved myocardium with lesser degree of damage. Pretreatment with Murraya leaf extract may replenish cardiomyocytes with antioxidants and promote the defense against doxorubicin-induced cardiotoxicity.

SUBMITTER: Sandamali JAN

PROVIDER: S-EPMC7142394 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cardioprotective Potential of <i>Murraya koenigii</i> (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats.

Sandamali Jayasinghe A N JAN Hewawasam Ruwani P RP Jayatilaka Kamani A P W KAPW Mudduwa Lakmini K B LKB

Evidence-based complementary and alternative medicine : eCAM 20200405

Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As <i>Murraya koenigii</i> leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardi ...[more]

PMID: 32308710

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Project description:Doxorubicin is a chemotherapy medication widely used to treat a variety of cancers. Even though it offers one of the most effective anti-cancer treatments, its clinical use is limited because of its strong cardiotoxicity that can lead to fatal conditions. Here, we show that sestrin 1 and sestrin 2, members of the sestrin family of proteins that are stress-inducible regulators of metabolism, are critical for suppressing doxorubicin cardiotoxicity and coordinating the AMPK-mammalian target of rapamycin complex 1 (mTORC1) autophagy signaling network for cardioprotection. Expression of both sestrin 1 and sestrin 2 was highly increased in the mouse heart after doxorubicin injection. Genetic ablation of sestrin 1 and sestrin 2 rendered mice more vulnerable to doxorubicin and exacerbated doxorubicin-induced cardiac pathologies including cardiomyocyte apoptosis and cardiac dysfunction. These pathologies were associated with strong dysregulation of the cardiac signaling network, including suppression of the AMPK pathway and activation of the mTORC1 pathway. Consistent with AMPK downregulation and mTORC1 upregulation, autophagic activity of heart tissue was diminished, leading to prominent accumulation of autophagy substrate, p62/SQSTM1. Taken together, our results indicate that sestrin 1 and sestrin 2 are important cardioprotective proteins that coordinate metabolic signaling pathways and autophagy to minimize cardiac damage in response to doxorubicin insult. Augmenting this protective mechanism could provide a novel therapeutic rationale for prevention and treatment of doxorubicin cardiotoxicity. NEW & NOTEWORTHY Doxorubicin is a highly efficient chemotherapeutic medicine; however, its use is limited because of its strong cardiotoxicity. Here, we show that sestrin 1 and sestrin 2 are critical protectors of cardiomyocytes from doxorubicin damage. By upregulating AMPK and autophagic activities and suppressing mammalian target of rapamycin complex 1 and oxidative stress, sestrins counteract detrimental effects of doxorubicin on cardiomyocytes. Correspondingly, loss of sestrin 1 and sestrin 2 produced remarkable dysregulation of these pathways, leading to prominent cardiac cell death and deterioration of heart function.

Project description:The study was undertaken to characterize the total phenolics, flavonoids, essential oils, quinones, tannins and antioxidant activity of 15 samples of wild Murraya koenigii (L.) Spreng. (MK) leaves obtained from different locations of Himachal Pradesh at various growth stages. The results indicated a significant variation in total phenolic content which ranged from [(170.09 ± 4.59 to 303.57 ± 7.94) in pre-flowering, (266.48 ± 7.49 to 450.01 ± 11.78) in the flowering stage, and (212.72 ± 5.37 to 363.85 ± 9.79) in fruiting stage], expressed as mg tannic acid equivalents (TAE)/g. The total flavonoid content ranged from [(15.17 ± 0.36 to 33.40 ± 0.81) in pre-flowering, (25.16 ± 0.67 to 58.17 ± 1.52) in flowering stage, and (17.54 ± 0.42 to 37.34 ± 0.97) in fruiting stage], expressed as mg catechin equivalent (CE)/g. Total tannin content ranged from [(75.75 ± 1.69 to 143 ± 3.74) in pre-flowering, (116 ± 3.26 to 207 ± 5.42) in the flowering stage, and (47 ± 1.18 to 156 ± 4.05) in fruiting stage], expressed as mg TAE/g. The essential oil content ranged from (0.64 ± 0.01 to 0.89 ± 0.02%) in pre-flowering, (0.85 ± 0.02 to 1 ± 0.02%) in flowering stage, and (0.54 ± 0.01 to 0.7 ± 0.01%) in fruiting stage. Quinones ranged from [(2.05 ± 0.05 to 2.97 ± 0.07) in pre-flowering, (3.07 ± 0.07 to 4.95 ± 0.13) in flowering stage, and (1.02 ± 0.02 to 1.96 ± 0.04) in fruiting stage], expressed as mM/min/g tissue. Antioxidant activity ranged from [(4.01 ± 0.09 to 7.42 ± 0.17) in pre-flowering, (8.08 ± 0.19 to 13.60 ± 0.35) in flowering stage, and (3.11 ± 0.06 to 6.37 ± 0.15) in fruiting stage], expressed as μg/ml. Data was subjected to multivariate analysis using principal component analysis (PCA), hierarchical clustering analysis (HCA). This was used for elucidating the intricate relationships between the phytochemical properties. All evaluated phytochemical parameters significantly increased during the growth transition from pre-flowering to the flowering stage, followed by their gradual decrease during the fruiting stage. The present study can serve as rationale for commercializing MK for aromatic and phytopharmaceutical industries.

Dataset Information

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats.

Publications

Cardioprotective Potential of <i>Murraya koenigii</i> (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats.

Similar Datasets

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