The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats

Arozal, Wawaimuli; Suyatna, Franciscus D.; Juniantito, Vetnizah; Rosdiana, Dewi Selviana; Amurugam, S.; Aulia, Rafidah; Monayo, E. R.; Siswandi, Riki

doi:10.1055/s-0034-1394457

Cited by 21 publications

(36 citation statements)

References 28 publications

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“…Instead of cardiac biochemical markers, TNF-a expression was used to assess cardiac damage because our previous work has already established that 15 mg/kg bw of DOX was able to cause significant increase of serum CK and LDH levels (Arozal et al, 2014). TNF-a has been widely accepted as an appropriate surrogate marker to assess heart damage because of strong positive correlation between its level and the degree of heart damage (Torre-Amione et al, 1996a,b).…”

Section: Discussionmentioning

confidence: 99%

“…The focus of the present study is to explore the possible molecular mechanism of MGR that involves intracellular calcium regulation. This study is a continuation of our previous study (Arozal et al, 2014) which focuses on MGR cardioprotective effect as an effort to enrich the use of evidence-based Indonesian natural herbal medicine.…”

Section: Introductionmentioning

confidence: 94%

“…Numerous studies have reported the potent antioxidant (Dar et al, 2005) and iron-chelating activities (Andreu et al, 2005) of MGR. The cardioprotective effect of MGR against DOX-induced cardiotoxicity has been proved in vivo in our previous study (Arozal et al, 2014) in which MGR treatment at the dose of 50 mg/kg bw/d was shown to improve biochemical, histological, and electrocardiographic alterations in DOX-induced rats. However, the same study also showed that MGR treatment at 100 mg/kg bw/d had inconsistent positive impact on the heart tissue of test subjects.…”

Section: Introductionmentioning

confidence: 94%

“…MGR 30 mg/kg bw was prepared by mixing 100 mg of MGR powder with 10 mL of 0.5% sodium CMC using mortar and pestle until MGR was perfectly suspended (Arozal et al, 2014). MGR 60 mg/kg bw was prepared with the same procedure, except the amount of MGR powder used was 200 mg.…”

Section: Dox and Mgr Preparationmentioning

confidence: 99%

“…The dose and the schedule of the study were determined according to our previous study (Arozal et al, 2014) with some adjustments. As has been mentioned earlier, the previous higher dose of MGR (100 mg/kg bw/d) was shown giving inconsistent results while the lower dose (50 mg/kg bw/d) gave optimal results.…”

Section: Experimental Designmentioning

confidence: 99%

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Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation

Agustini¹,

Arozal

Louisa

et al. 2015

Pharmaceutical Biology

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Context: The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves overproduction of free radicals that leads to intracellular calcium dysregulation and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has antioxidant and cardioprotective properties. However, its cardioprotection mechanism has yet to be revealed. Objective: This study determines whether the cardioprotective effect of MGR is caused by its effect on intracellular calcium regulation. Materials and methods: Male Sprague-Dawley rats were induced by DOX intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters examined were mRNA expression levels of proinflammatory cytokine gene (TNF-a), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and caspase-12), as well as cytosolic and mitochondrial calcium levels. Results: Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression levels of TNF-a by 44.55% and caspase-9 by 52.79%, as well as the cytosolic calcium level by 24.15% (p50.05). SERCA2a and caspase-12 expressions were only slightly affected (27.27% increase and 24.85% decrease for SERCA2a and caspase-12, respectively, p40.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant results in all parameters. Discussion and conclusion: MGR protected against DOX-induced cardiac inflammation and apoptosis via down-regulation of proapoptotic and proinflammatory gene expressions, upregulation of SERCA2a gene expression, and normalization of cytosolic calcium level. Thus, the cardioprotective effect of MGR is at least in part due to the regulation of intracellular calcium homeostasis. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Section: Dox and Mgr Preparationmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

See 3 more Smart Citations

Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation

Agustini¹,

Arozal

Louisa

et al. 2015

Pharmaceutical Biology

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Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential

2016

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Over the last era, small molecules sourced from different plants have gained attention for their varied and long-term medicinal benefits. Their advantageous therapeutic effects in diverse pathological complications lead researchers to give an ever-increasing emphasis on them and discover their novel therapeutic potentials. Among these, the heat stable, xanthonoid group of organic molecules has gained special importance with distinctive regards to the bioactive molecule mangiferin due to its solubility in water. Mangiferin, a yellow polyphenol having C-glycosyl xanthone structure, is widely present in different edible sources like mango, and possesses numerous biological activities. Extensive research with this molecule shows its antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial, analgesic, and immunomodulatory properties. Thus, it provides protection against a wide range of physiological disorders. The C-glucosyl linkage and polyhydroxy groups in mangiferin's structure contribute essentially to its free radical-scavenging activity. Moreover, its ability in regulating various transcription factors like NF-κB, Nrf-2, etc. and modulating the expression of different proinflammatory signaling intermediates like tumor necrosis factor-α, COX-2, etc. contribute to its anti-inflammatory, anticancer, and antidiabetic potentials. In this comprehensive article, information has been provided about the sources, chemical structure, metabolism, and different biological activities of mangiferin with special emphasis on the underlying cellular signal transduction pathways. Insights into an in-depth assessment of mangiferin's anti-inflammatory therapeutic potential have also been discussed in detail. On an overall perspective, this review aims to stage mangiferin's diversified therapeutic applications and its emerging possibility as a promising drug in future based on its anti-inflammatory property. © 2016 BioFactors, 42(5):459-474, 2016.

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The potential role of mangiferin in cancer treatment through its immunomodulatory, anti‐angiogenic, apoptopic, and gene regulatory effects

2016

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Mangiferin (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) is a natural bioactive xanthonoid that can be found in many plant species, among which the mango tree (Mangifera indica L), a plant widely used in the traditional medicinal, is one of its primary sources. The use of mangiferin for cancer treatment has attracted the attention of research groups around the World. Single administration of mangiferin or in combination with known anticancer chemicals has shown the potential benefits of this molecule in lung, brain, breast, cervix, and prostate cancers, and leukemia. Mangiferin mechanisms of action against cancer cells through in vitro, ex vivo, or in vivo models are discussed besides its antioxidant and anti-inflammatory properties. Nevertheless, pharmaceutical development and, therefore, clinical trials on cancer targets are still lacking. © 2016 BioFactors, 42(5):475-491, 2016.

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The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats

Abstract: These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies.

Cited by 21 publications

References 28 publications

Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation

Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation

Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential

The potential role of mangiferin in cancer treatment through its immunomodulatory, anti‐angiogenic, apoptopic, and gene regulatory effects

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