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Evaluation of Methanol Extract of Aerial Parts of Daphne mucronata against Doxorubicin- Induced H9c2 Cardiomyocytes
Author(s):
1. Mudassar Azhar: Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; Department of Basic Medical Sciences, Faculty of Pharmacy, Salim Habib University, NC-24, DehDih, Korangi Creek, Karachi-74900, Karachi, Pakistan
2. Suraj Kishanchand: Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
3. Bina Siddiqui: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
Abstract:
Doxorubicin has been used in the management of cancer; however, cardiac toxicity limits prolong usage in the regimens. This toxicity mainly occurs due to increased oxidative stress and depletion of calcium stores. Earlier, Daphne mucronatahas displayed anticancer activity along with free radical scavenging properties. Keeping this in mind, the present study was framed. For this purpose, H9c2 (rat cardiomyocytes) cells were treated with the methanol extract of aerial parts ofDaphne mucronata (m-A-DM) to determine its toxicity/safety on cardiomyocytes. Later on, H9c2 cells were exposed to doxorubicin (0.5 µM) and then treated with m-A-DM (50 µg/mL) or Quercetin (50 µg/mL) to analyze its effect on: a) the intracellular oxidative stress, b) protection against cardiomyocyte injury, and c) cell survival. The results demonstrated that the IC50was 143 ± 1 µg/mL as compared to quercetin i.e., ~135 µg/mL indicating that it was less toxic than quercetin. Furthermore, both test agents displayed EC50 of ~50 µg/mL for reducing the intracellular oxidative stress. The gene expression of antioxidant enzymes (Nrf-2, SOD-1, and SOD-2) was also increased. Moreover, the ATP production was also increased in the doxorubicin treated H9c2 cells. This indicated that the cardiomyocyte injury was reduced in the presence of the tested extract. In addition, it was observed that the calcium levels were reduced, and cytochrome c release was inhibited along with the reduction in the apoptotic cells in the doxorubicin treated H9c2 cells. Altogether, our results suggested that the m-A-DM protected the cardiomyocyte injury via lowering the intracellular oxidative stress which was induced by the doxorubicin. Thus, providing valuable support to the plant-based management of cardiac toxicity for the population that prefer natural product for remedies. However, further detailed molecular, preclinical, and clinical studies will be required to establish its efficacy.
Page(s): 354-354
DOI: DOI not available
Published: Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023
Keywords:
Daphne mucronata , H9c2 Cardiomyocytes
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