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Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice

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Abstract

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 the serum. The mRNA expression of cardiac hypertrophy markers namely atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured using qRT-PCR. The levels of pro-inflammatory cytokines TNF-α and IL-6 were quantified by ELISA in isolated tissues and serum. Other tissue anti-oxidant parameters such as GST, GSH, SOD and TBARS were also measured. TUNEL assay was performed to detect apoptosis. Histology studies were performed using H & E and Masson trichome staining. Immunoblot analysis was used to quantify the protein expression of TLR-4 and NF-κB. ISO-alone-treated group showed significant increase in CK-MB, LDH along with increase in hypertrophic markers ANP and BNP, TNF-α and IL-6 levels in serum and tissues and increased cardiomyocyte apoptosis. Anti-oxidant parameters were significantly decreased and TLR-4 and NF-κB protein expression was found to be upregulated in comparison to the control group. Pretreatment with Arbutin-exhibited significant inhibition of TLR-4/NF-κB pathway with decreased levels of pro-inflammatory cytokines and enhanced myocardial anti-oxidant status. Our study demonstrated that pretreatment with Arbutin exhibits marked protective effects on ISO-induced cardiac hypertrophy in mice. Thus, Arbutin may be used as potential pharmacological interventions in the management of cardiac hypertrophy.

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Acknowledgements

Authors are grateful to Director, CSIR-IICT, Hyderabad, India for providing necessary facilities and continuous support. Nasiruddin Nalban thanks Indian Council of Medical Research (ICMR) New Delhi, India for financial assistance in the form of Junior Research Fellowship. RS thanks CSIR, New Delhi, India and SA thanks DST, New Delhi, India for providing the junior Research Fellowships. CSIR-IICT Manuscript communication number-IICT/Pubs./2019/117.

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Authors and Affiliations

  1. Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India

    Nasiruddin Nalban, Rajendra Sangaraju, Sateesh Alavala, Salma Mukhtar Mir & Ramakrishna Sistla

  2. Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201 002, India

    Nasiruddin Nalban, Rajendra Sangaraju & Ramakrishna Sistla

  3. Animal House Facility, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, 500 007, India

    Mahesh Kumar Jerald

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  1. Nasiruddin Nalban
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Nalban, N., Sangaraju, R., Alavala, S. et al. Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice. Cardiovasc Toxicol 20, 235–248 (2020). https://doi.org/10.1007/s12012-019-09548-3

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