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Yohimbine Treatment Alleviates Cardiac Inflammation/Injury and Improves Cardiac Hemodynamics by Modulating Pro-Inflammatory and Oxidative Stress Indicators

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Abstract

Acute myocarditis, also known as myocardial inflammation, is a self-limited condition caused by systemic infection with cardiotropic pathogens, primarily viruses, bacteria, or fungi. Despite significant research, inflammatory cardiomyopathy exacerbated by heart failure, arrhythmia, or left ventricular dysfunction and it has a dismal prognosis. In this study, we aimed to evaluate the therapeutic effect of yohimbine against lipopolysaccharide (LPS) induced myocarditis in rat model. The anti-inflammatory activity of yohimbine was assessed in in-vitro using RAW 264.7 and H9C2 cells. Myocarditis was induced in rats by injecting LPS (10 mg/kg), following the rats were treated with dexamethasone (2 mg/kg) or yohimbine (2.5, 5, and 10 mg/kg) for 12 h and their therapeutic activity was examined using various techniques. Yohimbine treatment significantly attenuated the LPS-mediated inflammatory markers expression in the in-vitro model. In-vivo studies proved that yohimbine treatment significantly reduced the LPS-induced increase of cardiac-specific markers, inflammatory cell counts, and pro-inflammatory markers expression compared to LPS-control samples. LPS administration considerably affected the ECG, RR, PR, QRS, QT, ST intervals, and hemodynamic parameters, and caused abnormal pathological parameters, in contrast, yohimbine treatment substantially improved the cardiac parameters, mitigated the apoptosis in myocardial cells and ameliorated the histopathological abnormalities that resulted in an improved survival rate. LPS-induced elevation of cardiac troponin-I, myeloperoxidase, CD-68, and neutrophil elastase levels were significantly attenuated upon yohimbine treatment. Further investigation showed that yohimbine exerts an anti-inflammatory effect partly by modulating the MAPK pathway. This study emphasizes yohimbine's therapeutic benefit against LPS-induced myocarditis and associated inflammatory markers response by regulating the MAPK pathway.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

ALT:

Alanine aminotransferase

CK-MB:

Creatine kinase-myoglobin binding

COX-2:

Cyclooxygenase-2

cTnI:

Cardiac troponin 1

CD-68:

Cluster of differentiation 68

DMEM:

Dulbecco’s modified eagle medium

DEX:

Dexamethasone

ECG:

Electrocardiogram

ELISA:

Enzyme-linked immunosorbent assay

HR:

Heart rate

h:

Hour

i.p.:

Intra-peritoneal

iNOS:

Inducible nitric oxide synthase

KH:

Krebs henseleit

LPS:

Lipopolysaccharide

Ly6C:

Lymphocyte antigen 6 family member C

LVDP:

Left ventricular developed pressure

LDH:

Lactate dehydrogenase

MPO:

Myeloperoxidase

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemoattractant protein-1

NE:

Neutrophil elastase

PBS:

Phosphate buffered saline

RT-qPCR:

Reverse transcriptase quantitative PCR

SRB:

Sulforhodamine-B

SD:

Sprague Dawley

YH:

Yohimbine hydrochloride

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Acknowledgements

Authors thank the Director, CSIR-IICT, Hyderabad, India, for providing the facilities and funding necessary for the conducting of this work. CSIR-IICT manuscript communication number: IICT/Pubs./2023/204. A. V acknowledges DST-Inspire (IF190483) for providing a fellowship. T.B.S and R.K acknowledge the Council of Scientific and Industrial Research, New Delhi for providing SRF. We acknowledge Prof. Gino A Kurian from the Department of Biotechnology, Sastra Deemed University for providing training on the Langendorff apparatus. The authors also acknowledge Dr C Yogesh (CSIR-IICT) for assistance in histological observations.

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Used internal funds of the institute. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

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

    Anjali Veeram, Taslim B. Shaikh, Rajwinder Kaur, E. Abhisheik Chowdary, Sai Balaji Andugulapati & Ramakrishna Sistla

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201 002, India

    Anjali Veeram, Taslim B. Shaikh, Rajwinder Kaur, Sai Balaji Andugulapati & Ramakrishna Sistla

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  1. Anjali Veeram
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Contributions

Conceptualization: S.B.A, S. R. K; Methodology: A. V, S.B.A, S. R. K.; In vitro cell culture: A. V; RT-qPCR, Western-blot analysis, A.V R.K; In vivo and ex-vivo experiments: A.V, T.B.S, A.E; Manuscript 1st draft writing: A.V, Manuscript writing - review & editing: S.B.A and S. R. K.; funding acquisition: S.R. K and S.B.A.

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Correspondence to Sai Balaji Andugulapati or Ramakrishna Sistla.

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Veeram, A., Shaikh, T.B., Kaur, R. et al. Yohimbine Treatment Alleviates Cardiac Inflammation/Injury and Improves Cardiac Hemodynamics by Modulating Pro-Inflammatory and Oxidative Stress Indicators. Inflammation (2024). https://doi.org/10.1007/s10753-024-01985-9

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