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Ameliorative Effect of Hesperidin Against Motion Sickness by Modulating Histamine and Histamine H1 Receptor Expression

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Abstract

Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict theory which proves histamine elevations as the primary reason for MS provides a path for an effective pharmaco-therapy. We aimed to evaluate the anti-MS effect of hesperidin (HSP) by modulating histamine and histamine receptor H1 (HRH1) expression. The inhibitory effect of HSP on histamine release was studied in KU812 cells treated with 10 µM calcium ionophore. The in vivo anti-MS effect of HSP was evaluated in Balb/c mice. Thirty six mice were divided into six groups namely, normal control (NC, no rotation), hesperidin at 80 mg/kg body weight control (HSP80, no rotation), motion sickness (MS, rotation induced), dimenhydrinate (Standard drug) at 20 mg/kg body weight + rotation (STD + MS), hesperidin at 40 mg/kg body weight + rotation (HSP40 + MS) and hesperidin at 80 mg/kg body weight + rotation (HSP80 + MS). Hypothalamus and brainstem samples were analysed for histamine levels and HRH1 expression by RT-PCR, Western blot and immunohistochemistry analysis. Calcium ionophore treated KU812 cells significantly increased histamine release when compared to control cells. Pre-treatment with HSP inhibited histamine, HRH1 mRNA and protein expression. Histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem samples of MS group increased significantly when compared to the NC group. Pre-treatment with HSP significantly reduced histamine, HRH1 mRNA and protein expression. Thus, indicating that HSP has a potent anti- MS effect by decreasing the elevated levels of histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem regions.

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Acknowledgements

The authors are thankful to the Director, Defence Food Research Laboratory, Defence Research and Development Organisation for his constant support and encouragement during the period of the study. The authors would like to acknowledge DST-SERB (EMR/2014/000600) for vibratome facility.

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Authors and Affiliations

  1. Nutrition, Biochemistry & Toxicology Division Defence Food Research Laboratory, DRDO-SRF, Siddarthanagar, Mysore, 570011, India

    Uma Maheswari Deshetty

  2. DRDO- Bharathiar University Centre for Life Sciences Bharathiar University Campus, 641046, Coimbatore, India

    Monojit Bhattacharjee

  3. Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641046, India

    Ekambaram Perumal

  4. Food Biotechnology Division Defence Food Research Laboratory, Siddarthanagar, Mysore, 570011, India

    Gopalan Natarajan

  5. Nutrition, Biochemistry & Toxicology Division, Defence Food Research Laboratory, Siddarthanagar, Mysore, 570011, India

    Anand Tamatam & Farhath Khanum

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  1. Uma Maheswari Deshetty
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  2. Anand Tamatam
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Correspondence to Anand Tamatam.

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Deshetty, U.M., Tamatam, A., Bhattacharjee, M. et al. Ameliorative Effect of Hesperidin Against Motion Sickness by Modulating Histamine and Histamine H1 Receptor Expression. Neurochem Res 45, 371–384 (2020). https://doi.org/10.1007/s11064-019-02923-0

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  • DOI: https://doi.org/10.1007/s11064-019-02923-0

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