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Ameliorative effects of Garcinia pedunculata fruit extract on adenine-induced chronic kidney disease in mice, and the role of Garcinol: relevance to hyperuricemia and urolithiasis

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Abstract

With ageing of the global population, and increased prevalence of diabetes and hypertension, the incidences of chronic kidney disease (CKD) is also on the rise. We have recently demonstrated that high adenine diet leads to CKD with hyperuricemia, and deposition of uroliths of adenine and 2, 8-dihydroxyadenine. Production of uric acid and 2,8-dihydroxyadenine are catalyzed by xanthine oxidoreductase (XOR). The present study was undertaken to elucidate renoprotective potentials of aqueous fruit extract of Garcinia pedunculata (2% w/v mixed with drinking water) in animal model of CKD, in terms of serum parameters and urolithiasis. To develop the mice model, the mice were given high adenine (0.3% w/w) diet mixed with feed. Elevation in the levels of serum urea and uric acid, and renal histopathological changes were regarded as parameters to validate the model. Aqueous fruit extract of G. pedunculata significantly ameliorated the serum levels of urea and uric acid, and histological alterations. Since Garcinol is one of the principal constituents of the plant, computational modelling was performed to determine inhibitory potential of Garcinol on XOR. The computational modelling revealed that Garcinol may directly inhibit XOR by interacting with the active site of the enzyme. Our findings demonstrated that the fruit extract of G. pedunculata may ameliorate adenine-induced CKD in mice, in terms of haematological and histopathological changes, the mechanism of which has been proposed to be inhibition of XOR by Garcinol. Thus, the present study is important in the treatment paradigm of CKD as a whole, and urolithiasis and hyperuricemia in particular.

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Acknowledgement

We heartily acknowledge the e-journal facility (through DeLCON, funded by the Department of Biotechnology [DBT], Govt. of India) and software support (through DBT-Bioinformatics Infrastructure Facility) provided by the Bioinformatics Centre, Assam University, Silchar.

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Authors and Affiliations

  1. Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, 788011, India

    Rubul Saikia, Anupom Borah & Muhammed Khairujjaman Mazumder

  2. Central Instrumentation Laboratory, Assam University, Silchar, Assam, 788011, India

    Shuvasish Choudhury & Muhammed Khairujjaman Mazumder

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  1. Rubul Saikia
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  2. Shuvasish Choudhury
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  3. Anupom Borah
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Correspondence to Muhammed Khairujjaman Mazumder.

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Ethical statement

Handling of the experimental mice was carried out in accordance with the guidelines of the Institutional Animal Ethics Committee of Assam University, Silchar, India (IEC/AUS/2013-055 dated 20/03/2013, and AUS/IAEC/2017/PC/01 dated 25/10/2017). This article does not contain any studies with human participants.

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Rubul Saikia has no conflict of interest. Shuvasish Choudhury has no conflict of interest. Anupom Borah has no conflict of interest. Muhammed Khairujjaman Mazumder has no conflict of interest.

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Saikia, R., Choudhury, S., Borah, A. et al. Ameliorative effects of Garcinia pedunculata fruit extract on adenine-induced chronic kidney disease in mice, and the role of Garcinol: relevance to hyperuricemia and urolithiasis. ADV TRADIT MED (ADTM) 20, 255–261 (2020). https://doi.org/10.1007/s13596-019-00402-z

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