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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

        Saikia Rubul,Choudhury Shuvasish,Borah Anupom,Mazumder Muhammed Khairujjaman 경희대학교 융합한의과학연구소 2020 Oriental Pharmacy and Experimental Medicine Vol.20 No.2

        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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