Morus alba Leaf Bioactives Modulate Peroxisome Proliferator Activated Receptor γ in the Kidney of Diabetic Rat and Impart Beneficial Effect

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Abstract
Peroxisome proliferator activated receptor gamma (PPARү) are ligand-activated nuclear receptors that can be activated or repressed by several exogenous and endogenous ligands and act by modulating genes which regulate lipid, glucose, and insulin homeostasis. In kidney, they are involved in normal kidney development and other physiological functions. In our earlier report, we showed that feeding Morus alba leaves to experimental diabetic rats ameliorated diabetic nephropathy and significantly decreased microalbuminuria. In this paper, we have attempted to look into the molecular mechanism involving PPARү modulation by mulberry leaf bioactives by in vitro and in vivo methods and its impact on key molecules of inflammatory markers. In vitro assay by TR-FRET suggested that mulberry leaf extracts can serve as putative modulator of PPARү. High glucose conditions in vitro and in vivo increased PPARү levels which were ameliorated by mulberry leaves or its extracts. Interestingly, PPARү was significantly phosphorylated at Ser112 by upstream kinases ERK42/44 in kidney of diabetic animals on feeding mulberry leaves. In vitro studies using MDCK cell line revealed that increased Ser112 phosphorylation was observed when treated with bound phenolic acid rich- extract but not with free phenolic acid-rich extracts. HPLC analysis and bioassay-guided activity revealed that coumaric acid was the bioactive molecule amongst bound phenolic acid-rich extract that was responsible for increased ERK 42/44-mediated phosphorylation at Ser112. Furthermore, mulberry leaf bioactives showed beneficial effect on the tested inflammatory markers.
Funding Information
  • Indian Council of Medical Research
  • Council of Scientific and Industrial Research

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