Hypolipidemic and Antioxidant Properties of Oryzanol Concentrate in Reducing Diabetic Nephropathy via SREBP1 Downregulation Rather than β-Oxidation

Abstract

Scope: Diabetic nephropathy (DN) is a micro-vascular complication of chronic diabetes. Sterol regulatory element binding protein1 (SREBP1) participation in the development of DN is reported. Oryzanol concentrate (OC) at 0.1% and 0.3% is tested for its antioxidant and hypolipidemic effects. The aim of the work is to study the involvement of OC in the amelioration of DN in STZ-induced diabetic animal model.

Methods and results: Animals were grouped into starch, high-fat, and OC-treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD). The markers of DN, increased glomerular filtration rate and kidney weight, were evident in HFD and reduced in OFD group by ≈1.09 and ≈1.3 fold, respectively. The amelioration of defensive antioxidant enzyme activities and lipid peroxidation, expressions of lipid-associated biomolecules (SREBP1 and FAS) were also observed. HFD showed increased ECM accumulation of glycoproteins, particularly Type IV collagen, fibronectin. SREBP1-associated gene transforming growth factor-β (TGF-β) was reduced on treatment (OFD ≈ 1.3 fold) as to HFD (≈2.7 fold).

Conclusion: Oryzanol concentrate, having hypolipidemic and antioxidant properties, also downregulated the lipid biosynthesis through reduced SREBP1-TGF-β interactions (EMSA) and could effectively ameliorate DN. Gene (ACC2, Cpt1, and ACOX) expression studies showed that β-oxidation was not involved in reducing DN.

Keywords: PAS; TGF-β; diabetic nephropathy; oryzanol; type IV collagen.