Abelmoschus esculentus subfractions improved nephropathy with regulating dipeptidyl peptidase-4 and type 1 glucagon-like peptide receptor in type 2 diabetic rats

Chiung-Huei Peng a, Hsing-Chun Lin b, Chih-Li Lin c, Chau-Jong Wang d,**,1, Chien-Ning Huang c,e,*,1

a Division of Basic Medical Science, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung City, 43302, Taiwan

b Department of Nutrition, Chung-Shan Medical University, Number 110, Section 1, Jianguo North Road, Taichung, 402, Taiwan

c Institute of Medicine, Chung-Shan Medical University, Number 110, Section 1, Jianguo North Road, Taichung, 402, Taiwan

d Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Number 110, Section 1, Jianguo North Road, Taichung, 402, Taiwan

e Department of Internal Medicine, Chung-Shan Medical University Hospital, Number 110, Section 1, Jianguo North Road, Taichung, 402, Taiwan

Abelmoschus esculentus (AE) has been used in traditional medicine to ameliorate hyperglycemia, but its mucilage increased bioassay difficulties. We have obtained a series of AE subfractions. Among them F1 and F2 regulated dipeptidyl peptidase-4 (DPP-4) and type 1 glucagon-like peptide receptor (GLP-1R), the treatment targets for type 2 diabetes. F1, F2 and fraction residues (FR) showed advantage on different aspects, which attenuates insulin resistance and metabolic disorder in vivo, and prevents renal-tubular change in vitro. In the present study, using type 2 diabetes model induced by high fat diet (HFD) and streptozotocin (STZ), we aim to investigate whether AE prevent diabetic nephropathy by regulating the putative markers. The results showed that all the subfractions ameliorated albuminuria and renal hyperfiltration (measured by creatinine clearance rate; CCr) accompanied with diabetes, while F2 acted most promptly and consistently. Histologically AE reduced renal tubular change, fibrosis and fat deposition. F2 and FR exerted significant effects to decrease DPP-4 while increase GLP-1R. Although all the subfractions were effective to reduce oxidative stress, only F2 acted on kidneys specifically. In conclusion, we have demonstrated AE has benefits to regulate DPP-4 and GLP-1R, to reduce oxidative stress and renal fibrosis, with resultant to improve renal function and prevent diabetic renal damage. Taken together, F2 could be more promising to be developed as adjuvant for diabetic nephropathy.

Keywords: Abelmoschus esculentus, Diabetic nephropathy, Dipeptidyl peptidase-4, Type 1 glucagon-like peptide, receptor