PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Protective Effects of Phyllanthus emblica L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model
Version 1
: Received: 8 May 2024 / Approved: 8 May 2024 / Online: 9 May 2024 (16:10:12 CEST)
How to cite:
Lin, C.-H.; Shih, C.-C. Protective Effects of Phyllanthus emblica L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model. Preprints2024, 2024050545. https://doi.org/10.20944/preprints202405.0545.v1
Lin, C.-H.; Shih, C.-C. Protective Effects of Phyllanthus emblica L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model. Preprints 2024, 2024050545. https://doi.org/10.20944/preprints202405.0545.v1
Lin, C.-H.; Shih, C.-C. Protective Effects of Phyllanthus emblica L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model. Preprints2024, 2024050545. https://doi.org/10.20944/preprints202405.0545.v1
APA Style
Lin, C. H., & Shih, C. C. (2024). Protective Effects of <em>Phyllanthus emblica</em> L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model. Preprints. https://doi.org/10.20944/preprints202405.0545.v1
Chicago/Turabian Style
Lin, C. and Chun-Ching Shih. 2024 "Protective Effects of <em>Phyllanthus emblica</em> L. Extract against Renal Dysfunction, Angiogenesis, and Fibrosis Occur through the Regulation of PKCα Activation, Vegf, and TGF-β1 in a Diabetic Nephropathy Model" Preprints. https://doi.org/10.20944/preprints202405.0545.v1
Abstract
Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
