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Hibiscus sabdariffa Polyphenols Alleviate Insulin Resistance and Renal Epithelial to Mesenchymal Transition: A Novel Action Mechanism Mediated by Type 4 Dipeptidyl Peptidase

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    Hibiscus sabdariffa Polyphenols Alleviate Insulin Resistance and Renal Epithelial to Mesenchymal Transition: A Novel Action Mechanism Mediated by Type 4 Dipeptidyl Peptidase
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    † Division of Basic Medical Science, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung City 43302, Taiwan
    ‡ Department of Internal Medicine, Chung-Shan Medical University Hospital, Number 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
    § Institute of Medicine, Chung-Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
    ∥ School of Medicine, Chung-Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
    ⊥ Institute of Biochemistry and Biotechnology, Chung-Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
    *Institute of Medicine, Chung-Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan. E-mail: [email protected]. Fax: 866-4-24739220.
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    Journal of Agricultural and Food Chemistry

    Cite this: J. Agric. Food Chem. 2014, 62, 40, 9736–9743
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    https://doi.org/10.1021/jf5024092
    Published September 16, 2014
    Copyright © 2014 American Chemical Society
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    Abstract

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    The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.

    Copyright © 2014 American Chemical Society

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    Supporting Information

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    Table of retention time, UV–vis, and mass spectral characteristics for the phenolics identified in HPE (S1); graphic depicting glucose uptake assay (S2); and graphics depicting DPP-4 inhibited by the phenolics of HPE and vimentin reduced by the phenolics of HPE (S3). This material is available free of charge via the Internet at http://pubs.acs.org.

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    This article is cited by 17 publications.

    1. Jing-Hsien Chen, Pei-Tzu Wu, Charng-Cherng Chyau, Pei-Hsuan Wu, Hui-Hsuan Lin. The Nephroprotective Effects of Hibiscus sabdariffa Leaf and Ellagic Acid in Vitro and in Vivo Models of Hyperuricemic Nephropathy. Journal of Agricultural and Food Chemistry 2023, 71 (1) , 382-397. https://doi.org/10.1021/acs.jafc.2c05720
    2. José João Caires Serina, Paula Cristina Machado Ferreira Castilho. Using polyphenols as a relevant therapy to diabetes and its complications, a review. Critical Reviews in Food Science and Nutrition 2022, 62 (30) , 8355-8387. https://doi.org/10.1080/10408398.2021.1927977
    3. Daniel Jamrozik, Weronika Borymska, Ilona Kaczmarczyk-Żebrowska. Hibiscus sabdariffa in Diabetes Prevention and Treatment—Does It Work? An Evidence-Based Review. Foods 2022, 11 (14) , 2134. https://doi.org/10.3390/foods11142134
    4. Anuj Kumar Borah, Semim Akhtar Ahmed, Jagat C. Borah. Phytomedicine as a source of SGLT2 inhibitors, GLP-1 secretagogues and DPP-IV inhibitors for mitigation of Diabetic Nephropathy. Phytomedicine Plus 2022, 2 (2) , 100225. https://doi.org/10.1016/j.phyplu.2022.100225
    5. Amylee Amos, Bashar Khiatah. Mechanisms of Action of Nutritionally Rich Hibiscus sabdariffa's Therapeutic Uses in Major Common Chronic Diseases: A Literature Review. Journal of the American Nutrition Association 2022, 41 (1) , 116-124. https://doi.org/10.1080/07315724.2020.1848662
    6. Ebru KOCADAĞ KOCAZORBAZ, Kerem TOK, Hichem MOULAHOUM, Rabia Nur ÜN. Phytochemical and Bioactivity Analysis of Several Methanolic Extracts of Nine Bryophytes Species. Sakarya University Journal of Science 2021, 25 (4) , 938-949. https://doi.org/10.16984/saufenbilder.868944
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    10. Chiung-Huei Peng, Hsing-Chun Lin, Chih-Li Lin, Chau-Jong Wang, Chien-Ning Huang. Abelmoschus esculentus subfractions improved nephropathy with regulating dipeptidyl peptidase-4 and type 1 glucagon-like peptide receptor in type 2 diabetic rats. Journal of Food and Drug Analysis 2019, 27 (1) , 135-144. https://doi.org/10.1016/j.jfda.2018.07.004
    11. Shian-Ren Lin, Chia-Hsiang Chang, May-Jwan Tsai, Henrich Cheng, Jian-Chyi Chen, Max K. Leong, Ching-Feng Weng. The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo. Therapeutic Advances in Chronic Disease 2019, 10 https://doi.org/10.1177/2040622319875305
    12. J. Bradley Morris, Ming Li Wang. Updated review of potential medicinal genetic resources in the USDA, ARS, PGRCU industrial and legume crop germplasm collections. Industrial Crops and Products 2018, 123 , 470-479. https://doi.org/10.1016/j.indcrop.2018.07.014
    13. J. Domínguez Avila, Joaquín Rodrigo García, Gustavo González Aguilar, Laura De la Rosa. The Antidiabetic Mechanisms of Polyphenols Related to Increased Glucagon-Like Peptide-1 (GLP1) and Insulin Signaling. Molecules 2017, 22 (6) , 903. https://doi.org/10.3390/molecules22060903
    14. Tsung‐Chang Tsai, Hui‐Pei Huang, Kai‐Ting Chang, Chau‐Jong Wang, Yun‐Ching Chang. Anthocyanins from roselle extract arrest cell cycle G2/M phase transition via ATM/Chk pathway in p53‐deficient leukemia HL‐60 cells. Environmental Toxicology 2017, 32 (4) , 1290-1304. https://doi.org/10.1002/tox.22324
    15. Jiyoung Park, Hyeung-Jin Jang. Anti-diabetic effects of natural products an overview of therapeutic strategies. Molecular & Cellular Toxicology 2017, 13 (1) , 1-20. https://doi.org/10.1007/s13273-017-0001-1
    16. Chien-Ning Huang, Chau-Jong Wang, Yi-Sun Yang, Chih-Li Lin, Chiung-Huei Peng. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance. Food & Function 2016, 7 (1) , 475-482. https://doi.org/10.1039/C5FO00464K
    17. Chiung-Huei Peng, Charng-Cherng Chyau, Chau-Jong Wang, Huei-Ting Lin, Chien-Ning Huang, Yaw-Bee Ker. Abelmoschus esculentus fractions potently inhibited the pathogenic targets associated with diabetic renal epithelial to mesenchymal transition. Food & Function 2016, 7 (2) , 728-740. https://doi.org/10.1039/C5FO01214G
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    Journal of Agricultural and Food Chemistry

    Cite this: J. Agric. Food Chem. 2014, 62, 40, 9736–9743
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jf5024092
    Published September 16, 2014
    Copyright © 2014 American Chemical Society
    Request reuse permissions

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