Skip to main content
Log in

Hypoglycemic mechanism of polysaccharide from Cyclocarya paliurus leaves in type 2 diabetic rats by gut microbiota and host metabolism alteration

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Diabetes mellitus is a serious threat to human health. Cyclocarya paliurus (Batal.) Iljinskaja (C.paliurus) is one of the traditional herbal medicine and food in China for treating type 2 diabetes, and the C. paliurus polysaccharides (CP) were found to be one of its major functional constituents. This research aimed at investigating the hypoglycemic mechanism for CP. It was found that CP markedly attenuated the symptoms of diabetes, and inhibited the protein expression of Bax, improved the expression of Bcl-2 in pancreas of diabetic rats, normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreatic β-cell and insulin resistance. CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes, and the fecal short-chain fatty acids levels were elevated. Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism (amino acids and purine) and energy metabolism (TCA cycle), which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes. Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Amato, K.R., Yeoman, C.J., Kent, A., Righini, N., Carbonero, F., Estrada, A., Rex Gaskins, H., Stumpf, R.M., Yildirim, S., Torralba, M., et al. (2013). Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes. ISME J 7, 1344–1353.

    CAS  PubMed  PubMed Central  Google Scholar 

  • American Diabetes Association. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care 37, S81–S90.

    Google Scholar 

  • Bergman, E.N. (1990). Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev 70, 567–590.

    CAS  PubMed  Google Scholar 

  • Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R.A., and Butler, P.C. (2003). β-cell deficit and increasedβ-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102–110.

    CAS  Google Scholar 

  • Cani, P.D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A.M., Delzenne, N.M., and Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 1470–1481.

    CAS  PubMed  Google Scholar 

  • Chang, C.J., Lin, C.S., Lu, C.C., Martel, J., Ko, Y.F., Ojcius, D.M., Tseng, S.F., Wu, T.R., Chen, Y.Y.M., Young, J.D., et al. (2015). Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 6, 7489.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cox, A.J., West, N.P., and Cripps, A.W. (2015). Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol 3, 207–215.

    CAS  PubMed  Google Scholar 

  • De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., and Mithieux, G. (2014). Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96.

    CAS  PubMed  Google Scholar 

  • Ehses, J.A., Lacraz, G., Giroix, M.H., Schmidlin, F., Coulaud, J., Kassis, N., Irminger, J.C., Kergoat, M., Portha, B., Homo-Delarche, F., et al. (2009). IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Natl Acad Sci USA 106, 13998–14003.

    CAS  PubMed  Google Scholar 

  • Everard, A., Lazarevic, V., Derrien, M., Girard, M., Muccioli, G.G., Muccioli, G.M., Neyrinck, A.M., Possemiers, S., Van Holle, A., François, P., et al. (2011). Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775–2786.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fugmann, M., Breier, M., Rottenkolber, M., Banning, F., Ferrari, U., Sacco, V., Grallert, H., Parhofer, K.G., Seissler, J., Clavel, T., et al. (2015). The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. Sci Rep 5, 13212.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Furet, J.P., Kong, L.C., Tap, J., Poitou, C., Basdevant, A., Bouillot, J.L., Mariat, D., Corthier, G., Doré, J., Henegar, C., et al. (2010). Differential Adaptation of Human Gut Microbiota to Bariatric Surgery-Induced Weight Loss: Links With Metabolic and Low-Grade Inflammation Markers. Diabetes 59, 3049–3057.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gagen, E.J., Padmanabha, J., Denman, S.E., and McSweeney, C.S. (2015). Hydrogenotrophic culture enrichment reveals rumen Lachnospiraceae and Ruminococcaceae acetogens and hydrogen-responsive Bacteroidetes from pasture-fed cattle. FEMS Microbiol Lett 362, fnv104.

    PubMed  Google Scholar 

  • Hu, C., and Jia, W. (2018). Diabetes in China: epidemiology and genetic risk factors and their clinical utility in personalized medication. Diabetes 67, 3–11.

    CAS  PubMed  Google Scholar 

  • Hu, J.L., Nie, S.P., Min, F.F., and Xie, M.Y. (2012). Polysaccharide from seeds of Plantago asiatica L. increases short-chain fatty acid production and fecal moisture along with lowering pH in mouse colon. J Agric Food Chem 60, 11525–11532.

    CAS  PubMed  Google Scholar 

  • Huang, L., Gao, R., Yu, N., Zhu, Y., Ding, Y., and Qin, H. (2019). Dysbiosis of gut microbiota was closely associated with psoriasis. Sci China Life Sci 62, 807–815.

    CAS  PubMed  Google Scholar 

  • Jiang, C., Wang, Q., Wei, Y.J., Yao, N., Wu, Z., Ma, Y., Lin, Z., Zhao, M., Che, C., Yao, X., et al. (2015). Cholesterol-lowering effects and potential mechanisms of different polar extracts from Cyclocarya paliurus leave in hyperlipidemic mice. J Ethnopharmacol 176, 17–26.

    CAS  PubMed  Google Scholar 

  • Jin, M., Zhao, K., Huang, Q., and Shang, P. (2014). Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol 64, 257–266.

    CAS  PubMed  Google Scholar 

  • Kovatcheva-Datchary, P., Nilsson, A., Akrami, R., Lee, Y.S., De Vadder, F., Arora, T., Hallen, A., Martens, E., Björck, I., and Bäckhed, F. (2015). Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab 22, 971–982.

    CAS  PubMed  Google Scholar 

  • Lozupone, C., Lladser, M.E., Knights, D., Stombaugh, J., and Knight, R. (2011). UniFrac: an effective distance metric for microbial community comparison. ISME J 5, 169–172.

    PubMed  Google Scholar 

  • Maslowski, K.M., Vieira, A.T., Ng, A., Kranich, J., Sierro, F., Schilter, H. C., Rolph, M.S., Mackay, F., Artis, D., Xavier, R.J., et al. (2009). Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nie, Q., Chen, H., Hu, J., Gao, H., Fan, L., Long, Z., and Nie, S. (2018). Arabinoxylan attenuates type 2 diabetes by improvement of carbohydrate, lipid, and amino acid metabolism. Mol Nutr Food Res 62, 1800222.

    Google Scholar 

  • Nie, Q., Hu, J., Gao, H., Fan, L., Chen, H., and Nie, S. (2019). Polysaccharide from Plantago asiatica L. attenuates hyperglycemia, hyperlipidemia and affects colon microbiota in type 2 diabetic rats. Food Hydrocolloids 86, 34–42.

    CAS  Google Scholar 

  • Qin, C., Zhang, H., Zhao, L., Zeng, M., Huang, W., Fu, G., Zhou, W., Wang, H., and Yan, H. (2018). Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis. Sci China Life Sci 61, 1537–1544.

    CAS  PubMed  Google Scholar 

  • Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60.

    CAS  PubMed  Google Scholar 

  • Shi, H., Kokoeva, M.V., Inouye, K., Tzameli, I., Yin, H., and Flier, J.S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116, 3015–3025.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, N.R., Lee, J.C., Lee, H.Y., Kim, M.S., Whon, T.W., Lee, M.S., and Bae, J.W. (2014). An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735.

    CAS  PubMed  Google Scholar 

  • Sina, C., Gavrilova, O., Förster, M., Till, A., Derer, S., Hildebrand, F., Raabe, B., Chalaris, A., Scheller, J., Rehmann, A., et al. (2009). G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol 183, 7514–7522.

    CAS  PubMed  Google Scholar 

  • Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly-Y, M., Glickman, J.N., and Garrett, W.S. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573.

    CAS  PubMed  Google Scholar 

  • Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J.J., Blugeon, S., Bridonneau, C., Furet, J.P., Corthier, G., et al. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105, 16731–16736.

    CAS  PubMed  Google Scholar 

  • Sommer, F., Anderson, J.M., Bharti, R., Raes, J., and Rosenstiel, P. (2017). The resilience of the intestinal microbiota influences health and disease. Nat Rev Microbiol 15, 630–638.

    CAS  PubMed  Google Scholar 

  • Sonnenburg, E.D., Zheng, H., Joglekar, P., Higginbottom, S.K., Firbank, S. J., Bolam, D.N., and Sonnenburg, J.L. (2010). Specificity of polysaccharide use in intestinal Bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241–1252.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stone, R. (2008). Lifting the veil on traditional Chinese medicine. Science 319, 709–710.

    CAS  PubMed  Google Scholar 

  • Tahrani, A.A., Barnett, A.H., and Bailey, C.J. (2016). Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nat Rev Endocrinol 12, 566–592.

    CAS  PubMed  Google Scholar 

  • Tang, J.L., Liu, B.Y., and Ma, K.W. (2008). Traditional Chinese medicine. Lancet 372, 1938–1940.

    PubMed  Google Scholar 

  • Tilg, H., and Moschen, A.R. (2014). Microbiota and diabetes: an evolving relationship. Gut 63, 1513–1521.

    CAS  PubMed  Google Scholar 

  • Tolhurst, G., Heffron, H., Lam, Y.S., Parker, H.E., Habib, A.M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., and Gribble, F.M. (2012). Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364–371.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tramontano, M., Andrejev, S., Pruteanu, M., Klünemann, M., Kuhn, M., Galardini, M., Jouhten, P., Zelezniak, A., Zeller, G., Bork, P., et al. (2018). Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nat Microbiol 3, 514–522.

    CAS  PubMed  Google Scholar 

  • Tremaroli, V., and Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249.

    CAS  PubMed  Google Scholar 

  • Wang, Z., Xie, J., Yang, Y., Zhang, F., Wang, S., Wu, T., Shen, M., and Xie, M. (2017). Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice. Sci Rep 7, 40402.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wen, S., Wang, C., Gong, M., and Zhou, L. (2019). An overview of energy and metabolic regulation. Sci China Life Sci 62, 771–790.

    PubMed  Google Scholar 

  • Xie, J.H., Xie, M.Y., Nie, S.P., Shen, M.Y., Wang, Y.X., and Li, C. (2010). Isolation, chemical composition and antioxidant activities of a water-soluble polysaccharide from Cyclocarya paliurus (Batal.) Iljinskaja. Food Chem 119, 1626–1632.

    CAS  Google Scholar 

  • Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M.A., Motoike, T., Kedzierski, R.M., and Yanagisawa, M. (2004). Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci USA 101, 1045–1050.

    CAS  PubMed  Google Scholar 

  • Xu, J., Lian, F., Zhao, L., Zhao, Y., Chen, X., Zhang, X., Guo, Y., Zhang, C., Zhou, Q., Xue, Z., et al. (2015). Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J 9, 552–562.

    PubMed  Google Scholar 

  • Yang, Z.W., Ouyang, K.H., Zhao, J., Chen, H., Xiong, L., and Wang, W.J. (2016). Structural characterization and hypolipidemic effect of Cyclocarya paliurus polysaccharide in rat. Int J Biol Macromol 91, 1073–1080.

    CAS  PubMed  Google Scholar 

  • Zhang, X., Duan, X., Liu, X., Liang, C., and Xiao, S. (2010). The effectof Cyclocarya paliurus polysaccharide (CP) on blood glucose and histo-morphology of pancreas in diabetic mice (in Chinese). Acta Med Sin 23, 15–17.

    Google Scholar 

  • Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y.Y., Wang, X., Fu, H., Xue, X., Lu, C., Ma, J., et al. (2018). Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156.

    CAS  PubMed  Google Scholar 

  • Zhu, H.Y., Chen, G.T., Meng, G.L., and Xu, J.L. (2015). Characterization of pumpkin polysaccharides and protective effects on streptozotocin-damaged islet cells (in Chinese). Chin J Nat Med 13, 199–207.

    CAS  PubMed  Google Scholar 

  • Zhu, K., Nie, S., Song, D., Li, C., Lin, S., and Xie, M. (2013). Protective effect of polysaccharide from Ganoderma atrum on fasting blood glucose, serum lipids and arteriosclerotic narrowing of superior me-senteric arteries in type II diabetic rats (in Chinese). Food Sci 34, 300–304.

    CAS  Google Scholar 

  • Zhu, K.X., Nie, S.P., Li, C., Gong, D., and Xie, M.Y. (2014). Ganoderma atrum polysaccharide improves aortic relaxation in diabetic rats via PI3K/Akt pathway. Carbohyd Polym 103, 520–527.

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China for Distinguished Young Scholars (31825020), the Outstanding Science and Technology Innovation Team Project in Jiangxi Province (20165BCB19001), the Project of Academic Leaders of the Major Disciplines in Jiangxi Province (20162BCB22008), the Young Key Project of Natural Science Foundation of Jiangxi Province (20171ACB21013), the Collaborative Project in Agriculture and Food Field between China and Canada (2017ZJGH0102001), and the Research Project of State Key Laboratory of Food Science and Technology (SKLF-ZZA-201611). We thank all the volunteers for their help in collecting samples of animal tissues and feces.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shaoping Nie.

Ethics declarations

Compliance and ethics The author(s) declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Q., Hu, J., Nie, Q. et al. Hypoglycemic mechanism of polysaccharide from Cyclocarya paliurus leaves in type 2 diabetic rats by gut microbiota and host metabolism alteration. Sci. China Life Sci. 64, 117–132 (2021). https://doi.org/10.1007/s11427-019-1647-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-019-1647-6

Keywords

Navigation