Corn silk ameliorates fatty liver disease by modulating the gut microbiota and metabolites in the serum and liver

1. Sheka, A. C. et al. Nonalcoholic steatohepatitis: A review. JAMA 323, 1175–1183. https://doi.org/10.1001/jama.2020.2298 (2020).

   Google Scholar 

2. Younossi, Z. et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 15, 11–20. https://doi.org/10.1038/nrgastro.2017.109 (2018).

   Google Scholar 

3. Yan, T. et al. Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharm. Sin. B 10, 3–18. https://doi.org/10.1016/j.apsb.2019.11.017 (2020).

   Google Scholar 

4. Li, J. et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct. 12, 3898–3918. https://doi.org/10.1039/d0fo02736g (2021).

   Google Scholar 

5. Wang, S. et al. Isoliensinine from plumula nelumbinis attenuates hepatic fibrosis in metabolic associated fatty liver disease through regulating lipid droplet metabolism. J. Futur. Food. https://doi.org/10.1016/j.jfutfo.2025.07.022 (2025).

   Google Scholar 

6. Cao, L. et al. Cornus officinalis vinegar alters the gut microbiota, regulating lipid droplet changes in nonalcoholic fatty liver disease model mice. Food Med. Homol. https://doi.org/10.26599/fmh.2024.9420002 (2024).

   Google Scholar 

7. Cai, T. et al. Effects of plant natural products on metabolic-associated fatty liver disease and the underlying mechanisms: A narrative review with a focus on the modulation of the gut microbiota. Front. Cell. Infect. Microbiol. 14, 1323261. https://doi.org/10.3389/fcimb.2024.1323261 (2024).

   Google Scholar 

8. Huang, Y. et al. Oroxin B improves metabolic-associated fatty liver disease by alleviating gut microbiota dysbiosis in a high-fat diet-induced rat model. Eur. J. Pharmacol. 951, 175788. https://doi.org/10.1016/j.ejphar.2023.175788 (2023).

   Google Scholar 

9. Hao, X.-T. et al. The food and medicinal homological resources benefiting patients with hyperlipidemia: Categories, functional components, and mechanisms. Food Med. Homol. https://doi.org/10.26599/fmh.2024.9420003 (2024).

   Google Scholar 

10. Zhang, Z., Wang, S., Liu, Q., Cao, G. & Liu, Y. Extraction, purification, structural characteristics, and pharmacological activities of the polysaccharides from corn silk: A review. Int. J. Biol. Macromol. 274, 133433. https://doi.org/10.1016/j.ijbiomac.2024.133433 (2024).

    Google Scholar 

11. George, G. O. & Idu, F. K. Corn silk aqueous extracts and intraocular pressure of systemic and non-systemic hypertensive subjects. Clin. Exp. Optom. 98, 138–149. https://doi.org/10.1111/cxo.12240 (2015).

    Google Scholar 

12. Chaudhary, R. K., Karoli, S. S., Dwivedi, P. S. R. & Bhandari, R. Anti-diabetic potential of corn silk (Stigma maydis): An in-silico approach. J. Diabet. Metab. Disord. 21, 445–454. https://doi.org/10.1007/s40200-022-00992-7 (2022).

    Google Scholar 

13. Hasanudin, K., Hashim, P. & Mustafa, S. Corn silk (Stigma maydis) in healthcare: A phytochemical and pharmacological review. Molecules 17, 9697–9715. https://doi.org/10.3390/molecules17089697 (2012).

    Google Scholar 

14. Singh, J., Rasane, P., Nanda, V. & Kaur, S. Bioactive compounds of corn silk and their role in management of glycaemic response. J. Food Sci. Technol. 60, 1695–1710. https://doi.org/10.1007/s13197-022-05442-z (2023).

    Google Scholar 

15. Cha, J. H. et al. Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat diets. Nutr. Res. Pract. 10, 501–506. https://doi.org/10.4162/nrp.2016.10.5.501 (2016).

    Google Scholar 

16. Mohammadi, A. et al. Hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice. Gastroenterol. Hepatol. Bed Bench 17, 64–73. https://doi.org/10.22037/ghfbb.v17i1.2806 (2024).

    Google Scholar 

17. Ding, L. et al. Modulation of gut microbiota and fecal metabolites by corn silk among high-fat diet-induced hypercholesterolemia mice. Front. Nutr. 9, 935612. https://doi.org/10.3389/fnut.2022.935612 (2022).

    Google Scholar 

18. Liu, Q. et al. Rapid discovery and global characterization of multiple components in corn silk using a multivariate data processing approach based on UHPLC coupled with electrospray ionization/quadrupole time-of-flight mass spectrometry. J. Sep. Sci. 41, 4022–4030. https://doi.org/10.1002/jssc.201800605 (2018).

    Google Scholar 

19. Khan, U. et al. Optimizing extraction conditions and isolation of bound phenolic compounds from corn silk (Stigma maydis) and their antioxidant effects. J. Food Sci. 88, 3341–3356. https://doi.org/10.1111/1750-3841.16682 (2023).

    Google Scholar 

20. Wang, B., Xiao, T., Ruan, J. & Liu, W. Beneficial effects of corn silk on metabolic syndrome. Curr. Pharm. Des. 23, 5097–5103. https://doi.org/10.2174/1381612823666170926152425 (2017).

    Google Scholar 

21. Oh, K. K., Adnan, M. & Cho, D. H. Elucidating drug-like compounds and potential mechanisms of corn silk (Stigma maydis) against obesity: A network pharmacology study. Curr. Issues Mol. Biol. 43, 1906–1936. https://doi.org/10.3390/cimb43030133 (2021).

    Google Scholar 

22. Wang, X., Dong, L., Dong, Y., Bao, Z. & Lin, S. Corn silk flavonoids ameliorate hyperuricemia via PI3K/AKT/NF-kappaB pathway. J. Agric. Food Chem. 71, 9429–9440. https://doi.org/10.1021/acs.jafc.3c03422 (2023).

    Google Scholar 

23. Wang, X. et al. Research on the mechanism and material basis of corn (Zea mays L.) waste regulating dyslipidemia. Pharmaceuticals (Basel) https://doi.org/10.3390/ph17070868 (2024).

    Google Scholar 

24. Lambert, J. E., Ramos-Roman, M. A., Browning, J. D. & Parks, E. J. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146, 726–735. https://doi.org/10.1053/j.gastro.2013.11.049 (2014).

    Google Scholar 

25. Sakurai, Y., Kubota, N., Yamauchi, T. & Kadowaki, T. Role of insulin resistance in MAFLD. Int. J. Mol. Sci. https://doi.org/10.3390/ijms22084156 (2021).

    Google Scholar 

26. Hotamisligil, G. S. & Erbay, E. Nutrient sensing and inflammation in metabolic diseases. Nat. Rev. Immunol. 8, 923–934. https://doi.org/10.1038/nri2449 (2008).

    Google Scholar 

27. Tilg, H. & Moschen, A. R. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology 52, 1836–1846. https://doi.org/10.1002/hep.24001 (2010).

    Google Scholar 

28. McCall, K. D. et al. Anti-inflammatory and therapeutic effects of a novel small-molecule inhibitor of inflammation in a male C57BL/6J mouse model of obesity-induced NAFLD/MAFLD. J. Inflamm. Res. 16, 5339–5366. https://doi.org/10.2147/JIR.S413565 (2023).

    Google Scholar 

29. Fujio-Vejar, S. et al. The gut microbiota of healthy Chilean subjects reveals a high abundance of the phylum Verrucomicrobia. Front. Microbiol. 8, 1221. https://doi.org/10.3389/fmicb.2017.01221 (2017).

    Google Scholar 

30. Zhai, Q., Feng, S., Arjan, N. & Chen, W. A next generation probiotic, Akkermansia muciniphila. Crit. Rev. Food Sci. Nutr. 59, 3227–3236. https://doi.org/10.1080/10408398.2018.1517725 (2019).

    Google Scholar 

31. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. U. S. A. 110, 9066–9071. https://doi.org/10.1073/pnas.1219451110 (2013).

    Google Scholar 

32. Nian, F. et al. Akkermansia muciniphila and Bifidobacterium bifidum prevent NAFLD by regulating FXR expression and gut microbiota. J. Clin. Transl. Hepatol. 11, 763–776. https://doi.org/10.14218/JCTH.2022.00415 (2023).

    Google Scholar 

33. Juarez-Fernandez, M. et al. The synbiotic combination of Akkermansia muciniphila and Quercetin ameliorates early obesity and NAFLD through gut microbiota reshaping and bile acid metabolism modulation. Antioxidants https://doi.org/10.3390/antiox10122001 (2021).

    Google Scholar 

34. Wu, G. et al. A core microbiome signature as an indicator of health. Cell 187, 6550-6565 e6511. https://doi.org/10.1016/j.cell.2024.09.019 (2024).

    Google Scholar 

35. Li, F., Wang, M., Wang, J., Li, R. & Zhang, Y. Alterations to the gut microbiota and their correlation with inflammatory factors in chronic kidney disease. Front. Cell. Infect. Microbiol. 9, 206. https://doi.org/10.3389/fcimb.2019.00206 (2019).

    Google Scholar 

36. Traughber, C. A. et al. Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice. bioRxiv https://doi.org/10.1101/2023.10.17.562757 (2023).

    Google Scholar 

37. Yuan, Y. et al. Combinations of Tibetan tea and medicine food homology herbs: A new strategy for obesity prevention. Food Sci. Nutr. 11, 504–515. https://doi.org/10.1002/fsn3.3081 (2023).

    Google Scholar 

38. Jiang, M. et al. Effects of buffalo milk and cow milk on lipid metabolism in obese mice induced by high fat. Front. Nutr. 9, 841800. https://doi.org/10.3389/fnut.2022.841800 (2022).

    Google Scholar 

39. Yang, J. et al. PAMK ameliorates non-alcoholic steatohepatitis and associated anxiety/depression-like behaviors through restoring gut microbiota and metabolites in mice. Nutrients https://doi.org/10.3390/nu16223837 (2024).

    Google Scholar 

40. Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M. & Trauner, M. Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives. Hepatology 65, 350–362. https://doi.org/10.1002/hep.28709 (2017).

    Google Scholar 

41. Jiao, N. et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut 67, 1881–1891. https://doi.org/10.1136/gutjnl-2017-314307 (2018).

    Google Scholar 

42. Torres, S. et al. Unravelling the metabolic alterations of liver damage induced by thirdhand smoke. Environ. Int. 146, 106242. https://doi.org/10.1016/j.envint.2020.106242 (2021).

    Google Scholar 

43. Wang, R., Yao, L., Lin, X., Hu, X. & Wang, L. Exploring the potential mechanism of Rhodomyrtus tomentosa (Ait.) Hassk fruit phenolic rich extract on ameliorating nonalcoholic fatty liver disease by integration of transcriptomics and metabolomics profiling. Food Res. Int. 151, 110824. https://doi.org/10.1016/j.foodres.2021.110824 (2022).

    Google Scholar 

44. Hu, J. P. et al. Effects of Lactobacillus plantarum FZU3013-fermented Laminaria japonica on lipid metabolism and gut microbiota in hyperlipidaemic rats. Front. Nutr. 8, 786571. https://doi.org/10.3389/fnut.2021.786571 (2021).

    Google Scholar 

45. Chen, Z., Tian, R., She, Z., Cai, J. & Li, H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic. Biol. Med. 152, 116–141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025 (2020).

    Google Scholar 

Download references