Skip to content
2000
Volume 28, Issue 17
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Purpose

miR-122 is upregulated in non-alcoholic fatty liver disease (NAFLD) liver tissue, and knockdown of miR-122 protects hepatocytes from lipid metabolism disorders. This study aimed to investigate whether Huazhi Rougan Granule (HRG) alleviates NAFLD liver and intestinal injury by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

Methods

Rats with NAFLD were constructed by high-fat feeding. Serum levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using a fully automated biochemical instrument. Histopathological changes in the liver and small intestine were observed by HE staining. QRT-PCR detected the expression level of miR-122 in the liver tissues. The protein expression of TLR4, MyD88, NF-κB p65, and p-p65 in liver tissues was detected by western blotting.

Results

HRG slowed down the weight gain of NAFLD rats, decreased (<0.05) the levels of TC, TG, ALT, AST, TNF-α, IL-1β, IL-6, LPS, and Hpt, improved the pathological status of liver and small intestine tissues, upregulated (<0.05) the expression of ZO-1 and Occludin, down-regulated (<0.05) the protein expression of TLR4, MyD88, and p-p65, and inhibited (<0.05) the expression of miR-122.

Conclusion

HRG may alleviate hepatic and intestinal injuries in rats with NAFLD by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073290372240603090844
2024-11-19
2025-12-22

  • From This Site

    /content/journals/cchts/10.2174/0113862073290372240603090844
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AbdelmalekM.F. Nonalcoholic fatty liver disease: Another leap forward.Nat. Rev. Gastroenterol. Hepatol.2021182858610.1038/s41575‑020‑00406‑0 33420415
     [Google Scholar]
  2. MauriceJ. ManousouP. Non-alcoholic fatty liver disease.Clin. Med. (Lond.)201818324525010.7861/clinmedicine.18‑3‑245 29858436
     [Google Scholar]
  3. Carbajo-PescadorS. PorrasD. García-MediavillaM.V. Martínez-FlórezS. Juarez-FernándezM. CuevasM.J. MaurizJ.L. González-GallegoJ. NistalE. Sánchez-CamposS. Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease.Dis. Model. Mech.2019125dmm03920610.1242/dmm.039206 30971408
     [Google Scholar]
  4. BenceK.K. BirnbaumM.J. Metabolic drivers of non-alcoholic fatty liver disease.Mol. Metab.20215010114310.1016/j.molmet.2020.101143 33346069
     [Google Scholar]
  5. FilippatosT.D. AlexakisK. MavrikakiV. MikhailidisD.P. Nonalcoholic fatty pancreas disease: Role in Metabolic syndrome, “Prediabetes,” diabetes and atherosclerosis.Dig. Dis. Sci.2022671264110.1007/s10620‑021‑06824‑7 33469809
     [Google Scholar]
  6. BauerK.C. LittlejohnP.T. AyalaV. Creus-CuadrosA. FinlayB.B. Nonalcoholic fatty liver disease and the gut-liver axis: Exploring an undernutrition perspective.Gastroenterology202216271858187510.1053/j.gastro.2022.01.058
     [Google Scholar]
  7. Gómez-PérezA.M. Ruiz-LimónP. Salas-SalvadóJ. VioqueJ. CorellaD. FitóM. VidalJ. AtzeniA. Torres-ColladoL. Álvarez-SalaA. MartínezM.Á. GodayA. BenaigesD. García-GavilánJ. Bernal LópezM.R. Moreno-IndiasI. TinahonesF.J. Gut microbiota in nonalcoholic fatty liver disease: A PREDIMED-Plus trial sub analysis.Gut Microbes2023151222333910.1080/19490976.2023.2223339 37345236
     [Google Scholar]
  8. BatistaK.S. SoaresN.L. DorandV.A.M. AlvesA.F. dos Santos LimaM. de Alencar PereiraR. Leite de SouzaE. MagnaniM. PersuhnD.C. de Souza AquinoJ. Acerola fruit by-product alleviates lipid, glucose, and inflammatory changes in the enterohepatic axis of rats fed a high-fat diet.Food Chem.202340313432210.1016/j.foodchem.2022.134322 36166922
     [Google Scholar]
  9. ZouY. YanH. LiC. WenF. JizeX. ZhangC. LiuS. ZhaoY. FuY. LiL. LiuF. ChenJ. LiR. ChenX. TianM. A pectic polysaccharide from Codonopsis pilosula alleviates inflammatory response and oxidative stress of aging mice via modulating intestinal microbiota-related gut–liver axis.Antioxidants2023129178110.3390/antiox12091781 37760084
     [Google Scholar]
  10. FlingR.R. ZacharewskiT.R. Aryl Hydrocarbon Receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dose-dependently shifts the gut microbiome consistent with the progression of non-alcoholic fatty liver disease.Int. J. Mol. Sci.202122221243110.3390/ijms222212431 34830313
     [Google Scholar]
  11. SuzukiT. Regulation of the intestinal barrier by nutrients: The role of tight junctions.Anim. Sci. J.2020911e1335710.1111/asj.13357 32219956
     [Google Scholar]
  12. CheQ. LuoT. ShiJ. HeY. XuD.L. Mechanisms by which traditional chinese medicines influence the intestinal flora and intestinal barrier.Front. Cell. Infect. Microbiol.20221286377910.3389/fcimb.2022.863779 35573786
     [Google Scholar]
  13. ChenK. LinT. YaoW. ChenX. XiongX. HuangZ. Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1.Gastroenterol. Hepatol.202346753154110.1016/j.gastrohep.2022.12.003 36584755
     [Google Scholar]
  14. ZussoM. LunardiV. FranceschiniD. PagettaA. LoR. StifaniS. FrigoA.C. GiustiP. MoroS. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway.J. Neuroinflammation201916114810.1186/s12974‑019‑1538‑9 31319868
     [Google Scholar]
  15. WangQ. OuY. HuG. WenC. YueS. ChenC. XuL. XieJ. DaiH. XiaoH. ZhangY. QiR. Naringenin attenuates non‐alcoholic fatty liver disease by down‐regulating the NLRP3/NF‐κB pathway in mice.Br. J. Pharmacol.202017781806182110.1111/bph.14938 31758699
     [Google Scholar]
  16. LeeS.M. KohD.H. JunD.W. RohY.J. KangH.T. OhJ.H. KimH.S. Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- κB signaling pathways.Clin. Mol. Hepatol.202228482784010.3350/cmh.2022.0068 35730208
     [Google Scholar]
  17. WangT. SongJ. HuJ. FengS. ZhangH. WangH. LiB. Efficacy and safety of Huazhi Rougan granule in the treatment of non-alcoholic fatty liver: A systematic review and meta-analysis.Ann. Palliat. Med.20211012129691298410.21037/apm‑20‑1613 33691456
     [Google Scholar]
  18. LiuY. TanY. HuangJ. WuC. FanX. StalinA. LuS. WangH. ZhangJ. ZhangF. WuZ. LiB. HuangZ. ChenM. ChengG. MouY. WuJ. Revealing the mechanism of huazhi rougan granule in the treatment of nonalcoholic fatty liver through intestinal flora based on 16S rRNA, metagenomic sequencing and network pharmacology.Front. Pharmacol.20221387570010.3389/fphar.2022.875700 35559233
     [Google Scholar]
  19. IpsenD.H. LykkesfeldtJ. Tveden-NyborgP. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease.Cell. Mol. Life Sci.201875183313332710.1007/s00018‑018‑2860‑6 29936596
     [Google Scholar]
  20. LongJ.K. DaiW. ZhengY.W. ZhaoS.P. miR-122 promotes hepatic lipogenesis via inhibiting the LKB1/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease.Mol. Med.20192512610.1186/s10020‑019‑0085‑2 31195981
     [Google Scholar]
  21. PurohitV. RussoD. CoatesP.M. Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: Introduction and summary of the symposium.Alcohol20043413810.1016/j.alcohol.2004.06.008 15670659
     [Google Scholar]
  22. MunJ. KimS. YoonH.G. YouY. KimO.K. ChoiK.C. LeeY.H. LeeJ. ParkJ. JunW. Water extract of Curcuma longa L. ameliorates non-alcoholic fatty liver disease.Nutrients20191110253610.3390/nu11102536 31640183
     [Google Scholar]
  23. KimY. YouY. YoonH.G. LeeY.H. KimK. LeeJ. KimM.S. KimJ.C. JunW. Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats.Food Chem.201415114815310.1016/j.foodchem.2013.11.058 24423514
     [Google Scholar]
  24. AndersonN. BorlakJ. Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis.Pharmacol. Rev.200860331135710.1124/pr.108.00001 18922966
     [Google Scholar]
  25. PawlakM. LefebvreP. StaelsB. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease.J. Hepatol.201562372073310.1016/j.jhep.2014.10.039 25450203
     [Google Scholar]
  26. GuoS. Al-SadiR. SaidH.M. MaT.Y. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14.Am. J. Pathol.2013182237538710.1016/j.ajpath.2012.10.014 23201091
     [Google Scholar]
  27. FukunishiS. SujishiT. TakeshitaA. OhamaH. TsuchimotoY. AsaiA. TsudaY. HiguchiK. Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats.J. Clin. Biochem. Nutr.2014541394410.3164/jcbn.13‑49 24426189
     [Google Scholar]
  28. MaciejewskaD. ŁukomskaA. DecK. Skonieczna-ŻydeckaK. GutowskaI. Skórka-MajewiczM. StyburskiD. Misiakiewicz-HasK. PilutinA. PalmaJ. SieletyckaK. MarliczW. StachowskaE. Diet-Induced Rat Model of Gradual development of Non-Alcoholic Fatty Liver Disease (NAFLD) with Lipopolysaccharides (LPS) Secretion.Diagnostics (Basel)20199420510.3390/diagnostics9040205 31783667
     [Google Scholar]
  29. XinD. Zong-ShunL. Bang-MaoW. LuZ. Expression of intestinal tight junction proteins in patients with non-alcoholic fatty liver disease.Hepatogastroenterology201461129136140 24895809
     [Google Scholar]
  30. ShenS. WangK. ZhiY. DongY. Gypenosides counteract hepatic steatosis and intestinal barrier injury in rats with metabolic associated fatty liver disease by modulating the adenosine monophosphate activated protein kinase and Toll-like receptor 4/nuclear factor kappa B pathways.Pharm. Biol.20226011949195910.1080/13880209.2022.2126503 36205541
     [Google Scholar]
  31. JampokaK. MuangpaisarnP. KhongnomnanK. TreeprasertsukS. TangkijvanichP. PayungpornS. Serum miR-29a and miR-122 as Potential Biomarkers for Non-Alcoholic Fatty Liver Disease (NAFLD).MicroRNA20187321522210.2174/2211536607666180531093302 29848284
     [Google Scholar]
  32. YeD. ZhangT. LouG. XuW. DongF. ChenG. LiuY. Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients.Life Sci.201820820120710.1016/j.lfs.2018.07.029 30030064
     [Google Scholar]
  33. AkutaN. KawamuraY. SuzukiF. SaitohS. AraseY. FujiyamaS. SezakiH. HosakaT. KobayashiM. SuzukiY. KobayashiM. IkedaK. KumadaH. Analysis of association between circulating miR-122 and histopathological features of nonalcoholic fatty liver disease in patients free of hepatocellular carcinoma.BMC Gastroenterol.201616114110.1186/s12876‑016‑0557‑6 27955628
     [Google Scholar]
  34. WangL. JiaZ. WangB. ZhangB. Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4/MyD88/NF-κB pathway.Turk. J. Gastroenterol.2021311290290910.5152/tjg.2020.19568 33626003
     [Google Scholar]
  35. TangY.L. ZhuL. TaoY. LuW. ChengH. Role of targeting TLR4 signaling axis in liver-related diseases.Pathol. Res. Pract.202324415441010.1016/j.prp.2023.154410 36917917
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073290372240603090844
Loading
Huazhi Rougan Granule Alleviates Liver and Intestinal Damage in Non-Alcoholic Fatty Liver Disease by Regulating miR-122 Expression and TLR4/MyD88/NF-κB Pathway Activation
Comb Chem High Throughput Screen 28, 3002 (2025); https://doi.org/10.2174/0113862073290372240603090844
/content/journals/cchts/10.2174/0113862073290372240603090844
/content/journals/cchts/10.2174/0113862073290372240603090844
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): aspartate aminotransferase; intestinal injury; liver; miR-122; Non-alcoholic fatty liver; TLR4/MyD88/NF-κB pathway

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test