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2000
Volume 25, Issue 13
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.

Objective

Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl-induced hepatic fibrosis and explored the autophagy pathway as the possible molecular target of chlorogenic acid.

Methods

Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.

Results

CCl elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.

Conclusion

Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.

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2025-10-22
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References

  1. D’AmicoG. MorabitoA. D’AmicoM. PastaL. MaliziaG. ReboraP. ValsecchiM.G. New concepts on the clinical course and stratification of compensated and decompensated cirrhosis.Hepatol. Int.201812S1344310.1007/s12072‑017‑9808‑z28681347
    [Google Scholar]
  2. LlovetJ.M. Zucman-RossiJ. PikarskyE. SangroB. SchwartzM. ShermanM. GoresG. Hepatocellular carcinoma.Nat. Rev. Dis. Primers2016211601810.1038/nrdp.2016.1827158749
    [Google Scholar]
  3. MarcellinP. KutalaB.K. Liver diseases: A major, neglected global public health problem requiring urgent actions and large‐scale screening.Liver Int.201838S12610.1111/liv.1368229427496
    [Google Scholar]
  4. IredaleJ.P. Models of liver fibrosis: Exploring the dynamic nature of inflammation and repair in a solid organ.J. Clin. Invest.2007117353954810.1172/JCI3054217332881
    [Google Scholar]
  5. ChangS.N. KimS.H. DeyD.K. ParkS.M. NasifO. BajpaiV.K. KangS.C. LeeJ. ParkJ.G. 5-O-Demethylnobiletin alleviates CCl4-Induced acute liver injury by equilibrating ros-mediated apoptosis and autophagy induction.Int. J. Mol. Sci.2021223108310.3390/ijms2203108333499185
    [Google Scholar]
  6. HuangH.L. WangY.J. ZhangQ.Y. LiuB. WangF.Y. LiJ.J. ZhuR.Z. Hepatoprotective effects of baicalein against CCl 4 -induced acute liver injury in mice.World J. Gastroenterol.201218456605661310.3748/wjg.v18.i45.660523236235
    [Google Scholar]
  7. MizushimaN. KomatsuM. Autophagy: Renovation of cells and tissues.Cell2011147472874110.1016/j.cell.2011.10.02622078875
    [Google Scholar]
  8. ThoenL.F.R. GuimarãesE.L.M. DolléL. MannaertsI. NajimiM. SokalE. van GrunsvenL.A. A role for autophagy during hepatic stellate cell activation.J. Hepatol.20115561353136010.1016/j.jhep.2011.07.01021803012
    [Google Scholar]
  9. YeH.L. ZhangJ.W. ChenX.Z. WuP.B. ChenL. ZhangG. Ursodeoxycholic acid alleviates experimental liver fibrosis involving inhibition of autophagy.Life Sci.202024211717510.1016/j.lfs.2019.11717531843528
    [Google Scholar]
  10. NiH.M. WoolbrightB.L. WilliamsJ. CoppleB. CuiW. LuyendykJ.P. JaeschkeH. DingW.X. Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy.J. Hepatol.201461361762510.1016/j.jhep.2014.04.04324815875
    [Google Scholar]
  11. ZhangF. NiY. YuanY. YinW. GaoY. Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model.Sci. China Life Sci.201861111369138110.1007/s11427‑017‑9268‑y29961236
    [Google Scholar]
  12. TanejaS. KumarP. DusejaA. SinghV. DhimanR.K. ChawlaY. Honeycomb cyst of the liver.J. Clin. Exp. Hepatol.20166325025110.1016/j.jceh.2016.03.00127746624
    [Google Scholar]
  13. EllisE.L. MannD.A. Clinical evidence for the regression of liver fibrosis.J. Hepatol.20125651171118010.1016/j.jhep.2011.09.02422245903
    [Google Scholar]
  14. MXu. Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: Inhibition by dietary fisetin intervention.Food & Function201910313021316
    [Google Scholar]
  15. LatiefU.U.L. AhmadR.R.A. Herbal remedies for liver fibrosis: A review on the mode of action of fifty herbs.J. Tradit. Med. Complement.201783352360
    [Google Scholar]
  16. UpadhyayR.R.U. RaoL. An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities.Crit. Rev. Food Sci. Nutr.2013539968984
    [Google Scholar]
  17. KremrD. BajerT. BajerováP. SurmováS. VenturaK. Unremitting problems with chlorogenic acid nomenclature: A review.Quim. Nova20163953053310.5935/0100‑4042.20160063
    [Google Scholar]
  18. LukitasariM. NugrohoD.A. WidodoN. Chlorogenic acid: The conceivable chemosensitizer leading to cancer growth suppression.J. Evid. Based Integr. Med.2018232515690X18789628
    [Google Scholar]
  19. YangF. LuoL. ZhuZ.D. ZhouX. WangY. XueJ. ZhangJ. CaiX. ChenZ.L. MaQ. ChenY.F. WangY.J. LuoY.Y. LiuP. ZhaoL. Chlorogenic acid inhibits liver fibrosis by blocking the miR-21-regulated TGF-β1/Smad7 signaling pathway in vitro and in vivo.Front. Pharmacol.2017892910.3389/fphar.2017.0092929311932
    [Google Scholar]
  20. ShiH. DongL. BaiY. ZhaoJ. ZhangY. ZhangL. Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats.Eur. J. Pharmacol.20096231-311912410.1016/j.ejphar.2009.09.02619786014
    [Google Scholar]
  21. LiuX. HuangK. NiuZ. MeiD. ZhangB. Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice.Basic Clin. Pharmacol. Toxicol.2019124214415310.1111/bcpt.1312230180301
    [Google Scholar]
  22. BarghiM. AshrafiM. AminlariM. NamaziF. NazifiS. The protective effect of Zataria multiflora Boiss essential oil on CCl 4 induced liver fibrosis in rats.Drug Chem. Toxicol.202144322923710.1080/01480545.2019.157150230746963
    [Google Scholar]
  23. TappelA.L. ZalkinH. Inhibition of lipide peroxidation in mitochondria by vitamin E.Arch. Biochem. Biophys.195980233333610.1016/0003‑9861(59)90259‑0
    [Google Scholar]
  24. JollowD.J. MitchellJ.R. ZampaglioneN. GilletteJ.R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite.Pharmacology197411315116910.1159/0001364854831804
    [Google Scholar]
  25. SchmittgenT.D. Real-time quantitative PCR.Methods.200125438338510.1006/meth.2001.1260
    [Google Scholar]
  26. RoehlenN. CrouchetE. BaumertT.F. Liver fibrosis: Mechanistic concepts and therapeutic perspectives.Cells20209487510.3390/cells904087532260126
    [Google Scholar]
  27. GilgenkrantzH. MallatA. MoreauR. LotersztajnS. Targeting cell-intrinsic metabolism for antifibrotic therapy.J. Hepatol.20217461442145410.1016/j.jhep.2021.02.01233631228
    [Google Scholar]
  28. ShanL. WangF. ZhaiD. MengX. LiuJ. LvX. New drugs for hepatic fibrosis.Front. Pharmacol.20221387440810.3389/fphar.2022.87440835770089
    [Google Scholar]
  29. RosadaM. WasityastutiW. PratamaY.Y. SiwiK. WidasariD.I. WahyuniT.S. The effects of high-fat diet and CCl4 administration on liver function and lipid profile in non-alcoholic fatty liver disease rat model7th International Conference on Biological Science202110.2991/absr.k.220406.075
    [Google Scholar]
  30. LeeU.E. FriedmanS.L. Mechanisms of hepatic fibrogenesis.Best Pract. Res. Clin. Gastroenterol.201125219520610.1016/j.bpg.2011.02.00521497738
    [Google Scholar]
  31. ShenH. ShengL. ChenZ. JiangL. SuH. YinL. OmaryM.B. RuiL. Mouse hepatocyte overexpression of NF‐κB‐inducing kinase (NIK) triggers fatal macrophage‐dependent liver injury and fibrosis.Hepatology20146062065207610.1002/hep.2734825088600
    [Google Scholar]
  32. KusogluA. BagcaB.G. AyN.P.O. SaydamG. AvciC.B. Ruxolitinib regulates the autophagy machinery in multiple myeloma cells.Anticancer. Agents Med. Chem.202020182316232310.2174/187152062066620021810515932067619
    [Google Scholar]
  33. KeP.Y. Diverse functions of autophagy in liver physiology and liver diseases.Int. J. Mol. Sci.201920230010.3390/ijms2002030030642133
    [Google Scholar]
  34. KhambuB. YanS. HudaN. LiuG. YinX-M. Homeostatic role of autophagy in hepatocytes, Seminars in liver disease.Thieme Medical Publishers2018308319
    [Google Scholar]
  35. ZhangX.W. ZhouJ.C. PengD. HuaF. LiK. YuJ.J. LvX.X. CuiB. LiuS.S. YuJ.M. WangF. JinC.C. YangZ.N. ZhaoC.X. HouX.Y. HuangB. HuZ.W. Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation.Autophagy202016578279610.1080/15548627.2019.163538331286822
    [Google Scholar]
  36. XuG. WangX. YuH. WangC. LiuY. ZhaoR. ZhangG. Beclin 1, LC3, and p62 expression in paraquat-induced pulmonary fibrosis.Hum. Exp. Toxicol.201938779480210.1177/096032711984263330977401
    [Google Scholar]
  37. LiW. JiangY. YuT.T. HaoW. WangG. Lycopene improves autophagy and attenuates carbon tetrachloride-induced hepatic fibrosis in rats.Croat. Med. J.202364424325510.3325/cmj.2023.64.24337654036
    [Google Scholar]
  38. KouroumalisE. VoumvourakiA. AugoustakiA. SamonakisD.N. Autophagy in liver diseases.World J. Hepatol.202113166510.4254/wjh.v13.i1.633584986
    [Google Scholar]
  39. XuZ. HanX. OuD. LiuT. LiZ. JiangG. LiuJ. ZhangJ. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy.Appl. Microbiol. Biotechnol.2020104257558710.1007/s00253‑019‑10257‑831832711
    [Google Scholar]
  40. XueJ.F. ShiZ.M. ZouJ. LiX.L. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis.Biomed. Pharmacother.2017891252126110.1016/j.biopha.2017.01.13028320092
    [Google Scholar]
  41. ZhuL. MouQ. WangY. ZhuZ. ChengM. Resveratrol contributes to the inhibition of liver fibrosis by inducing autophagy via the microRNA‑20a‑mediated activation of the PTEN/PI3K/AKT signaling pathway.Int. J. Mol. Med.20204662035204610.3892/ijmm.2020.474833125088
    [Google Scholar]
  42. SatoY. ItagakiS. KurokawaT. OguraJ. KobayashiM. HiranoT. SugawaraM. IsekiK. In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid.Int. J. Pharm.20114031-213613810.1016/j.ijpharm.2010.09.03520933071
    [Google Scholar]
  43. GonthierM.P. VernyM.A. BessonC. RémésyC. ScalbertA. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats.J. Nutr.200313361853185910.1093/jn/133.6.185312771329
    [Google Scholar]
  44. HsuY.W. ChenY.Y. TsaiC.F. Protective effects of chlorogenic acid against carbon tetrachloride-induced hepatotoxicity in mice.Processes20211013110.3390/pr10010031
    [Google Scholar]
  45. LiH. ChenP. ChenL. WangX. The natural flavonoid naringenin inhibits the cell growth of wilms tumor in children by suppressing TLR4/NF-κB signaling.Anticancer. Agents Med. Chem.20212191120112610.2174/187152062099920081815581432819237
    [Google Scholar]
  46. Maria Letícia de CastroB. NF-κB signaling pathway inhibitors as anticancer drug candidates.Anticancer. Agents Med. Chem.201717483490
    [Google Scholar]
  47. HeX. PuG. TangR. ZhangD. PanW. Correction: Activation of nuclear factor kappa B in the hepatic stellate cells of mice with Schistosomiasis japonica.PLoS One20201512e024366710.1371/journal.pone.024366733332436
    [Google Scholar]
  48. ZhaoJ. HeB. ZhangS. HuangW. LiX. Ginsenoside Rg1 alleviates acute liver injury through the induction of autophagy and suppressing NF-κB/NLRP3 inflammasome signaling pathway.Int. J. Med. Sci.20211861382138910.7150/ijms.5091933628094
    [Google Scholar]
  49. WangX. LiuJ. XieZ. RaoJ. XuG. HuangK. LiW. YinZ. Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway.J. Pharm. Pharmacol.20197171100110910.1111/jphp.1309530989669
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): Beclin-1; CCl4, mTOR; Chlorogenic acid; hepatic fibrosis; LC3
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