Skip to content
2000
Volume 25, Issue 4
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

Duk is a well-established traditional drug that has been used since time immemorial by Indian practitioners to cure various human ailments.

Objective

The purpose of this study was to explore the anti-cancer activity and the possible mechanism of Duk against diethylnitrosamine (DEN)-initiated hepatocarcinogenesis.

Methods

We administered Duk at 3 doses, , 75, 150, and 300 mg/kg/day, 2 weeks before the DEN and continued it for 16 weeks. After 1 week of DEN recovery, 2-aminoacetylflourine (2-AAF) was administered to promote hepatocarcinogenesis.

Results

We found that Duk significantly reduced the DEN and 2-AAF induced phenotypical changes in rats and restored the levels of liver function markers. Furthermore, Duk counteracted the oxidative stress induced by carcinogens as observed by restoration in the levels of superoxide dismutase (SOD) and catalase (CAT). Duk significantly diminished the levels of malondialdehyde (MDA) in a dose dependent manner and restored the liver microarchitecture as assessed by histopathological studies. The results of immunohistochemical staining showed that Duk inhibited the DEN-induced decrease in the number of cells positive for Bid and Caspase-9. It also reduces the number of cells positive for Cyclin D.

Conclusion

Duk significantly protects rat liver from hepatocarcinogenesis by regulating oxidative damage and restoring liver function markers. The chemopreventive effect of Duk might be through the induction of apoptosis.

Loading

Article metrics loading...

/content/journals/ccdt/10.2174/1568009623666230818115905
2024-10-25
2025-06-18
Loading full text...

Full text loading...

References

  1. FekryM.I. EzzatS.M. SalamaM.M. AlshehriO.Y. Al-AbdA.M. Bioactive glycoalkaloides isolated from Solanum melongena fruit peels with potential anticancer properties against hepatocellular carcinoma cells.Sci. Rep.201991174610.1038/s41598‑018‑36089‑630741973
    [Google Scholar]
  2. GuptaM. ChandanK. SarwatM. Role of microRNA and long non-coding RNA in hepatocellular carcinoma.Curr. Pharm. Des.202026441542810.2174/138161282666620011509383531939724
    [Google Scholar]
  3. FornerA. Da FonsecaL.G. Díaz-GonzálezÁ. Sanduzzi-ZamparelliM. ReigM. BruixJ. Controversies in the management of hepatocellular carcinoma.JHEP Reports201911172910.1016/j.jhepr.2019.02.00332039350
    [Google Scholar]
  4. LlovetJ.M. KelleyR.K. VillanuevaA. SingalA.G. PikarskyE. RoayaieS. LencioniR. KoikeK. Zucman-RossiJ. FinnR.S. Hepatocellular carcinoma.Nat. Rev. Dis. Primers20217163410.1038/s41572‑020‑00240‑333479224
    [Google Scholar]
  5. Abdel-HamidN.M. AbassS.A. MohamedA.A. Muneam HamidD. Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors.Biomed. Pharmacother.20181071246125810.1016/j.biopha.2018.08.10430257339
    [Google Scholar]
  6. HusainA. SofiG.D. TajuddinD.R. KumarN. Unani system of medicine-introduction and challenges.Med J Islamic World Acad Sci2010182730
    [Google Scholar]
  7. MahajanN. LokhandeB. ThengeR. GanganeP. DumoreN. Polyherbal formulation containing antioxidants may serve as a prophylactic measure to diabetic cataract: Preclinical investigations in rat model.Pharmacogn. Mag.2018145857257710.4103/pm.pm_622_17
    [Google Scholar]
  8. ParasuramanS. ThingG. DhanarajS. Polyherbal formulation: Concept of ayurveda.Pharmacogn. Rev.2014816738010.4103/0973‑7847.13422925125878
    [Google Scholar]
  9. KabeeruddinM. Bayaz e Kabeer-II. Maktaba Al-Shifa, Kucha Chilan.Daryaganj20182354
    [Google Scholar]
  10. GuptaM. SumaiyaS. AliS. NavedT. SharmaA. AhmadA. SikanderM. SarwatM. Pharmacognostical and phytochemical evaluation of a unani polyherbal formulation: Dawa ul Kurkum by HPTLC.Separations20231028910.3390/separations10020089
    [Google Scholar]
  11. ReshiM.R. GulatiK. KhanA.A. RayA. Effects of Dawa-ul-Kurkum, a Unani polyherbal preparation, in anti-tubercular drug induced hepatotoxicity in rats and its possible mechanisms.Int. J. Herb. Med.202085762
    [Google Scholar]
  12. GulatiK. ReshiM.R. Rais-ur-Rahman AJ, Ray A. Hepatoprotective effects of Dawa-Ul-Kurkum a unani polyherbal preparation and the possible mechanisms in experimental model of D-galactosamine induced liver damage in rats.EC Pharmacol Toxicol20197948960
    [Google Scholar]
  13. ReshiM.R. GulatiK. NaqviM. HassanN. RayA. Hepatoprotective effects of Dawa-Ul-Kurkum, a unani polyherbal preparation and the possible mechanisms in experimental model of ethanol induced liver damage in rats.J. Pharm. Pharmacogn. Res.20226122130
    [Google Scholar]
  14. ReshiM.R. GulatiK. AneesS. NaqviM. HasanN. RayA. Immunomodulatory effect of Dawa-Ul-Kurkum a unani preparation and its possible mechanisms in experimental model of ethanol induced liver damage in rats.Int J Toxicol Pharmacol Res202212314322
    [Google Scholar]
  15. LinL.T. WuS.J. LinC.C. The anticancer properties and apoptosis-inducing mechanisms of cinnamaldehyde and the herbal prescription Huang-Lian-Jie-Du-Tang in human hepatoma cells.J. Tradit. Complement. Med.2013322723310.4103/2225‑4110.11973224716182
    [Google Scholar]
  16. AminA. HamzaA.A. DaoudS. KhazanehdariK. HroutA.A. BaigB. ChaiboonchoeA. AdrianT.E. ZakiN. Salehi-AshtianiK. Saffron-based crocin prevents early lesions of liver cancer: In vivo, in vitro and network analyses.Recent Patents Anticancer Drug Discov.201611112113310.2174/157489281066615110211024826522014
    [Google Scholar]
  17. KrishnanP. SalamS. VelliS.K. MuruganM. SelvanathanI. SundaramJ. Citral attenuates n-nitrosodiethylamine induced liver carcinogenesis in experimental wistar rats.Int. J. Pharm. Sci. Res.201892463247010.13040/ijpsr.09758232
    [Google Scholar]
  18. El-NabiS.H. El-GarawaniI. El-BerryA. The apoptotic properties of Cinnamomum zeylanicum and Cymbopogon citratus on human hepatocellular carcinoma cell line (HepG2).Eur. J. Pharm. Med. Res.201634448
    [Google Scholar]
  19. ElsayedH.H. Abd-ElmonemM. GabrO. BadriaF.E. Saussurea lappa root extract accelerates the reversion of liver fibrosis induced by carbon tetrachloride in rats.Benha Med. J.201532211612510.4103/1110‑208X.180324
    [Google Scholar]
  20. MoonD.O. ParkS.Y. ChoiY.H. AhnJ.S. KimG.Y. Guggulsterone sensitizes hepatoma cells to TRAIL-induced apoptosis through the induction of CHOP-dependent DR5: Involvement of ROS-dependent ER-stress.Biochem. Pharmacol.201182111641165010.1016/j.bcp.2011.08.01921903093
    [Google Scholar]
  21. BhagatM. PanditaR.M. SaxenaA.K. In vitro and in vivo biological activities of Nardostachys jatamansi roots.Med. Aromat. Plants2013262167041210.4172/2167‑0412.1000142
    [Google Scholar]
  22. ChuangL.Y. GuhJ.Y. ChaoL.K. LuY.C. HwangJ.Y. YangY.L. ChengT-H. YangW-Y. ChienY-J. HuangJ-S. Anti-proliferative effects of cinnamaldehyde on human hepatoma cell lines.Food Chem.201213341603161010.1016/j.foodchem.2012.02.059
    [Google Scholar]
  23. AminA. HamzaA.A. BajboujK. AshrafS.S. DaoudS. Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma.Hepatology201154385786710.1002/hep.2443321607999
    [Google Scholar]
  24. MalikS. BhatnagarS. ChaudharyN. KatareD.P. JainS.K. DEN+2-AAF-induced multistep hepatotumorigenesis in Wistar rats: Supportive evidence and insights.Protoplasma2013250117518310.1007/s00709‑012‑0392‑822456951
    [Google Scholar]
  25. WasefL. NassarA.M.K. El-SayedY.S. SamakD. NoreldinA. ElshonyN. SalehH. ElewaY.H.A. HassanS.M.A. SaatiA.A. HettaH.F. BatihaG.E.S. UmezawaM. ShaheenH.M. The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis.Sci. Rep.2021111131010.1038/s41598‑020‑79479‑533446707
    [Google Scholar]
  26. GuptaM. GhufranS.M. KausarT. AliR. BiswasS. NayeemS.M. IshratR. AliS. AhmadA. RatherI.A. SarwatM. Z-Guggulsterone is a potential lead molecule of Dawa-ul-Kurkum against hepatocellular carcinoma.Molecules20222716510410.3390/molecules2716510436014345
    [Google Scholar]
  27. AbuzinadahM.F. AhmadA. Pharmacological studies on the efficacy of a thymoquinone-containing novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in rats.J. Food Biochem.2020442e1313110.1111/jfbc.1313131876968
    [Google Scholar]
  28. DunsfordH.A. KarnasutaC. HuntJ.M. SellS. Different lineages of chemically induced hepatocellular carcinoma in rats defined by monoclonal antibodies.Cancer Res.19894917489449002474377
    [Google Scholar]
  29. JooM. KangY.K. KimM.R. LeeH.K. JangJ.J. Cyclin D1 overexpression in hepatocellular carcinoma.Liver2001212899510.1034/j.1600‑0676.2001.021002089.x11318977
    [Google Scholar]
  30. PatilM.A. LeeS.A. MaciasE. LamE.T. XuC. JonesK.D. HoC. Rodriguez-PueblaM. ChenX. Role of cyclin D1 as a mediator of c-Met- and β-catenin-induced hepatocarcinogenesis.Cancer Res.200969125326110.1158/0008‑5472.CAN‑08‑251419118010
    [Google Scholar]
  31. ChenG.G. LaiP.B.S. ChakE.C.W. XuH. LeeK.M. LauW.Y. Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis, hepatocellular carcinoma and liver metastases.Cancer Lett.20011721758210.1016/S0304‑3835(01)00630‑911595132
    [Google Scholar]
  32. ChenG.G. LaiP.B.S. ChanP.K.S. ChakE.C.W. YipJ.H.Y. HoR.L.K. LeungB.C.S. LauW.Y. Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein.Eur. J. Cancer200137131695170210.1016/S0959‑8049(01)00182‑411527698
    [Google Scholar]
  33. EckleV.S. BuchmannA. BurschW. Schulte-HermannR. SchwarzM. Immunohistochemical detection of activated caspases in apoptotic hepatocytes in rat liver.Toxicol. Pathol.200432191510.1080/0192623049026067314713542
    [Google Scholar]
  34. HuangH. ZhangX.F. ZhouH.J. XueY.H. DongQ.Z. YeQ.H. QinL.X. Expression and prognostic significance of osteopontin and caspase-3 in hepatocellular carcinoma patients after curative resection.Cancer Sci.201010151314131910.1111/j.1349‑7006.2010.01524.x20345480
    [Google Scholar]
/content/journals/ccdt/10.2174/1568009623666230818115905
Loading
/content/journals/ccdt/10.2174/1568009623666230818115905
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s web site along with the published article.


  • Article Type:
    Research Article
Keyword(s): apoptosis; Duk; Hepatocellular carcinoma; oxidative stress; polyherbal formulation; saffron
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