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BMC Complementary Medicine and Therapies

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Open Access 01-12-2013 | Research article

Gene expression profiling reveals underlying molecular mechanism of hepatoprotective effect of Phyllanthus niruri on thioacetamide-induced hepatotoxicity in Sprague Dawley rats

Authors: Zahra A Amin, Mohammed A Alshawsh, Mustafa Kassim, Hapipah M Ali, Mahmood A Abdulla

Published in: BMC Complementary Medicine and Therapies | Issue 1/2013

Abstract

Background

The liver plays an essential role in the body by regulating several important metabolic functions. Liver injury is associated with the distortion of these functions causing many health problems. Pharmaceutical drugs treat liver disorders but cause further damage to it. Hence, herbal drugs are used worldwide and are becoming increasingly popular.

Methods

The hepatoprotective activity of Phyllanthus niruri (PN) was evaluated against liver cirrhosis induced by thioacetamide (TAA) in male Sprague Dawley rats. Rats received intraperitoneal injections of thioacetamide (TAA, 200 mg/kg, b.w. three times weekly) for eight weeks. Daily treatments with plant extract (200 mg/kg) were administered orally for eight weeks. At the end of the study, hepatic damage was evaluated by monitoring transforming growth factor (TGFβ), collagen α1 (Collα1), matrix metalloproteinase-2 (MMP2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression by real-time PCR. Moreover, different chromatographic techniques including column chromatography, thin layer chromatography, and Ultra Performance Liquid Chromatography (UPLC) with Liquid Chromatography/Mass Spectrometry (LC/MS) were used to isolate the active constituents of the plant.

Results

The results revealed that treatment with PN significantly reduced the effect of thioacetamide toxicity and exhibited effective hepatoprotective activity. The mechanism of the hepatoprotective effect of PN is proposed to be by normalizing ROSs. Additionally, PN treatment regulated the expression of TGFβ, Collα1, MMP2, and TIMP1 genes. In the active fraction of P. niruri, the isolated chemical constituents were 4-O-caffeoylquinic acid and quercetin 3-O-rhamnoside.

Conclusions

The results of the present study indicate that PN ethanol extracts possess hepatoprotective activity that is most likely because of the isolated chemical constituents.

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Ong H, Norzalina J: Malay herbal medicine in Gemencheh, Negri Sembilan, Malaysia. Fitoterapia. 1999, 70 (1): 10-14. 10.1016/S0367-326X(98)00023-9.CrossRef

Freitas A, Schor N, Boim M: The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int. 2002, 89 (9): 829-834. 10.1046/j.1464-410X.2002.02794.x.CrossRefPubMed

Boim MA, Heilberg IP, Schor N: Phyllanthus niruri as a promising alternative treatment for nephrolithiasis. Int Braz J Urol. 2010, 36 (6): 657-664. 10.1590/S1677-55382010000600002.CrossRefPubMed

Barros ME, Lima R, Mercuri LP, Matos JR, Schor N, Boim MA: Effect of extract of Phyllanthus niruri on crystal deposition in experimental urolithiasis. Urol Res. 2006, 34 (6): 351-357. 10.1007/s00240-006-0065-1.CrossRefPubMed

Murugaiyah V, Chan KL: Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. J Ethnopharmacol. 2009, 124 (2): 233-239. 10.1016/j.jep.2009.04.026.CrossRefPubMed

Harish R, Shivanandappa T: Antioxidant activity and hepatoprotective potential of Phyllanthus niruri. Food Chem. 2006, 95 (2): 180-185. 10.1016/j.foodchem.2004.11.049.CrossRef

Manjrekar A, Jisha V, Bag P, Adhikary B, Pai M, Hegde A, Nandini M: Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl4 induced hepatotoxic rats. Indian J Exp Biol. 2008, 46 (7): 514-520.PubMed

Bhattacharjee R, Sil P: Protein isolate from the herb, Phyllanthus niruri L.(Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Food Chem Toxicol. 2007, 45 (5): 817-826. 10.1016/j.fct.2006.10.029.CrossRefPubMed

Amin ZA, Bilgen M, Alshawsh MA, Ali HM, Hadi AHA, Abdulla MA: Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver Cirrhosis in Rat Model. Evidence-Based Complementary and Alternative Medicine. 2012, 2012:

10.

Zahra AA, Kadir FA, Mahmood AA, AA A h, Suzy SM, Sabri SZ, Latif II, Ketuly K: Acute toxicity study and wound healing potential of Gynura procumbens leaf extract in rats. Journal of Medicinal Plants Research. 2011, 5 (12): 2551-2558.

11.

Alshawsh MA, Abdulla MA, Ismail S, Amin ZA: Hepatoprotective Effects of Orthosiphon stamineus Extract on Thioacetamide-Induced Liver Cirrhosis in Rats. Evidence-based Complementary and Alternative Medicine: eCAM. 2011, 2011:

12.

Fraga CG, Martino VS, Ferraro GE, Coussio JD, Boveris A: Flavonoids as antioxidants evaluated by in vitro and in situ liver chemiluminescence. Biochem Pharmacol. 1987, 36 (5): 717-720. 10.1016/0006-2952(87)90724-6.CrossRefPubMed

13.

Bravo L, Goya L, Lecumberri E: LC/MS characterization of phenolic constituents of mate (Ilex paraguariensis, St. Hil.) and its antioxidant activity compared to commonly consumed beverages. Food Res Int. 2007, 40 (3): 393-405. 10.1016/j.foodres.2006.10.016.CrossRef

14.

Seeram NP, Lee R, Scheuller HS, Heber D: Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectroscopy. Food Chem. 2006, 97 (1): 1-11. 10.1016/j.foodchem.2005.02.047.CrossRef

15.

Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Yanase K, Namisaki T, Imazu H: Tissue inhibitor of metalloproteinases‒1 attenuates spontaneous liver fibrosis resolution in the transgenic mouse. Hepatology. 2002, 36 (4): 850-860.CrossRefPubMed

16.

Arthur MJP: Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2000, 279 (2): G245-G249.PubMed

17.

Chilakapati J, Shankar K, Korrapati MC, Hill RA, Mehendale HM: Saturation toxicokinetics of thioacetamide: role in initiation of liver injury. Drug Metab Dispos. 2005, 33 (12): 1877-1885.PubMed

18.

Yogalakshmi B, Viswanathan P, Anuradha CV: Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology. 2010, 268 (3): 204-212. 10.1016/j.tox.2009.12.018.CrossRefPubMed

19.

Wang H, Zhao YP, Gao CF, Ji Q, Gressner AM, Yang ZX, Weiskirchen R: Transforming growth factor β1 gene variants increase transcription and are associated with liver cirrhosis in Chinese. Cytokine. 2008, 43 (1): 20-25. 10.1016/j.cyto.2008.04.013.CrossRefPubMed

20.

Mormone E, George J, Nieto N: Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem Biol Interact. 2011, 193 (3): 225-231. 10.1016/j.cbi.2011.07.001.CrossRefPubMedPubMedCentral

21.

Wills P, Asha V: Protective mechanism of Lygodium flexuosum extract in treating and preventing carbon tetrachloride induced hepatic fibrosis in rats. Chem Biol Interact. 2007, 165 (1): 76-85. 10.1016/j.cbi.2006.10.010.CrossRefPubMed

22.

Chen IS, Chen YC, Chou CH, Chuang RF, Sheen LY, Chiu CH: Hepatoprotection of silymarin against thioacetamide‒induced chronic liver fibrosis. J Sci Food Agric. 2012, 92 (7): 1441-1447. 10.1002/jsfa.4723.CrossRefPubMed

23.

Di Sario EB A, Taffetani S, Omenetti A, Candelaresi C, Marzioni M, De Minicis S, Benedetti A: Hepatoprotective and antifibrotic effect of a new silybin–phosphatidylcholine–Vitamin E complex in rats. Dig Liver Dis. 2005, 37: 869-876. 10.1016/j.dld.2005.05.011.CrossRef

24.

Silva BM, Andrade PB, Valentão P, Ferreres F, Seabra RM, Ferreira MA: Quince (Cydonia oblonga Miller) fruit (pulp, peel, and seed) and jam: antioxidant activity. J Agric Food Chem. 2004, 52 (15): 4705-4712. 10.1021/jf040057v.CrossRefPubMed

25.

Adzet T, Camarasa J, Laguna JC: Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod. 1987, 50 (4): 612-617. 10.1021/np50052a004.CrossRefPubMed

26.

Kapil A, Koul I, Suri O: Antihepatotoxic effects of chlorogenic acid from Anthocephalus cadamba. Phytother Res. 1995, 9 (3): 189-193. 10.1002/ptr.2650090307.CrossRef

27.

Kähkönen MP, Hopia AI, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M: Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem. 1999, 47 (10): 3954-3962. 10.1021/jf990146l.CrossRefPubMed

28.

Zayachkivska O, Konturek S, Drozdowicz D, Konturek P, Brzozowski T, Ghegotsky M: Gastroprotective effects of flavonoids in plant extracts. J Physiol Pharmacol. 2005, 56 (Suppl 1): 219-231.PubMed

29.

Ozcelik B, Orhan I, Toker G: Antiviral and antimicrobial assessment of some selected flavonoids. Zeits Chrift Fur Natur Forschung C. 2006, 61 (9/10): 632-

30.

Oh H, Kim DH, Cho JH, Kim YC: Hepatoprotective and free radical scavenging activities of phenolic petrosins and flavonoids isolated from < i > Equisetum arvense</i>. J Ethnopharmacol. 2004, 95 (2): 421-424.CrossRefPubMed

31.

Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM: Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001, 74 (4): 418-425.PubMed

32.

Zhang YJ, Abe T, Tanaka T, Yang CR, Kouno I: Two new acylated flavanone glycosides from the leaves and branches of Phyllanthus emblica. Chem Pharm Bull. 2002, 50 (6): 841-843. 10.1248/cpb.50.841.CrossRefPubMed

33.

Calixto JB, Santos A, Cechinel FV, Yunes RA: A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential. Medicinal research reviews. 1998, 18 (4): 225-10.1002/(SICI)1098-1128(199807)18:4<225::AID-MED2>3.0.CO;2-X.CrossRefPubMed

34.

Kuti JO, Konuru HB: Antioxidant capacity and phenolic content in leaf extracts of tree spinach (Cnidoscolus spp.). J Agric Food Chem. 2004, 52 (1): 117-121. 10.1021/jf030246y.CrossRefPubMed

35.

Bravo L: Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev. 1998, 56 (11): 317-333.CrossRefPubMed

36.

Ullah MF, Khan MW: Food as medicine: potential therapeutic tendencies of plant derived polyphenolic compounds. Asian Pac J Cancer Prev. 2008, 9 (2): 187-196.PubMed

37.

Shimoda H, Tanaka J, Kikuchi M, Fukuda T, Ito H, Hatano T, Yoshida T: Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut. J Agric Food Chem. 2008, 56 (12): 4444-4449. 10.1021/jf8002174.CrossRefPubMed

38.

Chen X, Sun CK, Han GZ, Peng JY, Li Y, Liu YX, Lv YY, Liu KX, Zhou Q, Sun HJ: Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression. World journal of gastroenterology: WJG. 2009, 15 (15): 1829-10.3748/wjg.15.1829.CrossRefPubMedPubMedCentral

39.

Madani H, Talebolhosseini M, Asgary S, Naderi G: Hepatoprotective activity of Silybum marianum and Cichorium intybus against thioacetamide in rat. Pak J Nutr. 2008, 7 (1): 172-176. 10.3923/pjn.2008.172.176.CrossRef

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/13/160/prepub

Title: Gene expression profiling reveals underlying molecular mechanism of hepatoprotective effect of Phyllanthus niruri on thioacetamide-induced hepatotoxicity in Sprague Dawley rats
Authors: Zahra A Amin
Mohammed A Alshawsh
Mustafa Kassim
Hapipah M Ali
Mahmood A Abdulla
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2013
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/1472-6882-13-160

At a glance: The STEP trials

Springer Medicine

Gene expression profiling reveals underlying molecular mechanism of hepatoprotective effect of Phyllanthus niruri on thioacetamide-induced hepatotoxicity in Sprague Dawley rats

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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