Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul 5:13:160.
doi: 10.1186/1472-6882-13-160.

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

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

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

Zahra A Amin et al. BMC Complement Altern Med. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A typical ethidium bromide-stained agarose gel shows the integrity of the extracted RNA; (A) visualized under a Vilber Lourmat gel documentation system (B) visualized under UV light.
Figure 2
Figure 2
Real-time PCR analysis shows the relative fold changes of transforming growth factor beta (TGFβ), matrix metalloproteinase 2 (MMP2), tissue inhibitors of metalloproteinases 1 (TIMP1), and collagen alpha (Collα1) between all experimental groups. Values expressed as the mean ± S.E.M. Different superscripts state significant differences. (a) Indicates significance versus the Normal group at P ≤ 0.05; (b) indicates significance versus the TAA-treated group at P ≤ 0.05 and (c) indicates significance versus the TAA-treated group at P ≤ 0.01.
Figure 3
Figure 3
The effects of P. niruri fractions on human peripheral blood mononuclear cell (PBMC) proliferation. Data are expressed as the mean ± SEM for triplicates; (*) indicates significance versus the control group (CTRL = dH2O) at P ≤ 0.05.
Figure 4
Figure 4
LC-TOF/MS and UV diode array chromatograms of P. niruri fraction 1 (PNF1); (A) UV diode array spectra at 280 nm (B) UV diode array spectra at a range between 190 and 800 nm (C) TOF/MS peaks in the positive mode ionization.
Figure 5
Figure 5
UV max spectra and mass spectrum (TOF MS ES+) of peak no. 2 in P. niruri F1 (identified as 4-O-caffeoylquinic acid).
Figure 6
Figure 6
UV max spectra and mass spectrum (TOF MS ES+) of peak no. 4 in P. niruri F1 (identified as quercetin 3-O-rhamnoside).
Figure 7
Figure 7
Putative mechanism of Phyllanthus niruri hepatoprotective effect as a response to TAA-induced hepatotoxicity.
See this image and copyright information in PMC

References

    1. Ong H, Norzalina J. Malay herbal medicine in Gemencheh, Negri Sembilan, Malaysia. Fitoterapia. 1999;70(1):10–14. doi: 10.1016/S0367-326X(98)00023-9. - DOI
    1. 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. doi: 10.1046/j.1464-410X.2002.02794.x. - DOI - PubMed
    1. Boim MA, Heilberg IP, Schor N. Phyllanthus niruri as a promising alternative treatment for nephrolithiasis. Int Braz J Urol. 2010;36(6):657–664. doi: 10.1590/S1677-55382010000600002. - DOI - PubMed
    1. 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. doi: 10.1007/s00240-006-0065-1. - DOI - PubMed
    1. Murugaiyah V, Chan KL. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. J Ethnopharmacol. 2009;124(2):233–239. doi: 10.1016/j.jep.2009.04.026. - DOI - PubMed

Publication types

MeSH terms