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Cited by 136Phytochemistry and Bioactivity StudiesDrug-Induced Hepatotoxicity and ProtectionLiver physiology and pathology

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Isolation, characterization and antioxidative effect of phyllanthin against CCl4-induced toxicity in HepG2 cell line

Krithika, Rajesh, Mohankumar, Ramasamy, Verma, Ramtej J., Shrivastav, Pranav S., Mohamad, Illiyas L., Gunasekaran, Palani, Narasimhan, Srinivasan·2009·Chemico-Biological Interactions
DOI 10.1016/j.cbi.2009.06.014
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Abstract

The present study was an attempt to investigate the hepatoprotective and antioxidative property of Phyllanthus amarus (P. amarus) extract and phyllanthin. Phyllanthin, one of the active lignin present in this plant species was isolated from the aerial parts, by silica gel column chromatography employing gradient elution with hexane-ethyl acetate solvent mixture. It was obtained in high yields (1.23%), compared to reported procedures and the purity was ascertained by HPTLC and reversed-phase HPLC analysis. Characterization of phyllanthin was done by mp, UV-Visible spectrophotometry, elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectral analysis. Free radical scavenging activity of P. amarus extract and phyllanthin was also examined using DPPH assay. The protective effect of P. amarus extract and phyllanthin was studied on CCl4-induced toxicity in human hepatoma HepG2 cell line. The results indicated that CCl4 treatment caused a significant decrease in cell viability. In addition, the toxin treatment initiated lipid peroxidation (LPO), caused leakage of enzymes like alanine transaminase (ALT) and lactate dehydrogenase (LDH) with a significant decrease in glutathione (GSH) levels. It was observed that phyllanthin effectively alleviated the changes induced by CCl4 in a concentration-dependent manner, with much smaller strengths as compared to P. amarus extract.

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  • For preliminary screening for hepatoprotection, liver cell lines such as BRL3A and HepG2 have been routinely used, since they resemble in vivo models.

    “For preliminary screening for hepatoprotection, liver cell lines such as BRL3A and HepG2 have been routinely used, since they resemble to the in vivo models. 37”

    From Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 (2017) · cites this paper as [37]

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Research works printed but not linked: 44

  1. Bhattacharjee, 2007, Protein isolates from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties, Food Chem. Toxicol., 45, 817, 10.1016/j.fct.2006.10.029 · DOI
  2. Sane, 1997, Studies on Phyllanthus amarus, Indian Drugs—Part II, 34, 654
  3. Qian-Cutrone, 1996, Niruside, a new HIV REV/RRE binding inhibitor from Phyllanthus niruri, J. Nat. Prod., 59, 196, 10.1021/np9600560 · DOI
  4. Wongnawa, 2005, Effect of Phyllanthus amarus Schum & Thonn. and its protective mechanism on paracetomol hepatotoxicity in rats, Acta Hort., 680, 195, 10.17660/ActaHortic.2005.680.30 · DOI
  5. Sane, 1995, Hepatoprotection by Phyllanthus amarus and Phyllanthus debili in CCl4-induced liver dysfunction, Curr. Sci., 68, 1243
  6. Pramyothin, 2007, Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: in vitro and in vivo studies, J. Ethnopharmacol., 114, 169, 10.1016/j.jep.2007.07.037 · DOI
  7. Naaz, 2007, Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum. et Thonn. on aflatoxin B1-induced liver damage in Mice, J. Ethnopharmacol., 113, 503, 10.1016/j.jep.2007.07.017 · DOI
  8. N. Kongstan, Effect of Phyllanthus amarus on hepatotoxicity induced by galactosamine in rats, Master's Thesis, Department of Toxicology, Faculty of Science, Mahidol University, 2000.
  9. Raphael, 2003, Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract, J. Ethnopharmacol., 87, 193, 10.1016/S0378-8741(03)00120-X · DOI
  10. Okafor, 2008, Inhibitory action of Phyllanthus amarus extracts on the corrosion of mild steel in acidic media, Corros. Sci., 50, 2310, 10.1016/j.corsci.2008.05.009 · DOI
  11. Thyagarajan, 1987, Effects of an extracts from Phyllanthus niruri on hepatitis B and woodchuck hepatitis virus: in vitro and in vivo studies, Proc. Natl. Acad. Sci. USA, 84, 274, 10.1073/pnas.84.1.274 · DOI
  12. Yadav, 2008, Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4-induced hepatotoxicity in Rattus norvegicus, Phytomedicine, 15, 1053, 10.1016/j.phymed.2008.08.002 · DOI
  13. Shamasundar, 1985, Antihepatoprotective principles of Phyllanthus niruri herbs, J. Ethnopharmacol., 14, 41, 10.1016/0378-8741(85)90026-1 · DOI
  14. Krishnamurti, 1946, The bitter principle of Phylanthus niruri, Proc. Indian Acad. Sci., 24, 357, 10.1007/BF03171072 · DOI
  15. Row, 1967, Crystalline constituents of euphorbiaceae-VI: the synthesis and absolute configuration of phyllanthin, Tetrahedron, 23, 1915, 10.1016/S0040-4020(01)82594-1 · DOI
  16. Row, 1966, Crystalline constituents of Euphorbiaceae-V new lignans from Phyllanthus Niruri Linn—the constitution of phyllanthin, Tetrahedron, 22, 2899, 10.1016/S0040-4020(01)99083-0 · DOI
  17. Anjaneyulu, 1973, Crystalline constituents of Euphorbiaceae-XII, isolation and structural elucidation of three new lignans from the leaves of Phyllanthus Niruri Linn, Tetrahedron, 29, 1291, 10.1016/S0040-4020(01)83146-X · DOI
  18. Somanabandhu, 1993, 1H- and 13C-NMR assignments of phyllanthin and hypophyllanthin: lignans that enhance cytotoxic responses with cultured multi-drug resistant cells, J. Nat. Prod., 56, 233, 10.1021/np50092a008 · DOI
  19. Murugaiyah, 2007, Determination of four lignans in Phyllanthus niruri L. by a simple high-performance liquid chromatography method with fluorescence detection, J. Chromatogr. A, 1154, 198, 10.1016/j.chroma.2007.03.079 · DOI
  20. Willfor, 2005, Chromatographic analysis of lignans, J. Chromatogr. A, 1112, 64, 10.1016/j.chroma.2005.11.054 · DOI
  21. Murugaiyah, 2007, Analysis of lignans from Phyllanthus niruri L. in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study, J. Chromatogr. B, 852, 138, 10.1016/j.jchromb.2007.01.014 · DOI
  22. Boll, 2001, Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites, Z. Naturforsch. [C], 56, 649, 10.1515/znc-2001-7-826 · DOI
  23. Weddle, 1976, Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride, J. Biol. Chem., 251, 4973, 10.1016/S0021-9258(17)33209-X · DOI
  24. Sundararajan, 2006, Cystisus scoparius—a natural antioxidant, BMC Complement. Altern. Med., 6, 8, 10.1186/1472-6882-6-8 · DOI
  25. Ko, 1993, Impaired hepatic antioxidant status in carbon tetrachloride intoxicated rats an in vivo model for screening herbal extracts with antioxidant activities, Fitoterapia, 64, 539
  26. Kim, 2001, α-Phenyl-N-t-butylnitrone protects oxidative damage to HepG2 cells, J. Biochem. Mol. Biol., 34, 43
  27. Moya, 2008, Protection of human Hepg2 cells against oxidative stress by cocoa phenolic extract, J. Agric. Food Chem., 56, 7765, 10.1021/jf801744r · DOI
  28. Thabrew, 1997, Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay, J. Pharm. Pharmacol., 49, 1132, 10.1111/j.2042-7158.1997.tb06055.x · DOI
  29. Tripathi, 2006, Quantitative determination of phyllanthin and hypophyllanthin in Phyllanthus species by high-performance thin layer chromatography, Phytochem. Anal., 17, 394, 10.1002/pca.936 · DOI
  30. Rao, 2008, Antioxidant and cytotoxic activities of naturally occurring phenolic and related compounds: a comparative study, Food Chem. Toxicol., 45, 1770, 10.1016/j.fct.2007.03.012 · DOI
  31. Harries, 2001, The use of genomics technology to investigate gene expression changes in cultured human liver cells, Toxicol. In Vitro, 15, 399, 10.1016/S0887-2333(01)00043-1 · DOI
  32. Wu, 2008, Development and properties of HepG2 cells that constitutively express CYP2E1, Methods Mol. Biol., 447, 137, 10.1007/978-1-59745-242-7_11 · DOI
  33. Lowry, 1951, Protein measurement with Folin phenol reagent, J. Biol. Chem., 193, 265, 10.1016/S0021-9258(19)52451-6 · DOI
  34. Fang, 2008, Anti-oxidant and inflammatory mediator's growth inhibitory effects of compounds isolated from Phyllanthus urinaria, J. Ethnopharmacol., 116, 333, 10.1016/j.jep.2007.11.040 · DOI
  35. Sassa, 1987, Drug metabolism by the human hepatoma cell, HepG2 27, Biochem. Biophys. Res. Commun., 143, 52, 10.1016/0006-291X(87)90628-0 · DOI
  36. Duthie, 1994, Bromobenzene detoxification in the human, liver-derived HepG2 cell line, Xenobiotica, 24, 265, 10.3109/00498259409043238 · DOI
  37. Lima, 2007, Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage, Chem. Biol. Interact., 167, 107, 10.1016/j.cbi.2007.01.020 · DOI
  38. Chen, 1996, Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity possibly through C1b receptor in rat hepatocytes, Biochem. Biophys. Res. Commun., 218, 865, 10.1006/bbrc.1996.0154 · DOI
  39. Patlolla, 2009, Potassium dichromate induced cytotoxicity, genotoxicity and oxidative stress in human liver carcinoma (HepG2) cells, Int. J. Environ. Res. Public Health, 6, 643, 10.3390/ijerph6020643 · DOI
  40. Berger, 1986, CC14-induced toxicity in isolated hepatocytes: the importance of direct solvent injury, Hepatology, 6, 36, 10.1002/hep.1840060108 · DOI
  41. Holden, 2000, Identification of a possible association between carbon tetrachloride-induced hepatotoxicity and interleukin-8 expression, J. Biochem. Mol. Toxicol., 14, 283, 10.1002/1099-0461(2000)14:5<283::AID-JBT7>3.0.CO;2-S · DOI
  42. Marinovich, 1988, The HepG2 cell line as a possible alternative to isolated hepatocytes in cytotoxicity studies, ATLA, 16, 16
  43. Gutierrez-Ruiz, 1999, Cytokines, growth factors, and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde, and LPS, Toxicology, 134, 197, 10.1016/S0300-483X(99)00044-X · DOI
  44. Yasuda, 1980, The protective effect of tinoridine against carbon tetrachloride hepatotoxicity, Toxicol. Appl. Pharmacol., 52, 407, 10.1016/0041-008X(80)90335-X · DOI

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Metadata

Authors
Krithika, R., Mohankumar, R., Verma, R. J., Shrivastav, P. S., Mohamad, I. L., Gunasekaran, P., & Narasimhan, S.
Affiliations
  • Gujarat University (IN)
  • King Institute of Preventive Medicine and Research (IN)
Corresponding author
Verma, Ramtej J.
ORCID
Venue
Chemico-Biological Interactions
Publisher
Elsevier BV
Published
2009-10
Volume
181
Issue
3
Pages
351-358
ISSN
0009-2797 (ISSN-L)
DOI
10.1016/j.cbi.2009.06.014
OpenAlex
W2022877915
Cited by
136
References
2
Citations by year
2026: 6 · 2025: 12 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 7
FWCI
3.97
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Chemico-Biological Interactions (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Phytochemistry and Bioactivity Studies
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
phyllanthin, Phyllanthus amarus, hepatoprotection, carbon tetrachloride poisoning, oxidative stress, lipid peroxidation, free radical scavenging, lignans, glutathione depletion, alanine aminotransferase, lactate dehydrogenase, HepG2 cells, natural product isolation
MeSH terms
Antioxidants, Carbon Tetrachloride Poisoning, Cell Line, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Humans, Magnetic Resonance Spectroscopy, Spectrophotometry, Ultraviolet, Lipid Peroxidation, Spectroscopy, Fourier Transform Infrared, Lignans, Chemical and Drug Induced Liver Injury

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