Skip to main content
SpringerLink
Log in

Hepatoprotective constituents in plants 15: protective effects of natural-occurring flavonoids and miscellaneous phenolic compounds as determined in an HepG2 cell cytotoxicity assay

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

In order to clarify the efficacy of natural-occurring hepatoprotective flavonoids and related miscellaneous compounds, we have investigated the hepatoprotective activity of 41 phenolic compounds on human liver-derived HepG2 cells and evaluated their structure-activity relationships. The hepatoprotective activity of catechin (cyanidanol), which has been used to treat chronic hepatitis, was almost equal to that of glycyrrhizin at 200 μM. The structure-activity relationships of flavanol derivatives as revealed by this investigation suggest that (1) the configuration of the hydroxy group at C-3 does not affect the hepatoprotective activity; (2) the pyrogallol and catechol groups in the B-ring are almost comparable in terms of hepatoprotection; (3) the galloyl group is a key factor for enhancing hepatoprotective activity; (4) the free carboxyl group of gallic acid reduces hepatoprotective activity. The common structural features of the most potent hepatoprotective phenolic compounds are summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Van Acker SABE, Van Balen GP, Van den Berg D, Bast A, Van der Vijgh WJF (1998) Influence of iron chelation on the antioxidant activity of flavonoids. Biochem Pharmacol 56:935–943

    Article  PubMed  Google Scholar 

  2. Marena C, Lampertico M (1991) Preliminary clinical development of Silipide: a new complex of silybin in toxic liver disorders. Planta Med 57[Suppl 2]:A124–A125

    Google Scholar 

  3. Koda A (1993) Pharmacological effects of Scutellaria baicalensis, particularly on baicalin and baicalein as the components of the crude drug. Gendai Toyo Igaku 14:95–100

    Google Scholar 

  4. Patrick L (1999) Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Altern Med Rev 4:220–238

    PubMed  Google Scholar 

  5. Kinjo J, Hirakawa T, Tsuchihashi R, Nagao T, Okawa M, Nohara T, Okabe H (2003) Hepatoprotective constituents in plants 14 Effects of soyasapogenol B, sophoradiol, and their glucuronides on the cytotoxicity of tert-butyl hydroperoxide to HepG2 cells. Biol Pharm Bull 26:1357–1360

    Article  PubMed  Google Scholar 

  6. Kinjo J, Nagao T, Tanaka T, Nonaka G, Okawa M, Nohara T, Okabe H (2002) Activity-guided fractionation of green tea extract with antiproliferative activity against human stomach cancer cells. Biol Pharm Bull 25:1238–1240

    Article  Google Scholar 

  7. Kinjo J, Nagao T, Tanaka T, Nonaka G, Okabe H (2001) Antiproliferative constituents in the plants 8 Seeds of Rhynchosia volubilis. Biol Pharm Bull 24:1443—1445

    Article  PubMed  Google Scholar 

  8. Korematsu Y, Nagao T, Kinjo J, Okabe H, (2002) Abstracts of papers. In: The 49th Annu Meet Jpn Soc Pharmacognosy. Fukuoka, p 215

  9. Okawa M, Kinjo J, Nohara T, Ono M (2001) DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants. Biol Pharm Bull 24:1202–1205

    Article  PubMed  Google Scholar 

  10. Kataoka S, Masuda K, Mizutani K, Tanaka O, Kozuka M, Tokuda H, Nishino H, (1995) In: Abstracts of papers. 42th Annu Meet Jpn Soc Pharmacognosy. Fukuyama, p 179

  11. Tamura K, Miyoshi S, Sogabe T, Miyakoshi M, Niiho D, Kohbara T, Mizutani K, Tanaka O, Ikeda T, (2001) Abstracts of papers. 48th Ann Meet Jpn Soc Pharmacognosy. Kanazawa, p 100

  12. Ishimatsu M, Tanaka T, Nonaka G, Nishioka I, Nishizawa M, Yamagishi T (1989) Isolation and characterization of novel dimeric and trimeric hydrolyzable tannins, nuphrins C, D, E and F, from Nuphar japonicum. Chem Pharm Bull 37:1735–1743

    Google Scholar 

  13. Saijyo R, Nonaka G, Nishioka I, Chen IS, Hwang TH (1989) Isolation and characterization of hydrolyzable tannins from Mallotus japonicus and M Philippinensis. Chem Pharm Bull 37:2940–2947

    Google Scholar 

  14. Kinjo J, Hitoshi M, Eguchi M, Miyata C, Matsushita K, Nagao T, Okabe H, Tsuchihashi R, Okawa M, Nohara T, (2002) Abstracts of papers. 49th Ann Meet Jpn Soc Pharmacognosy. Fukuoka, p 217

  15. Lancaster MV, Fields RD (1996) US Patent 5501959

  16. Thabrew MI, Hughes RD, McFarlane IG (1997) Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J Pharm Pharmacol 49:1132–1135

    PubMed  Google Scholar 

  17. Fields RD, Lancaster MV (1993) Dual-attribute continuous monitoring of cell proliferation/cytotoxicity. Am Biotech Lab 11:48–50

    Google Scholar 

  18. Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7

    PubMed  Google Scholar 

  19. Miguez MP, Anundi I, Sainz-Pardo LA, Lindros KO (1994) Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chem Biol Interact 91:51–63

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This investigation was supported by a Grant-in-Aid for Scientific Research ©) (No. 13672246) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Fukuoka, 814-0180, Japan

    Junei Kinjo, Masahiro Hitoshi, Ryota Tsuchihashi, Yoshiaki Korematsu, Masafumi Okawa & Hikaru Okabe

  2. Maruzen Pharmaceutical Co., Ltd, 1089-8 Sagata, Shin-Ichi, Hiroshima, 729-3102, Japan

    Masazumi Miyakoshi, Toshiyuki Murakami, Daisuke Niiho & Kenji Mizutani

  3. School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyomachi, Nagasaki, 852-8521, Japan

    Takashi Tanaka

  4. Usaien Pharmaceutical Co., Ltd, 1-3-17 Zaimoku, Saga, 840-0055, Japan

    Genichiro Nonaka

  5. Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oehonmachi, Kumamoto, 862-0973, Japan

    Toshihiro Nohara

Authors
  1. Junei Kinjo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Hitoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryota Tsuchihashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshiaki Korematsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masazumi Miyakoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshiyuki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daisuke Niiho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kenji Mizutani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takashi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Genichiro Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toshihiro Nohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masafumi Okawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hikaru Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junei Kinjo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinjo, J., Hitoshi, M., Tsuchihashi, R. et al. Hepatoprotective constituents in plants 15: protective effects of natural-occurring flavonoids and miscellaneous phenolic compounds as determined in an HepG2 cell cytotoxicity assay. J Nat Med 60, 36–41 (2006). https://doi.org/10.1007/s11418-005-0002-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-005-0002-6

Keywords

Search

Navigation