Skip to main content
SpringerLink
Log in

Cytotoxic metabolites from the cultures of endophytic fungi from Panax ginseng

  • Biotechnological products and process engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Two strains of endophytic fungi, Penicillium melinii Yuan-25 and Penicillium janthinellum Yuan-27, with strong anti-Pyricularia oryzae activity, were obtained from the roots of Panax ginseng. Based on bioactivity-oriented isolation, a new benzaldehyde derivative, ginsenocin (1), together with six known compounds, methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (2), 3,4,5-trimethyl-1,2-benzenediol (3), penicillic acid (4), mannitol (5), ergosterol (6), and ergosterol peroxide (7), were separated from the EtOAc extract of Yuan-25 culture, while brefeldin A (8) was isolated as the major constituent from the EtOAc extract of Yuan-27 culture. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1–8 were evaluated for their cytotoxicity against six human cancer cell lines. Brefeldin A (8) was the most cytotoxic constituent against all the tested cell lines with IC50 values <0.12 μg/ml, while ginsenocin (1) and penicillic acid (4) also exhibited potent cytotoxicity with IC50 values ranging from 0.49 to 7.46 μg/ml. Our results suggest that endophytic fungi isolated from P. ginseng are a promising natural source of potential anticancer agents.

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
Fig. 4

Similar content being viewed by others

References

  • Aly AH, Debbab A, Kjer J, Proksch P (2010) Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products. Fungal Diversity 41(1):1–16

    Article  Google Scholar 

  • Ciegler A, Detroy RW, Lillehoj EB (1971) Microbial toxins (chapter 6): patulin, penicillic acid, and other carcinogenic lactones. Academic, New York, p 417

    Google Scholar 

  • Coon JT, Ernst E (2002) Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf 25(5):323–244

    Article  PubMed  CAS  Google Scholar 

  • Cui HB, Mei WL, Han Z, Wu J, Lin HP, Hong K, Dai HF (2008) Antibacterial metabolites from the fermentation broth of marine fungus 095407. Chin J Med Chem 18:131–134

    CAS  Google Scholar 

  • Ernst E (2010) Panax ginseng: an overview of the clinical evidence. J Ginseng Res 34(4):259–263

    Article  Google Scholar 

  • Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod 69(3):509–526

    Article  PubMed  CAS  Google Scholar 

  • Gunji S, Arima K, Beppu T (1983) Screening of antifungal antibiotics according to activities inducing morphological abnormalities. Agric Biol Chem 47(9):2061–2069

    Article  CAS  Google Scholar 

  • Guo H, O'Doherty GA (2008) De novo asymmetric synthesis of anthrax tetrasaccharide and related tetrasaccharide. J Org Chem 73(14):5211–5220

    Article  PubMed  CAS  Google Scholar 

  • Guo LD, Huang GR, Wang Y, He WH, Zheng WH, Hyde KD (2003) Molecular identification of white morphotype strains of endophytic fungi from Pinus tabulaeformis. Mycol Res 107(Pt 6):680–688

    Article  PubMed  CAS  Google Scholar 

  • Haerri E (1963) A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity produced by Penicillium brefeldianum Dodge. Helv Chim Acta 46:1235

    Article  CAS  Google Scholar 

  • Han Z, Mei WL, Cui HB, Zeng YB, Lin HP, Hong K, Dai HF (2008) Antibacterial constituents from the endophytic fungus Penicillium sp. of mangrove plant Cerbera manghas. Acta Chim Sinica 29:749–752

    CAS  Google Scholar 

  • Han Z, Mei WL, Zhao YX, Deng YY, Dai HF (2009) A new cytotoxic isocoumarin from endophytic fungus Penicillium sp. 091402 of the mangrove plant Bruguiera sexangula. Chem Nat Comp 45:805–807

    Article  CAS  Google Scholar 

  • Hendriksen HV, Mathiasen TE, Adler-Nissen J, Frisvad JC, Emborg C (1988) Production of mannitol by Penicillium strains. J Chem Technol Bitechnol 43(3):223–228

    Article  CAS  Google Scholar 

  • Higgins KL, Arnold AE, Miadlikowska J, Sarvate SD, Lutzoni F (2007) Phylogenetic relationships, host affinity, and geographic structure of boreal and arctic endophytes from three major plant lineages. Mol Phylogenet Evol 42(2):543–555

    Article  PubMed  CAS  Google Scholar 

  • Jasinghe VJ, Perera CO, Barlow PJ (2005) Bioavailability of vitamin D2 from irradiated mushrooms: an in vivo study. Brit J Nutr 93(6):951–956

    Article  PubMed  CAS  Google Scholar 

  • Kamoldinov KS, Eshbakova KA, Bobakulov KM, Abdullaev ND (2011) Components of Fraxinus raibocarpa. Chem Nat Comp 47(3):448–449

    Article  CAS  Google Scholar 

  • Kim HL, Kochevar J (1995) Isolation of brefeldin A. Gen Pharmacol 26(2):363–364

    Article  PubMed  CAS  Google Scholar 

  • Kimura Y, Nakahara S, Fujioka S (1996) Aspyrone, a nematicidal compound isolated from the fungus, Aspergillus melleus. Biosci Biotechnol Biochem 60:1375–1376

    Article  CAS  Google Scholar 

  • Klausner RD, Donaldson JG, Lippincott-Schwartz J (1992) Brefeldin A: insights into the control of membrane traffic and organelle structure. J Cell Biol 116(5):1071–1080

    Article  PubMed  CAS  Google Scholar 

  • Kuo LM, Chen KY, Hwang SY, Chen JL, Liu YY, Liaw CC, Ye PH, Chou CJ, Shen CC, Kuo YH (2005) DNA topoisomerase I inhibitor, ergosterol peroxide from Penicillium oxalicum. Planta Med 71(1):77–79

    Article  PubMed  CAS  Google Scholar 

  • Kuo CF, Hsieh CH, Lin WY (2011) Proteomic response of LAP-activated RAW 264.7 macrophages to the anti-inflammatory property of fungal ergosterol. Food Chem 126(1):207–212

    Article  CAS  Google Scholar 

  • Kwon HC, Zee SD, Cho SY, Choi SU, Lee KR (2002) Cytotoxic ergosterols from Paecilomyces sp. J300. Arch Pharm Res 25(6):851–855

    Article  PubMed  CAS  Google Scholar 

  • Li C, Cai J, Geng J, Li Y, Wang Z, Li R (2012a) Purification, characterization and anticancer activity of a polysaccharide from Panax ginseng. Int J Biol Macromol 51(5):968–973

    Article  CAS  Google Scholar 

  • Li JT, Chen QQ, Zeng Y, Wang Q, Zhao PJ (2012b) A new phenol compound from endophytic Phomopsis sp. DC01. Nat Prod Res 26:2008–2012

    Article  CAS  Google Scholar 

  • Park JD, Rhee DK, Lee YH (2005) Biological activities and chemistry of saponins from Panax ginseng. Phytochem Rev 4:159–175

    Article  CAS  Google Scholar 

  • Qi LW, Wang CZ, Yuan CS (2011) Ginsenosides from American ginseng: chemical and pharmacological diversity. Phytochemistry 72(8):689–699

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez RJ, White JF Jr, Arnold AE, Redman RS (2009) Fungal endophytes: diversity and functional roles. New Phytol 182(2):314–330

    Article  PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4(4):406–425

    PubMed  CAS  Google Scholar 

  • Sausville EA, Duncan KL, Senderowicz A, Plowman J, Randazzo PA, Kahn R, Malspeis L, Grever MR (1996) Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A. Cancer J Sci Am 2(1):52–58

    PubMed  CAS  Google Scholar 

  • Saw CLL, Wu Q, Kong ANT (2010) Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2) anti-oxidative stress/anti-inflammatory pathways. Chin Med 5:37–43

    Article  PubMed  Google Scholar 

  • Schulz B, Boyle C, Draeger S, AK R m, Krohn K (2002) Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol Res 106(9):996–1004

    Article  CAS  Google Scholar 

  • Shawkat H, Westwood MM, Mortimer A (2012) Mannitol: a review of its clinical uses. Contin Educ Anaesth Crit Care Pain 12(2):82–85

    Article  Google Scholar 

  • Shin HR, Kim JY, Yun TK, Morgan G, Vainio H (2000) The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 11(6):565–576

    Article  PubMed  CAS  Google Scholar 

  • Soman AG, Gloer JB, Wicklow DT (1999) Antifungal and antibacterial metabolites from a sclerotium-colonizing isolate of Mortierella vinacea. J Nat Prod 62:386–388

    Article  PubMed  CAS  Google Scholar 

  • Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260(5105):214–216

    Article  PubMed  CAS  Google Scholar 

  • Strobel GA (2003) Endophytes as sources of bioactive products. Microbes Infect 5:535–544

    Article  PubMed  CAS  Google Scholar 

  • Sun PX, Zheng CJ, Li WC, Jin GL, Huang F, Qin LP (2011) Trichodermanin A, a novel diterpenoid from endophytic fungus culture. J Nat Med 65:381–384

    Google Scholar 

  • Suzuki S, Kimura T, Saito F, Ando K (1971) Antitumor and antiviral properties of penicillic acid. Agr Biol Chem 35(2):287–290

    Article  CAS  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25(24):4876–4882

    Article  PubMed  CAS  Google Scholar 

  • Wang FW (2012) Bioactive metabolites from Guignardia sp., an endophytic fungus residing in Undaria pinnatifida. Chin J Nat Med 10:72–76

    Article  PubMed  CAS  Google Scholar 

  • Wang JF, Huang YJ, Fang MJ, Zhang YJ, Zheng ZH, Zhao YF, Su WJ (2002) Brefeldin A, a cytotoxin produced by Paecilomyces sp. and Aspergillus clavatus isolated from Taxus mairei and Torreya grandis. FEMS Immunol Med Microbiol 34:51–57

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Wu J, Huang W, Tan R (2006) Laccase production by Monotospora sp., an endophytic fungus in Cynodon dactylon. Bioresour Technol 97(5):786–789

    Article  PubMed  CAS  Google Scholar 

  • Wang LW, Xu BG, Wang JY, Su ZZ, Lin FC, Zhang CL, Kubicek CP (2012) Bioactive metabolites from Phoma species, an endophytic fungus from the Chinese medicinal plant Arisaema erubescens. Appl Microbiol Biotechnol 93(3):1231–1239

    Article  PubMed  CAS  Google Scholar 

  • Wu LS, Hu CL, Han T, Zheng CJ, Ma XQ, Rahmand K, Qin LP (2012) Cytotoxic metabolites from Perenniporia tephropora, an endophytic fungus from Taxus chinensis var. mairei. Appl Microbiol Biotechnol 97:305–315. doi:10.1007/s00253-012-4189-7

  • Xu LL, Han T, Wu JZ, Zhang QY, Zhang H, Huang BK, Rahman K, Qin LP (2009) Comparative research of chemical constituents, antifungal and antitumor properties of ether extracts of Panax ginseng and its endophytic fungus. Phytomedicine 16(6):609–616

    Article  PubMed  CAS  Google Scholar 

  • Yu HS, Zhang L, Li L, Zheng CJ, Guo L, Li WC, Sun PX, Qin LP (2010) Recent developments and future prospects of antimicrobial metabolites produced by endophytes. Microbiol Res 165:437–449

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Shan T, Mou Y, Zhou L (2011) Plant-derived bioactive compounds produced by endophytic fungi. Mini-Rev Med Chem 11(2):159–168

    Article  PubMed  CAS  Google Scholar 

  • Zheng CJ, Li L, Han T, Qin LP (2012) Identification of a quinazoline alkaloid produced by Penicillium vinaceum, an endophytic fungus from Crocus sativus. Pharm Biol 50(2):129–133

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, People’s Republic of China

    Cheng-Jian Zheng, Yuan-Yuan Li, Ting Han, Qiao-Yan Zhang, Qian-Liang Ming & Lu-Ping Qin

  2. The Research Institute of TCM Literature, Shanghai TCM University, Shanghai, 201203, People’s Republic of China

    Li-Li Xu

  3. Faculty of Science, School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England, UK

    Khalid Rahman

  4. Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Shanghai, 200433, People’s Republic of China

    Lu-Ping Qin

Authors
  1. Cheng-Jian Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-Li Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan-Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ting Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiao-Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qian-Liang Ming
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Khalid Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lu-Ping Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ting Han or Lu-Ping Qin.

Additional information

Cheng-Jian Zheng and Li-Li Xu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zheng, CJ., Xu, LL., Li, YY. et al. Cytotoxic metabolites from the cultures of endophytic fungi from Panax ginseng . Appl Microbiol Biotechnol 97, 7617–7625 (2013). https://doi.org/10.1007/s00253-013-5015-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-013-5015-6

Keywords

Search

Navigation