Production of bioactive triterpenes by Eriobotrya japonica calli

doi:10.1016/S0031-9422(01)00455-1

Phytochemistry

Volume 59, Issue 3, February 2002, Pages 315-323

https://doi.org/10.1016/S0031-9422(01)00455-1 Get rights and content

Abstract

Callus tissue cultures induced from an axenic leaf of Eriobotrya japonica (Rosaceae) produced triterpenes in large amounts (ca. 50 mg/g dry wt). Nine triterpenes were characterized as ursolic acid, oleanolic acid, 2α-hydoxyursolic acid, maslinic acid, tormentic acid, 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid, hyptadienic acid and a mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid. The triterpene composition in the callus tissues was noticeably different from that in intact leaves. The contents of tormentic acid with antidiabetic action, and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid with anti-HIV activity, were much larger than those in the intact leaves. All of the triterpenes isolated from the callus tissues showed an inhibitory effect comparable to (−)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein–Barr virus early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 2α, 19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid was the most potent inhibitor among them and caused a significant delay of two-stage carcinogenesis on mouse skin.

Callus tissue of Eriobotrya japonica (Rosaceae) producing triterpenes in large amounts (ca. 50 mg/g dry wt) was established. All of the triterpenes from the calli showed inhibitory effect on the activation of Epstein–Barr virus early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).

Introduction

Leaves of Eriobotrya japonica Lindl. (Rosaceae) have been used in folk medicine to treat various skin diseases and diabetes mellitus. Triterpenoid constituents have been isolated from the leaves of this plant, and several of them were reported to have anti-tumor, antiviral, and anti-inflammatory properties (Shimizu et al., 1986, Shimizu et al., 1996, Liang et al., 1990, Tommasi et al., 1992, Nozato et al., 1994). Occurrence of polyphenolic constituents in the leaves and their cytotoxicity against human oral tumor cell lines were also reported (Ito et al., 2000).

We previously reported the production of pharmacologically active compounds by plant cell cultures induced from medicinal plants (Taniguchi et al., 1997, Taniguchi et al., 1998, Taniguchi et al., 2000). In the course of this study, we have established callus cultures of E. japonica which produce large amounts of bioactive triterpenes. This paper deals with the characterization of triterpenes produced in the cultured calli, and the difference in the triterpene composition from that in the intact leaves. The anti-tumor properties of these triterpenes are also reported.

Section snippets

Establishment of callus tissues

Callus tissues of E. japonica were induced from an axenic leaf of a seedling on Linsmaier–Skoog (LS) agar medium (Linsmaier and Skoog, 1965) supplemented with 10 μM 1-naphthaleneacetic acid (NAA) and 10 μM 6-benzyladenine (BA), and maintained for over 4 years by subculturing on LS agar medium containing the above plant hormones at 1 monthly intervals at 25 °C in the dark. The calli appear pale yellow and tend to aggregate to form clusters. The callus cells grew constantly to reach 5 times the

Conclusion

We established cultures of callus tissue of Eriobotrya japonica producing triterpenes with biological activity. Among the triterpenes isolated from the tissues, compounds 6, 7, 8 and 9 have not been reported as constituents of intact E. japonica. The triterpene composition of the callus tissues was noticeably different from that of the leaves of the source plant, the calli producing more hydroxylated and oxidized compounds. The difference in the triterpene composition between callus tissues and

General procedures

¹H and ¹³C NMR spectra were measured in pyridine-d₅ or CDCl₃ on a Varian VXR-500 instrument (500 MHz for ¹H NMR and 126 MHz for ¹³C NMR). ESIMS were obtained using a Micromass Auto Spec OA-Tof mass spectrometer with a solvent of 50% MeOH+0.1% AcONH₄. The flow rate was set at 20 μl/min.

Callus induction and subculture condition

Seedlings were obtained from surface-sterilized seeds (10% antifolmin sol. containing 0.5% Tween 80, 1 h) on sucrose-free LS agar medium. The callus tissues were induced by 1 month-incubation after the inoculation

Acknowledgements

The NMR instrument used in this study is the property of the SC NMR Laboratory of Okayama University, which is gratefully acknowledged.

References (26)

S. Fujisawa et al.
Application of bis-eugenol to a zinc oxide eugenol cement
Journal of Dentistry
(1999)
H. Fukuda et al.
Inhibition of protein serine/threonine phosphatases by fumonisin B1, A mycotoxin
Biochemical and Biophysical Research Communications
(1996)
A. Ikuta et al.
Triterpenoids from callus tissue cultures of Paeonia species
Phytochemistry
(1995)
H. Ito et al.
Anti-tumor promoting activity of polyphenols from Cowania mexicana and Coleogyne ramosissima
Cancer Letters
(1999)
S. Taniguchi et al.
Production of macrocyclic ellagitannin oligomers by Oenothera laciniata callus culture
Phytochemistry
(1998)
S. Taniguchi et al.
Production of tannic acid by Rhus javanica cell cultures
Phytochemistry
(1997)
S. Taniguchi et al.
Galloylglucoses and riccionidin A in Rhus javanica adventitious root cultures
Phytochemistry
(2000)
H. Tokuda et al.
Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate
Cancer Letters
(1986)
G. Henle et al.
Immunofluorescence in cells derived from Burkitt's lymphoma
Journal of Bacteriology
(1966)
Isobe, T., Noda, Y., Kozo, S., Fujii, J., 1996. Terpenoids from Rabdosia effusa Hara. Nippon Kagaku Kaishi,...

H. Ito et al.

Polyphenols from Eriobotrya japonica and their cytotoxicity against human oral tumor cell lines

Chemical and Pharmaceutical Bulletin

(2000)

M.D. Ivorra et al.

Hypoglycemic and insulin release effects of tormentic acida new hypoglycemic natural product

Planta Medica

(1988)

J. Kitajima et al.

Constituents of Prunus zippeliana leaves and branches

Chemical and Pharmaceutical Bulletin

(1993)

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Production of bioactive triterpenes by Eriobotrya japonica calli

Abstract

Introduction

Section snippets

Establishment of callus tissues

Conclusion

General procedures

Callus induction and subculture condition

Acknowledgements

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Chemical and Pharmaceutical Bulletin