Region-selective biosynthesis of artemisinic acid glycosides by crown galls of Panax quinquefolium and their in vitro antitumor activities

Jianhua Zhu; Lijia Chen; Xianjing Hu; Liyan Song; Mingxuan Wang; Rongmin Yu

Articles

Abstract

Pharmacognosy Magazine,2015,11,43,518-523.

DOI:10.4103/0973-1296.160460

Published:July 2015

Type:Original Article

Authors:

Author(s) affiliations:

Jianhua Zhu¹, Lijia Chen², Xianjing Hu³, Liyan Song³, Mingxuan Wang², Rongmin Yu¹
¹ Biotechnological Institute of Chinese Materia Medica, Jinan University; Department of Natural Medicinal Chemistry, Jinan University, Guangzhou 510632, China
² Biotechnological Institute of Chinese Materia Medica, Jinan University, China
³ Department of Pharmacology, Jinan University, Guangzhou 510632, China

Abstract:

Background: The biosynthesis of artemisinin derivatives is one of the interesting subjects. Artemisinic acid (AA) has been widely studied as a supposed intermediate in the biosynthetic pathway leading to artemisinin in Artemisia annua. Objective: To investigate the bioconversion of AA by transgenic crown galls of Panax quinquefolium. Materials and Methods: AA was administered into crown galls of P. quinquefolium and co cultured for 2 days. The methanol extract was separated by column chromatography, and the structures of two biosynthesis products were elucidated by physicochemical and spectroscopic methods. Co culture time curves on conversion were also established. In addition, the effects of AA on the growth and ginsenosides production of crown galls of P. quinquefolium were investigated. Furthermore, the in vitro antitumor activities of AA and two glycosides against HepG2 cell line were evaluated by 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyl tetrazolium bromide (MTT) assay. Results: Glycosylation of AA by crown galls of P. quinquefolium was observed, and two region selectively glycosylated products were obtained (AA-1, AA-2), involving one new compound (AA-2). Their structures were elucidated to be AA β-D-glucopyranosyl ester (AA-1) and AA β-D-glucopyranosyl (2 → 1) β-D-glucopyranosyl ester (AA 2). The maximum yield of AA 1 was 19.3% on the 1^st co culture day while that of AA 2 was 59.1% on the 2^nd day. MTT assay showed that the activity of monosaccharide glycoside (AA 1) was better than that of disaccharide glycoside (AA 2). Conclusion: Two AA glycosides involved one new compound with potential antitumor activity were obtained by region selective biosynthesis with crown galls of P. quinquefolium.