Tetrahedron Letters
Biopreparation of an anti-inflammatory agent, diarctigenin,
from arctiin isolated from Arctium lappa by Rhizoctonia solani AG-4
⇑
Ping-Chung Kuo , Zi-Yu Chen, Miao-Fan Chen
Department of Biotechnology, National Formosa University, Yunlin 632, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
In the preliminary screening for the plant-derived pesticides against Rhizoctonia solani Kühn AG-4 (RS
AG-4), the indicator compounds arctiin (1) and arctigenin (2) in methanol extracts of Arctium lappa L.
were consumed and transformed to other compounds. Thus, in the present study RS AG-4 was used as
a biocatalyst and the biotransformation of arctiin (1) was investigated. Conversion of arctiin (1) to arc-
tigenin (2) was achieved by the enzymatic hydrolysis of sugar moiety. In addition, an anti-inflammatory
lignan dimer reported from the Arctium species, diarctigenin (3) was afforded in good yields. The HPLC
monitoring of the biotransformation process indicated the possible mechanism. It would be an excellent
method to produce a large scale of diarctigenin (3) for the successive medicinal examinations.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 4 August 2013
Revised 30 August 2013
Accepted 14 October 2013
Available online 20 October 2013
Keywords:
Rhizoctonia
Arctium lappa
Arctiin
Diarctigenin
Biotransformation
Small organic molecules purified from natural sources provide an
incomparable source of inspiration for advances in organic chemis-
try and disease treatment due to their significant biological proper-
ties.1–7 Although some compounds can be easily synthesized by
chemical ways, some issues still remain, including complex opera-
tion, safety, pollution, and production cost. Biopreparation has been
considered to be an economical technology by synthetic organic
chemists in the development of new production routes for chemical
and pharmaceutical compounds. As compared with chemical syn-
thesis, biotransformation is a useful method to produce bioactive
compounds with advantages such as high stereo- and regio-selectiv-
ity, as well as milder reaction conditions, simple operation proce-
dures, and environmental safety.8–10
Arctium lappa L. is a perennial herb that has been cultivated as a
vegetable in many countries for a long time. The seeds of A. lappa L.
are extensively used in traditional medicines as diuretic, anti-
inflammatory, and detoxifying agents. The Arctium genus is a plen-
tiful source for the dibenzylbutyrolactone lignans, which are fa-
mous for their anti-proliferative and apoptotic effects. In the
previous literature, a dimeric lignan, diarctigenin (3), was reported
with significant inhibitory activity on nitric oxide (NO) production
in LPS-activated mouse peritoneal macrophages.11,12 Inflammation
is related to morbidity and mortality of many diseases and is
recognized as part of the complex biological response of vascular
tissues to harmful stimuli. It is the host response to infection or in-
jury, which involves the recruitment of leukocytes and the release
of inflammatory mediators, including NO. Sustained NO release by
inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2)
production by cyclooxy-genase 2 (COX2) have been implicated as
mediators of inflammation and are induced by bacterial lipopoly-
saccharide (LPS) or immunological stimuli. It has been reported
that excess production of NO and PGE2 by macrophages and other
cells exposed to endotoxins may contribute to septic shock, cere-
bral injury, myocardical ischemia, diabetes, arteriosclerosis, and
other local or systemic inflammatory disorders.13–16 Thus, inhibi-
tion of NO synthesis and PGE2 production stands as an important
therapeutic goal. Due to the low cytotoxicity of diarctigenin,12 it
could be a good candidate for the treatment of various anti-inflam-
matory diseases. However, the natural abundance of this dimeric
lignan is very limited for the successive bioactivity examinations.
O
7'
2'
H3CO
3'
9'
8'
1'
6'
O
4'
8
9
7
HO
5'
1
2
2
6
5
3
4
OCH3
OCH3
⇑
Corresponding author. Tel.: +886 5 6315491; fax: +886 5 6315502.
Figure 1. Chemical structure of diarctigenin (3) and significant HMBC (?)
correlations.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.