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. 2016 Mar 21;17(3):398.
doi: 10.3390/ijms17030398.

Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis

Michal Korinek  1   2 , Vitthal D Wagh  3 , I-Wen Lo  4 , Yu-Ming Hsu  5 , Hsue-Yin Hsu  6 , Tsong-Long Hwang  7   8   9 , Yang-Chang Wu  10   11   12   13 , Yuan-Bin Cheng  14   15 , Bing-Hung Chen  16   17 , Fang-Rong Chang  18   19   20   21
Affiliations

Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis

Michal Korinek et al. Int J Mol Sci. .

Abstract

The Aquilaria malaccensis (Thymelaeaceae) tree is a source of precious fragrant resin, called agarwood, which is widely used in traditional medicines in East Asia against diseases such as asthma. In our continuous search for active natural products, A. malaccensis seeds ethanolic extract demonstrated antiallergic effect with an IC50 value less than 1 µg/mL. Therefore, the present research aimed to purify and identify the antiallergic principle of A. malaccensis through a bioactivity-guided fractionation approach. We found that phorbol ester-rich fraction was responsible for the antiallergic activity of A. malaccensis seeds. One new active phorbol ester, 12-O-(2Z,4E,6E)-tetradeca-2,4,6-trienoylphorbol-13-acetate, aquimavitalin (1) was isolated. The structure of 1 was assigned by means of 1D and 2D NMR data and high-resolution mass spectrometry (HR-MS). Aquimavitalin (1) showed strong inhibitory activity in A23187- and antigen-induced degranulation assay with IC50 values of 1.7 and 11 nM, respectively, with a therapeutic index up to 71,000. The antiallergic activities of A. malaccensis seeds and aquimavitalin (1) have never been revealed before. The results indicated that A. malaccensis seeds and the pure compound have the potential for use in the treatment of allergy.

Keywords: Aquilaria malaccensis seeds; antiallergic; bioactivity-guided fractionation; degranulation; phorbol ester.

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Figures

Figure 1
Figure 1
Activity of phorbol ester-rich fraction (AM4) and aquimavitalin (1) on stimulant-free degranulation in RBL-2H3 cells. The RBL-2H3 cells were treated with AM4 (10 µg/mL) and aquimavitalin (10 µg/mL) for 10 h. Tyrode’s buffer supplemented with glucose, bovine serum albumin (BSA) and glutamine was used as a medium. A23187 (1 µM) was used as a positive control. Data are expressed as mean ± SD (n = 3). ** p < 0.001 compared with the control value.
Figure 2
Figure 2
Structure of aquimavitalin (1).
Figure 3
Figure 3
Key 1H–1H correlation spectroscopy (COSY) (bold) and HMBC (arrow) correlations of aquimavitalin (1).
Figure 4
Figure 4
Key NOESY (double-headed arrow) correlations of aquimavitalin (1). Grey color represents carbon, red color oxygen and white color proton.
See this image and copyright information in PMC

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