Anti-inflammatory 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones from agarwood of Aquilaria sinensis.

Four new 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, aqulisinone A (1), (5S, 6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-[2-(4'-methoxyphenylethyl)]-5,6,7,8-tetrahydrochromone (2), (5S,6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromone (3), (5S*,6R*,7R*,8S*)-8-chloro-5-ethoxy-6,7-dihydroxy-2-[2-(3'-hydroxy-4'-methoxy-phenylethyl)-5,6,7,8-tetrahydrochromone (4), and seven known analogues (5-11) were isolated from agarwood produced of Aquilaria sinensis. Among the new compounds, 4 is an artifact. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. The absolute configurations of 1-3 were defined based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) data. Compound 1 features a (5,5'')-carbon-carbon bond linkage connecting two 2-(2-phenylethyl)chromone monomeric units. All the new compounds were evaluated for their anti-inflammatory activities by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) release in RAW264.7 cells, 2 with an IC50 value of 3.46 µM.

Agarwood Extract Mitigates Intestinal Injury in Fluorouracil-Induced Mice.

Agarwood is used to treat gastrointestinal diseases. Although our previous studies demonstrated that agarwood ethanol extract produced by the whole-tree agarwood-inducing technique (WTAAE) improves intestinal peristalsis, the intestinal protective effect of WTAAE remains unclear. This study aimed to evaluate the protective effect of WTAAE on the intestinal injury induced by fluorouracil (5-FU) and explore its potential mechanism. Institute of Cancer Research (ICR) mice were given agarwood ethanol extracts (AAEs) (details in materials part), including WTAAE (0.71, 1.42 and 2.84 g/kg), wild agarwood ethanol extract (WAAE) and burning-chisel-drilling agarwood ethanol extract (FBAAE) (2.84 g/kg). A colon injury model was induced by 5-FU. After 14 d of treatment, the histopathology and biochemical and molecular parameters were measured. Our results indicated that WTAAE enhanced the intestinal advancing rate and alleviated the severity of colon injury similar the WAAE and better than FBAAE. Simultaneously, WTAAE reduced the nitric oxide (NO) concentration and increased the glutathione (GSH) and superoxide dismutase (SOD) levels. WTAAE also reduced the levels of interleukin-17 (IL-17) and IL-33 and elevated the level of IL-10. Furthermore, WTAAE upregulated the mRNA expression of the nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and downregulated the mRNA levels of the nuclear factor-kappaB (NF-κB) pathway. WTAAE had a mitigating effect on intestinal damage, suggesting that it could be used as an intestinal protective and adjuvant therapy drug for intestinal injury induced by chemical drugs.

[Anti-inflammatory sesquiterpenes from agarwood produced via whole-tree agarwood-inducing technique of Aquilaria sinensis].

The present study is to investigate the chemical constituents and anti-inflammation of agarwood produced via whole-tree agarwood-inducing technique( Agar-Wit) from Aquilaria sinensis by column chromatographic technique and semi-preparation HPLC.Eleven sesquiterpenes were isolated from the agarwood produced by Agar-Wit,and their structures were identified on the basis of physiochemical characteristics and spectroscopic data analysis as baimuxinol( 1),5α,7α( H)-eudesm-11( 13)-en-4α-ol( 2),( 7 S,9 S,10 S)-( +)-9-hydroxy-selina-4,11-dien-14-al( 3),petafolia A( 4),7( 11)-eremophilen-8-one( 5),neopetasane( 6),petafolia B( 7),11-hydroxy-valenc-1( 10)-en-2-one( 8),( 4αß,7ß,8αß)-3,4,4α,5,6,7,8,8α-octahydro-7-[1-( hydroxymethyl) ethenyl]-4α-methylnaphthalene-1-carboxaldehyde( 9),12-hydroxy-4( 5),11( 13)-eudesmadien-15-al( 10),and( 4 R,5 R,7 S,9 S,10 S)-(-)-eudesma-11( 13)-en-4,9-diol( 11). Among them,compound 1 was a new natural product,and this is the first time to report its13 CNMR spectroscopic data. Compounds 4,9 and 10 were reported from Aquilaria for the first time,and all the compounds are firstly isolated by Agar-Wit from A. sinensis. The anti-inflammatory activity of RAW264. 7 cells with lipopolysaccharide-induced was evaluated.As a result,1,4 and 9 showed potential anti-inflammatory activities with IC50 values( 2. 5±0. 35),( 3. 2±0. 2),( 4. 3±0. 56) µmol·L-1,respectively. This work provided scientific foundation for quality evaluation of the agarwood produced by Agar-Wit.

Four New 2-(2-Phenylethyl)chromone Derivatives from Chinese Agarwood Produced via the Whole-Tree Agarwood-Inducing Technique.

Four new 2-(2-phenylethyl)chromone derivatives (1-4) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR, MS, 1D as well as 2D NMR. All of the isolates were then assessed for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7. Compound 1 exhibited significant inhibitory activity with an IC50 value of 4.6 µM.

2-(2-Phenylethyl)chromones increase in Aquilaria sinensis with the formation of agarwood.

Obtained from Aquilaria Lam. and Gyrinops Gaertn., agarwood is a prestigious perfume and medicinal material in the world. Its primary chemical constituents and indicators of agarwood's development are 2-(2-phenylethyl)chromones (PECs). However, how PECs affect its quality, accumulation, and transformation pattern is still unclear. The present study investigated this issue by monitoring resin filling in agarwood generated by the whole-tree agarwood-inducing technique over a span of a year, observing the ethanol extract concentration at different sampling times, and statistically examining PECs in agarwood from each sampling period. In agarwood, the resin accumulated over time, except during the 4th-6th month due to the creation of a barrier layer. The relative content of total PECs demonstrated an overall increase throughout the year but a decrease from the 4th month to the 6th month, and the relative content of 19 PECs that persisted throughout the year was positively correlated with the content of ethanol extracts. In addition, the process of chromone accumulation was accompanied by the production and transformation of different types of chromones, with flindersia type 2-(2-phenylethyl)chromones, epoxy-2-(2-phenylethyl)chromones, and diepoxy-2-(2-phenylethyl)chromones being the major chromone components; in addition, the content of 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones kept increasing after 6 months of agarwood formation. Three main trends were identified from 58 analogs of PECs, each with notable variation. The first type had the highest content at the beginning of resin formation. The second type had the highest content at 6 months and then started to decrease, and the third type had a slowly increasing content. As a whole, this study systematically investigated the accumulation of PECs during injury-induced agarwood production in A. sinensis, which is of scientific significance in resolving the transformation of PECs and revealing the secret of agarwood formation.

Temporal characteristics of agarwood formation in Aquilaria sinensis after applying whole-tree agarwood-inducing technique.

Objective: Agarwood-a resinous wood produced by Aquilaria plants in response to injury or artificial induction-is a valuable medicinal and fragrance resource. Whole-Tree Agarwood-Inducing Technique (Agar-WIT) has been widely used to produce agarwood. However, the time-dependent characteristics of agarwood formation induced by Agar-WIT are yet to be clarified. To promote technologically efficient utilization and upgradation of Agar-WIT, the dynamic process and mechanism of agarwood formation were analyzed for one year. Methods: Agarwood formation percentage, barrier layer microscopic properties, extract levels, compound level, and characteristic chromatograms of agarwood were examined by referring to the Chinese Pharmacopeia (2020 version). Results: Agar-WIT could maintain a high percentage of agarwood formation over one year compared with that of healthy plants. Alcohol-soluble extract and agarotetrol levels showed fluctuating cyclic changes with peaks occurring first during the fifth and sixth months, and subsequently in the 11th month. Aquilaria trees subjected to Agar-WIT treatment for 1-12 months showed significant characteristics of a dynamic agarwood formation process. The barrier layer began to appear in the fourth month after treatment. Alcohol-soluble extractive levels in agarwood formed in the second month, and thereafter, exceeded 10.0%, and agarotetrol in agarwood produced after four months or later, exceeded 0.10%. Conclusion: According to the Chinese Pharmacopoeia, alcohol-soluble extractive levels in agarwood should not be less than 10.0% and agarotetrol level should exceed 0.10%. After four months of Agar-WIT treatment, the formed agarwood theoretically met these standards and was suitable for developed and utilization. However, the optimal harvest time was found to be the 11th month, followed by the sixth month after Agar-WIT treatment. Therefore, Agar-WIT resulted in swift agarwood formation and stable accumulation of alcohol-soluble extracts and agarotetrol. Thus, this method is efficient for large-scale cultivation of Aquilaria sinensis to produce agarwood and provide raw materials for the agarwood medicinal industry.

New 2-(2-phenylethyl)chromone derivatives from agarwood and their inhibitory effects on tumor cells.

Two new chromone derivatives, 7-hydroxy-2-[2-(3'-methoxy-4'-hydroxyphenyl)-ethyl]chromone (1), and 6,7-dimethoxy-2-[2-(3'-hydroxyphenyl)-ethyl]chromone (2) were isolated from the EtOH extract of agarwood of Aquilaria sinensis, together with eleven known analogues. Their structures were established by detailed HR-ESIMS, 1D and 2D NMR spectroscopic analysis, as well as comparison with the literature data. Selected the isolates (1, 2, 4-8, 10, 11) were tested for their antitumor activities against SMMC-7721, MGC-803 and OV-90 cell lines using the MTT method with cisplatin and paclitaxel as the positive control. All the tested compounds showed weak cytotoxic activities with IC50 values ranged from 18.82 to 37.95 µg/ml.

Anti-inflammatory Chromones from Agarwood Produced Via Whole-Tree Agarwood-Inducing Technique of Aquilaria sinensis / 中国药学杂志

OBJECTIVE: To investigate the chromones and anti-inflammation effect of agarwood produced via whole-tree agarwood-inducing technique (Agar-Wit) from A. sinensis. METHODS: The constituents were isolated and purified by chromatographic technique and semi-preparation HPLC. RAW264.7 cell model induced by lipopolysaccharide was used to evaluate the anti-inflammatory activity of some compounds, and the secretion level of TNF-α was detected by ELISA. RESULTS: A new 2-(2-phenylethyl) chromone, (7'R)-2-[2-(7'-hydroxyphenyl)ethyl] chromone (1), along with nine analogues (2-10) were isolated from the agarwood produced by Agar-Wit, their structures were identified on the basis of physicochemical characteristics and spectroscopic data analysis as 6,7-dimethoxy-2-[2-(7'-hydroxyphenyl)ethyl] chromone (2), 6-hydroxy-2-[2-(7'-hydroxyphenyl)ethyl] chromone (3), 8-chloro-6-hydroxy-2-(2-phenylethyl)chromen-4-one (4), 8-chloro-6-hydroxy-2-[2-(4'-methoxyphenyl)ethyl] chromone (5), 8-chloro-6-hydroxy-2-[2-(3'-hydroxy-4'-methoxyphenyl)ethyl] chromone (6), 7-hydroxy-6-methoxy-2-(2-phenylethyl) chromone (7), 6-hydroxy-7-dimethoxy-2-[2-(4'-hydroxyethyl)] chromone (8), 6-hydroxy-2-[2-(3'-methoxy-4'-hydroxy)ethyl] chromone (9), 6-hydroxy-2-[2-(3'-hydroxy-4'-methoxyphenyl)ethyl] chromone (10). The results showed that compounds 1, 4, 6, 9 significantly inhibited the release of TNF-α inflammatory factors in RAW264.7 cells induced by LPS, with IC50 values of 13.30, 8.53, 7.72, and 10.87 μg•mL-1, respectively. CONCLUSION: Compound 1 is a new compound. The crystal structure of compound 4 is reported for the first time. Compounds 1, 4, 6, 9 show significant anti-inflammation activities.

Anti-inflammatory sesquiterpenes from agarwood produced via whole-tree agarwood-inducing technique of Aquilaria sinensis / 中国中药杂志

The present study is to investigate the chemical constituents and anti-inflammation of agarwood produced via whole-tree agarwood-inducing technique( Agar-Wit) from Aquilaria sinensis by column chromatographic technique and semi-preparation HPLC.Eleven sesquiterpenes were isolated from the agarwood produced by Agar-Wit,and their structures were identified on the basis of physiochemical characteristics and spectroscopic data analysis as baimuxinol( 1),5α,7α( H)-eudesm-11( 13)-en-4α-ol( 2),( 7 S,9 S,10 S)-( +)-9-hydroxy-selina-4,11-dien-14-al( 3),petafolia A( 4),7( 11)-eremophilen-8-one( 5),neopetasane( 6),petafolia B( 7),11-hydroxy-valenc-1( 10)-en-2-one( 8),( 4αβ,7β,8αβ)-3,4,4α,5,6,7,8,8α-octahydro-7-[1-( hydroxymethyl) ethenyl]-4α-methylnaphthalene-1-carboxaldehyde( 9),12-hydroxy-4( 5),11( 13)-eudesmadien-15-al( 10),and( 4 R,5 R,7 S,9 S,10 S)-(-)-eudesma-11( 13)-en-4,9-diol( 11). Among them,compound 1 was a new natural product,and this is the first time to report its13 CNMR spectroscopic data. Compounds 4,9 and 10 were reported from Aquilaria for the first time,and all the compounds are firstly isolated by Agar-Wit from A. sinensis. The anti-inflammatory activity of RAW264. 7 cells with lipopolysaccharide-induced was evaluated.As a result,1,4 and 9 showed potential anti-inflammatory activities with IC50 values( 2. 5±0. 35),( 3. 2±0. 2),( 4. 3±0. 56) μmol·L-1,respectively. This work provided scientific foundation for quality evaluation of the agarwood produced by Agar-Wit.

Quality of Agarwood Produced by Whole Tree Agarwood-inducing Technique (Agar-Wit) from China and Southeast Asian Countries / 中国药学杂志

OBJECTIVE: To investigate the similarities and differences of the quality of agarwood produced by agar-wit from China and Southeast Asian countries. METHODS: The sensory characteristic, identification item, extract, content determination, characteristic chromatogram and total chromone content of agarwood produced by agar-wit from 11 place of origins of China and Southeast Asian countries were mainly evaluated, according to the Chinese Pharmacopoeia (2015 edition). RESULTS: The morphological characteristics, TLC and characteristic chromatograms of 11 batches of agarwood produced by agar-wit were similar. Special structures such as included phloem, vessel and rays were observed in all samples. The extract and total chromone contents of agarwood produced by agar-wit from the six producing areas in China were higher than those from the five producing areas in Southeast Asia. Compared with other agarwood-inducing method, the sensory characteristics of the agarwood produced by agar-wit were relatively stable, and the average contents of the extract and total chromone were significantly higher, but the average content of agarotetrol was slightly lower than that of the agarwood produced by peripheral-inducing and iron-inducing. CONCLUSION: In terms of quality, the agar-wit is superior to the traditional agarwood-inducing method. It is not only applicable to the agarwood production of Aquilaria sinensis in China, but also applicable to the species of Aquilaria Lam. in Southeast Asian countries. The quality of agarwood produced by agar-wit is good in general, but the quality of the agarwood produced by A. sinensis is better than the species of Aquilaria Lam. in the Southeast Asian.