Chemical Constituents and Pharmacological Activity of Agarwood and Aquilaria Plants
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molecules Review Chemical Constituents and Pharmacological Activity of Agarwood and Aquilaria Plants Shuai Wang 1,2,† ID , Zhangxin Yu 3,4,†, Canhong Wang 3,4, Chongming Wu 5, Peng Guo 5,* and Jianhe Wei 1,2,3,4,* 1 Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; [email protected] 2 Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China 3 Conservation and Development of Southern Medicine, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Haikou 570311, China; [email protected] (Z.Y.); [email protected] (C.W.) 4 Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Haikou 570311, China 5 Pharmacology and Toxicology Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; [email protected] * Correspondence: [email protected] (P.G.); [email protected] (J.W.); Tel.: +86-010-5783-3235 (P.G.); +86-010-5783-3016 (J.W.) † These authors contributed equally to this work. Received: 10 January 2018; Accepted: 31 January 2018; Published: 7 February 2018 Abstract: Agarwood, a highly precious non-timber fragrant wood of Aquilaria spp. (Thymelaeaceae), has been widely used in traditional medicine, religious rites, and cultural activities. Due to the inflated demanding and depleted natural resources, the yields of agarwood collected from the wild are shrinking, and the price is constantly rising, which restricts agarwood scientific research and wide application. With the sustainable planting and management of agarwood applied, and especially the artificial-inducing methods being used in China and Southeast Asian countries, agarwood yields are increasing, and the price is becoming more reasonable. Under this condition, illuminating the scientific nature of traditional agarwood application and developing new products and drugs from agarwood have become vitally important. Recently, the phytochemical investigations have achieved fruitful results, and more than 300 compounds have been isolated, including numerous new compounds that might be the characteristic constituents with physiological action. However, no one has focused on the new compounds and presented a summary until now. Alongside phytochemical advances, bioactivity screening and pharmacological investigation have also made a certain progress. Therefore, this review discussed the new compounds isolated after 2010, and summarized the pharmacological progress on agarwood and Aquilaria plants. Keywords: agarwood; Aquilaria plants; chemical constitutes; bioactive compounds; pharmacological function 1. Introduction Agarwood, known as chenxiang in Chinese and called aloeswood, agalloch, eaglewood, jinkoh, gaharu, or kanankoh in different regions, is a highly valuable non-timber fragrant wood of Aquilaria spp. (Thymelaeaceae) [1–4]. There are 31 species of Aquilaria found worldwide in Indonesia, Malaysia, Molecules 2018, 23, 342; doi:10.3390/molecules23020342 www.mdpi.com/journal/molecules Molecules 2018, 23, 342 2 of 21 China, India, Philippines, Cambodia, Vietnam, Laos, Thailand, Papua New Guinea, and Singapore [5,6], among which 19 species can produce agarwood after being attacked by physical force [7,8], insects [9], or bacteria/fungi infection [10–12]. Agarwood is used for incense, perfume, traditional medicine, and other products in the world market. In traditional Chinese medicine, agarwood is used as a qi-regulating drug and carminative medicine to relieve gastric problems, coughs, rheumatism, and high fever. It can promote qi circulation to relieve pain, warm the middle energizer to arrest vomiting, and regulate respiration to relieve asthma [13]. In traditional Arabian medicine, agarwood essential oil is used for aromatherapy. Simultaneously, agarwood has also been widely used for centuries as incense in Buddhist, Hindu, and Islamic ceremonies. With the increasing demand for agarwood, the population of Aquilaria species is declining rapidly in the wild, and all species of Aquilaria have been placed on the Appendix II list of the Convention on International Trade in Endangered Species of Wild Fauna and Flora since 2004 [1]. In response to this situation, sustainable planting and management of agarwood with artificial methods are arising, and the agarwood yield is increasing. As a result, agarwood no longer needs to be obtained from wild natural resources, enabling its wider application and investigation, especially on pharmaceutical study. Based on the phytochemical studies, a number of new compounds have been isolated and identified from agarwood and Aquilaria plants. However, there is no literature concentrating on the new compounds, even though earlier literature have summarized the chemical constituents of agarwood and related plants [6,14,15]. Therefore, this review discussed the new compounds isolated after 2010, and summarized the pharmacological progress on agarwood and Aquilaria plants. 2. Results and Discussion 2.1. New Compounds from Agarwood and Aquilaria Plants The chemical constitutes of agarwood originating from the genus Aquilaria, include 2-(2-phenylethyl)-4H-chromen-4-one derivatives, terpenoids, flavonoids etc., in which 2-(2-phenylethyl)-4H-chromen-4-one derivatives and sesquiterpenes are the two predominant constituents in agarwood. There have been 154 new compounds (Table1) isolated from agarwood and genus Aquilaria trees since 132 compounds were summarized in June 2010 [14]. 2.1.1. 2-(2-Phenylethyl)chromones In total, 88 new 2-(2-phenylethyl)chromone compounds (1–88) have been isolated from agarwood and genus Aquilaria plants (Figures1–5). Yang et al. [ 16] carried out a bioassay-guided isolation strategy from A. sinensis, resulting in seven new 2-(2-phenylethl)chromone derivatives (1–7) and a new 2-(2-phenylethenyl)chromone (8) being obtained from an ethanol (EtOH) extract. The investigation of EtOH extract obtained another three 2-(2-phenylethl)chromones (9–11)[17,18] and eight derivatives (12–19) from different fractions [19]. Liao et al. [20] reported seven new 2-(2-phenylethyl)chromone derivatives (20–26), including a chlorinated one (23) from the ethyl acetate (EtOAc) fraction of artificial agarwood (A. sinensis). The EtOAc fraction also contained three 2-(2-phenylethyl)chromones (27–29)[8] and four new bi-phenylethylchromones (30–33)[21]. A phytochemical investigation of a resinous wood (A. sinensis) led to the isolation of nine new 2-(2-phenylethyl)chromone derivatives, aquilarones A–I (34–42) from a chloroform (CHCl3) fraction [22]. Liu et al. found four new 2-(2-phenylethyl)chromone derivatives (43–46) from Chinese agarwood produced via the whole-tree agarwood-inducing technique [23]. Huo et al. gained five new 2-(2-phenylethyl)chromone derivatives (47–51)[24] and sixteen dimeric 2-(2-phenylethyl)chromones (52–67) from the resinous wood of A. sinensis [25]. Liao et al. isolated thirteen 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones (68–80)[26] from the artificial agarwood of A. sinensis. Additionally, one 2-(2-phenylethyl)chromone compound (81) was isolated from the stem bark EtOH extract of A. sinensis [27]. “Qi-Nan” is regarded as the highest quality agarwood, valued for its mysterious oriental odor that can be smelt without burning, unlike other kinds of agarwood. The investigation of EtOH extract of Molecules 2018, 23, x 3 of 24 Molecules 2018, 23, 342 3 of 21 “Qi-Nan” is regarded as the highest quality agarwood, valued for its mysterious oriental odor that can be smelt without burning, unlike other kinds of agarwood. The investigation of EtOH high-qualityextract Chinese of high-quality agarwood Chinese “Qi-Nan” agarwood (A. sinensis “Qi-Nan”) obtained (A. sevensinensis new) obtained 2-(2-phenylethl)chromone seven new derivatives2-(2-phenylethl)chromone (82–88)[28,29]. derivatives (82–88) [28,29]. NO. R1 R2 R3 R4 R5 R6 R7 R8 NO. R1 R2 R3 R4 R5 R6 R7 R8 1 H OH OCH3 H H H OH OCH3 1 H OH OCH H H H OH OCH 2 H OCH3 3OCH3 H H H OH OCH3 3 2 H OCH3 OCH3 H H H OH OCH3 3 H OCH3 OH H H H OH OCH3 3 H OCH3 OH H H H OH OCH3 4 H OCH3 OCH3 H H H OCH3 OH 4 H OCH3 OCH3 H H H OCH3 OH 5 H5 OHH OH OH OH HH H HH H H OCH3 H OCH3 6 H6 OHH OH OCH 3OCH3 HH H HH H H OH H OH 7 H7 OHH OHH H OHOH H HH OH H OCH3 OH OCH3 9 OH OH OH OH H H OH OCH 9 OH OH OH OH H H OH OCH3 3 10 H OH H Cl H H H H 10 H OH H Cl H H H H 11 H OH H Cl H H H OCH3 11 H OH H Cl H H H OCH3 12 H OCH3 OH H H H H OCH3 12 H OCH3 OH H H H H OCH3 20 H OH OCH3 H H H H OCH3 21 H20 OHH OH HOCH3 HH H HH H H OCH OCH3 3 OCH3 22 H21 OHH OH HH OHH H HH OCH H3 OCH3 H OCH3 23 H22 OHH OH HH ClOH H HH H H OCH3 OH OCH3 24 OCH OH H H H H OH OCH 3 23 H OH H Cl H H OH OCH3 3 25 H OCH3 OCH3 H a-OH H H H 24 OCH3 OH H H H H OH OCH3 26 H OCH3 OCH3 H b-OH H H H 25 H OCH3 OCH3 H α-OH H H H 27 H OCH3 H H H H OH OCH3 3 3 28 OH26 OCHH 3 OCHH OCH HH β-OH H H H H H OH OCH3 40 H27 OHH OCH OCH3 3 H HH H HH OH H OCH OCH3 3 OH 41 H28 OCHOH3 OCHH3 H HH H HH OH H OCH3 H OH 42 H40 OHH OH HOCH3 HH H HH OCH H3 OH OH OCH3 43 OH H OCH3 H H H H OCH3 41 H OCH3 H H H H H OH 44 OH OCH3 H OH H H H H 42 H OH H H H H OH OCH3 46 H OCH3 H H H OH OH OH 43 OH H OCH3 H H H H OCH3 47 OH OCH3 OCH3 H H H H OCH3 81 H44 OCHOH3 OCHOH3 H HOH H HH H H H H H 82 H46 HH OCH H3 H HH H HOH OH H OH OH OCH3 83 H47 OH H OCH H3 OCH3 HH H HH H H OCH OCH3 3 OH 84 H H H H H OH H OCH 81 H OCH3 OH H H H H H 3 85 H H H H H H H OH 82 H H H H H H OH OCH3 86 H H H H H H OH H 87 H83 HH H HH HH H HH OCH OH3 OH H H 88 H84 HH H HH HH H OHOH H H OCH3 H H 85 H H H H H H H OH 86Figure H 1.