Aquilaria spp. (agarwood) as source of health beneficial compounds: A review of traditional use, phytochemistry and pharmacology

Agarwood (also known as aloeswood or eaglewood) normally refers to dense, heavy and fragrant resinous wood which is formed in the trees of Aquilaria, Gonystylus and Gyrinops. According to Swee (2008), the term ‘agarwood’ refers to resin-impregnated pieces of wood that have been at least partially shaved from the non-impregnated woods. Throughout this review, the term ‘agarwood’ denotes the above definitions unless otherwise stated. The term ‘heartwood’ is also used interchangeably with ‘agarwood’ based on its occurrence in many of the literature reviewed for this work. More discussion on the accurate term to use with particular reference to pharmacological activities can be found in Section 6.1 of this review.

Agarwood is considered to be the finest natural incense and has been used in many communities to fulfil cultural, religious and medicinal purposes for centuries. It is known by many names; it is called ‘gaharu’ in Indonesia and Malaysia, ‘jin-koh’ in Japan, ‘chen hsiang’ or ‘chenxiang’ in China, ‘agar’ in India (from Sanskrit ‘aguru’), ‘chim-hyuang’ in Korea, ‘kritsana noi’ in Thailand, ‘tram huong’ in Vietnam, ‘bols d′agle’, ‘bols d′aloes’, ‘calambac’ or ‘calambour’ in French and ‘oud’ in the Middle East (Burkill, 1935, Ng et al., 1997, Sidiyasa, 1986). Previously, at least in the Malay language, the agarwood tree was known as ‘karas’ or ‘kekaras’, whereas ‘gaharu’ referred to heavy fragrant wood (Burkill, 1935). However, current practice uses ‘gaharu’ as the generic term to refer to both the tree and its resin, similar to the term ‘agarwood’.

The economic interest in agarwood has always been directed towards its pathological heavy and dense resin-impregnated wood, which is formed in the tissues of the stem in response to injury. The formation and infiltration of resin in agarwood trees is beyond the scope of this review. Briefly, the resin could develop through pathological, wounding and non-pathological mechanisms (Ng et al., 1997). These mechanisms have been the basis for inoculation or induction techniques to induce resin formation in cultivated agarwood trees, where the techniques often involve physical penetration into the trunk (wounding), insertion of a microbial (mainly fungal) concoction (pathology) and response of the tree towards the administered stress (non-pathological). A method of producing agarwood resin by creating an artificial wound in the xylem of agarwood trees have been patented (Blanchette and van Beek, 2005). Further discussions on various aspects of agarwood resin formation can be found in publications from Xu et al., 2013, Mohamad and Zali, 2010, Bhore and Kandasamy, 2013.

The fragrant wood has many ties with cultures around the world, such as the Arabian, Chinese and Japanese cultures, and is also associated with religious history, rituals and ceremonies in Buddhism, Christianity, Hinduism, and Islam (Barden et al., 2000). Nevertheless, other materials from the agarwood plant have also found prominent uses in the traditional medicine practices of the Southeast Asian communities, such as Chinese, Tibetan, Unani and Ayurvedic medicines (Barden et al., 2000, Blanchette and van Beek, 2005). This ethnopharmacological evidence, together with the current trends in bioprospecting, have spurred the interest of the scientific community to investigate claims using modern tools. This is manifested in the surge of the number of scientific publications in recent years, particularly those describing the pharmacological actions of agarwood, including the anti-diabetic (Feng et al., 2011, Jiang and Tu, 2011, Pranakhon et al., 2015, Zulkiflie et al., 2013), anti-inflammatory (Chitre et al., 2007, Kumphune et al., 2011, Rahman et al., 2012, Sattayasai et al., 2012, Zhou et al., 2008), anti-cancer (Dahham et al., 2014, Dahham et al., 2015a, Gunasekera et al., 1981, Hashim et al., 2014a), anti-depressant (Okugawa et al., 1993, Takemoto et al., 2008), and anti-oxidant (Dahham et al., 2014, Han and Li, 2012, Huda et al., 2009, Kamonwannasit et al., 2013, Miniyar et al., 2008, Moosa, 2010, Nik Wil et al., 2014, Owen and Jones, 2002, Ray et al., 2014, Sattayasai et al., 2012, Tay et al., 2014) activities of agarwood plant materials.

The diminishing number of these trees in the wild due to indiscriminate felling in search of the resin has led to conservation actions by listing the genus Aquilaria in Appendix II of Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) (UNEP-WCMC (Comps.), 2014). The International Union for Conservation of Nature and Natural Resources (IUCN) Red List of Threatened Species has listed Aquilaria crassna as critically endangered, and Aquilaria malaccensis and Aquilaria sinensis are listed as vulnerable (Asian Regional Workshop (Asian Regional Workshop Conservation and Sustainable Management of Trees, 1996)). In response to this situation, sustainable agarwood planting and management with artificial induction of agarwood resin formation have been implemented. This has led to a ready supply of different parts of the agarwood plant, which provides opportunities for the development of a range of value added products.

Although earlier literature concentrated on the phytochemistry of the resinous wood, and to some extent the oil produced from the resinous wood (Ishihara et al., 1991a, Ishihara et al., 1991b, Jain, 1959, Nakanishi et al., 1981, Nakanishi et al., 1983, Nakanishi et al., 1984, Varma et al., 1965, Yoneda et al., 1984), the review literature on current work related to the compounds and bioactivities of the different parts of the agarwood plant is very limited, with existing publications focused on specific species, namely, Aquilaria agallocha (Alam et al., 2015) and Aquilaria sinensis (Li et al., 2014). Another review attempted to report the pharmacological properties of Aquilaria spp., but provided limited information (Jok and Ku Hamid, 2015).

Therefore, this paper aims to provide an overview of the phytochemistry, ethnomedicinal use, pharmacological activities, toxicity and safety of plant materials derived from Aquilaria spp. This review will provide a platform to appraise the potential use of agarwood plant parts as sources of health beneficial compounds towards the development of value added products, including pharmaceuticals. Literature abstracts and full text articles from journals, books, reports and electronic searches (Google Scholar, Elsevier, PubMed, Read Cube, Scopus, Springer, and Web of Science), as well as from other relevant websites, are surveyed, analysed and included in this review.