Accepted Manuscript

Title: Pharmacological properties of agarwood tea derived

from Aquilaria (Thymelaeaceae) leaves: an emerging
contemporary herbal drink

Authors: Aimi Zafirah Adam, Shiou Yih Lee, Rozi Mohamed

PII: S2210-8033(17)30047-7
DOI: http://dx.doi.org/doi:10.1016/j.hermed.2017.06.002
Reference: HERMED 183

To appear in:

Received date: 14-11-2016

Revised date: 5-6-2017
Accepted date: 26-6-2017

Please cite this article as: Adam, Aimi Zafirah, Lee, Shiou Yih, Mohamed, Rozi,
Pharmacological properties of agarwood tea derived from Aquilaria (Thymelaeaceae)
leaves: an emerging contemporary herbal drink.Journal of Herbal Medicine
http://dx.doi.org/10.1016/j.hermed.2017.06.002

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Type of paper: Review
Title:

Pharmacological properties of agarwood tea derived from Aquilaria (Thymelaeaceae) leaves:

an emerging contemporary herbal drink

Authors:
Aimi Zafirah ADAM, Shiou Yih LEE, Rozi MOHAMED*

Authors addresses:
Forest Biotech Laboratory, Department of Forest Management, Faculty of Forestry, Universiti
Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

*Corresponding Author: Rozi MOHAMED, Contact: 60-3-8946 7183 (Off), 60-3-8943 2514 (Fax)
Email: rozimohd@upm.edu.my

Abstracts
Agarwood tea is made from the leaves of Aquilaria, a protected tree species of the tropical forest.
Trees in this genus produce agarwood, a highly-prized resin-impregnated wood formed in the main
stem. The last decade has seen a steady expansion in Aquilaria plantation establishment. The
popular plantation species are Aquilaria crassna, A. malaccensis, and A. sinensis. Farmers
capitalized on the leaves of their planted Aquilaria tree by producing a tea drink, and thus the name
‘agarwood tea’. The leaves contain various chemical constituents including 2-(2-phenylethyl)
chromones, phenolic acids, steroids, fatty acids, benzophenones, xanthonoids, flavonoids,
terpenoids, and alkanes that may be related to beneficial pharmacological properties. Such
properties include analgesic, anti-arthritic, anti-inflammatory, anticancer, antitumor, antioxidant,
antibacterial, antifungal, antidiabetic, antihistaminic, lipid-lowering, laxative, acetylcholinesterase
(AChE) inhibitory and hepatoprotective. Here, we summarize the various active ingredients found
in Aquilaria leaves and their pharmacological properties, thus serving as a reference material for
their usage as herbal drinks.

1
Keywords: Agarwood cultivation; chemical constituents; gaharu; herbal drink; medicinal
properties

1. Introduction
Tea is the second most consumed drink after water. The tradition of drinking tea has been around
in most parts of the world for the past 2000 years (Cabrera et al., 2006). Tea is often associated
with pleasant aroma and good taste, acts as a refreshing beverage, and provides health benefits.
Generally, tea is produced from the young leaves and leaf buds of Camellia sinensis, a cultivated
evergreen plant belonging to the family Theaceae. Originating from China, the plant is now widely
cultivated in countries/regions such as India, Indonesia, Japan, Malaysia, Sri Lanka, Taiwan, and
Central Africa, due to favorable local conditions such as having high humidity, fair temperature,
and acidic soil (Kuo et al., 2005).
Tea is categorized by the differences in tea plant variety, type of tea, grade, market name,
and location of the tea production. There are various kinds of tea in the world, such as green, black,
white, ‘oolong’, and ‘pu’erh’, which are categorised based on the process by which they were
manufactured. For instance, green tea and white tea are unfermented and slightly fermented teas
that have undergone a minimal process where no oxidation occurs; ‘oolong’ tea is a semi-
fermented tea, which has been subjected to partial oxidation; and black tea is a fully fermented tea
that has undergone complete oxidation. Meanwhile, the processing of ‘pu’erh’ tea is very different
from the other types of tea because it is subjected to microbial fermentation by Aspergillus niger
(Sharangi, 2009). In fermented teas, the color of the tea leaf turns brown due to the action of leaf
oxidizing enzymes that alter the tannins and catechins in the leaves (Gupta et al., 2008). One type
of tea produced from C. sinensis known as ‘kombucha’, is made through the fermentation of tea
and sugar by a symbiotic association of bacteria and yeasts forming a ‘tea fungus’. It tastes like a
sparkling apple cider that is slightly acidic but has sweet flavor (Jayabalan et al., 2007). The level
of acceptance for ‘kombucha’ tea has increased across the world like many other traditional
beverages, due to its beneficial effects on human health and ease of preparation (Jayabalan et al.,
2014).
The worldwide arithmetic mean per capita consumption of tea is 120 ml brewed tea per
day (Cabrera et al., 2006). Approximately 77% of the tea produced and consumed is black tea, the
most popular drink in Western countries; 21% is green tea and is mainly consumed in Asian

2
countries like China, Japan, Korea and Thailand; and less than 2% is ‘oolong’ tea, which is most
popular in China and Taiwan (Lee, 2009). China is famous for its tea traditions and is referred to
as the ‘homeland of tea’. Meanwhile, green tea is preferred by the Japanese and they usually serve
‘sencha’ green tea to visitors at home or at the workplace (Surak, 2012). In England, the tradition
of enjoying afternoon or late-afternoon tea is increasing (Rose, 2010). In traditional medicine, teas
treat insomnia, give a calming effect, break down oil and fats, relieve joint pains, improve
digestion, blood circulation, and urine flow, speed up bowel evacuation, and serve as a
detoxification agent (Gupta et al., 2008).
Tea composition differs by species, plant variety, season, climate, leaf age, plucking
position and horticultural practices (Kuo et al., 2005). Chemical constituents of tea are mainly
polysaccharides, amino acids, sterols, polyphenols, vitamins, minerals, proteins, triterpenoids,
organic acids and volatile compounds (Chen et al., 2008; Xiao et al., 2011). Tea also contains
caffeine (1–5%) and some amounts of other xanthine alkaloids and fats (4–16%). Green tea, when
compared to black tea, contains higher amounts of tannins or phenolic substances (5–27%)
consisting of catechin (flavanol) and gallic acid (Wang and Ho, 2009). Nowadays, tea is becoming
more popular as it provides health-promoting effects to human. For instance, polysaccharides in
tea possess several pharmacological effects such as antioxidant, antiviral, hepatoprotective,
immune stimulating, antitumour, anti-obesity and antidiabetic activities (Chen et al., 2016).
Catechin and the flavins are two examples of major active polyphenols in tea. Polyphenols in tea
are known to have fungal inhibitory (Sitheeque et al., 2009) and anti-inflammatory properties (Cao
et al., 2007). Polyphenols also possess anti-mutagenic activity as shown from their inhibitory effect
on spontaneous mutations in Salmonella typhimurium TA100 strain (Zhao et al., 2014). In
addition, polyphenols have anti-oxidative effect as demonstrated from the DPPH radical
scavenging activity on a dose-dependent manner of tea extract (Cao et al., 2007), anti-carcinogenic
effect as shown from the inhibition of the development of cancer for oral, esophageal, stomach,
intestinal, colon, skin, liver, bladder, prostate, and breast cancer in in vivo studies (Yang et al.,
2009), antitumor activity against SKOV-3 cells (Fan et al., 2011), lowering of plasma cholesterol
and triglyceride levels as well as reduction of blood pressure and platelet aggregation in several
systems (Bursill et al., 2007). Studies on ‘kombucha’ tea demonstrated that it has antibiotic
properties, intestinal and glandular activities, regulation of gastric, relief of joint rheumatism, gout
and hemorrhoids, positive influence on the cholesterol level, arteriosclerosis, toxin excretion and

3
blood cleansing, diabetes, nervousness, and aging problems (Jayabalan et al., 2007). In vitro
studies proved that hibiscus tea, or commonly known as roselle tea, can reduce high blood pressure
in pre- and mild-hypertensive adults due to the existence of major flavonoid components,
delphinidin-3-sambubioside and cyanidin-3-sambubioside (McKay et al., 2010). Meanwhile,
peppermint tea possesses significant antimicrobial and antiviral activities, strong antioxidant and
antitumor actions, and some antiallergenic potential. Despite the numerous health benefits, herbal
tea like any other herbal product needs to be consumed in a safe amount since depending on the
plant used side effects may be experienced especially if taken in high doses. An allergic reaction
to chamomile for example is not unusual. Hence, a thorough consideration on the effects of tea
will be required for better understanding of its toxic effects on human (Jain et al., 2013).
Due to the high demand for tea from people who are trying to look for new ways to improve
their health rather than depending on modern medicine, tea production has been increasing, and
includes several other kinds of plant materials besides C. sinensis. For instance, the leaves of
Mentha piperita (peppermint), Hibiscus sabdariffa (roselle), Gingko biloba (gingko), Orthosiphon
aristatus (‘misai kucing’), Psidium guajava (guava), Cymbopogon citratus (lemon grass),
Momordica charantia (bitter gourd), Ficus deltoidea (‘mas cotek’), flowers of Chrysanthemum
morifolium, Matricaria chamomilla (chamomile), Jasminum sambac (jasmine) and many more
have been used in tea preparation (Chan et al., 2010). In the last ten years, a new source of plant
has emerged. Tea is now also being derived from Aquilaria leaves and the consumption is growing
rapidly, due to the popularity of agarwood, the main product from Aquilaria tree. Here, we review
the chemical composition and pharmacological effects of Aquilaria leaves, which are commonly
known as agarwood tea.

2. The Emergence of Agarwood Tea

The plant genus Aquilaria, from the family Thymelaeaceae, is an evergreen tropical woody tree
that is well-known for its fragrant resin called agarwood. Agarwood is often used in several
applications, such as incense, perfumery, medicine, religious ceremony, and as ornamentals (Lee
and Mohamed, 2016). Incenses made from agarwood produce a pleasant aroma when burnt and
are used in rituals in many beliefs, while the wood is carved into religious objects such as idols
and praying beads (Lee and Mohamed, 2016). Agarwood is distilled into essential oil and is highly
prized in Middle-Eastern countries. The oil is generally used in perfumery and cosmetic products.

4
 As demand for agarwood is high in the market, natural Aquilaria stands in the wild are
heavily exploited in the search for agarwood. Illegal and indiscriminate harvesting of Aquilaria
trees greatly reduce their natural population sizes. Survival of the trees in the wild is under threat
as mother trees are felled and the regeneration cycle disturbed. Drastic decline in the numbers of
Aquilaria trees in natural forests has earned it the endangered status. The genus is currently listed
in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna
and Flora (CITES) (CITES, 2011). As agarwood resources in the wild are scarce, there is a need
to produce sustainable agarwood and this leads to Aquilaria tree cultivation in agarwood-
producing countries including China, Malaysia, Thailand, Indonesia, Cambodia, Vietnam, Laos,
Australia, and Sri Lanka (UNEP-WCMC, 2015; Yin et al., 2016; Subasinghe et al., 2012).
Nonetheless, trees in the wild are still exposed to illegal harvesters and traders. Technology
advances have also assisted in the effort toward sustainable agarwood production by enhancing
production of valuable agarwood through stimulating the tree defense mechanism (Rasool and
Mohamed, 2016). However, to produce sufficient agarwood, the trees must first grow to a certain
age and size, normally between five to seven years before they can undergo induction (Liu et al.,
2013, Mohamed et al., 2014). After induction, the trees are left for an additional one to two years
in the field for continuous production and maturation of the agarwood. Due to the long period of
time invested in tree growth and induction, many farmers opt to sustain their living by exploring
into alternatives such as producing tea derived from the abundant Aquilaria leaves in the plantation
(Zhou et al., 2008; Pranakhon et al., 2011). There is no formal record on when agarwood tea
became a commercial product, however the earliest scientific report was recorded in 2007, by a
group of Chinese researchers assessing the toxicological safety of agarwood tea (also known as
‘Chenxiang’ tea) sold in the markets in Hainan, China (Wu et al., 2007).
There are currently few reports on the benefits of Aquilaria leaves to humans. The leaves
of A. sinensis are applied in traditional medicine for treatment of trauma-related illnesses such as
fractures and bruises (Zhou et al., 2008). The leaves of A. crassna are useful as a supplement to
combat various health conditions such as high blood pressure, constipation, headache and diabetes
(Pranakhon et al., 2011), and in treating digestive ailments and as a mild sedative (Kakino et al.,
2010). In recent years, the use of Aquilaria leaves in food products has been diversified and sold
in the forms of tea in sachets, or mixed with coffee, biscuits, and ice-creams. It has also been used
as essence in ointments. Agarwood tea, also known as ‘teh gaharu’ or ‘teh karas’ in the Malay

5
language, is usually produced from the young shoots of Aquilaria trees. Similar to other common
teas, agarwood tea is accepted as a new herbal drink and is believed to have health benefits to
humans.

3. Preparation of agarwood tea from Aquilaria leaves

Agarwood tea products are mainly manufactured in China, Malaysia and Indonesia. Generally, the
process of making agarwood tea is similar to other common teas (Samsuri and Fitriyani, 2013).
The processing step begins with collection of the leaves from Aquilaria trees, cleaning the leaves
in flowing water, and drying in a drying chamber at about 40°C until the leaves turn brown. The
dried leaves are then finely chopped and ready for use in making herbal tea drinks (Nasution et al.,
2015). At present, the preparation of agarwood tea is considered a trade secret. Most of the
agarwood tea manufacturers in China patented their tea-making methods and do not reveal the
artificial additives and preservatives used in their tea preparations. Nonetheless, agarwood tea
should be safe to consume, has no bitter taste, and has rich aroma (Nasution et al., 2015).
In China, the young shoot, and the first and second leaflets, are selected for making tea.
Initially, collected leaves are rinsed through with clean water to remove dirt, followed by the
drying step either under the sun or in the drying chamber. In some cases, the dried leaves undergo
a freeze thaw process after the drying step (CN106173114A, 2016). Subsequently, leaves are
fermented using fermentation agents, such as lactic acid bacteria, yeast, Penicillium sp.,
Aspergillus niger, Rhizopus sp. or submerged in licorice syrup to enhance the tea aroma and reduce
bitterness. Fermented leaves are then air-dried, roasted several times before being rolled or
crumpled into small bead-like form, either by hand or machine (CN102613356B, 2014;
CN104206582B, 2016; CN106173114A, 2016). Packaging is often vacuumed to avoid changes in
air moisture content, which may deteriorate the tea quality. Alternatively, some manufacturers do
not include the fermentation step (CN102224864A, 2011). Another popular preparation is by
crushing the leaves and packing them into tea bags (TRAFFIC East Asia-Taipei and TRAFFIC
Southeast Asia, 2005).

4. Chemical Composition of Aquilaria Leaves

Chemical composition of the leaves of Aquilaria species are reportedly compounds like 2-(2-
phenylethyl) chromones, phenolic acids, steroids, fatty acids, benzophenones, xanthonoids,

6
flavonoids, terpenoids, nucleosides and alkanes (Table 1). A number of them are species specific,
but methods of extraction may also affect the composition.
For example, the essential oil from A. sinensis leaves extracted by steam distillation and
separated by capillary column chromatography has hexadecanoic acid (48.86%), 6, 10, 14-
trimethy l-2-pentadecanone (8.22%), tetradecanoic acid (7.22%), (E)-9-octadecenoic acid (6.04%),
pentadecanoic acid (2.58%), 4, 8, 12, 16-tetramethylheptadecan-4-olide (2.31%), phytol (1.91%),
nonanoic acid (1.73%), isophytol (1.38%), and octadecanoic acid (1.31%), as its constituents (Liu
et al., 2007). These chemical components were quantitatively determined with normalization and
identified by gas chromatography-mass spectrometry (GC-MS) method. Methanolic extract of A.
sinensis contains groups of phenolic acids such as vanillic acid, p-hydroxybenzoic acid, syringic
acid and isovanillic acid (Kang et al., 2014). When A. sinensis leaves were macerated in methanol
and ethanol solvents, sterols were present. Steroids group such as β-sitosterol, β-sitostenone and
stigmasterol are found in methanol extracts fractioned with n-hexane, CH2Cl2, acetone and
methanol (Kang et al., 2014), while β-daucosterol and 7α-hydroxy-β-sitosterol are found in ethanol
extracts fractioned with petroleum ether, ethyl acetate and n-butanol (Wang et al., 2008).
Mangiferin, genkwanin and iriflophenone glycosides are generally found in A. crassna and A.
sinensis leaves when extracted in ethanol using the maceration method and detected using liquid
chromatography-mass spectrometry (LC-MS) and silica gel column chromatography (SGCC)
(Wang et al., 2008; Qi et al., 2009; Feng et al., 2011; Ito et al., 2012; Yu et al., 2013; Wang et al.,
2015). Meanwhile, the identification of chemical constituents in A. sinensis leaves using reversed-
phase high performance liquid chromatography coupled with UV detector (HPLC-UV) revealed
the presence of several major constituents like iriflophenone 3-C-β-D-glucoside, iriflophenone
3,5-C-β-D-diglucoside, mangiferin, and iriflophenone 2-O-α-L-rhamnoside (Xia et al., 2015).
Major compounds like ergosterol, quercetin-3-O-β-Dgalactopyranoside, stigmasterol, 5,4-
dihydroxy-7 methoxyflavanone, β-sitosterol and quercetin-3-O-β-D-glucopyranoside were found
in ethyl acetate extracts of A. sinensis leaves. These compounds were detected by several
techniques such as silica gel column chromatography, gel filtration chromatography (Sephadex
LH-20) and preparative high performance liquid chromatography (PHPLC) (Yang et al., 2014).
Besides that, the identification of 4’-hydroxyacetanilide or also known as acetaminophen using
High Performance Liquid Chromatography (HPLC) in A. malaccencis leaf extracts showed that
this compound is widely used in nonprescription analgesic and antipyretic medication (Afiffudden

7
et al., 2015). The presence of various bioactive compounds in the leaves of Aquilaria is important
to register agarwood tea as a healthy drink and for use in traditional practices for treating various
health problems. It also indicates its potential as a source for the development of useful drugs.

5. Pharmacological Properties of Aquilaria Leaves

Knowledge of the identity of bioactive compounds in plants is useful in the discovery of novel
compounds that may have potential as remedial agents. In this paper, the pharmacological
properties of Aquilaria leaves are summarized in Table 2.

5.1 Analgesics, anti-arthritic and anti-inflammatory activities

Alkaloids have the potential to treat toothache, colic, severe headache, rheumatism, and
pains during pregnancy (Aniszewski, 2015). Studies on leaves and flowers of Psychotria
colorata extracts using formalin, acetic acid-induced writhing, and tail-flick tests proved
that alkaloids in the leaves and flowers of P. colorata extracts demonstrated an analgesic
activity (Malairajan et al., 2006). The detection of alkaloids in Aquilaria leaves extracts
indicates its potential use as an analgesic agent for pain relief. Polyphenolic compounds
like flavonoids exhibit anti-inflammatory activities by decreasing the release of
inflammatory mediators and stabilizing cell membranes (Kumar and Pandey, 2013; Martini
et al., 2014), and friedelan-3-one also exhibits anti-inflammatory (Wei and Bin, 2011). A.
sinensis is reportedly shown to have anti-inflammatory activity through xylene-induced
edema model, carrageenan-induced edema model, and carboxymethylcellulose sodium-
induced leukocyte migration model (Zhou et al., 2008). This could be due to the flavonoids
presence in the leaves (Wang et al., 2008; Qi et al., 2009; Feng et al., 2011; Ito et al., 2012).
Ethanolic extract of A. agallocha (synonym A. malaccensis) leaves has the potential as an
anti-arthritic agent (Rahman et al., 2016). Generally, rheumatoid arthritis is caused by the
denaturation of protein due to the production of auto-antigens in certain rheumatic diseases.
The presence of chemical constituents such as glycosides, tannins, terpenoids, oleic acids,
terpenes and phenolic compounds in the extracts are thought to restrain heat-induced
protein denaturation (Rahman et al., 2016).

8
5.2 Anticancer and antitumor activities
Generally, cucurbitacin, a group of tetracyclic triterpenoids are mostly found in the family
Cucurbitaceae but they also exist in several other families of the plant kingdom. Aquilaria
leaves contain cucurbitacin glycosides such as 2-O-β-D-glucopyranosyl cucurbitacin I and
bryoamaride (Sun et al., 2015). In the 1960s, cucurbitacins had attracted the attention of
the drug industry because of their potential antitumor and anticancer activities to various
kinds of cancers (Chen et al., 2005). For instance, cucurbitacins B, D, E and I, found in
fruit extracts of Cucurbita andreana possess strong anticancer activity as well as specific
COX-2 enzyme inhibition (Kaushik et al., 2015). In Aquilaria, cucurbitacin I that is found
in A. malaccensis callus and shoot, can inhibit cancer cells, displays cytotoxicity against
MDA-MB-468 human breast cancer cells, and indirectly interrupts actin dynamics (Knecht
et al., 2010). Chemical constituent like isocorydine, an aporphine alkaloid in A. sinensis
leaves (Nie et al., 2009) is known to possess anticancer activity (Zhong et al., 2014). The
results from in vitro and in vivo experiments demonstrated that the effectiveness of
anticancer activities could be improved significantly by modifying the chemical structure
of isocorydine. For instance, isocorydine derivatives like 8-amino-isocorydine and 6α,7-
dihydrogen-isocorydione could prevent the growth of human lung (A549), gastric
(SGC7901) and liver (HepG2) cancer cell lines in vitro. Isocorydione and 8-acetamino-
isocorydine have also been shown to prevent growth of murine sarcoma S180 tumor and
murine hepatoma H22-induced tumors, respectively (Zhong et al., 2014). Another
chemical constituent, squalene, which is a polyunsaturated triterpene that belongs to the
terpenoid family can inhibit the development of various tumors and enhances the immune
response to various associated antigens (Reddy and Couvreur, 2009). 1-hexacosanol found
in A. sinensis leaves also possesses antitumor effect (Wei and Bin, 2011). Gastrointestinal
infections and tumor growth could be prevented with the presence of glycosides moieties
like saponins, anthraquinones, cardiac glycosides and flavonoids (Abubakar, 2009).

5.3 Antioxidant activities

Flavonoids extracted from A. sinensis leaves have strong antioxidant activity to scavenge
1,1-diphenyl-2-picrylhydrazyl (DPPH) and ABTS radicals (Duan et al., 2015). Specifically,
luteolin and genkwanin have the ability to protect hydroxyl-induced DNA damage at

9
certain doses. Its mechanism is exerted via radical-scavenging, metal-chelating and
scavenging free radicals via donating hydrogen atom or electron (Han, 2013). In addition,
ethanolic extract of agarwood tea displayed excellent in vitro antioxidant activity (Han and
Li, 2012), but the activity can be affected by the form of the tea leaves (Simatupang et al.,
2015). Antioxidant activity assessment showed that the highest antioxidant activity is
derived from fine particles of agarwood tea leaves when compared to two other forms,
whole and cut leaves (Simatupang et al., 2015).

5.4 Antibacterial and antifungal activities

One of the major compounds in methanolic extracts of Aquilaria leaves is hexadecanoic
acid (Khalil et al., 2013). It is one of the most common saturated fatty acid and has potential
in antibacterial activities. Hexadecanoic acid has antibacterial activity against Gram-
positive and Gram-negative bacteria, comparable to ampicillin, and in the case of
Streptococci, greater than that of ampicillin (Saidana et al., 2008). The aqueous extract of
A. crassna leaves has antibacterial activity against Staphylococcus epidermidis, a causal
agent of skin disease. The extract caused rupture of bacterial cell wall after 24 h of
treatment (Kamonwannasit et al., 2013). In addition, cucurbitacin found in A. malaccensis
and A. crassna has the ability to fight against bacterial and fungal pathogens (Chen et al.,
2014).

5.5 Antidiabetic activities / Hypoglycemic effects

The ethanolic extract of A. sinensis leaves has been shown to possess hypoglycemic effects.
Tests on the hypoglycemic effect is often carried out using diabetic mice/rats. The extract
significantly reduces the blood glucose levels; this may be due to the blood sugar reducing
activity of 2α-hydroxy ursolic acid (Mei et al., 2013). Furthermore, the methanol and water
extracts from A. sinensis leaves have anti-hyperglycemic activity similar to effects exerted
by insulin (Pranakhon et al., 2011). Fractions of ethanol water and ethyl acetate of A.
malaccensis leaves also improve glucose uptake by elevating levels of glucose transporter
type 4 (GLUT4), a regulator of whole-body glucose homeostasis. The extracts are known
to exhibit increased GLUT4 level more than pioglitazone (Said et al., 2016). Chemical
compounds in ethanol extract of A. sinensis leaves such as mangiferin, iriflophenone 2-O-

10
α-L-rhamnopyranoside, iriflophenone 3-C-β-D-glucoside and iriflophenone 3,5-C-β-D-
diglucopyranoside demonstrate a strong α-glucosidase inhibitory activity. These
compounds act as an antidiabetic agent and reduce the blood glucose level by controlling
carbohydrate absorption from the intestine (Feng et al., 2011).

5.6 Lipid-lowering effects

A compound in the aqueous extract of A. sinensis leaves, mangiferin, has lipid-lowering
effect. Mangiferin is a polyphenol compound which is useful in the treatment of
hyperlipidemia, a genetic disorder that results in a high level of lipids. The aqueous extract
of A. sinensis leaves has been shown to lower total triglyceride and total cholesterol content
in a laboratory experiment (Wu et al., 2012).

5.7 Laxative effects

Leaves of A. sinesis have the ability to improve intestinal movement function (Li et al.,
2013). Mangiferin and genkwanin-5-O-β-premeveroside found in ethanol extracts of both
A. sinensis and A. crassna, promote contraction tension of the small intestine in mice,
resulting in increased number and weight of stool beads (Kakino et al., 2010, Kakino and
Hara, 2016).

5.8 Acetylcholinesterase (AChE) inhibitory effects

Kaempferol 3,4,7-trimethylether in the crude extract of A. subintegra exhibits AChE
inhibitory effect, which significantly reduces the number of repeated entries into the arms
of radial arm maze in valium-impaired memory model. The extract can be used as a natural
AChE inhibitor as a substitute for berberine for the treatment of Alzheimer's disease
(Bahrani et al., 2014).

5.9 Hepatoprotective effects

Ethanolic extracts of A. agallocha leaves possess hepatoprotective effects, which prevents
damage to the liver against paracetamol (PCM)-induced hepatotoxicity in Sprague Dawley
rats. The extract has been shown to lower the level of several biochemical parameters such
as serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline

11
phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol and bilirubin, in these rats
(Alam et al., 2016). Hepatoprotective effect may be due to the antioxidant property of the
chemical constituents in the ethanolic extract of A. agallocha leaves, which reduces the
oxidative stress enforced by PCM preventing the inflammatory hepatic damage (Alam et
al., 2016).

5.10 Antihistaminic activities

Excessive production of histamine in the body can generate allergic and inflammatory
responses. The release of histamine, one of the potential mediators of allergic reactions
may lead to the constriction of respiratory airways, which involved in early asthmatic
responses (Liu et al., 1990). The presence of certain chemical constituents like flavonoids
in the leaf extracts possess antihistaminic, antiallergic and mast cell degranulation
properties (Kumar et al., 2011). Chemical compounds such as genkwanin and luteolin in
Aquilaria leaves have potentials in relieving cough and soothing asthma (Wang, 2008; Lin
et al., 2012). The ethanol extract of A. sinensis leaves has antihistaminic activity, which
significantly prolongs asthma latency that is caused by the presence of excessive histamine
as shown in a laboratory experiment (Wu et al., 2013).

5.11 Other effects

Chemical constituents like phytol have the ability to control neuronal function, influencing
neurotransmitter systems, and modulating the release and synthesis of inhibitory
neurotransmitters related to the seizure process (Costa et al., 2012). Phytol has been
reported from Aquilaria (Khalil et al., 2013; Bahrani et al., 2014). Other chemical
constituent like flavonoids are known to inhibit the oxidation of low-density lipoprotein
(LDL), which is associated to cardiovascular disease (Martini et al., 2014). Aquilaria
leaves contain a variety of nutritional active ingredients such as amino acids,
polysaccharides, volatile oils, flavonoids, glycosides, and phenols. The leaves can be given
as feeds to farm animals to improve their performance in nutrient digestibility and growth
(Huang et al., 2016; Suhatri et al., 2017).

12
 6. Toxicological effect of Aquilaria leaves
Scientific evidence for the safe consumption of Aquilaria leaves is still lacking. Such studies are
important to determine the potential adverse effects from the introduction of agarwood tea as an
herbal drink. The acute oral toxicity test is one way of determining toxicological effects of new
foods. The effect of ethanol extracts from A. crassna leaves showed no significant level of toxicity
when taken orally as shown using laboratory mice even when used at a high dosage
(Kamonwannasit et al., 2013; Ghan et al., 2016). The ethanolic extract of A. agallocha leaves
evaluated according to the Organization for Economic Cooperation and Development (OECD)
423 guidelines showed that it is non-toxic and safe up to the dose of 2,000 mg/kg (Alam et al.,
2016). The leaves of A. sinensis had no acute oral toxicity and genetic toxicity effects as no
significant differences in micronucleus rate, sperm shape abnormality rate and reverse mutation
number were observed when compared to the negative control (Li et al., 2015). Meanwhile, the
kaempferol extracts of A. subintegra leaves showed no significant cytotoxicity effects in various
human cell lines (Bahrani et al., 2014). These findings demonstrate that Aquilaria leaf extracts are
relatively safe to consume without major toxicity concern, depending on the doses tested.

Conclusion and Future Perspectives

For many decades, Aquilaria planters focus only on the agarwood induced in the tree trunk as their
primary source of income. Recently, leaves from Aquilaria are treasured for making tea. Such
trend has been spreading in several countries such as China, Indonesia, Malaysia, Thailand and
Vietnam. Based on its chemical constituents, the leaves possess a wide range of pharmacological
properties, which benefits may attract consumers. Agarwood tea can be consumed as a healthy
drink, and thus has a broad market prospect and high exploitation potential. Still, phytochemicals
in Aquilaria leaves need to be studied further and their effects confirmed through model studies
and clinical trials.

Conflict of Interests
The authors declare that there is no conflict of interests.

Acknowledgments

13
We thank Dr. Yangyang Liu of the Institute of Medicinal Plant Development (IMPLAD), Hainan
branch, China, for assistance in collecting publications in Mandarin language journals, and Dr.
Wei Lun Ng of the School of Life Sciences, Sun Yat-sen University, Guangzhou, China, for
comments on earlier drafts of this manuscript. This work was supported by a research grant from
Universiti Putra Malaysia (Project No. GP-I/2014/9439600).

14
References

Abubakar, E.M.M., 2009. Antibacterial activity of crude extracts of Euphorbia hirta against some
bacteria associated with enteric infections. J. Med. Plants Res. 3, 498-505.
Afiffudden, S.K.N., Alwi, H., Hamid, K.H.K., 2015. Determination of 4’-Hydroxyacetanilide in
leaves extract of Aquilaria malaccencis by high pressure liquid chromatograph. Procedia
Soc. Behav. Sci. 195, 2726-2733.
Alam, J., Mujahid, M., Jahan, Y., Bagga, P., Rahman, M.A., 2016. Hepatoprotective potential of
ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity
in SD rats. J. Tradit. Complement. Med. 7, 9-13.
Andres, C., Chieh Chen, Wen., Ollert, M., Mempel, M., Darsow, U., Ring, J. 2009. Anaphylactic
Reaction to Camomile Tea. Allergology International 58:135-136
Aniszewski, T., 2015. Alkaloids: Chemistry, Biology, Ecology, and Applications. Elsevier,
Netherlands.
Arriffin, N.M., Alimon, H., Sukari, M.A., Naz, H., 2013. Chemical study of Aquilaria
crassna. Chem. Nat. Compd. 49, 575-576.
Bahrani, H., Mohamad, J., Paydar, M.J., Rothan, H.A., 2014. Isolation and characterization of
acetylcholinesterase inhibitors from Aquilaria subintegra for the treatment of Alzheimer’s
disease (AD). Curr. Alzheimer Res. 11, 206-14.
Bursill, C.A., Abbey, M., Roach, P.D., 2007. A green tea extract lowers plasma cholesterol
by inhibiting cholesterol synthesis and upregulating the LDL receptor in the cholesterol-
fed rabbit. Atherosclerosis 193, 86-93.
Cabrera, C., Artacho, R., Giménez, R., 2006. Beneficial effects of green tea—a review. J. Am.
Coll. Nutr. 25, 79-99.
Cao, H., Kelly, M.A., Kari, F., Dawson, H.D., Urban, J.F., Coves, S., Roussel, A.M., Anderson,
R.A., 2007. Green tea increases anti-inflammatory tristetraprolin and decreases pro-
inflammatory tumor necrosis factor mRNA levels in rats. J. Inflam. 4, 1-12.
Chan, E.W.C., Lim, Y.Y., Chong, K.L., Tan, J.B.L., Wong, S.K., 2010. Antioxidant properties of
tropical and temperate herbal teas. J. Food Comp. Anal. 23, 185-189.

15
Chen, J.C., Chiu, M.H., Nie, R.L., Cordell, G.A., Qiu, S.X., 2005. Cucurbitacins and cucurbitane
glycosides: structures and biological activities. Nat. Prod. Rep. 22, 386-399.
Chen, H.X., Zhang, M., Qu, Z.S., Xie, B.J., 2008. Antioxidant activities of different fractions of
polysaccharide conjugates from green tea (Camellia sinensis). Food Chem. 106, 559–563.
Chen Y., 2011. CN102224864A. Beijing: State intellectual property office of the P.R.C.
Chen, C.H., Kuo, T.C.Y., Yang, M.H., Chien, T.Y., Chu, M.J., Huang, L.C., Chen, C.Y., Lo, H.F.,
Jeng, S.T., Chen, L.F.O., 2014. Identification of cucurbitacins and assembly of a draft
genome for Aquilaria agallocha. BMC Genomics 15, 1-11.
Chen, G., Yuan, Q., Saeeduddin, M., Ou, S., Zeng, X., Ye, H., 2016. Recent advances in tea
polysaccharides: Extraction, purification, physicochemical characterization and
bioactivities. Carbohydr. Polym. 153, 663-678.
CITES, 2011. Convention on international trade in endangered species of wild fauna and flora
appendices I, II and III. http://www.cites.org/eng/app/appendices.php (accessed 16.06.16).
Costa, J.P., Ferreira, P.B., De Sousa, D.P., Jordan, J., Freitas, R.M., 2012. Anticonvulsant effect
of phytol in a model pilocarpine in mice. Neurosci. Lett. 523, 115-118.
Dahham, S.S., Tabana, Y.M., Iqbal, M.A., Ahamed, M.B., Ezzat, M.O., Majid, A.S., Majid, A.M.,
2015. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-
caryophyllene from the essential oil of Aquilaria crassna. Molecules 20, 11808-11829.
Duan, Z., Li, W., Dou, Z., Xie, H., He, A., Shi, M., 2015. Extraction and antioxidant activity of
flavonoids from Aquilaria sinensis (Lour.) Gilg leaves. J. Food Sci. 36, 45-50.
Fan, D., He, T., Wang, Y., Kong, G., Jiang, T., Zhou, D., 2011. Production, preliminary
characterization and antitumor activity (SKOV-3 cell lines) in vitro of glycans from green
tea. Carbohydr. Polym. 86, 1651-1656.
Fang, W., 2014. CN102613356B. Beijing: State intellectual property office of the P.R.C.
Feng, J., Yang, X.W., & Wang, R.F., 2011. Bio-assay guided isolation and identification of α-
glucosidase inhibitors from the leaves of Aquilaria sinensis. Phytochemistry 72, 242-247.
Ghan, S.Y., Chin, J.H., Thoo, Y.Y., Yim, H.S., Ho, C.W., 2016. Acute oral toxicity study of
Aquilaria crassna and α-tocopherol in mice. Int. J. Pharm. Sci. Res. 7, 1456-1461.
Gupta, J., Siddique, Y.H., Beg, T., Ara, G., Afzal, M., 2008. A review on the beneficial effects of
tea polyphenols on human health. Int. J. Pharm. 4, 314-338.

16
Han, W., Li, X., 2012. Antioxidant activity of aloeswood tea in vitro. Spatula DD-Peer Reviewed
J. Complement. Med. Drug Discovery 2, 43-50.
Han, W., 2013. Protective effect and mechanism of aloeswood tea against hydroxyl radical-
induced DNA damage. Masters Thesis. Guangzhou University of Chinese Traditional
Medicine.
Huang, J., Chen, H., Yu, Z., Zhou, Y., Ning, G., 2016. Effects of different ratios of Aquilaria
sinensis leaf meal on the growth performance, slaughter performance and nutrients
digestibility of broiler. China Feed 11, 36-42.
Huda, A.W.N., Munira, M.A.S., Fitrya, S.D., Salmah, M., 2009. Antioxidant activity of Aquilaria
malaccensis (Thymelaeaceae) leaves. Pharmacognosy Res. 1, 270-273.
Ito, T., Kakino, M., Tazawa, S., Oyama, M., Maruyama, H., Araki, Y, Hara, H., Iinuma, M., 2012.
Identification of phenolic compounds in Aquilaria crassna leaves via liquid
chromatography-electrospray ionization mass spectroscopy. Food Sci. Technol. Res. 18,
259-262.
Jayabalan, R., Marimuthu, S., Swaminathan, K., 2007. Changes in content of organic acids and tea
polyphenols during kombucha tea fermentation. Food Chem. 102, 392-398.
Jayabalan, R., Malbaša, R.V., Lončar, E.S., Vitas, J.S., Sathishkumar, M., 2014. A review on
kombucha tea—microbiology, composition, fermentation, beneficial effects, toxicity, and
tea fungus. Compr. Rev. Food. Sci. Food. Saf. 13, 538-550.
Jain A, Manghani C, Kohli S, Nigam D, Rani V., 2013. Tea and human health: The dark shadows.
Toxicol. Lett. 220, 82-87.
Jiang, S., Jiang, Y., Guan, Y., Tu, P., Wang, K., Chen, J., 2011. Effects of 95% ethanol extract of
Aquilaria sinensis leaves on hyperglycemia in diabetic db/db mice. J Chin. Pharm. Sci. 20,
609-614.
Kakino, M., Tazawa, S., Maruyama, H., Tsuruma, K., Araki, Y., Shimazawa, M., Hara, H., 2010.
Laxative effects of agarwood on low-fiber diet-induced constipation in rats. BMC
Complement. Altern. Med. 10, 1-8.
Kakino, M., Hara, H., 2016. Pharmacological effects of Aquilaria spp. leaves and their chemical
constituents, in: Mohamed, R., (Ed.), Agarwood. Springer, Singapore, pp. 125-136.
Kamonwannasit, S., Nantapong, N., Kumkrai, P., Luecha, P., Kupittayanant, S., Chudapongse,

17
 N., 2013. Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus
epidermidis by disruption of cell wall. Ann. Clin. Microbiol. Antimicrob. 12, 1-7.
Kang, Y.F., Chien, S.L., Wu, H.M., Li, W.J., Chen, C.T., Li, H.T., Chen, H.L., Chao, D., Chen,
S.J., Huang, C.T., Chen, C.Y., 2014. Secondary metabolites from the leaves of Aquilaria
sinensis. Chem. Nat. Compd. 50, 1110-1112.
Kaushik, U., Aeri, V., Mir, S.R., 2015. Cucurbitacins–An insight into medicinal leads from
nature. Pharmacogn. Rev. 9, 12-18.
Khalil, A.S., Rahim, A.A., Taha, K.K., Abdallah, K.B., 2013. Characterization of methanolic
extracts of agarwood leaves. J. App. Industrial Sci. 1, 78-88.
Knecht, D.A., LaFleur, R.A., Kahsai, A.W., Argueta, C.E., Beshir, A.B., Fenteany, G., 2010.
Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. PLoS
One 5, 1-11.
Kumar, D., Bhat, Z.A., Singh, P., Bhujbal, S.S., Deoda, R.S., 2011. Antihistaminic activity of
aqueous extract of stem bark of Ailanthus excelsa Roxb. Pharmacognosy Res. 3, 220-227.
Kumar, S., Pandey, A.K., 2013. Chemistry and biological activities of flavonoids: an
overview. Sci. World J. doi:http://dx.doi.org/10.1155/2013/162750
Kumphune, S., Prompunt, E., Phaebuaw, K., Sriudwong, P., Pankla, R., Thongyoo, P., 2011.
Anti-inflammatory effects of the ethyl acetate extract of Aquilaria crassna inhibits LPS-
induced tumour necrosis factor-alpha production by attenuating P38 MAPK activation. Int.
J. Green Pharm. 5, 43-52.
Kuo, K.L., Weng, M.S., Chiang, C.T., Tsai, Y.J., Lin-Shiau, S.Y., Lin, J.K., 2005. Comparative
studies on the hypolipidemic and growth suppressive effects of oolong, black, pu-erh, and
green tea leaves in rats. J. Agric. Food Chem. 53, 480-489.
Lee, J., 2009. Green tea: Flavor characteristics of a wide range of teas including brewing,
processing, and storage variations and consumer acceptance of teas in three
countries (Doctoral dissertation, Kansas State University).
Lee, S.Y., Mohamed, R., 2016. The Origin and Domestication of Aquilaria, an Important
Agarwood-Producing Genus, in: Mohamed, R., (Ed.), Agarwood. Springer, Singapore, pp.
1-20.

18
Li, H., Jiang, Z., Mei, Q., 2013. Comparative study on the effect of Aquilaria sinensis leaf tea and
agarwood on promoting small intestine propulsion. Asia-Pacific Traditional Medicine 9,
24-25.
Li, Q., Huang, J., Yang, Y., Chen, M., Liang, Y., Chen, X., 2015. Research on the acute toxicity
and genetic toxicity of Aquilaria sinensis (Lour.) Gilg. leaf. Chinese Journal of Health
Laboratory Technology 25, 1518-1521.
Lin, F., Peng, Y., Ke, F., Deng, Y., 2012. Experimental study on the content, antioxidant activity
in vitro, and delaying aging effect of tannins from the leaf of Aquilaria sinensis (Lour.)
Gilg. Journal of Guangdong Pharmaceutical University 28, 259-262.
Lin, H., Li, H., Mei, Q., 2013. Comparative Study on Anti-inflammation activity between chinese
eaglewood leaves and chinese eaglewood. Chinese Archives of Traditional Chinese
Medicine 3, 037-043.
Liu, M.C., Bleecker, E.R., Lichtenstein, L.M., Kagey-Sobotka, A., Niv, Y., McLemore, T.L.,
Permutt, S., Proud, D., Hubbard, W.C., 1990. Evidence for elevated levels of histamine,
prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects
with mild asthma. Am. Rev. Respir. Dis. 142, 126-132.
Liu, Y., Yang, X., Liu, T., 2007. GC-MS analysis of essential oil from the leaves of Aquilaria
sinensis. Modern Chinese Medicine 9, 7-11.
Liu, Y., Chen, H., Yang, Y., Zhang, Z., Wei, J., Meng, H., Chen, W., Feng, J., Gan, B., Chen, X.,
Gao, Z., Huang, J., Chen, B., Chen, H., 2013. Whole-tree agarwood-inducing technique:
An efficient novel technique for producing high-quality agarwood in cultivated Aquilaria
sinensis trees. Molecules 18, 3086-3106.
Liu D., 2016. CN104206582B. Beijing: State intellectual property office of the P.R.C.
Malairajan, P., Gopalakrishnan, G., Narasimhan, S., Veni, K. J. K. 2006. Analgesic activity
of some Indian medicinal plants. J. Ethnopharmacol. 106, 425-428.
Martini, N.D., Katerere, D.R.P., Eloff, J.N., 2014. Biological activity of five antibacterial
flavonoids from Combretum erythrophyllum (Combretaceae). J. Ethnopharmacol. 93, 207-
212.
McKay, D.L., Chen, C.O., Saltzman, E., Blumberg, J.B., 2010. Hibiscus sabdariffa L. tea (tisane)
lowers blood pressure in prehypertensive and mildly hypertensive adults. J. Nutr. 140, 298-
303.

19
Mei, Q., Li, H., Lin, H., Wu, X., Liang, L., Yang, H., Lan, Z., 2013. Comparative study on
hypoglycemic effect between Aquilaria sinensis leaves and agarwood. Lishizhen Med.
Mat. Med. Res. 24, 1606-1607.
Mohamed, R., Jong, P.L., Kamziah, A.K., 2014. Fungal inoculation induces agarwood in young
Aquilaria malaccensis trees in the nursery. J. For. Res. 25, 201-204.
Nasution, P.A., Batubara, R., Surjanto, S., 2015. Level of antioxidants power and society interest
of aloes tea (Aquilaria malaccensis Lamk) based of induction tree and non-induction
treatment. Peronema Forestry Science Journal 4, 1-12.
Nie, C., Song, Y., Chen, D., Xue, P., Tu, P., Wang, K., Chen, J., 2009. Studies on chemical
constituents of leaves of Aquilaria sinensis. China Journal of Chinese Materia Medica 34,
858-860.
Pranakhon R., Pannangpetch P., Aromdee C., 2011.Antihyperglycemic activity of agarwood
leaf extracts in STZ-induced diabetic rats and glucose uptake enhancement activity in rat
adipocytes. Songklanakarin J. Sci. Technol. 33, 405-410.
Pranakhon, R., Aromdee, C., Pannangpetch, P., 2015. Effects of iriflophenone 3-C-β- glucoside
on fasting blood glucose level and glucose uptake. Pharmacogn. Mag. 11, 82-89.
Qi, J., Lu, J.J., Liu, J.H., Yu, B.Y., 2009. Flavonoid and a rare benzophenone glycoside from the
leaves of Aquilaria sinensis. Chem. Pharm. Bull. 57, 134-137.
Rahman, H., Eswaraiah, M.C., Dutta, A.M., 2016. Anti-arthritic activity of leaves and oil of
Aquilaria agallocha. Saudi J. Life Sci. 1, 34-43.
Rasool, S., Mohamed, R., 2016. Understanding Agarwood Formation and Its Challenges, in:
Mohamed, R., (Ed.), Agarwood. Springer, pp. 39-56.
Ray, G., Jiratchariyakul, W., Sithisarn, P., Leelamanit, W., 2013. Antioxidant Activity of Aquilaria
subintegra Ethanolic Leaf Extract.
http://www.grad.mahidol.ac.th/storage/Internet/grad_conference/paper/2556/1/5610312/F
-5610312.doc (accessed 15.08.16)
Reddy, L.H., Couvreur, P., 2009. Squalene: A Natural triterpene Management and Therapy for use
in disease. Adv. Drug Deliv. Rev. 61, 1412-1426.
Rose, S., 2010. For All the Tea in China: How England Stole the World's Favorite Drink and
Changed History. Penguin.

20
Said, F., Kamaluddin, M.T., Theodorus, 2016. Efficacy of the Aquilaria malaccensis leaves active
fraction in glucose uptake in skeletal muscle on diabetic wistar rats. Int. J. Health Sci.
Res. 6, 162-167.
Saidana, D., Mahjoub, S., Boussaada, O., Chriaa, J., Mahjoub, M.A., Cheraif, I., Daami, D., Mighri,
Z., Helal, A.N., 2008. Antibacterial and antifungal activities of the essential oils of two
saltcedar species from Tunisia. J. Am. Oil Chem. Soc. 85, 817-826.
Samsuri, T., Fitriani, H., 2013. Tea making from Gyrinops versteegii leaves (author's transl). Jurnal
Ilmiah Biologi 1, 1-8.
Sattayasai, J., Bantadkit, J., Aromdee, C., Lattmann, E., Airarat, W., 2012. Antipyretic, analgesic
and anti-oxidative activities of Aquilaria crassna leaves extract in rodents. J.
Ayurveda Integr. Med. 3, 175-179.
Sharangi, A.B., 2009. Medicinal and therapeutic potentialities of tea (Camellia sinensis L.)–A
review. Food Res. Int. 42, 529-535.
Simatupang, J., Batubara, R., Julianti, E., 2015. Consumers’ acceptance and antioxidant of the
agarwood (Aquilaria malaccensis Lamk.) leaves tea based on the shape and size of leaves.
Peronema Forestry Science Journal 4, 1-11.
Sitheeque, M.A.M., Panagoda, G.J., Yau, J., Amarakoon, A.M.T., Udagama, U.R.N.,
Samaranayake, L.P., 2009. Antifungal activity of black tea polyphenols (catechins and
theaflavins) against Candida species. Chemotherapy 55, 189-196.
Subasinghe, S.M.C.U.P, Hettiarachchi, D.S, Rathnamalala, E., 2012. Agarwood-type resin from
Gyrinops walla Gaertn: a new discovery. J. Trop. For. Env. 2, 1-6.
Suhatri, S., Putra, D.Z., Elisma, E., 2017. Effect of aloe leaf extract (Aquilaria malaccensis Lamk.)
on atherosclerosis in quail bull (Coturnix-coturnix japonica) (author's transl). Jurnal
Farmasi Higea 6, 174-182.
Sun, J., Wang, S., Xia, F., Wang, K.Y., Chen, J.M., Tu, P.F., 2014. Five new benzophenone
glycosides from the leaves of Aquilaria sinensis (Lour.) Gilg. Chin. Chem. Lett. 25, 1573-
1576.
Sun, J., Xia, F., Wang, S., Wang, K.Y., Chen, J.M., Tu, P.F., 2015. Structural elucidation of two
new megastigmane glycosides from the leaves of Aquilaria sinensis. Chin. J. Nat. Med. 13,
0290-0294.

21
Surak, K., 2012. Making tea, making Japan: Cultural nationalism in practice. Stanford University
Press, California.
Tay, P.Y., Tan, C.P., Abas, F., Yim, H.S., Ho, C.W., 2014. Assessment of extraction parameters
on antioxidant capacity, polyphenol content, epigallocatechin gallate (EGCG), epicatechin
gallate (ecg) and iriflophenone 3-C-β-glucoside of agarwood (Aquilaria crassna) young
leaves. Molecules 19, 12304-12319.
TRAFFIC East Asia-Taipei and TRAFFIC Southeast Asia. 2005. The Trade and Use of
Agarwood in Taiwan, Province of China. TRAFFIC International, Cambridge.
UNEP-WCMC (Comps.), 2015. The Checklist of CITES Species Website. CITES Secretariat,
Geneva. http://checklist.cites.org (accessed 15.04.16).
Wang, H., 2008. Determination of Genkwanin in the leaves of Aquilaria sinensis (Lour.) Gilg with
HPLC. Guiding J. Trad. Chin. Med. Pharm. 14, 69-70.
Wang, H., Zhou, M., Lu, J., Yu, B., 2008. Antitumor constituents from the leaves of Aquilaria
sinensis (Lour.) Gilg. Linchan Huaxue Yu Gongye 28, 1-5.
Wang, Y., Ho, C.T., 2009. Polyphenolic chemistry of tea and coffee: a century of progress. J.
Agric. Food Chem. 57, 8109-8114.
Wang, S.C., Wang, F., Yue, C.H., 2015. Chemical constituents from the petioles and leaves of
Aquilaria sinensis. Biochem. Syst. Ecol. 61, 458-461.
Wei, Z., Bin, N., 2011. GC-MS analysis of the chemical components of the volatile oil from leaves
of Aquilaria sinensis (Lour.) Gilg. Med. Plant 2, 34-36.
Wu, W., Zhu, Z., Lin, L., Chen, D., Yao, J., Liao, F., 2012. The active ingredient for hypolipidemic
effect in Aquilaria sinensis leaves. Proceedings of the National Symposium on the Twelfth
Chinese Medicine and Natural Medicine, 274-278.
Wu, X., Li, H., Mei, Q., Lin, H., Liang, L., Yang, H., Lan, Z., 2013. A comparative study on the
asthma effect of Aquilaria leaves and agarwood. Pharmacy Today 23, 346-347.
Wu, A., Zheng, D., Huang, Y., Wang, Z., Zhang, X., 2007. Toxicology assessment of safety of
Chenxiang tea in Hainan. Chin. Trop. Med. 7, 1226-1227.
Xia, F., Sun, J., Jiang, Y., Tu, P., 2013. Further chemical inverstigation of leaves of Aquilaria
sinensis. China Journal of Chinese Materia Medica 39, 3299-3303.

22
Xia, F., Lv, H.N., Jiang, Y., Tu, P.F., 2015. Simultaneous determination of benzophenones and
xanthone in leaves of Aquilaria sinensis by RP-HPLC-UV. China Journal of Chinese
Materia Medica 40, 1342-1346.
Xiao, J.B., Huo, J.L., Jiang, H.X., Yang, F., 2011. Chemical compositions and bioactivities of
crude polysaccharides from tea leaves beyond their useful date. Int. J. Biol. Macromolec.
49, 1143–1151.
Yang, C.S., Lambert, J.D., Sang, S., 2009. Antioxidative and anti-carcinogenic activities of tea
polyphenols. Arch. Toxicol. 83, 11-21.
Yang, M., Liang, Y., Chen, H., Huang, Y., Gong, H., 2014. Isolation and identification of the
chemical constituents in ethyl acetate extracts of wild Aquilaria sinensis leaves. Modern
Food Science and Technology 31, 128-163.
Yin, Y., Jiao, L., Dong, M., Jiang, X., Zhang, S., 2016. Wood Resources, Identification, and
Utilization of Agarwood in China, in: Mohamed, R., (Ed.), Agarwood. Springer,
Singapore, pp. 21-38.
Yu, Q., Qi, J., Yu, H.X., Chen, L.L., Kou, J.P., Liu, S.J., Yu, B.Y., 2013. Qualitative and
quantitative analysis of phenolic compounds in the leaves of Aquilaria sinensis using liquid
chromatography–mass spectrometry. Phytochem. Anal. 24, 349-356.
Zhang Z., Zhou Y., 2016. CN106173114A. Beijing: State intellectual property office of the P.R.C.
Zhao, X., Wang, Q., Li, G., Chen, F., Qian, Y., Wang, R., 2014. In vitro antioxidant, anti-
mutagenic, anti-cancer and anti-angiogenic effects of chinese bowl tea. J. Funct. Foods 7,
590-598.
Zhong, M., Liu, Y., Liu, J., Di, D., Xu, M., Yang, Y., Li, W., Chen, Y., Liu, J., 2014. Isocorydine
derivatives and their anticancer activities. Molecules 19, 12099-12115.
Zhou, M., Wang, H., Kou, J., Yu, B., 2008. Antinociceptive and anti-inflammatory activities of
Aquilaria sinensis (Lour.) Gilg. leaves extract. J. Ethnopharmacol. 117, 345-350.

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Table 1: Chemical constituents in Aquilaria leaves
Category/Class Chemical constituents References
5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone Wang et al. (2015)
2-(2-Phenylethyl)
6-methoxy-2-[2-(3-methoxy-4- Wang et al. (2015)
chromones
hydroxyphenyl)ethyl]chromone
6-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone Wang et al. (2015)
Phenolic acids p-hydroxybenzoic acid Wang et al. (2008),
Feng et al. (2011)
and Kang et al.
(2014)
Vanillic acid Kang et al. (2014)
Isovanillic acid Kang et al. (2014)
Methylparaben Kang et al. (2014)
Syringic acid Kang et al. (2014)
Protocatechuic acid Pranakhon et al.
(2015)
Phytosterols/ Ergosterol Yang et al. (2015)
Steroids β-sitosterol Kang et al. (2014)
β-sitostenone Kang et al. (2014)
Stigmasterol Kang et al. (2014)
Stigmasta-4,22-dien-3-one
β- daucosterol Wang et al. (2008)
Fatty acids N- hexadecanoic acid Khalil et al. (2013)
Nonanoic acid Bahrani et al.
(2014)
Pentadecanoic acid Bahrani et al.
(2014)
1,2,3-propanetriol, monoacetate Khalil et al. (2013)
9,12,15-Octadecatrienoic acid, (z,z,z)- Khalil et al. (2013)
Dodecyl acrylate Khalil et al. (2013)
1-Tetradecanol Khalil et al. (2013)
Pyranones 2,3-Dihydro-3,5-Dihydroxy-6-methyl-4H-pyran-4-one Khalil et al. (2013)
Quinones 6-ethyl-5-hydroxy-2,3n,7-trimethoxynaphthoquinone Khalil et al. (2013)

24
Carbohydrates/ Glycerine Khalil et al. (2013)
carbohydrates 1,3 dihydroxy Khalil et al. (2013)
conjugates Phenyl-β-D-glucoside Khalil et al. (2013)
Benzophenones Aquilarisinin Feng et al. (2011)
Aquilarinoside Feng et al. (2011)
and Qi et al. (2009)
Aquilarinensides Sun et al. (2014)
Iriflophenone 2-O-α-L-rhamnopyranoside Feng et al. (2011)
and Yu et al. (2013)
Iriflophenone 3-C-β-D-glucoside Ito et al. (2012),
Feng et al. (2011)
and Yu et al. (2013)
Iriflophenone 3,5-C-β-D-diglucopyranoside Feng et al. (2011)
and Yu et al. (2013)
Xanthonoids Aquilarixanthone Yu et al. (2013)
Mangiferin Ito et al. (2012) and
Yu et al. (2013)
Neomangiferin Yu et al. (2013)
Homomangiferin Yu et al. (2013)
Isomangiferin Yu et al. (2013)
Flavonoids Apigenin -7, 4'-dimethyl ether Wang et al. (2008),
Kang et al. (2014)
and Arriffin et al.
(2013)
Genkwanin Wang et al. (2008),
Ito et al. (2012), Yu
et al. (2013) and Qi
et al. (2009)
Hydroxygenkwanin Wang et al. (2008)
and Yu et al. (2013)
Luteolin Wang et al. (2008)
and Qi et al. (2009)
Luteolin-7, 3 ', 4'-methyl ether Kang et al. (2014)

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 Luteolin-7, 4'-dimethyl ether Kang et al. (2014)
5-hydroxy-4’,7-dimethoxyflavonoid Kang et al. (2014)
5,3’-dihydroxy-7,4’-dimethoxyflavone Kang et al. (2014)
Delphinidin-3-glucoside Bahrani et al.
(2014)
Hypolaetin 5-O-β-D-glucuronopyranoside Feng et al. (2011)
and Yu et al. (2013)
Epicatechin gallate Tay et al. (2014)
Epigallocatechin gallate Tay et al. (2014)
Vitexin Nie et al. (2009)
Cucurbitacin 2-O-β-D-glucopyranosyl cucurbitacin I Sun et al. (2015)
glycosides Cucurbitacin Feng et al. (2011)
Bryoamaride Sun et al. (2015)
Megastigmane Citroside B Sun et al. (2015)
glycosides Corchoionoside C Sun et al. (2015)
Macarangloside D Sun et al. (2015)
Staphylionoside H Sun et al. (2015)
(9S) megastigma-4,7-diene-2,3,9-triol 9-O-β-D- Sun et al. (2015)
glucopyranoside
(9S) megastigma-4(13),7-diene-3,6,9-triol 9-O-β-D- Sun et al. (2015)
glucopyranoside
(+) 3-oxo-α-ionol-β-D-glucopyranoside Sun et al. (2015)
(–) 3-oxo-α-ionol-β-D-glucopyranoside Sun et al. (2015)
Terpenoids Phytol Khalil et al. (2013)
and Bahrani et al.
(2014)
Squalene Arriffin et al.
(2013) and Khalil et
al. (2013)
Friedelan-3-one Wei and Bin (2011)
Epifriedelanol Arriffin et al.
(2013)
Friedelin Nie et al. (2009)

26
Nucleosides Adenosine Wang et al. (2015)
Cytidine Wang et al. (2015)
Guanosine Wang et al. (2015)
Inosine Wang et al. (2015)
Thymidine Wang et al. (2015)
Uridine Wang et al. (2015)
Alkanes Tetracosane Wei and Bin (2011)
Docosane Wei and Bin (2011)
Dodecane Wei and Bin (2011)
9-Hexacosene Wei and Bin (2011)
Octacosane Wei and Bin (2011)
z-14-Nonacosane Wei and Bin (2011)
1-Bromodocosane Wei and Bin (2011)
Hexadecane ,1-iodo Wei and Bin (2011)
Hexadecane ,7 ,9- dimethyl- Wei and Bin (2011)
Heptadecane Wei and Bin (2011)
Heneicosane Wei and Bin (2011)
1-hexacosene Wei and Bin (2011)
Triacontane Wei and Bin (2011)
Alkaloids Isocorydine Nie et al. (2009)
Others Vitamin E Xia et al. (2013)

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Table 2 Summary of biological activities in several Aquilaria leaves

Aquilaria Species Biological Activities References

Aquilaria malaccensis Antibacterial activity Chen et al. (2014)
Antidiabetic activity Said et al. (2016)
Antioxidant activity Huda et al. (2009)
Hepatoprotective effect Alam et al. (2016)
Aquilaria sinensis Anticancer Nie et al. (2009), Zhong et al.
(2014) and Sun et al. (2015)
Antihistaminic activity Wu et al. (2013)
Anti hyperglycemic Pranakhon et al. (2011) and
activity/Anti diabetic Mei et al. (2013)
Anti-inflammatory activities Zhou et al. (2008) and Lin et
al. (2013)
Antioxidant activities Han and Li (2012), Han
(2013) and Duan et al. (2015)
Antitumor activities Wang et al. (2008) and Wei
and Bin (2011)
AMP-activated protein kinase Jiang et al. (2011)
(AMPK) activating effect
Reduce fasting blood glucose
and glycosylated hemoglobin
levels)
Analgesics activities Lin et al. (2013)
Laxative effect Kakino et al. (2010)
Lipid-lowering effect Wu et al. (2012)
α-glucosidase inhibitory Feng et al. (2011)
activity
Aquilaria crassna Analgesics activities Sattayasai et al. (2012)
Antibacterial activities Kamonwannasit et al. (2013)
and Chen et al. (2014)

28
 Anticancer Dahham et al. (2015)
Anti-inflammatory activities Kumphune et al. (2011)
Antioxidant activities Dahham et al. (2015)
Antipyretic activities Sattayasai et al. (2012)
Laxative effect Kakino et al. (2010)
Aquilaria subintegra Acetylcholinesterase (AChE) Bahrani et al. (2014)
inhibitory activity
(Treat Alzheimer's disease)
Antioxidant activities Ray et al. (2013)

29