Beneficial Effects of Cinnamon on the Metabolic Syndrome, Inflammation, and Pain, and Mechanisms Underlying These Effects – A Review

Abstract

Cinnamon is one of the most important herbal drugs and has been widely used in Asia for more than 4000 years. As a folk medicine, cinnamon has been traditionally applied to the treatment of inflammatory disorders and gastric diseases. After chemical profiling of cinnamon's components, their biological activities including antimicrobial, antiviral, antioxidant, antitumor, antihypertension, antilipemic, antidiabetes, gastroprotective and immunomodulatory were reported by many investigators. As a result, current studies have been performed mostly focusing on the bioactivity of cinnamon toward the recently generalized metabolic syndrome involving diabetes. In this review article, we provide an overview of the recent literature describing cinnamon's potential for preventing the metabolic syndrome.

Full text

Journal of Traditional and Complementary Medicine Vo1. 2, No. 1, pp. 27-32
Copyright © 2011 Committee on Chinese Medicine and Pharmacy, Taiwan.
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27
Beneficial Effects of
Cinnamon
on the Metabolic
Syndrome, Inflammation, and Pain, and
Mechanisms Underlying These Effects – A Review
Yan Shen1,*, Liu-Nan Jia2, Natsumi Honma1, Takashi Hosono1, Toyohiko Ariga1,
and Taiichiro Seki1,*
1 Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource
Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa 252-0880, Japan
2 School of Pharmacy, Nihon University; 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
Abstract
Cinnamon
is one of the most important herbal drugs and has been widely used in Asia for more than 4000 years. As a
folk medicine,
cinnamon
has been traditionally applied to the treatment of inammatory disorders and gastric diseases.
After chemical profiling of
cinnamon
’s components, their biological activities including antimicrobial, antiviral,
antioxidant, antitumor, antihypertension, antilipemic, antidiabetes, gastroprotective and immunomodulatory were
reported by many investigators. As a result, current studies have been performed mostly focusing on the bioactivity of
cinnamon
toward the recently generalized metabolic syndrome involving diabetes. In this review article, we provide an
overview of the recent literature describing
cinnamon
’s potential for preventing the metabolic syndrome.
Key words:
Cinnamon
, Spice, Diabetes, Metabolic syndrome, Inammation, Insulin
*
Correspondence to:
Prof. Taiichiro Seki. E-mail: tseki@brs.nihon-u.ac.jp, FAX:+81-466-84-3949
Dr. Yan Shen. E-mail: shen.yan@nihon-u.ac.jp, FAX: +81-466-84-3949
Introduction
The genus
Cinnamon
is an aromatic tree belonging
to the family Lauraceae, and is one of the most widely
studied flowering families, comprising about 250
species. Members of this family are evergreen trees,
up to 10-17 m high, that grow in south-eastern Asia,
Australia, and South America (Cheng, 1983). The
flowers are bisexual, colored yellow with 9 stamens,
and the fruits occur mostly as 10-15- mm long black
ellipsoids (Cheng, 1983). Traditional uses of Cinnamon
throughout Asia, Africa, and Europe have been
recorded, where it has been used as a medicine for
diarrhea, nausea and chill, or as a spice for seasoning
meats. Cinnamon bark (肉桂 ròu guì) is an important
source for these purposes, since it contains a great
amount of the function-bearing essential oil. The bark-
derived cinnamon (termed cinnamon hereafter) contains
45% ~ 65% cinnamaldehyde, 12% ~ 18% eugenol
(Cheng, 1983) and small amounts of cinnzeylanine,
cinnzeylanol, arabinoxylan, 2’-hydroxycinnamalde-
hyde, and 2’-benzoloxycinnamaldehyde (Lee, 1999).
As a major ingredient, cinnamaldehyde has been
well investigated; and its diverse biological activities
against central nervous system depression (Harada,
1976) and high blood pressure (Harada, 1975), as
well as its analgesic effect (Harada, 1972), have been
reported. A water extract of cinnamon was reported to
have anti-allergic, anti-inflammatory (Nagai, 1982a;
1982b; 1982c), antipyretic, analgesic (Ozaki,1972)
and antithrombotic effects (Terasawa, 1983). Recently,
This is an open access article under the CC BY-NC-ND license.

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Shen
et al
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the interest of investigators seems to have shifted
to become narrowly centered on the verification of
cinnamon’s potential for preventing the metabolic
syndrome (Kannappan, 2006; Blevins, 2007) and
diabetes (Anderson, 2004; Chase, 2007; Pham, 2007;
Shen, 2010).
This review summarizes the up-to-date and
comprehensive information on cinnamon regarding
its traditional use, for which modern scientists have
solved its pharmacological functions together with its
toxicological aspects. Then we discuss a possible trend
and scope for future research on cinnamon.
Cinnamon as a traditional medicine
Trees belonging to the genus
Cinnamomum
are one
of the major materials used in traditional Chinese
medicine. Preparations containing the bark of Cinnamon
have been prescribed for more than 2000 years in China,
where the first record of its use was described in the
Divine Husbandman’s Herbal Foundation Canon (see
the review introduced by Cheng, 1983). Owing to its
roles in dispelling colds (祛寒 qū hán), threading an
occluded vasa vasorum, and controlling yin/yang (陰
陽 yīn yang) as mentioned in the old Chinese literature,
cinnamon has been widely used in China and Japan for
the treatment of fever and inflammation as well as for
improvement of an appetite depressed by influenza or
the common cold (Cheng, 1983). In addition, cinnamon
has been used as an aromatic for the preparation of fruit
juices, wine, and cakes as well as for cooking meat.
Cinnamon extracts have been used for the improvement
of or protection against the common cold, diarrhea, and
pain (Cheng, 1983). It has also been reported that the
cinnamon ameliorates nephritis, purulent dermatitis, and
hypertension, as well as potentiates wound healing, even
that due to snake or viper bites (Nagai, 1982a; 1982b;
Cheng, 1983). However, these effects are not fully
supported by experimental or clinical data so far.
Functional components in
Cinnamomum
plants
Cin namaldehyde is a major constituent (45~65%
of the essential oil in cinnamon bark) of the plants
belonging to genus
Cinnamomum
(Cheng, 1983).
Eugenol is contained as a second major constituent; and
cinnzeylanine, cinnzeylanol (Isogai, 1977), arabinoxylan
(Gowda, 1987), 2’-hydroxycinnamaldehyde, and
2’-benzoloxycinnamaldehyde (Lee, 1999) are also
detected. Chemical structures of these compounds
are shown in Fig. 1. A hot-water extract of cinnamon
sticks (dried barks of cinnamon trees) yields 8.5 mg/ml
cinnamaldehyde and 3.6 mg/ml cinnamyl alcohol (Shen,
2010).
Pharmacological effects of cinnamon
In vitro
and
in vivo
studies on cinnamon extracts
or its components (mainly cinnamaldehyde) revealed
that these substances exhibit a wide variety of
pharmacological effects, such as antifungal, anti-
cardiovascular, anticancer, antiinammatory, antiulcer,
antidiabetes, antiviral, antihypertensive, antioxidant,
and cholesterol- and lipid-lowering ones. Some of
the relevant literature on these therapeutic effects is
summarized in Table 1, and some of the observations
made are discussed in the following sections.
Antifungal effect
The antifungal activity of cinnamaldehyde, which is
used as a vapor to treat respiratory tract mycoses, has
been reported. Cinnamon tree power (we usually call
it “cinnamon”) acts against infectious fungi including
Aspergillus niger
,
A. fumigatus
,
A. nidulans
,
A. avus
,
Candida albicans
,
C. tropicalis
,
C. pseudotropicalis
,
Figure 1. Compounds found in the Cinnamon barks

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Shen
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. / Journal of Traditional and Complementary Medicine 2 (2012) 27-32
and
Histoplasma capsulatum
(Singh, 1995; Lima, 1993;
Quale, 1996). In these cited studies, the following data
were reported: the minimum inhibitory concentration
(MIC), minimum lethal concentration (MLC) and
exposure duration for its fun gicid al action at MIC
and higher doses, as well as incubation temperatures
for expression of its fungitoxicity. The inhalation of
cinnamaldehyde appears to be an ideal chemotherapy
against respiratory tract mycoses.
Effects on cardiovascular system and gastrointestinal
tract
Cinnamophilin in cinnamon was found to be a
thromboxane A2 (TXA2) receptor-blocking agent; and
therefore its antagonistic effect was shown in TXA2-
induced human platelet aggregation, rat aortic ring
contraction, and contraction of guinea pig tracheal rings
(Yu, 1994a). Intravenous administration of arachidonic
acid (50 μg/kg body weight) to a guinea pig induces
bronchoconstriction, whereas when cinnamophilin is
pre-administered (0.1 mg/kg body weight,
i.v.
at 1 min
before arachidonic acid), the bronchoconstriction is
abolished (Yu, 1994a). Cinnamophilin (1-15 μM) also
possesses a voltage-dependent Ca2+ channel-blocking
action, which was judged from its antagonism toward
high K+(60 mM)- and Bay K 8644 (0.1 μM)-induced
contraction of rat thoracic aorta (Yu, 1994b). Su
et
al
. demonstrated that the inhibition of sodium inward
current, calcium inward current, and transient outward
currents of both may contribute to the anti-arrhythmic
activity of cinnamophilin against ischemia-reperfusion
arrhythmia (Su, 1999).
Anticancer and immunomodulatory activities
An early study on water-soluble extracts of cinnamon
showed that it increases the glutathione
S
-transferase
(GST) activity in mice administered urethane, a
carcinogenic substance, and prevents carcinogenesis
(Abraham, 1998). Furthermore, an aqueous extract
of cinnamon reduces cellular proliferation and blocks
the cell cycle of Jurkat, Wurzburg, and U937 cells at
the G2/M phase (Schoene, 2005). Cinnamaldehyde
or its source
C. cassia
powder is reportedly a potent
inducer of apoptosis in human promyelocytic leukemia
cells, in which the aldehyde stimulates an apoptotic
cascade leading to the activation of caspase-3 (Ka,
2003, Nishida, 2003). 2’-Hydroxycinnamaldehyde and
2’-benzoloxycinnamaldehyde isolated from the bark
Table 1. Pharmacological activity of cinnamon and its compounds

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Shen
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of
C. cassia
show cytotoxicity against several human
solid tumor cells such as HCT-15 and SK-MEL-2 cells
(Lee, 1999). Koh
et al
. (1998) reported that both of
these compounds inhibit lymphocyte proliferation and
modulate T-cell differentiation
in vitro
.
Antiulcerative activity
The antiulcerative effect of a cinnamon extract has
not yet been claried, but the effect of a water extract of
cinnamon on serotonin-induced gastric lesions in mice
was studied. A palliative effect is observed after oral
administration of the extract at a dosage of 5–10 mg/kg
body weight
(Keller, 1992).
Antiinammatory activity
Nagai
et al
. (1982a, 1982b) proved that complement-
dependent reactions including reversed passive
cutaneous anaphylaxis, Forssman cutaneous vasculitis,
nephrotoxic serum nephritis classified as type II, and
the Arthus reaction classified as type III are clearly
inhibited by an aqueous extract of
C. cassia
. However,
this extract does not affect the nephritis caused by the
F(ab')2 portion of the nephrotoxic IgG antibody. The
aqueous extract of
C. cassia
at a high concentration
(200 mg/kg
body weight
) inhibits the immunological
hemolysis and the chemotactic migration of neutrophils
caused by
activated serum complement as well as the
generation of chemotactic factors. They also showed
that the type IV reaction found in contact dermatitis
is not affected by the aqueous extract of
C. cassia
but
that the production of hemolytic plaque-forming cells
is slightly inhibited by it. Their ndings suggest that an
aqueous extract of
C. cassia
has an anti-complement
activity and inhibits complement-dependent allergic
reactions.
Antioxidant activity
Mancini-Filho
et al
. (1998) demonstrated the
antioxidant activity of cinnamon extracts by using an
oxidative β-carotene/linoleic acid system, and they
suggested that the cinnamon extracts can be used not
only for improvement of food palatability but also for
prevention of food oxidation.
Cinnamon bark extracts prepared with water and
alcohol as well as its essential oil were tested in two
different
in vitro
systems, i.e., peroxynitrite-induced
nitration and lipid peroxidation. The essential oil and its
component eugenol both show antioxidant activity in
these systems (Shobana, 2000; Dragland, 2003; Khan,
2003; Chericoni, 2005; Kim, 2006a).
Cinnamon barks from
C. zeylanicum
,
C. cassia
or ot he r cinnamon species are repo rt ed to exhibi t
antioxidant and free radical-scavenging activities, some
of which were measured by using 1,1-diphenyl-2-
picrylhydrazine (DPPH; Mancini-Filho, 1998; Shobana,
2000; Okawa, 2001; Dragland, 2003).
Cholesterol- and lipid-lowering effects
Administration of cinnamon to mice increases their
HDL-cholesterol level and decreases their plasma
triglyceride one (Kim, 2006a). Khan
et al
. (2003)
reported that cinnamon improves the blood glucose,
triglyceride, total cholesterol, HDL cholesterol and LDL
cholesterol levels in patients with type 2 diabetes.
Antidiabetes effect
Recently, the anti-diabetic effect of cinnamon
has been studied intensively by many investigators
(Anderson, 2004; Chase, 2007; Pham, 2007; Shen,
2010). They commonly found that cinnamon improves
insulin resistance and glucose metabolism
in vitro
and
in vivo
(Subash, 2007; Kannappan, 2006; Kim, 2006a;
Berrio, 1992; Broadhurst, 2000; Cao, 2007; Imparl-
Radosevich, 1998; Jarvill-Taylor, 2001; Khan, 1990;
Kim, 2006b; Kreydiyyeh, 2000; Lee, 2011; Roffey,
2006; Taher, 2004; Talpur, 2005; Ond ero glu , 1999;
Qin; 2003; Qin, 2004; Verspohl, 2005). Among the
components of cinnamon, cinnamaldehyde signicantly
and dose-dependently decreases the plasma glucose
concentration of streptozotocin-induced diabetic
rats (Subash, 2007). Regarding the mechanism
underlying these effects, Shen
et al
. (2010) reported
that cinnamon extracts promote the transportation of
glucose
by glucose
transporter 4 in brown adipose
tissue and muscles. Clinical research studies support
the positive effects of cinnamon on both types 1 and 2
diabetes mellitus (Mang, 2006; Suppapitiporn, 2006;
Vanschoonbeek, 2006; Altschuler, 2007; Blevins, 2007;
Wang, 2007).
Conclusions
As has been reported, cinnamon, as forms of bark,
bark powder, extracts or its isolated components, has
multifunctional activities promoting the health of human
beings. Different from therapeutic drugs, cinnamon can
be used daily in our diet without ill effect. Therefore, it
may be preventive especially against the lifestyle-related
illness or metabolic syndrome.
Although we did not mention in this review on
cinnamon that it is also a representative agonist of the
transient receptor potential A1 (TRPA1) cation channel

31
Shen
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(Iwasaki, 2008)
, many of the pharmacological activities
of cinnamon might be exhibited via this receptor;
e.g. the effects on cardiovascular and gastrointestinal
systems might be regulated more or less by nervous
systems via TRPA1. The anticancer and anti-
inflammatory activities could also be explained partly
by sympathetic nerves stimulated via TRPA1.
Taking the self-protective antifungal and antioxidant
activities of cinnamon into account, cinnamaldehyde,
cinnamophilin, and other components possess both
direct and indirect activities; i.e., the antifungal and
antioxidant activities occur by direct action on fungus
or oxidant, whereas the antidiabetic, anticancer, and
antiinflammatory ones occur indirectly via some yet
undened receptor-mediated mechanisms.
The remarkable health benefits of cinnamon prompt
us to explore derivatives of cinnamon that might
be much more useful structures for overcoming the
metabolic syndrome.
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