Journal of Ethnopharmacology 156 (2014) 216–221

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep

The effects of seeds with hot and cold temperaments on serum thyroid
hormones, corticosterone and urine vanillylmandelic acid
concentrations of healthy rats
Shirin Parvinroo a, Farzaneh Naghibi b,c, Saleh Zahediasl d, Mohammad Kamalinejad c,
Masoumeh Sabetkasaei e,n
a
Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
b
Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
d
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
e
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

art ic l e i nf o a b s t r a c t

Article history: Ethnopharmacological relevance: Hot and cold temperaments are the basic concepts of Iranian traditional
Received 26 February 2014 medicine (ITM). Nevertheless, studies on the functional mechanisms of medicinal herbs based on hot and
Received in revised form cold temperaments are not very extensive. This study aimed to evaluate the effects of diets containing
22 August 2014
hot or cold temperament seeds according to ITM on some hormonal and neuromediator parameters with
Accepted 24 August 2014
Available online 1 September 2014
a regulatory role in thermogenesis and energy metabolism in acute (24 hr) and subacute (7-day)
experiments that were performed on rats.
Keywords: Materials and methods: Each experiment was performed on 42 male Wistar rats, which were randomly
Iranian Traditional Medicine divided into 7 groups. while 1 group received usual diet (controls), 6 other groups were fed with a diet
Temperament
containing 10% seeds, namely, anise, fennel, or ajowan (hot temperament groups) or cucumber, pumpkin,
Seeds
or watermelon (cold temperament groups), respectively. The levels of the rats' serum free thyroxin (FT4),
Vanillylmandelic acid
Thyroid hormones free triiodothyronin (FT3), triiodothyronin (T3), thyroxin (T4), corticosterone and urine vanillylmandelic
Corticosterone acid (VMA) were analyzed.
Results: After 24 hours, a significant decrease in FT3 was observed in groups that were fed anise or fennel
seeds. However, a significant increase in T3 was observed in the ajowan seed-fed group, and no changes
in other parameters were observed in this group. On the 7th day, FT4 was significantly increased in
fennel seed-fed group; T3 was significantly increased in the anise, fennel, ajowan and watermelon seed-
fed groups; corticosterone was significantly increased in the watermelon and pumpkin seed-fed groups;
and VMA was significantly increased in the fennel seed-fed group and significantly decreased in the
cucumber seed-fed group.
Conclusion: Alterations induced by hot and cold temperament seeds in measured hormonal and
neuromediator levels that have a regulatory role in thermogenesis and the body's energy metabolism
revealed that hot and cold temperament characteristics of studied seeds may most likely be related to
their intervention in the body's energy metabolism, in that hot temperament seeds may increase energy
metabolism and cold temperament ones may decrease it.
& 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
According to Iranian traditional medicine (ITM) manuscripts,
four elements of fire, air, water and soil are essential constituents
of human and nonhuman beings. Each of these elements has a pair
of qualities consisting of warmness or coldness, and wetness or
n
Corresponding author. Tel.: þ 98 21 23872539; fax: þ 98 21 22439969.
E-mail address: fkasaei@yahoo.com (M. Sabetkasaei).
dryness. Fire is warm and dry, air is warm and wet, water is cold
and wet, and soil is cold and dry. Temperament (nature or mizaj)
as a main concept in ITM means a quality/qualities produced by
interaction of opposite qualities of small particles that exist in the
mentioned elements. In this concept, each person and even each
medicine has its own specific temperament (or temperaments)
that falls into one of three categories of simple (hot, cold, wet, and
dry), complex (hot-dry, hot-wet, cold-dry, and cold-wet) or mod-
erate (equal quantity of elements) (Ahvazi, 2009).

http://dx.doi.org/10.1016/j.jep.2014.08.026
0378-8741/& 2014 Elsevier Ireland Ltd. All rights reserved.
 S. Parvinroo et al. / Journal of Ethnopharmacology 156 (2014) 216–221
Temperament as a basic concept exists in other traditional
medical theories as well, including Unani (Greek), Arabic, Roman,
Indian, European and Chinese traditional medicines (Shahabi et al.,
2008). Based on the ITM's principles, occurrence of an imbalance
in the body's temperament leads to the onset of disease condition,
and from that point on, treatment is based on restoring the
balanced state of the body using medicines with opposite tem-
perament (Avicenna, 2010a).
In ITM, the term “nature” has been used for several meanings and
concepts; in one specific concept, it is believed that nature (Qovveh
modabbereh) keeps the body healthy and helps cure diseases; in fact,
using medicines or foods aids patients' nature to return to its healthy
condition (Ibn Hindu, 1990). Traditional physicians considered nature's
functions in accordance with natural affairs (Umoor-e-Tabee-ye)
(Aghilikhorasani, 2007). Natural affairs are principles on which the
body's existence and consistency are based and consist of seven factors
including elements (Arkan), temperament (Mizaj), humors (Akhlat),
organs (Azaa), spirits (Arvah), forces (Quwa), and functions (Af'al)
(Arzani, 2013).
Maintenance of a relatively stable internal environment is
termed homeostasis (homeo means “the same”; stasis means “to
stand or stay”). Physiologists believe that several body systems
using specific mechanisms and functions contribute to maintain
homeostasis. When any factor (external or internal) starts to move
the internal environment away from optimal conditions, the
body's systems initiate appropriate counteractions to minimize
the change. For example, when working out, there is a production
of extra heat that tends to raise the body temperature, and the
body responds by sweating (Sherwood, 2010).
Because nature (Qovveh modabbereh) focuses on the integrity
of the human body and is featured as a self-controlled system,
which is close to the concept of homeostasis, it can be postulated
that medicines with hot and cold temperaments contribute to
restore the balanced state or homeostasis of the body.
There are few studies that have investigated the ITM theory of hot
and cold temperaments affecting homeostasis. A study by Shahabi
et al. (2008) showed that hot temperament persons had a more active
sympathetic nervous system; a less active parasympathetic nervous
system; adrenal corticosteroid and adrenal sympathetic activities; and
a higher rate of deviation of the immune system toward T-helper
2 responses in comparison with cold temperament persons. In our
previous study, hot temperament seeds decreased food intake and
weight gain and increased serum glucose levels with no significant
differences in water consumption and urine output compared to cold
temperament seeds in healthy rats (Parvinroo et al., 2014).
Mostafavi (2005) believed that hot temperament people have
higher basal metabolic rate in comparison to cold temperament
people. He also compared properties of hot and cold temperament
Table 1
Names and traditional uses of seeds with hot and cold temperaments.
Scientific name Family Common Traditional
name name
Foeniculum vulgare Mill. Apiaceae Fennel Razianaj
Pimpinella anisum L. Apiaceae Anise Anisun
Trachyspermum ammi Apiaceae Ajowan Nankhah
(L.) Sprague
Cucurbita pepo L. Cucurbitaceae Pumpkin Qar
Citrullus lanatus Cucurbitaceae Watermelon Bettikh
(Thunb.) Matsum. & hendi
Nakai
Cucumis sativus L. Cucurbitaceae Cucumber Qathad
217
persons with thyroidal dysfunction symptoms and signs and
suggested that cold temperament persons show hypothyroid
symptoms such as hypothermia; however, hot temperament
people have hyperthyroid symptoms such as hyperthermia.
Hypothermia and hyperthermia are related to imbalanced heat
production, thermogenesis, and energy homeostasis.
Thyroid hormone is the major regulator of thermogenesis and
works synergistically with the sympathetic nervous system (SNS)
in homeothermic species (Silva, 2006). T3 is the most metaboli-
cally active thyroid hormone (Kelly, 2000) and increases energy
metabolism, heat production and thermogenesis (Silva, 1995; Kim,
2008). The SNS and the adrenal medulla are considered to be the
two parts of a system, called sympathoadrenal system. Norepi-
nephrine is the main SNS neurotransmitter, and epinephrine is
predominantly synthesized in the adrenal medulla. Assessment of
sympathoadrenal system activity has usually been based on the
measurement of catecholamines in urine and plasma (such as
epinephrine and norepinephrine). The SNS has a critical role in
mammalian thermogenesis when exposed to cold and dietary
intake (Landsberg and Young, 1983). Glucocorticoids also have
complex effects on thermogenesis and temperature homeostasis.
It is not a primary function of these hormones to increase
thermogenesis but rather to coordinate thermogenic responses
to substrate or food availability (Silva, 2006). Corticosterone (the
major glucocorticoid in rodents) has been shown to be essential
for the maintenance of body temperature during cold stress
(Maickel et al., 1967). Studies show that corticosterone can lead
to impaired energy metabolism in rat liver (Jani et al., 1991) and
brain mitochondria (Katyare et al., 2003).
The objectives of this study were to assess the differences
between the effects of seeds with hot-dry and cold-wet tempera-
ments on several neuro-hormonal parameters with a regulatory
role in thermogenesis and energy metabolism. In this study,
the effects of three hot temperament seeds including fennel
(Foeniculum vulgare Mill.), anise (Pimpinella anisum L.), and ajowan
(Trachyspermum ammi [L.] Sprague) from the family Apiaceae and
three cold temperament seeds including watermelon (Citrullus
lanatus [Thunb.] Matsum. & Nakai), pumpkin (Cucurbita pepo L.)
and cucumber (Cucumis sativus L.) from the family Cucurbitaceae
on serum free thyroxin (FT4), free triiodothyronin (FT3), triio-
dothyronin (T3), thyroxin (T4), corticosterone (the major gluco-
corticoid in rodents) and urine vanillylmandelic acid (VMA) as the
principal end-product of epinephrine and norepinephrine in
healthy rats after feeding periods of 24 h (acute study) and 7 days
(subacute study) are investigated. Because hot and cold qualities
have been considered as principal qualities in ITM manuscripts
(Avicenna, 2010a), in this study, we describe the studied seeds'
temperaments in two categories of hot and cold. Names and
Traditional uses
Strengthening eye-sight, increasing milk secretion, lithotrity, diuretic, emmenagogue, carminative,
and treating nausea and chronic diarrhea.
Cough, dyspnea, increasing milk secretion, lithotrity, diaphoretic, emmenagogue, diuretic,
aphrodisiac, carminative, and treating halitosis, hemorrhoid, diarrhea, borborygmus, cold
headache and vertigo.
Increasing milk secretion, diaphoretic, diuretic, emmenagogue, carminative and treating paralysis,
trembeling, hiccough, vomiting, nausea, severe dyspepsia, kidney and bladder stones, and
borborygmus.
Fattening and treating hemoptysis, cough, fever, bladder and intestinal ulcers,and dysuria.
Fattening and treating hemoptysis, cough, fever, bladder and intestinal ulcers, and dysuria.
Diuretic and treating dysuria, spleen and liver tumefaction, and fever.
218 S. Parvinroo et al. / Journal of Ethnopharmacology 156 (2014) 216–221

traditional uses (Momen Tonekaboni, 2008; Aghilikhorasani,
2009; Avicenna, 2010b) of the selected seeds are shown in Table 1.
2. Materials and methods
The seeds were purchased from a local market in Tehran and
authenticated by a botanist at the Traditional Medicine and
Materia Medica Research Center (TMRC), Shahid Beheshti Univer-
sity of Medical Sciences, Tehran, Iran. Voucher samples of surveyed
seeds are deposited at TMRC; fennel (105-HMS), anise (104-HMS),
ajowan (103-HMS), watermelon (106-HMS), pumpkin (108-HMS),
and cucumber (107-HMS). Because the experimental materials
were purchased from a local market, their authentication was
performed only based on macroscopic characteristics. Any varia-
tions in their chemical composition were ignored. For preparation
of the diets, pellets (1350 g) and seeds (150 g) were powdered by
an electric grinder (cold herbs were sieved to remove seed's
crusts) and mixed thoroughly with some water in a household
mixer. From this dough, pellets were prepared using a manually
operated pelletizing machine. Pellets were spread on a flat surface
for drying at room temperature for 3 days.
had 0.5 ml calibration between 2 and 15 ml. To reduce the effect
of evaporation on urine volume, every 8 h urine samples were
moved from a small container below the metabolic cage to a
sealed tube and stored at  70 1C. Upon completion of the
experiments, animals were sacrificed under CO2 anesthesia, and
their blood was collected by the cardiac puncture method. Blood
was centrifuged at 3000 rpm for 10 min, and the serum was stored
at 70 1C for biochemical analysis. Thyroid hormones concentra-
tions (T3, T4, FT3, and FT4) were determined separately using their
specific ELISA kits, (Diaplus Inc., San Francisco, U.S.A). Corticoster-
one concentrations were also measured using an ELISA kit
(DRG Instruments GmbH, Marburg, Germany), and urine VMA
concentrations were determined by a rat ELISA kit (CUSABIO
Biotech, Wuhan, China).
2.3. Statistical analysis
All the data are presented as the means 7SEM. Concentrations
of serum thyroid hormones, corticosterone and urine VMA were
analyzed using a One-way ANOVA with Dunnett post-hoc test.
P values o0.05 were considered significant.

2.1. Animals 3. Results

Male Wistar rats weighting 200–260 g (5–6 months old) were
obtained from the animal house of Shahid Beheshti University of
Medical Sciences and were acclimated for 7 days prior to the
experiments. The animals were caged individually and maintained
in constant conditions of temperature (2472 1C) and light/dark
schedule (12 h light and 12 h dark) with free access to diet and
water. The rats were divided randomly into 7 groups (n ¼6) for
each test. All experiments were performed in accordance with the
Ethics Committee Guidelines for Research on Laboratory Animals
of Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2.2. Experimental design
Two experiments were performed. The effects of hot and cold
temperament seeds on serum thyroid hormones, corticosterone
and urine vanillylmandelic acid concentrations after 24 h, and
after 7 days were examined. A day before starting the tests, rats
were placed in metabolic cages for 24 h to collect the base urine
rate for assaying VMA (the first day was to accustom the rats to the
cages). In these experiments, while controls received the usual
diet, the other groups were fed with prepared diets. In both
experiments, animals had free access to water and food. Urine
volume was determined by 24-h collections via test tubes that
3.1. Effects of diets containing hot or cold temperament seeds on
serum thyroid hormones levels
The effects of diets containing hot or cold temperament seeds
on serum thyroid hormones concentrations of normal rats are
illustrated in Table 2. In the 24-h experiment, the groups fed with
anise or fennel seeds had a significant decrease (P o0.05) in serum
FT3 levels, and the ajowan seed-fed group showed a significant
increase (P o0.05) in serum T3 levels. On the 7th day, the fennel
seed-fed group had a significant increase (Po 0.01) in serum FT4
concentration, whereas the groups fed with anise, fennel, ajowan
and watermelon seeds had a significant increase (P o0.01) in
serum T3 levels.
3.2. Effects of diets containing hot or cold temperament seeds on
serum corticosterone levels
The effects of diets containing hot or cold temperament seeds
on serum corticosterone levels are shown in Fig. 1. There was no
difference in corticosterone levels among the studied groups
compared to controls after 24 h. On the 7th day, the watermelon
(P o0.001) and pumpkin (P o0.01) seed-fed groups had a sig-
nificant increase in serum corticosterone levels.

Table 2
Effects of diets containing hot or cold temperament seeds on serum thyroid hormones levels.

Thyroid hormones

Groups FT3 (pg/ml) FT4 (ng/dl) T3 (ng/ml) T4 (μg/dl)

24 h 7 days 24 h 7 days 24 h 7 days 24 h 7 days

Control 5.5 7 0.4 5.17 0.1 2.6 7 0.2 1.9 7 0.1 1.5 7 0.1 1.6 70.0 3.4 7 0.2 3.6 7 0.1
Anise 4.17 0.2n 4.9 7 0.3 2.4 7 0.2 2.7 7 0.3 1.8 7 0.0 1.9 70.0nn 3.3 7 0.1 3.6 7 0.2
Fennel 3.9 7 0.3n 5.4 7 0.2 2.6 7 0.2 3.2 7 0.3nn 1.17 0.0 1.9 70.0nn 3.2 7 0.1 2.9 7 0.1
Ajowan 4.2 7 0.3 5.2 7 0.1 2.7 7 0.1 2.4 7 0.2 1.9 7 0.0n 1.9 70.0nn 3.3 7 0.1 3.4 7 0.1
Cucumber 5.5 7 0.4 4.9 7 0.1 2.7 7 0.3 2.2 7 0.2 1.5 7 0.0 1.8 70.0 5.2 7 0.3 3.2 7 0.1
Watermelon 4.6 7 0.1 5.7 7 0.5 2.8 7 0.0 2.6 7 0.2 1.3 7 0.0 2.0 70.1nn 4.5 7 1.1 3.4 7 0.2
Pumpkin 5.7 7 0.5 5.4 7 01 2.9 7 0.2 2.17 0.1 1.6 7 0.1 1.6 70.0 3.4 7 0.3 3.7 7 0.3

Data are expressed as the means 7 SEM. n¼ 6.

n
Po 0.05 denote a significant difference compared to controls.
nn
Po 0.01 denote a significant difference compared to controls.
 S. Parvinroo et al. / Journal of Ethnopharmacology 156 (2014) 216–221 219

200 1000
∗∗∗

Corticosterone (ng/ml)

Corticosterone(ng/ml)
150 800

600 ∗∗
100
400
50
200

0 0

el
se
ol

an

in
on
r

in
el

r
se

on
ol

an
be

be
nn

pk
tr

nn

pk
tr
ni

ni
el

el
um

um
on

on
jo
A

jo
Fe

A
m
m

m
Fe

m
C

A
Pu
er

Pu
er
uc

uc
at

at
C

C
W

W
Groups Groups

Fig. 1. Effects of diets containing hot or cold temperament seeds on serum corticosterone levels after 24 h (A) and 7 days (B). Data are expressed as the means 7SEM. n¼ 6;
**
Po 0.01, ***Po 0.001 denote a significant increase compared to controls.

300 400
∗
300
VMA(μ g/kg/24h)
VMA(μ g/kg/24h)

200
200
∗∗
100
100

0 0

n
on
r
e

l
ol

an
in
on
se

el
ol

an

be
s

i
be

nn

pk
tr
nn

pk
tr

ni

el
ni

el

um
on
um
on

jo
A

m
m
Fe
jo
A

m
Fe

Pu
er
C

uc
er

Pu
uc

at
at

C
C

W
W

Groups Groups

Fig. 2. Effects of diets containing hot or cold temperament seeds on urine VMA after 24 h (A) and 7 days (B). Data are expressed as the means 7 SEM. n¼6; *Po 0.05,
**
Po 0.01 denote a significant difference compared to controls.

3.3. Effects of diets containing hot or cold temperament seeds on
urine VMA levels
Effects of diets containing hot or cold temperament seeds on
urine VMA levels are shown in Fig. 2. There were no significant
differences in the urine VMA levels of the groups consuming either
hot or cold temperament diets in the 24-h experiment. On the 7th
day, the fennel seed-fed group had a significant increase in urine
VMA levels (P o0.05), and the cucumber seed-fed group had a
significant decrease (P o0.01) in urine VMA levels (Fig. 2).
4. Discussion
In normal adult vertebrates, the plasma total concentrations of
T4 and T3 are in the nanomolar range. The vast majority of
both hormones are bound to plasma proteins, whereas the free
hormones are in the picomolar range for all vertebrates, approxi-
mately consisting 0.01–0.1% of the total hormone concentrations.
It is the level of free thyroid hormones that is the more physio-
logically important concentration (Robbins et al., 1957; Mendel,
1989). In fact, only free hormones in the plasma can cross cell-
surface membranes and exert biological effects. However, it must
be noted that the intercellular concentrations of the thyroid
hormones depend on the concentration of protein-bound hor-
mones in the plasma, as well (Mendel, 1992).
Our results showed that, in the acute phase of the study, FT3
was decreased in two of the hot temperament seed-fed groups,
fennel and anise, and T3 was increased in the hot temperament
group fed ajowan seeds. In the subacute phase of the study, T3 was
increased in the groups that were fed with the hot temperament
seeds anise, fennel and ajowan and the watermelon cold tempera-
ment seeds. FT4 was increased in the ajowan seed hot tempera-
ment group in the subacute phase.
The probable mode of action of the studied seeds on the
thyroid hormone levels may be mediated through two mechan-
isms. The first possible mechanism is through increasing produc-
tion of thyroid hormones. Both T4 and T3 are synthesized by the
thyroid gland. However, T4 is the major hormone produced by
the thyroid, and most of the circulating T3 (approximately 80%)
is formed from T4 in peripheral tissues by the activity of type-I
5ʹ-iodothyronine monodeiodinase (5ʹ-DI) (Ko, 2000). Thus,
any changes in the activity of 5ʹ-DI will lead to changes in the
concentration of T4 and T3. In fact, stimulation of 5ʹ-DI activity is
reflected by an increase in T3 concentration and a decrease in T4
concentration. However, T3 was increased following the adminis-
tration of the diet containing ajowan in the acute phase of the
study and decreased following administration of diets containing
anise, fennel, ajowan and watermelon seeds in the subacute phase.
T4 remained unchanged in animals' serum. It seems that the
mentioned seeds, in addition to promoting conversion of T4 to T3,
most likely worked directly on the thyroid gland for generation of
T4. The second possible mechanism is through interfering with the
220 S. Parvinroo et al. / Journal of Ethnopharmacology 156 (2014) 216–221
binding of thyroid hormones with thyroid binding proteins. T3 and
T4 are predominantly bound to thyroid-binding proteins (TBP),
and small amounts of T3 and T4 are unbound or free (Davis et al.,
1970; Nilsson and Peterson, 1975). It appears that in the acute
phase of the study, hot temperament seeds of fennel and anise
increased the binding of T3 to TBP, which led to a decreased FT3
level, while in subacute phase, fennel seeds decreased the binding
of T4 to TBP, which led to an increased FT4 level.
Considering the metabolic and thermogenic effects of T3 in the
body (Silva, 1995; Kim, 2008) and increased level of T3 in all hot
temperament seed-fed groups, it seems that the hot tempera-
ments of anise, fennel, and ajowan are in some part in accordance
with increased T3 levels.
Among the cold temperament groups, T3 levels changed only
in the watermelon seed-fed group, and the effects were similar to
those observed in the hot temperament seed-fed groups. The
other cold temperament groups did not show any changes in T3
level. However, both watermelon and pumpkin seeds increased
the corticosterone levels remarkably. This finding is in accordance
with a study by Shahabi et al. (2008), which showed high adrenal
corticosteroid activity in cold temperament persons. Because of
the pituitary-adrenocorticoid response connectivity to the
parasympathetic nervous system, they concluded that cold tem-
perament participants had higher parasympathetic activity in
comparison with the hot temperament ones by considering the
ratio of blood norepinephrine to cortisol levels as the determinant
factor of the balance between peripheral sympathetic and para-
sympathetic nervous system activities. We did not measure
norepinephrine in this study. However, considering that no
changes were observed in VMA levels (a metabolite of norepi-
nephrine and epinephrine) and that an enhancement of corticos-
terone levels was observed in watermelon and pumpkin seed-fed
groups, it can be inferred that these seeds have high parasympa-
thetic activity. It is well known that parasympathetic activity can
cause hypothermia (Rothwell et al., 1981) and reduce thermogen-
esis (Bryant et al., 1983). Additionally parasympathetic blockade
stimulates heat production (Purcell, 1996; Kalow and Britt; 1973).
In various parts of the world, the seed extracts of watermelon are
used for hypertension (Yadav et al., 2011), a condition associated
with a hot temperament (Wan 2006), which can be related to
lower parasympathetic activity (Grossman et al., 1992). It is
possible that the T3 changes noted after consumption of water-
melon seeds are due to hypothermia, not a direct action of
watermelon seeds.
T3 actions are mediated by binding to nuclear receptors
(Oppenheimer et al., 1987). It must be noted that other iodothyr-
onines such as 3,5 diiodothyronine (T2) have biological activities,
including interfering with bioenergetic mechanisms (Goglia,
2005). There is a definite need for more studies considering
parameters such as T2 levels or T3 activities at the receptor level
to determine the effects of hot and cold temperament seeds
studied here on thyroid hormones functions.
Urine VMA was decreased and increased in animals that were
fed cucumber seed, which has cold temperament, and fennel seed,
which has hot temperament, respectively. VMA is the primary end
product of catecholamines (norepinephrine and epinephrine)
(Eisenhofer et al., 2004); in fact, fennel and cucumber seed-fed
groups indirectly showed increased and decreased levels of
catecholamines, respectively. A study by Liu et al. (2008) about
Traditional Chinese Medicine showed that herbs with a hot/warm
nature tend to stimulate the release of norepinephrine from rat
pheochromocytoma PC12 cells, while such a stimulatory effect
was not observed in the herbs with a cold/cool nature. In fact,
some herbs with a cold/cool nature significantly suppressed the
release of norepinephrine. Others have also found a thermogenic
effect, warming action and enhancement of energy metabolism
produced by various spices (hot temperament herbs in ITM) in
accordance with increased catecholamines levels in different
models that they studied (Watanabe et al., 1987; Kawada et al.,
1988; Yoshioka et al., 1995; Oi et al., 1999). It can be inferred that
the hot temperament of fennel and the cold temperament of
cucumber may likely be responsible, at least in part for the
increased and decreased levels, respectively of catecholamine
activity.
Similarities between our findings and a study by Shahabi et al.
(2008), such as high SNS activity produced by hot temperament
seeds (fennel) and found in hot temperament persons, low SNS
activity produced by cold temperament seeds (cucumber) and
found in cold temperament persons, and high corticosteroid
activity produced by cold temperament seeds (watermelon and
pumpkin) and found in cold temperament persons, indicate that
different homeostatic parameters in association with coldness or
warmness of the temperament of the body can be affected by cold
or hot temperament medicines, respectively. In other words, cold
temperament medicines are able to intensify the coldness of the
body and hot temperament medicines can act in the opposite
manner. These findings are in accordance with ITM principles and
its treatment procedures: treating hot with cold, and treating cold
with hot.
5. Conclusion
The parameters studied in this investigation were chosen
because, as mentioned in introduction, SNS, glucocorticoids and
thyroid hormones are critical in the body's thermogenesis and
energetic metabolism. Alterations induced by hot and cold tem-
perament seeds in measured hormonal and neuromediator levels,
such as increased levels of T3 or VMA by hot temperament seeds
and decreased levels of VMA and increased levels of corticosterone
by cold temperament seeds, indicate that the hot and cold
temperament characteristics of the studied seeds may most likely
be related to their intervention in the body's energy metabolism,
in the form that hot temperament seeds may increase it and cold
temperament ones may decrease it. Further studies are needed to
investigate other possible mechanisms of the hot and cold tem-
peraments of herbs.
Acknowledgments
This work was supported by a grant (No. 113) from the School
of Traditional Medicine, Shahid Beheshti University of Medical
Sciences, Tehran, Iran and contains some parts of the PhD thesis
(No. 118) of Shirin Parvinroo in traditional pharmacy, School of
Traditional Medicine, Shahid Beheshti University of Medical
Sciences, Tehran, Iran. The authors would like to thank Dr. Mehdi
Hedayati, PhD, for technical support.
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