You are on page 1of 10

Orient Pharm Exp Med (2016) 16:185–194 Online ISSN 2211-1069

DOI 10.1007/s13596-016-0235-9 Print ISSN 1598-2386

RESEARCH ARTICLE

Stress resistance promoting potentials of turmeric


oil and curcuminoids in mice
Suruchi Verma 1 & Deepak Mundkinajeddu 2 & Amit Agarwal 2 &
Shyam Sunder Chatterjee 3 & Vikas Kumar 1

Received: 14 December 2015 / Accepted: 1 July 2016 / Published online: 1 August 2016
# Institute of Korean Medicine, Kyung Hee University and Springer Science+Business Media Dordrecht 2016

Abstract Curcuma longa rhizomes (turmeric) are used as daily doses. Such effects of TO in the test was also observed
tonic in traditionally known Indian systems of medicine. after its higher tested daily doses only. Occasional foot shock
Aim of this study was to compare stress response suppressing stress triggered body weight losses and elevated basal
efficacies of a Curcuma longa extract (CLE) enriched in cur- core temperatures were also dose dependently antago-
cuminoids with those of curcumin and turmeric oil (TO). nized by CLE and TO. Unlike for curcumin or CLE no
Effects of daily oral treatments with curcumin (5 mg/kg/day) effects of TO in tail suspension and pentobarbital sleep
or CLE (5, 20, and 80 mg/kg/day) or TO (1, 3, 10, 30 and test were observed after its lower tested 11 daily doses.
100 mg/kg/day) to male mice on their body weight and core These observations reveal that volatile bioactive constitu-
temperature and in stress induced hyperthermia, tail suspen- ents of turmeric other than curcuminoids also possess
sion, and pentobarbital sleep tests were quantified. Although stress resistance promoting properties and suggest that
their single doses had no significant effects in foot shock stress such efficacy of turmeric powder do not depend on their
induced hyperthermia test, curcumin like and dose dependant curcumin or curcuminoids contents only. Mouse bioassay
suppressing effects of CLE were observed after its repeated procedure used in this study is well suited for pharmaco-
logical standardization of turmeric extracts and also for
Retired Head of Pharmacology Research Laboratories, Dr. Willmar
identifying their bioactive constituents.
Schwabe GmbH & Co. KG, Karlsruhe, Shyam Sunder Chatterjee,
Germany. Keywords Curcuma longa . Turmeric oil . Curcuminoids .
Foot-shock stress . Hyperthermia . Depression
* Vikas Kumar
vikas.phe@iitbhu.ac.in
Suruchi Verma Introduction
suruchi.verma.rs.phe13@iitbhu.ac.in
Deepak Mundkinajeddu Curcuma longa is a plant of the Zingiberaceae family (genus
deepak@naturalremedy.com curcuma) widely cultivated and diversely processed in India,
Amit Agarwal China and many other countries for obtaining its roots and
amit@naturalremedy.com diverse types of products derived from them for culinary as
Shyam Sunder Chatterjee
well as medicinal purposes (Li et al. 2011). Aromatic yellow
shyam.chatterjee@web.de colored roots of the plant, commonly known as turmeric, are
often used in Ayurvedic and other traditionally known sys-
1
Department of Pharmaceutics, Neuropharmacology Research tems of medicine as a tonic or as an adjuvant for prevention
Laboratory, Indian Institute of Technology (Banaras Hindu and cure of chronic inflammatory disorders. The structurally
University), Varanasi, Uttar Pradesh 221 005, India analogous yellow colored diarylheptanoids isolated from tur-
2
Research and Development Center, Natural Remedies Private meric, often collectively referred to as turmeric curcuminoids,
Limited, Bengaluru, Karnataka 560 100, India and are some of the quantitatively major bioactive constituents
3
Stettiner Straße 1, D-76138, Karlsruhe, Germany of the roots. Most currently commercialized turmeric
186 S. Verma et al.

preparations are now often analytically standardized to con- Materials and methods
tain 2–8 % curcuminoids (Aggarwal et al. 2007a, b;
Srivastava et al. 2010). However turmeric oils devoid of cur- Animals
cuminoids and enriched in sesquiterpinoids and other volatiles
are also often used for culinary as well for diverse medicinal Swiss albino male mice (20 ± 5 g) were obtained from the
purposes (Apisariyakul et al. 1995; Aratanechemuge et al. Central Animal House of the Institute of Medical
2002; Ferreira et al. 1992; Jayaprakasha et al. 2002; Negi Sciences, Banaras Hindu University, Varanasi, India
et al. 1999; Roth et al. 1998). A more recent computer assisted (Registration Number: 542/AB/CPCSEA). Prior approval
study has identified several such volatile molecules as some of from the Central Animal Ethical Committee of the
the major non-toxigenic bioactive constituents of turmeric University (CAECU) was taken for this study protocol
(Balaji and Chempakam 2010). (Dean/2014/CAEC/602, dated 30–05-2014). The animals
Information now available on medicinal phytochemistry were housed in groups of six in polypropylene cages at an
and phytopharmaclogy of turmeric and several other edible ambient temperature of 25 ± 1 °C and 45–55 % relative
adaptogenic herbs (Kumar et al. 2015) strongly suggest humidity, with a 12:12 h light/dark cycle. They were al-
that several of them can contribute to the psychological ways provided with commercial food pellets and water ad
well being of consumers and could as well be involved in libitum, and were acclimatized for at least 1 week before
their physical and mental health benefits (Murphy et al. using them for the experiments. Behavioural experiments
2014; Rooney et al. 2013). It is now well recognized also were conducted between 09.00 and 14.00 h, and
that additive or synergistic interactions between diverse BPrinciples of laboratory animal care^ (NIH publication
combinations of phytochemicals are involved in health number 85–23, revised in 1985) guidelines were always
benefits of vegetarian diets and herbal remedies (Liu followed.
2004), and that regular consumption of appropriate combi-
nations of some such edible phytochemicals with every
day meals could as well be used for prevention and cure Plant extract and analytical characterization
of mental health problems (Parletta et al. 2013). Therefore
efforts are now being made in several laboratories, includ- Purified curcumin and the Curcuma longa extract (CLE) high-
ing ours, to identify and pharmacologically standardize a ly enriched in turmeric curcuminoids (95.49 % w/w) used in
bioassay procedure that could be used for identifying edi- this study were generously supplied by R&D Center of
ble phytochemicals and their combinations potentially use- Natural Remedies Pvt. Ltd., Bengaluru, India. Pure curcumin
ful for prevention of such problems accompanying almost was isolated from the extract by using column chromatogra-
all so called lifestyle diseases. During such efforts it has phy. For such purposes, temperature of the column (Kromasil
consistently been observed that efficacies of numerous C18) oven was maintained on 27 ± 1 °C with flow rate 1.5 ml/
phytochemicals and their combinations in animal behav- min. 0.140 g of anhydrous potassium dihydrogen orthophos-
ioural models depend not only on their daily oral doses phate (KH2PO4) in 900 ml HPLC grade water with 0.5 ml of
but also on the number of days of treatments (Kumar and orthophosphoric acid in 1000 ml water was taken as mobile
Chatterjee 2014). More recent observations made in the phase. Curcuminoids contents of CLE were quantified by
realm of our psychopharmacological studies based on ho- using method USP 37-NF32 for the presence of total curcu-
listic Ayurvedic therapeutic principles (Chatterjee and minoids and the same method was used for assessing the pu-
Kumar 2012) have revealed that such are also the cases rity of the curcumin sample used (Fig. 1a and b). Analytical
for curcumin and other turmeric curcuminoids and strongly purity of the curcumin sample was 95.4 %, and the contents of
suggest that their primary sites of actions involved in their the three turmeric curcuminoids quantified in CLE were
stress response modulating activities reside inside the gas- curcumin (77.94 % w/w), demethoxycurcumin (15.03 % w/
trointestinal tract (Verma et al. 2014; Verma et al. 2015). w) and bisdemethoxycurcumin (2.52 % w/w). The turmeric
Results of two further experiments conducted to experi- oil (TO) sample used in this study was purchased from
mentally verify the possibility whether turmeric oil devoid Soulflower handmade factory, Mumbai, India. Three ma-
of curcumin and other turmeric curcuminoids also posses jor constituents of TO quantified by Gas Chromatography
stress response suppressing activities or not, and to reconfirm (Fig. 1c) were Turmeron-I (8.22 % w/w), ar-Turmeron
our earlier observations made with pure curcumin and turmer- ( 30 . 8 3 % w / w ) Tu r m e r o n- I I ( 5 . 0 3% w / w ) . C M C
ic curcuminoids has been described and discussed in this com- (Carboxymethyl cellulose; Central Drug House, Delhi,
munication. Implication of the reported observations for India), pentobarbital (Loba Chemie Pvt. Ltd., Mumbai,
obtaining pharmacologically better standardizes Curcuma India) and all other chemical and reagents used in this
longa extracts according to Ayurvedic therapeutic principles study were of highest analytical quality commercially
are also pointed out. available in India.
Potential of curcuminoids & turmeric oil for anti-stress activity 187

Fig. 1 HPLC chromatogram of


(a) pure curcumin (b)
curcuminoids (CLE) and (c) GC
chromatogram of turmeric oil

Animal grouping and drug treatments was compared with those of 5, or 20 or 80 mg/kg/day oral
doses of CLE, and in the second one efficacy of CLE (5 mg/
Two sets of experiments using randomly selected groups of kg/day; p.o.) was compared with those of graded oral doses (1,
six male mice each were conducted using the experimental 3, 10, 30 and 100 mg/kg/day) of TO.
procedure graphically summarized in Fig. 2. In each set of All test and reference agents were suspended in 0.3 %
experiment, the effect of different daily oral doses of a given CMC and orally administered for 11 consecutive days. The
test agent was compared to those observed after daily such vehicle treated control groups were similarly treated with
treatment with the vehicle or reference agent used. In one of CMC only. Orally administered volume of suspensions was
the experiments effects of 5 mg/kg/day oral dose curcumin always 10 ml/kg. Choice of dose of curcumin and CLE in the
188 S. Verma et al.

Fig. 2 Graphical representation


of experimental protocol used

first experiment was based on data available from our previ- posture. After initial vigorous movements, the mouse assumed
ous pilot studies (Verma et al. 2014; Verma et al. 2015). Since an immobile posture and the period of immobility during a
as yet no reports on pharmacologically interesting dose ranges 5 min observation period was noted (Thakur et al. 2015). Mice
of turmeric oils or of their bioactive constituents are available, were considered immobile when they hang passively and
the dose ranges of TO used in the second experiment were completely motionless. Before oral administrations of test
arbitrarily chosen. agents, weights of animals and their rectal temperatures were
recorded.
Stress induced hyperthermia test

On days 1, 5, 7 and 10 of the experiments and after Pentobarbital-induced sleep test


60 min of days oral treatments and basal rectal tempera-
ture recordings, an individual mouse from each group This test was conducted on 12th day of experiments when
was placed in a black box (24 × 29 × 40 cm) with a no oral treatment was given. On this day, the rectal tem-
grid floor for 1 min. Electric foot shock through the grid peratures and body weights of animals were recorded im-
floor (2 mA, 50 Hz of 2 ms duration) was delivered for mediately before pentobarbital challenges. Pentobarbital
stress induction. After 10 s of their stay in the box, five (40 mg/kg, i.p.) was administered to all animals of all
consecutive foot shocks of 2 mA at 10 s intervals were groups and onset of sleep (loss of righting reflex), and
given through the grid floor. Immediately thereafter the duration of sleep was recorded by a observer unaware of
animal were placed back in its home cages, and stress the treatments (Ojima et al. 1995).
induced change in its rectal temperature was assessed
after it had stayed in its home cage 10 min (Zethof
et al. 1994). All rectal temperatures were recorded by a Statistical analysis
calibrated rectal probe and electronic thermometer. The
difference in the rectal temperature recorded before and Mean ± standard error of mean (SEM) was calculated for
10 min after application of foot-shocks was considered to the observed values in each experimental group.
be the foot-shock stress induced transient hyperthermic Statistical analysis was performed by one way analysis
response of the animal. of variance (ANOVA) followed by Student-Newman-
Keuls multiple comparison test, two way ANOVA follow-
Tail suspension test ed by Bonferroni post hoc test. GraphPad Prism-5
(GraphPad Software Inc., La Jolla, California, USA) was
On the 11th experimental day and after 60 min of test com- used for statistical analysis. Origin-Pro 8 (OriginLab
pound administrations, the total duration of immobility in- Corporation, Massachusetts, USA) software was used for
duced by tail suspension was measured. For the test, individ- graphs representation. p-value less than 0.05 was consid-
ual mouse were hung on its tail on a wire in an upside down ered as statistically significant.
Potential of curcuminoids & turmeric oil for anti-stress activity 189

Results significantly different than, those of the mean values of the


corresponding vehicle treated control groups on that day.
Body weights Similarly, the differences between the mean vales of the con-
trol groups on the 1st observational day in the two experi-
Mean body weights of the control and different doses of test ments (36.20 ± 0.04 °C and 36.90 ± 0.09 °C) were also sta-
agents treated groups are summarized in the Fig. 3a and b. tistically not significantly different from each other. Since all
Mean body weights of the control animals recorded on the these values were within the physiological ranges of our
first observational day of a given experiment was not always mouse colony, and within the experimental errors of the meth-
significantly different from those of the group recorded on od used (using rectal probe) they seem to be independent of
subsequent observational. However, these mean values of the treatments received.
control groups in the experiments decreased consistently dur- However, recorded mean basal core temperatures of the
ing the 12 observational days. Results summarized in Fig. 3a vehicle treated control groups increased slightly and gradually
revealed that all tested oral dose of CLE (5, 20 and 80 mg/kg) during the course of the experiments and remained somewhat
ultimately afforded almost complete protection against such elevated on the 10th, 11th, and 12th days of the experiments.
body weight losses on the 12th observational day, and recon- Such daily handling and occasional foot shock stress triggered
firm that such is also the case for 5 mg/kg daily oral doses of elevation of basal core temperatures were not observed in the
purified curcumin. Statistically significant effects of 5 mg/kg/ purified curcumin or any of the CLE treated groups and these
day CLE were observed only after its 7 or more daily oral values of all these groups on the last three observational days
doses, whereas such efficacy of the same daily dose of puri- were statistically significantly lower than those of the vehicle
fied curcumin was observed already on the 5th treatment day. tread control groups. Although on the last three observational
Analogous to the observed effects 5 mg/kg daily CLE treat- days these mean values of the 3 mg/kg or higher daily oral TO
ments, dose dependant protective effects TO against stress treated groups were numerically lower than those of the cor-
triggered bodyweight losses were observed only after its 7 responding control group (Fig. 4b) no statistically significant
or more daily oral doses higher than 10 mg/kg (Fig. 3b). effect of the oils was observed during the course of the
However, changes in mean bodyweights of 5 mg/kg/day experiment.
CLE or of purified curcumin treated groups observed on the
12th days of the experiments were quite analogous to that of
the 100 mg/kg/day TO treated group. Stress induced hyperthermia

These results are summarized in Fig. 5a and b. After their


Basal core temperatures single oral doses no significant effects of any of the test agents
on foot shock stress triggered transient hyperthermic response
Mean basal rectal temperatures of different groups recorded were observed. This response of the vehicle treated control
during the course of the experiments are summarised in the groups increased somewhat on the 5th, 7th and 10th observa-
Fig. 4a and b. These mean values of the 5 mg/kg curcumin or tional days whereas those of purified curcumin or CLE treated
some of the TO treated groups on the 1st observational day groups continued decrease on those days. On all these three
were numerically somewhat higher than, but not statistically days the observed effects of 5 mg/kg daily oral doses of

Fig. 3 Effect of stress on body weight of male mice treated with (a) curcuminoids (CLE) and (b) Turmeric oil (TO). Values are mean ± SEM, n = 6.*
denotes statistically significant difference (Two way ANOVA followed by Bonferroni post hoc test) relative to control group (* = p < 0.05)
190 S. Verma et al.

Fig. 4 Effect of intermittent foot shocks on basal rectal temperature of difference (Two way ANOVA followed by Bonferroni post hoc test)
mice treated with (a) curcuminoids (CLE) and (b) Turmeric oil (TO). relative to control group (* = p < 0.05)
Values are mean ± SEM, n = 6. * denotes statistically significant

purified curcumin were always higher than those observed Pentobarbital-induced sleep test
with the 5 mg/kg daily CLE treated group, whereas those of
the 20 or 80 mg/kg/day CLE treated ones were similar to those Results summarized in Fig. 7 reveal that 24 h after 11 daily 20
of the 5 mg/kg/day purified curcumin treated ones (Fig. 5a). or 80 mg/kg oral doses of CLE significantly potentiated pen-
CLE like statistically significant effect of TO was observed tobarbital induced sedation and hypnosis. However, no such
after its 10 daily 100 mg/kg doses only (Fig. 5b). effects of 5 m/kg daily oral dose of CLE or of purified
curcumin were observed in this test. No statistically signifi-
cant effects of any of the TO doses were observed in this test
Tail suspension test (results not shown).

Results summarized in Fig. 6a reveal that quantitatively the


observed efficacies of eleven 5 mg/kg daily oral doses of Discussion
purified curcumin and CLE in this test for antidepressants
are almost equal, and that the effects of CLE in this test in- Reported observations reconfirm that 5 mg/kg daily oral doses
creases further with its increasing daily doses. Statistically of curcumin, or of turmeric curcuminoids in general, are high
significant and CLE like effects of TO in this test was ob- enough for protecting mice against chronic and unpredictable
served after its highest daily dose (100 mg/kg) tested. foot shock stress triggered alternations in body weight and

Fig. 5 Effect of foot-shock stress triggered transient hyperthermia in difference (Two way ANOVA followed by Bonferroni post hoc test)
mice treated with (a) curcuminoids (CLE) and (b) Turmeric oil (TO). relative to control group (* = p < 0.05)
Values are mean ± SEM, n = 6. * denotes statistically significant
Potential of curcuminoids & turmeric oil for anti-stress activity 191

Fig. 6 Effect of 11 daily oral


doses on immobility period of
mice treated with (a)
curcuminoids (CLE) and (b)
Turmeric oil (TO). Values are
mean ± SEM, n = 6. * denotes
statistically significant difference
(ANOVA) relative to control
group (* = p < 0.05)

thermoregulatory processes, and reveal that phytochemicals bioactivity profiles of turmeric curcuminoids and some known
present in turmeric oils devoid of curcuminoids also possess constituents of turmeric oil has also been observed in other
analogous protective effects. However, although CLE like laboratories (Sandur et al. 2007) it is apparent that the ob-
dose dependant protective effects of TO against stress trig- served differences between stress resistance increasing activ-
gered body weight losses were observed after its 3 mg/kg ity profiles TO and CLE is due to the presence of structurally
and higher daily oral doses, its efficacy to afford protection and functionally diverse bioactive constituents in them.
against stress triggered elevations in basal core temperature, or It was interesting to note though, that protective effects of
foot shock stress triggered transient hyperthermic responses 5 mg/kg daily oral doses of purified curcumin (devoid of de-
were observed only after its 30 mg/kg and higher daily doses. methoxy curcumin and bis-desmethoxy curcumin, but con-
Moreover, unlike curcuminoids, even 100 mg/kg daily TO taining some other minor impurities) against stress triggered
doses had no effects in the pentobarbital-induced sleep test body weight losses were observed after its 6 or more daily
and in the tail suspension test significant effects of the oil were doses, whereas that of the same dose of CLE was already
observed only after this highest tested daily dose. Therefore it apparent after its 4 daily doses. Analogous difference between
seems reasonable to assume that the biological processes and the effects of CLE and purified curcumin were also observed
mechanisms involved in observed stress response suppressing in foot shock stress induced hyperthermia test, and mean
activity profile of turmeric oils devoid of curcuminoids is not values of basal rectal temperature of the CLE or the vehicle
identical to those of turmeric curcuminoids and that effective- treated groups on the first treatment day were always lower
ness of turmeric curcuminoids as potential antidepressants are (but not statistically significantly different) than the purified
much higher than that of turmeric oils. TO was devoid of curcumin treated one. Although the observed effects of 5 mg/
curcuminoids, and was enriched in volatile secondary metab- kg daily dose of purified curcumin and CLE in tail suspension
olite of the plant like turmerone, α-turmerone, curlone, and test were quantitatively similar, such were not the observa-
diverse other volatile ones. CLE on the other hand was highly tions made in the pentobarbital-induced sleep test (Fig. 7).
enriched (95.4 % w/w) in structurally analogous These observed differences could as well be due to pharma-
diarylheptanoids commonly referred to as curcuminoids cological interactions between curcumin and other turmeric
(curcumin, demethoxycurcumin, and bisdemethoxycurcumin) constituents present in the samples tested. Hereupon, differ-
and devoid of turmeric volatiles. Since differences between ences in oral bio-availability or bio-accessibility or metabolic
profiles of structurally diverse curcuminoids as well differ-
ences in their bioactivity profiles (Ahmed and Gilani 2014)
could play important roles.
In any case, it remains certain that apart from curcumin and
other curcuminoids, Curcuma longa roots also possess other
stress response suppressing constituents, and that traditionally
known medicinal uses of diverse types of turmeric prepara-
tions must not necessarily be due to their curcumin or curcu-
minoids contents only. Our observations strongly suggest also
that regular intake of even fairly low daily oral doses of even
crude turmeric preparations can afford protection against
chronic mild stress triggered alterations in physiological pro-
Fig. 7 Effect of 11 daily oral doses on onset and duration of sleep in mice
treated with curcuminoids (CLE). Values are mean ± SEM, n = 6. *
cesses and mechanisms regulating body weight and tempera-
denotes statistically significant difference (ANOVA) relative to control ture. Body weights of elderly and multi-morbid patients are
group (* = p < 0.05) often lower than those of average healthy persons in a given
192 S. Verma et al.

society, whereas those of persons at higher risk to diverse 2011; Kassi et al. 2011) including those of the caregivers of
chronic life threatening diseases like diabetes, metabolic dis- patients suffering from or at risk to Alzheimer’s disease and
orders, and cancer are often higher than average or mean of the cancer (González et al. 1999; Kim and Given 2008).
general population. Although our current knowledge on the Demographic and epidemiological studies have often pointed
role of thermoregulatory processes in such diseases and ill- out that turmeric could be a food ingredient involved in pre-
nesses still remain uncertain, it has since long been well rec- ventive effects on of meals against diverse such medical con-
ognized that core temperature measurements is a feasible and ditions (Aggarwal et al. 2007a, b; Azmi et al. 2015; Fazel et al.
reliable means for assessing physical fitness (Moran and 2015) and it has recently been estimated that turmeric curcu-
Mendel 2002; Ring 1998; Romanovsky 2007). minoids consumed with curry products is less than 0.5 mg/
Earlier observations in our laboratories have revealed that person/day and that their contents vary considerably in differ-
curcuminoids or turmeric oil like low dose stress response ent such currently consumed products (Kim et al. 2015a,
modulating affects of several other phytochemicals ubiqui- 2015b). However, the questions whether other bioactive food
tously present in numerous edible or medicinal plants (Khan phytochemicals consumed with curry meals also contribute to
et al. 2015; Langstieh et al. 2014; Shivavedi et al. 2014a; the health benefits of turmeric curcuminoids, or whether cur-
Shivavedi et al. 2014b; Shrivastava et al. 2014). Salicylic cuminoids potentiates the effects of stress resistance promot-
and 4-hydroxybenzoic acids are just two examples of such ing and other effects of edible phytochemicals still remain
phytochemicals also encountered in turmeric, and it has re- open. Answering such questions is not only essential for
cently been suggested also that salicylic acid could as well obtaining optimal medicinal benefits from turmeric, but
be another health promoting bioactive constituent of turmeric also for designing more rational dietary therapies urgently
containing food ingredients like curry powder etc. (Duthie and needed for prevention of diabesity and other lifestyle as-
Wood 2011; Paterson et al. 2006; Wood et al. 2011). sociated medical conditions spreading like epidemics in
Therefore, it is apparent that traditionally known medicinal the twenty-first century.
uses of turmeric preparations, or for that matter of any herbal It is now well recognized that like numerous other food
preparation, do not solely depend on one or a few of their phytochemicals, curcuminoids are also extensively metabo-
bioactive constituents only and that proper understanding of lized inside the gastrointestinal tract, and that their broad spec-
biological interactions between them is essential for more ra- trums of bioactivity profiles is mainly due to their high chem-
tional understanding of their medicinal values or for obtaining ical reactivity to diverse biological targets (Heger et al. 2014).
novel therapeutic leads urgently needed for prevention and Observed low dose effects of turmeric derive product in this
cure of environmental or metabolic stress triggered patholo- and in our earlier study (Verma et al. 2015) strongly suggest
gies. Since bioactivity profiles of structurally diverse curcu- that alteration in gut microbial ecology and functions are in-
minoids are also not identical (Ahmed and Gilani 2014), it is volved in their stress resistance promoting effects in mice and
apparent that proper understanding of biological interactions that hereupon their microbicidal activities could also play a
between diverse bioactive constituents are necessary for better crucial roles. That such is indeed the case is further supported
understanding of the biological processes and mechanisms by a recent report demonstrating modulatory role of turmeric
involved in traditionally known medicinal uses of turmeric. meals on gut microbiota and gut motility (Dey et al. 2015).
For such purposes appropriate dose response and other studies Since disturbances in the physiological functions of gut mi-
using different types of analytically well characterizes turmer- crobiota affects visceral pain, i.e. a hall mark of functional
ic derived products, and the mouse bioassay procedure used in gastrointestinal disorders (O’Mahony et al. 2014) efforts will
this and in our earlier studies could be a feasible and more now be made in our laboratories to experimentally verify the
convenient starting point. Since numerous bioactive constitu- possibility whether low dose curcuminoids or turmeric oils or
ents of turmeric are structurally and functionally analogous to their combinations could also be used for prevention and cure
those encountered in diverse other traditionally known medic- of such disorders or for avoiding side effects of anti-
inal plants (Sun et al. 2016; Amalraj et al. 2016), observations inflammatory drugs and other currently available analgesics
made during such efforts could also be helpful for better un- or pain killers. Ultimate goal of these efforts is to obtain an
derstanding of therapeutic potentials other plants containing analytically as well as pharmacologically well standard-
such phytochemicals. ized turmeric extract that could be further developed as a
It is now well recognized that altered homeostasis in stress herbal therapeutic option for prevention and cure of cen-
response regulating systems leads to diabesity and other met- tral sensitivity syndromes accompanying almost all chron-
abolic disorders associated with mental health problems and ic inflammatory disorders.
that modulators of psychological and physiological stress re-
sponses could be useful for prevention and cure of such and
Acknowledgments Suruchi Verma thankfully acknowledges the
numerous other environmental stress related medical condi- Department of Science and Technology, Government of India, New
tions (Bystritsky et al. 2014; Chrousos 2009; Guarner et al. Delhi, for awarding INSPIRE Fellowship (IF131112).
Potential of curcuminoids & turmeric oil for anti-stress activity 193

Compliance with ethical standards Guarner LV, Rubio RME, Perez TI, Banos MCG (2011) Relation of aging
and sex hormones to metabolic syndrome and cardiovascular dis-
Ethical Statement The research was carried out according to the rules ease. Exp Gerontol 46:517–523
governing the use of laboratory animals as acceptable internationally and Heger M, Van Golen RF, Broekgaarden M, Michel MC (2014) The mo-
the experimental protocol was approved by the Animal Ethics lecular basis for the pharmacokinetics and pharmacodynamics of
Committee, Banaras Hindu University(Registration Number: 542/AB/ curcumin and its metabolites in relation to cancer. Pharmaco rev
CPCSEA) 66(1):222–307
Jayaprakasha GK, Jena BS, Negi PS, Sakariah KK (2002) Evaluation of
Conflict of Interest The authors declare that they have no conflicts of antioxidant activities and antimutagenicity of turmeric oil: A
interest. byproduct from curcumin production. Z Naturforsch C 57:828–835
Kassi E, Pervanidou P, Kaltsas G, Chrousos G (2011) Metabolic syn-
drome: definitions and controversies. BMC Med 9:48. doi:10.1186
/1741-7015-9-48.
Khan SA, Chatterjee SS, Kumar V (2015) Potential anti-stress, anxiolytic
and antidepressant like activities of mono-hydroxybenzoic acids and
References aspirin inrodents: A comparative study. Austin J Pharmacol Ther
3(3):1073–1082
Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007a) Curcumin: Kim Y, Given BA (2008) Quality of life of family caregivers of cancer
the Indian solid gold. In Adv Exp Med Biol 595:1–75 survivors. Cancer 112(11):2556–2568
Aggarwal BB, Surh YJ, Shishodia S (2007b) The molecular targets and Kim YJ, Lee HJ, Shin Y (2015a) Estimation of daily curcuminoid intake
therapeutic uses of curcumin in health and disease. Springer Science from commercial curry products. J Korean Soc Appl Biol Chem
& Business Media, New York 58(5):677–684
Ahmed T, Gilani AH (2014) Therapeutic potential of turmeric in Kim YJ, Lee HJ, Shin Y, Fazel NS, Thiagarajan R, Rastrelli L, Daglia M,
Alzheimer's disease: curcumin or curcuminoids? Phytother Res Sobarzo SE, Alinezhad H, Mohammad NS (2015b) Curcumin: a
28(4):517–525 natural product for diabetes and its complications. Curr Top Med
Amalraj A, Pius A, Gopi S, Gopi S (2016) Biological activities of curcu- Chem 15(23):2445–2455
minoids, other biomolecules from turmeric and their derivatives -A Kumar V, Chatterjee SS (2014) Single and repeated dose effects of phy-
r e v i e w. J Tr a d i t C o m p l e m e n t M e d . d o i : 1 0 . 1 0 1 6 / j . tochemicals in rodent behavioural models. Eur J Pharm Sci 1:16–18
jtcme.2016.05.005. Kumar V, Thakur AK, Verma S, Yadav V, Chatterjee SS (2015) Potential
Apisariyakul A, Vanittanakom N, Buddhasukh D (1995) Antifungal ac- of some traditionally used edible plants for prevention and cure of
tivity of turmeric oil extracted from Curcuma longa diabesity associated comorbidities. TANG (Humanitas Medicine) 5:
(Zingiberaceae). J Ethnopharmacol 49:163–169 1–22
Aratanechemuge Y, Komiya T, Moteki H, Katsuzaki H, Imai K, Hibasami Langstieh AJ, Verma P, Thakur AK, Chatterjee SS, Kumar V (2014)
H (2002) Selective induction of apoptosis by Ar-turmerone isolated Desensitization of mild stress triggered responses in mice by a
from turmeric (Curcuma longa ) in two human leukemia cell lines, Brassica juncea leaf extract and some ubiquitous secondary plant
but not in human stomach cancer cell line. Int J Mol Med 9:481–484 metabolites. Pharmacologia 5:326–338
Azmi L, Ojha SK, Rao CV (2015) Curcumin: boon for human being.
Li S, Yuan W, Deng G, Wang P, Yang P, Aggarwal B (2011) Chemical
World J Pharm Pharm Sci 4(6):239–249
composition and product quality control of turmeric (Curcuma
Balaji S, Chempakam B (2010) Toxicity prediction of compounds from longa L.). Phytochemistry 2:28–54
turmeric (Curcuma longa L). Food Chem Toxicol 48(10):2951–
Liu RH (2004) Potential synergy of phytochemicals in cancer prevention:
2959
mechanism of action. J Nutr 134(12):3479–3485
Bystritsky A, Danial J, Kronemyer D (2014) Interactions between diabe-
Moran DS, Mendel L (2002) Core temperature measurement: methods
tes and anxiety and depression: implications for treatment.
and current insights. Sports Med 32:879–885
Endocrinol Metab Clin N Am 43:269–283
Chatterjee SS, Kumar V (2012) Holistic psychopharmacology and pro- Murphy T, Dias GP, Thuret S (2014) Effects of diet on brain plasticity in
miscuous plants and principles of Ayurveda. Am J Plant Sci 3(7): animal and human studies: Mind the Gap. Neural Plast Article ID
1015–1021 563160, doi:10.1155/2014/563160.
Chrousos GP (2009) Stress and disorders of the stress system. Nat Rev Negi PS, Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK (1999)
Endocrinol 5:374–381 Antibacterial activity of turmeric oil: a byproduct from curcumin
Dey N, Wagner VE, Blanton LV, Cheng J, Fontana L, Haque R, manufacture. J Agric Food Chem 47: 4297–4300.
Gordon JI (2015) Regulators of gut motility revealed by a O’Mahony SM, Felice D, Nally K, Savignac HM, Claesson MJ, Scully P,
genotobiotic model of diet-microbiome interactions related to Cryan JF (2014) Disturbance of the gut microbiota in early-life
travel. Cell 163(1): 95–107. selectively affects visceral pain in adulthood without impacting cog-
Duthie GG, Wood AD (2011) Natural salicylates: foods, functions and nitive or anxiety-related behaviors in male rats. Neuroscience 277:
disease prevention. Food & funct 2(9):515–520 885–890
Fazel NS, Thiagarajan R, Rastrelli L, Daglia M, Sobarzo SE, Alinezhad H, Ojima K, Matsumoto K, Tohga M, Watanabe H (1995) Hyperactivity of
Mohammad NS (2015) Curcumin: a natural product for diabetes and central noradrenergic and CRF system is involved in social isolation-
its complications. Curr Top Med Chem 15:2445–2455 induced decrease in pentobarbitone sleep. Brain Res 684:87–94
Ferreira LA, Henriques OB, Andreoni AA, Vital GR, Campos MM, Parletta N, Milte CM, Meyer BJ (2013) Nutritional modulation of cogni-
Habermehl GG, deMoraes VL (1992) Antivenom and biological tive function and mental health. J Nutr Biochem 24(5):725–743
effects of ar-turmerone isolated from Curcuma longa Paterson JR, Srivastava R, Baxter GJ, Graham AB, Lawrence JR (2006)
(Zingiberaceae). Toxicon 30:1211–1218 Salicylic acid content of spices and its implications. J Agric Food
González SMT, Arango C, Lyketsos CG, Barba AC (1999) The stress and Chem 54(8):2891–2896
psychological morbidity of the Alzheimer patient caregiver. Int J Ring EFJ (1998) Progress in the measurement of human body tempera-
geriatric psychiatry 14(9):701–710 ture. IEEE Eng Med Biol Mag 17:19–24
194 S. Verma et al.

Romanovsky AA (2007) Thermoregulation: some concepts have Srivastava MR, Singh S, Dubey KS, Misra K, Khar A (2010)
changed. Functional architecture of the thermoregulatory system. Immunomodulatory and therapeutic activity of curcumin. Int
Am J Physiol Regul Integr Comp Physiol 292(1):37–46 Immunopharmacol 11:331–341
Rooney C, McKinley MC, Woodside JV (2013) The potential role of fruit Sun W, Wang S, Zhao W, Wu C, Guo S, Hongwei G (2016) Chemical
and vegetables in aspects of psychological well-being: a review of Constituents and Biological Research on Plants in the Genus
the literature and future directions. Proc Nutr Soc 72:420–432 C u rc u m a . C r i t R e v F o o d S c i N u t r. d o i : 1 0 . 1 0 8 0
Roth GN, Chandra A, Nair MG (1998) Novel bioactivities of Curcuma /10408398.2016.1176554.
longa constituents. J Nat Prod 61:542–545 Thakur AK, Chatterjee SS, Kumar V (2015) Antidepressant like
Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. effects of Brassica juncea L. leaves in diabetic rodents. Ind J
(2007) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, Exp Bio 52:613–622
tetrahydrocurcumin and turmerones differentially regulate Verma S, Chatterjee SS, Kumar V (2014) Comparative adaptogenic ac-
antiinflammatory and anti-proliferative responses through a ROS- tivity of bioavailable extracts of Curcuma longa and pure curcumin
independent mechanism. Carcinogenesis 28(8):1765–1773 in rodents. Indian J Pharmacol 46(1):S93–S94
Shivavedi N. Chatterjee SS, Kumar, V (2014a) Stress response modulat- Verma S, Chatterjee SS, Kumar V (2015) Metformin like stress response
ing effects of lactic acid in mice. Ther Targets Neurological Dis 1: modulating effects of turmeric curcuminoids in mice. SAJ Neurol
418–423. 1(1):102–110
Shivavedi N, Chatterjee SS, Kumar V (2014b) Evaluation of Wood A, Baxter G, Thies F, Kyle J, Duthie G (2011) A systematic review
Pharmacologically interesting dose range of ascorbic acid in mice. of salicylates in foods: estimated daily intake of a scottish popula-
SAJ Neurol 1(1):101–108 tion. Mol Nutr Food Res 55(1):7–14
Shrivastava N, Chatterjee SS, Kumar V (2014) Stress response Zethof TJ, Vander HJA, Tolboom JT, Olivie RB (1994) Stress-induced
desensitizing efficacies of triethylene glycol and quercetin in mice. hyperthermia in mice: a methodological study. Physiol Behav 55:
Indian J Pharmacol 46:91 109–115

You might also like