Volume: 1, No.: 4, Year: 2015
PHYTOCHEMISTRY AND PHARMACOLOGY OF TRIKATU
Vineet Sharma1, Kritika Hem1, Narendra Kumar Singh1, Dev Nath Singh Gautam2
1Ayurvedic Pharmacy Research laboratory, RGSC, BHU, Barkaccha, Mirzapur-231001 and 2Department of Rasa Shastra,
Faculty of Ayurveda, BHU, Varanasi-221 005, Email: firstname.lastname@example.org, Corresponding Author: Dev Nath Singh
Abstract: Trikatu is a very well known ‘Rasayana’ in Ayurveda and widely used as a polyherbal ayurvedic
formulation in India. It consists of three well known plants, viz., Piper longum Linn., Piper nigrum Linn. and
Zingiber officinale Rosc. in equal ratio. It is mentioned in the ancient books of Ayurveda used for the
treatment of fever, asthma, cold and cough, diabetes, nasal diseases, obesity, anorexia, digestive, respiratory
system and normal urinary tract function. Phytochemical investigations indicate that 3 compounds reported
from the polyherbal formulation and also it contains various chemical category viz. alkaloids, phytosterol,
triterpenes, flavonoids and various other phenolic compounds. Pharmacological activities of Trikatu
reported include hepatoprotective, antioxidant, analgesic, anti-anorectic, anti-inflammatory, antimicrobial,
antifungal, anthelminitic, anti-arthritic, adaptogenic, antihyperlipidemic and antitumor activity. In the
present review the literature data on the phytochemical and biological investigations on the Trikatu are
summarized up to March 2015.
Keywords: Trikatu; adaptogenic; antimicrobial; anthelminitic; anti-anorectic.
Introduction: The ancient documented
Ayurvedic Materia Medica which dates back to
6000 years BC mentioned these herbs used in
Trikatu as essential ingredients of numerous
prescriptions and formulations used for a wide
range of disorders . Out of the 370
formulations listed in the Handbook of Domestic
Medicine and Common Ayurvedic Remedies,
210 contain either Trikatu or its individual
components . As per Ayurvedic pharmacology,
‘Trikatu’ means ‘Katu-Tikta rasa’ (bitter-
pungent or acrid taste), ‘Usna’ (hot), ‘Virya’
(potency), ‘Madhura rasa’ (sweet taste) and
‘Vata-kapha Nasaka’ (air and mucus destroyer
under the disease conditions) .The Ayurvedic
system of medicine has described various herbal
formulations in the treatment of diseases, which
play an important role in modern health care and
curing various ailments and diseases. The uses of
herbal medicines are increasing as dietary
supplements to fight or prevent common
diseases. In Ayurvedic Formulary of India it is
used in various diseases like, Arocaka
(Tastelessness), Agnimandya (Digestive
impairment), Amadosa (Products of impaired
digestion and metabolism / consequences of
Ama), Gala Roga (Diseases of throat), Pinasa
(Chronic rhinitis/sinusitis), Kustha (Diseases of
skin), Swasa (Dyspnoea/Asthma), Kasa (Cough),
Tvakroga (Skin disease), Gulma (Abdominal
lump), Meha (Excessive flow of urine), Sthaulya
(Obesity), Slipada (Filariasis) .Trikatu is one of
the Ayurvedic preparations used from the period
between 7th century B.C. and the 6th century
A.D., for the treatment of a variety of ailments. It
is a combination of black pepper (Piper nigrum
Linn.), long pepper (Piper longum Linn.), and
ginger (Zingiber officinale Rosc.). Trikatu was
formulated by taking equal weight ratio of the
three crude drugs for therapeutic purposes.
Trikatu enhances the metabolic process by rapid
absorption of nutrients [5, 6].Which contains an
alkaloid as active component “Piperine”, which
enhances the bioavailability of drugs and
nutrients . These plant materials are also used
worldwide as spices. They are also used as
important ingredients in Ayurvedic, Siddha and
Unani (ASU) drugs and folklore medicine. The
consumption of Trikatu churna exert several
health benefits by the virtue of their innumerable
therapeutic potentials, such as in fever, asthma,
cold and cough , diabetes, nasal diseases,
obesity, anorexia , digestive, elephantiasis,
carminative, skin disorders, abdominal
Indian Journal of Agriculture
and Allied Sciences
A Refereed Research Journal
Received: 15.10.2015, Accepted: 25.11.2015
194 Indian Journal of Agriculture and Allied Sciences
distention, respiratory system diseases ,
dyspepsia and in urinary tract infection. Trikatu
is highly useful for vasodilatation and immune-
potentiating activity .Trikatu and its active
principles like piperine, 6-shogaol and 6-gingerol
showed promising anti-inflammatory effect in
both rheumatoid arthritis and acute gouty
arthritis [10, 11]. Decoction of sesame seeds (tila)
mixed with ghee, jaggery, Bharangi
(Clerodendrum serratum Linn.) root powder and
Trikatu powder is used as the best remedy for
amenorrhea and uterine tumor .It helps in the
improvement of gastric function .
Toxicity Study: Acute and sub-acute toxicity
study of Trikatu was performed in Charles Foster
rats for study of safety profiling .Results showed
that in acute toxicity experiment Trikatu (2000
mg/kg, b.w.) was well tolerated by the animals
under study and no significant changes were
observed in morbidity, mortality, gross
pathology, vital organ weight, gain in weight,
haemotological count and other necessary
parameters. Biochemical parameters such as
serum creatinine, SGPT, SGOT, serum lipid
profile and tissue biochemical parameters such as
reduced glutathione and malonaldehyde content
as oxidative stress markers were found normal
. Acute toxicity studies of Trikatu mega Ext
revealed that LD50 is 300mg/kg body weight in
Pharmacokinetics: Pharmacokinetic profile of
indomethacin along with Trikatu was performed
in rabbits. The results showed that Trikatu
enhanced the absorption of indomethacin which
was supposed due to the increase in
gastrointestinal blood flow as well as an
increased rate of transport across gastrointestinal
mucosa . Concomitant administration of
Trikatu and diclofenac sodium decreased
significantly the bioavailability of diclofenac
sodium .Piper longum (long pepper) increased
the blood levels of vasicine by nearly 233%.
Piperine, the active principle of Piper species,
increased blood levels of sparteine more than
100%. The effect of Trikatu on the
bioavailability and pharmacokinetics of isoniazid
was studied in rabbits. In a crossover study, ten
rabbits were administered either single dose
(orally) of isoniazid (14 mg/kg) alone or in
combination with Trikatu (piperine, 10mg/kg).
The study was carried out by collecting blood
sample at different time interval and assayed for
isoniazid by fluorimetric technique. Results
indicate that Trikatu decreases the bioavailability
of isoniazid . The effect of single and multiple
doses of Trikatu on the bioavailability and
pharmacokinetics of rifampicin were studied in
rabbits. Rabbits were administered a single dose
of rifampicin (24 mg/kg, p.o.) alone or in
combination with a single dose of Trikatu (500
mg/kg, p.o.). In the other experiment, six rabbits
were administered a single dose of rifampicin (24
mg/kg, p.o.) before and after multiple doses of
Trikatu (500 mg/kg, p.o.) for seven consecutive
days. In both studies, blood samples were
collected at 0, 0.5, 1, 1.5, 2, 4, 6, 9 and 12 h after
drug administration and assayed for rifampicin.
In animals groups treated with single dose of
Trikatu there was a significant decrease in the
peak plasma concentration (Cmax) of rifampicin.
Multiple doses of Trikatu also reduced the Cmax
and delayed the Tmax of rifampicin although not
to a statistically significant level. Other
pharmacokinetic parameters of rifampicin were
not significantly altered. Co-administration of
Trikatu does not influence the extent of
bioavailability but reduces the rate of
bioavailability (Cmax) of rifampicin . Several
studies have reported enhancement of blood
levels of drugs like vasicine, sparteine,
phenytoin, propranolol, theophylline,
sulphadiazine and tetracycline when co-
administered with Trikatu or piperine [18,19].
Trikatu has been shown to enhance the
bioavailability of number of drugs by nonspecific
and noncompetitive inhibition of the cytochrome
P450 enzyme system. The enhanced
bioavailability of drugs is a result of a non
specific and noncompetitive inhibition of drug
metabolising enzymes by Trikatu (piperine). It
has been shown to inhibit arylhydrocarbon
and 7-ethoxycoumarin-o-deethylation and 3-
hydroxybenzopyrene glucuronidation in a
nonspecific and noncompetitive manner in vitro.
It appears that the Trikatu group of drugs
increases bioavailability either by promoting
rapid absorption from the gastrointestinal tract,
or by protecting the drug from being metabolized
/oxidized in its first passage through the liver
after being absorbed, or by a combination of
these two mechanisms [20, 21, 8].
Antioxidant Activity: In vitro antioxidant
activity of petroleum ether, benzene, chloroform,
ethyl acetate, 70% ethanol and aqueous extract of
Trikatu was performed. Trikatu mega Ext
exhibited significant scavenging effects on 2, 2-
diphenyl-2-picryl hydroxyl (DPPH) free radicals,
super oxide anion. The scavenging effect of
Phytochemistry and Pharmacology of Trikatu 195
sample was found lower than that of ascorbic
acid. The sample possess statistically
significance DPPH free radical scavenging
activity at a concentration of 100 µg /ml,
inhibited the production of superoxide anion
radical by 89.74% showing strong superoxide
radical scavenging activity .
Antihyperlipidemic Activity: The effect of
Trikatu on lipid profile of Rattus norvegicus fed
with atherogenic diet and standard diet was
performed. Towards this goal an indigenous
preparation of Trikatu was fed to normal and
cholesterol fed male Rattus norvegicus to
ascertain its efficacy as a hypolipidaemic agent.
Its effects on body weight and lipid profiles were
measured. It was found that ‘Trikatu’ by virtue of
its ability to reduce triglycerides and LDL
cholesterol and to increase HDL cholesterol can
reduce the risk of hyperlipidaemia and
artherosclerosis. Hence ‘Trikatu’ can be used as
a potent hypolipidaemic agent and it can reduce
the atherosclerosis associated with a high fat diet
Antianorectic Activity: The anti-anorectic
activity of the hydro-alcoholic extracts of the
Trikatu was evaluated to determine its effects in
anorexia induced rats. Anorexia was induced in
rats by physical stress arising by immobilization
of animals for 60 min., intraperitoneal injection
of Escherichia coli lipopolysaccharide (LPS, 100
µg/kg body weights), intraperitoneal
administration of fluoxetine (8 mg/kg body
weight). Similar doses of the extracts were tested
on freely feeding rats and on rats that had been
deprived of food for 20 h. Results indicates that
hydro-alcoholic extract of Trikatu reduces the
marked anorexia induced by stress in a dose-
dependent manner. Pretreatment with Trikatu
extract at doses of 200 and 400 mg/kg
significantly reversed the anorectic effect
induced by restraint stress and by administration
of Fluoxetine hydrochloride (FLU). The
components of Trikatu failed to reverse the
inhibition of feeding individually. In contrast,
pretreatment of Trikatu reversed stress-,
fluoxetine-induced anorexia. The study provides
strong evidence of the synergistic action of
Trikatu to reduce stress-induced anorexia .
Antitumor Activity: Anti-tumor activity of
mercaptopurine in combination with aqueous
extract of Trikatu and Gomutra was conducted.
20-methylcholanthrene a polycyclic aromatic
hydrocarbons was used to induce tumor in albino
mice. Haematological and endogenous
antioxidant parameters were evaluated in the
study. Individual treatment with mercaptopurine
(5 mg/kg) and Trikatu (100 mg/kg) significantly
restored the altered haematological and
antioxidant parameters to normal values. Even
mercaptopurine (2.5 mg/kg) at its sub therapeutic
dose showed equivalent effects as that of
therapeutic dose of mercaptopurine (5 mg/kg)
when it was co administered along with Trikatu
[100 mg/kg] compared to the positive tumor
control group .
Hepatoprotective Activity: Protective and
curative effect of ethanolic extract of Trikatu
against carbon tetrachloride induced
hepatotoxicity in rats was examined. Carbon
tetrachloride (1 mL/kg−1) given through
intraperitonial route caused liver damage in rats
manifested by significant rise in serum enzymes
levels, declines in reduced glutathione level and
elevations in malondialdehyde levels. The oral
administration of ethanolic extract of Trikatu in a
dose of 150 mg/kg−1to carbon tetrachloride
intoxicated rats. The degree of protection was
measured using biochemical parameters such as
serum glutamate oxalate transaminase (SGOT),
serum glutamate pyruvate transaminase (SGPT),
alkaline phosphatase (ALP), bilirubin and total
protein. The ethanol extract at an oral dose of
150 mg/kg exhibited a significant protective
effect by lowering serum levels of glutamic
oxaloacetic transaminase, glutamic pyruvic
transaminase, alkaline phosphatase and total
bilirubin. Liv-52 syrup was used as positive
Antimicrobial Activity: The antibacterial
activity of the aqueous, ethanol, acetone and
methanolic extract of Trikatu was evaluated by
disc diffusion method. Trikatu extracts showed
strong antibacterial activity against S. aureus, S.
epidermidis, P. vulgaris, E. coli, P. aeruginosa,
B. subtilis and K. pneumoniae. Ampicillin was
used as positive control (10 mcg/ disc). The
antibacterial activities of aqueous, ethanol,
methanol and acetone extracts of Trikatu were
performed against enteric bacterial pathogens
such as E. coli, S. aureus, P. aeruginosa, P.
vulgaris, S. epidermidis, S. typhi, S. typhimurium
and E. aerogenes. Ethanol extract of Trikatu
showed moderate antibacterial activity against all
the bacterial pathogens while methanol extract
showed strong antibacterial activity against S.
epidermidis and S. aureus, moderate antibacterial
activity against P. vulgaris, P. aeruginosa, S.
typhi, E. coli, K. pneumoniae, S. typhimurium
and E. aerogenes. Acetone extract of Trikatu
showed strong antibacterial activity against S.
196 Indian Journal of Agriculture and Allied Sciences
epidermidis, S. aureus, P. vulgaris, S. typhi, E.
coli, K. pneumoniae and E. aerogenes whereas
moderate antibacterial activity against P.
aeruginosa and S. typhimurium [27, 28].
In another experiment antibacterial activity
of ethanol extracts of Trikatu had been
performed against E.coli and S. aureu using agar
well diffusion method. Ethanolic extract of
Trikatu showed moderate activity (17 ±0.11, 16
±0.12) against tested microbs as compared to
antibiotic streptomycin sulphate used as positive
control was found to be 20 ±0.12, 19 ±0.01
Anthelmintic Activity: Anthelmintic activities
of aqueous and ethanolic extract of Trikatu were
performed using adult earthworm P. posthuma.
Piperazine citrate was used as standard in the
study. Results indicated that ethanolic extract of
Trikatu was found more active as compared to
aqueous extract. Both aqueous and ethanolic
extract of Trikatu showed almost equal activity
as compared to standard drug piperazine citrate
. In another experiments it was found that
aqueous extract of Trikatu showed higher
anthelmintic activity as compared to the standard
drug albendazole .
Analgesic Activity: Analgesic effect of ethanol
extract of Trikatu was performed in albino mice
of either sex by using hot plate. At a dose of 250
mg/kg, b.w., Trikatu extract exhibited significant
analgesic activity as compared to standard drug
Antifungal Activity: In vitro antifungal activity
of ethanol extract of Trikatu had been tested
against Aspergillus niger, and mucor species
using agar well diffusion method. Ethanol extract
showed highest activity (6.2 ± 0.01, 7.0 ±0.05)
against tested fungus as compared to antifungal
agent Nystatin (9.0 + 0.12, 10 ± 0.11) used as
standard drug .
Immunomodulatory Activity: The
immunomodulator activity of the Trikatu mega
Ext (Pet. Ether, Benzene, Choloroform, Ethyl
acetate, 70% ethanol and water) was evaluated
by carbon clearance assay, Delayed Type
Hypersensitivity tests in oral administration of
mice at a dose of 100-200 mg/kg body weight.
The megaExt Showed significant (p<0.001)
increased in phagocytic index when compared to
control group indicates stimulation of the
reticulo-endothelial system and Potentiated the
delayed type hypersensitivity reaction induced by
sheep red blood cells. The results obtained in this
study indicate that Trikatu possesses potential
immunomodulatory activity and has therapeutic
potential for the prevention of autoimmune
diseases  in another study. In the present study,
Trikatu, (1000 mg/kg/b.wt.) was evaluated for its
immunomodulatory properties in comparation to
indomethacin (reference drug) in rats. The results
obtained in our study showed a significant
decrease in cell mediated immune responses,
humoral immune responses (haemagglutination
titre and plaque forming assay) and macrophage
phagocytic index of Trikatu compared to control
implying its immunosuppressive property .
Adaptogenic Activity: Adaptogenic activity of
megaext of Trikatu was evaluated by Swim
endurance test and anoxic tolerance test in mice.
The evaluation of adaptogenic potential by oral
administration of mega Extract of Trikatu (100-
200 mg/kg) evoked a significant increase in the
swimming time (min.) (p<0. 001) and also
increases in anoxic tolerance time (p<0. 001) in
physical and anoxic stress models as compared to
control thus confirming its adaptogenic nature
Anti-allergic activity: The topical preparation of
ethanolic extract of Trikatu did not show
additional effects for relieving mosquito bite
reaction as compared with the reference product
containing camphor, menthol, and eucalyptus.
However, both preparations can reduce papule
size and relieve erythema intensity, edema and
pruritis symptoms from mosquito bite reaction.
Thus Trikatu preparation containing Trikatu
extract, menthol, camphor, and eucalyptus did
not provide additional anti-inflammatory effect
compared to the reference product containing
camphor, menthol, and eucalyptus .
Anti-arthritic Activity: The anti-arthritic effect
of oral administration of oral administration of
Trikatu (1000 mg/kg body weight) and
indomethacin (3 mg/kg body weight,
intraperitoneal) on Freund’s adjuvant (0.1 mL)
into the foot pad of the right hind paw. The
thickness of the hind paw was monitored by
using a vernier scale periodically which was
markedly reduced on treatment with 1000 mg/kg
body weight Trikatu and 3 mg/kg body weight
indomethacin. The results evidenced a significant
lowering of all the biochemical and
immunological parameters to near normal levels
in arthritic rats as evidenced by the radiological
and histopathological assessments. Thus results
suggest that Trikatu could be a promising
alternative drug for the control and management
of rheumatoid arthritis .
Anti-inflammatory Activity: The anti-
inflammatory activity of the Trikatu was
Phytochemistry and Pharmacology of Trikatu 197
evaluated by carageenan-induced paw tests to
determine its effects on acute and chronic phase
of inflammation models in rabbits. Trikatu
showed Percent edema inhibition at the third
hour elicited by the combination of diclofenac
sodium and Trikatu (59.37%) was significantly
lower as compared to diclofenac alone (74.42%).
It is also observed that Trikatu by itself also
induced a significant reduction in edema
formation (62.85%) and the degree of inhibition
is comparable with that of diclofenac sodium
with Trikatu. Result indicate that the extent to
which edema was inhibited by the combination
of diclofenac and Trikatu was similar to that
shown by Trikatu alone, but significantly less
than that produced by the sole administration of
diclofenac. Likewise, Trikatu significantly
decreased the plasmatic concentrations of
In another study, Trikatu, (1000
mg/kg/b.w.) was evaluated for anti-inflammatory
activity in comparation to indomethacin
(reference drug) in rats. A significant anti-
inflammatory effects was observed in Trikatu
treated adjuvant induced arthritic rats by a
reduction in the levels of circulating immune
complexes and inflammatory mediators (TNF-
alpha and Interleukin-1beta) .
The anti-inflammatory activity of
methanolic extract of Trikatu was evaluated by
carageenan-induced paw edema to determine its
effects on acute and chronic phase of
inflammation models in rats. Methanolic extract
of Trikatu showed maximum inhibition (71.18%)
at a dose of 400 mg·kg−1 b.w. after 5 h of drug
administration in carageenan-induced paw
edema, whereas indomethacin produced 68.86%
of inhibition . In another study, methanolic
extract of Trikatu showing effective against
Carragenan- induced paw oedema in wistar rats.
Aspirin (150 mg/kg p.o.) used as suspension for
standard drug .
Phytochemistry: Phytochemical investigation
on Trikatu led to the isolation of 6-Shogaol (1),
6-gingerol (2),Piperine (3)  form its powder.
H H O
Conclusion: It is strongly believed that detailed
information as presented in this review on the phytochemical and various biological properties
of the polyherbal formulation Trikatu might
198 Indian Journal of Agriculture and Allied Sciences
provide detailed evidence for the use of this
formulation in different medicines and diseases.
Extracts and fractions of the formulation possess
anti-arthritic, mosquito bite, immunomodulatory,
adaptogenic, antifungal, anthelmintic,
bioavailability, toxicity studies, anti-anorectic,
hepatoprotective, antioxidant, analgesic, anti-
inflammatory, antihyperlipidemic, antimicrobial
and antitumor activity.
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