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International Journal of Green Pharmacy • July-Sep 2018 (Suppl) • 12 (3) | S437
Trikatu - A combination of three
bioavailability enhancers
Rahul Kaushik*, Jainendra Jain, Azhar Danish Khan, Pallavi Rai
1Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar
Pradesh, India
Abstract
Trikatu, as per Ayurveda’s Bhaisajyaratnawali is a compound herbal formulation containing three bitter herbs
mixed together in equal quantities. Dried fruits of Piper nigrum (Maricha) and Piper longum (Peepli) and dried
rhizomes of Zingiber officinale (Sunthi) are used to prepare this miraculous formulation. It is prescribed in
Ayurvedic system of medicine for treatment of tastelessness, digestive impairment, and diseases of nose and
throat such as chronic rhinitis/sinusitis, skin diseases, asthma, cough, frequent urination, obesity, and Filariasis.
Trikatu is also added in various Ayurvedic formulations with a view to restore the disturbed “tridoshas- vatta,
pitta and kapha.” It calms down the increased Vata and Kapha and increases the Pitta. It has pungent (katu)
taste, hot (ushna) potency, light (laghu) and dry (ruksha) quality, and digestive (amapachaka) therapeutic effect.
Modern pharmacological studies also revealed that Trikatu possesses the capability to enhance the bioavailability
of various phytoconstituents and synthetic drugs if incorporated with them thereby helping in achieving the
therapeutic goals. Apart from traditionally known health benefits, Trikatu also possesses immunomodulatory,
antiviral, expectorant, carminative, hypolipidemic, hypoglycemic, antiemetic, and anti-inflammatory potential.
Simply it is concluded that Trikatu is a miraculous combination which is needed to be explored more exhaustively
to solve the bioavailability issues of allopathic, ayurvedic, and other traditional systems of medicines.
Key words: Ayurvedic, bioavailability, Piper longum, Piper nigrum, trikatu, Zingiber officinale
Address for correspondence:
Rahul Kaushik, Ram-Eesh Institute of Vocational
and Technical Education, Plot No. 3, Knowledge
Park- I, Kasna Road, Greater Noida, Gautam Budh
Nagar- 201310, Uttar Pradesh, India.
Phone: +91-9999427794.E-mail: rahulkcsji@gmail.com
Received: 10-03-2018
Revised: 09-08-2018
Accepted: 27-08-2018
INTRODUCTION
Trikatu as the name itself indicates its
meaning, “tri” in Sanskrit stands for three
and “katu” stands for acrids. The three
acrid herbs including Maricha (Black pepper),
Peepli (Long Pepper), and Sunthi (Ginger),
when combined in equal quantities, forms the
miraculous formulation Trikatu. Trikatu is an
Ayurvedic formulation mentioned in Ayurveda
for a number of ailments. In Bhaisajyaratnawali,
Trikatu is mentioned as:
The shloka completely defines the procedure for
preparation of Trikatu and method of its use along
with the indications in which it is to be used.
Ayurvedic system of medicine prescribes
Trikatu for the management of tastelessness
(Arocaka) disturbed digestion (Agnimandya
and Amadosa), diseases of nose (Pinasa) and upper
respiratory tract (Gala and swasa roga, Kasa), excess
and frequent urination (Meha), edema (Gulma), obesity
(Sthaulya), Filariasis (Slipada), and skin diseases
(Tvakroga). Trikatu acts primarily by its effect on stomach,
liver, and pancreas. In stomach, it increases production
of digestive juices thereby stimulating digestion. In liver,
it acts as Cholagogue and increases production of bile
salts by stimulating gallbladder functioning. Trikatu also
has its influence on pancreatic functioning. In a nutshell,
Trikatu affects overall digestive system along with its
curative effects on respiratory, urinary, immunity, skin, and
metabolic systems of our body.
REVIEW ARTICLE
Kaushik, et al.: Trikatu - A combination of bioavailability enhancers
International Journal of Green Pharmacy • July-Sep 2018 (Suppl) • 12 (3) | S438
Trikatu is also added in various Ayurvedic formulations with
a view to restore the disturbed “tridoshas-vata, pitta, and
kapha.” It calms down the increased Vata and Kapha and
increases the Pitta. It has pungent (katu) taste, hot (ushna)
potency, light (laghu) and dry (ruksha) quality, and digestive
(amapachaka) therapeutic effect [Figure 1].[1]
METHOD OF PREPARATION
Equal quantities of all the three acrid herbs, dried fruits of Piper
longum Linn.(Long Pepper), Piper nigrum (Black Pepper),
and dried rhizomes of Zingiber officinale are finely powdered
separately in a mortar pestle or grinder. The fine powders of
individual herbs are weighed in equal quantities and mixed
together properly. This mixture of powders is then sieved
through sieve no. 80 to get extra fine powder which has more
therapeutic value due to more surface area. The fine powder
of Trikatu is then stored in moisture free airtight containers.[1]
Dosage
Ayurvedic texts prescribe 1–3 g of Trikatu churna to be
consumed with honey to mask the bitter taste or warm
water for maximum therapeutic benefits. Trikatu is added in
many Ayurvedic polyherbal formulations in such a quantity
that it will be sufficient to enhance the bioavailability of
the main ingredients of that formulation by acting through
various mechanisms. When added in formulations, the actual
pharmacological activity of Trikatu is not exhibited because
its dose is not the therapeutic dose.[1]
Chemistry of Trikatu
Trikatu contains the three herbs P. longum, P. nigrum, and
Z. officinale. The component herbs P. longum and P. nigrum
contain Piperine as the main chemical as well as a biological
marker along with other constituents in minor quantities.
Z. officinale contains chemical constituents such as Gingerols,
Gingiberene, Shagols, and other chemical components.
Chemical composition of P. longum
Piperine is the major and active constituent of long pepper. The
piperine content is 3–5% (on dry weight basis) in P. longum. The
fruit of P. longum contains a large number of alkaloids and related
compounds, the most abundant of which is piperine, methyl
piperine, iperonaline, piperettine, pellitorine, piperlongumine,
piperlonguminine, asarinine, piperundecalidine, refractomide
A, pipercide, piperderidine, longamide and tetrahydropiperine,
terahydro piperlongumine, dehydropipernonaline piperidine,
pregumidiene, brachystamide, brachystamide-A, brachystine,
terahydropiperlongumine, and trimethoxy cinnamoyl-
piperidine. Lignans Sesamin, pulvuatilol, fargesin, and others
have also been isolated from the fruit of P. longum.
Volatile oil of the fruit P. longum is a complex mixture. Major
components of essential oil are caryophyllene and pentadecane
(both about 17.8%) and bisaboline (11%) along with volatile
piperine. Other components include thujine, terpinoline,
p-cymene, p-methoxy acetophenone, and dihydrocarveol.[2]
Chemical Composition of P. nigrum
P. nigrum contains lignans, alkaloids, flavonoids, amides,
and other aromatic compounds along with approximate 3.5%
of volatile oil. Components of essential oil include sabinene,
pinene, linalool, limonene, and phellandrene. Piperine is an
alkaloid and the chemical marker of P. nigrum. Chavicine
which is an isomer of piperine is also present. Piperine and
Chavicine are not responsible for the aroma of the black pepper.
Piperine is responsible for pungency of the black pepper.[3]
Chemical Composition of Z. officinalis
Exhaustive chemical screening of ginger reveals that it contains
over 450 compounds. The major composition of ginger rhizomes
is carbohydrates (50–70%), lipids (3–8%), terpenes, phenolic
compounds, amino acids, raw fiber, ash, protein, phytosterols,
vitamins, and minerals. Volatile terpenoidal constituents of
Z. officinale include zingiberene, β-bisabolene, α-farnesene,
α-curcumene, and β-sesquiphellandrene. Phenolic compounds
include gingerol, paradols, and shogaol. Gingerols and shagols
are responsible for pungency of Ginger. These gingerols and
shogaol are found in higher quantities of up to 20–25%. Other
gingerol- or shogaol-related compounds (1–10%), which
have been reported in ginger rhizome, include 6-paradol,
1-dehydrogingerdione, 6- gingerdione and 10-gingerdione
4- gingerdiol, 6-gingerdiol, 8-gingerdiol, and 10-gingerdiol, and
diarylheptanoids. The characteristic odor and flavor of ginger are
due to a mixture of volatile oils such as shogaols and gingerols.[4]
Bioavailability Enhancers
• Bioavailability enhancers are drug facilitators.
• They are molecules which by themselves do not show
typical drug activity.Figure 1: Formulation of Trikatu
Kaushik, et al.: Trikatu - A combination of bioavailability enhancers
International Journal of Green Pharmacy • July-Sep 2018 (Suppl) • 12 (3) | S439
• However, when used in combination, they enhance the
activity of the drug molecule in various ways.
Simply, a bioavailability enhancer is an agent capable of
enhancing bioavailability and bioefficacy of a particular
drug with which it is combined without any typical
pharmacological activity of its own at the dose used.
Need of Bioavailability Enhancers
Many allopathic and herbal formulations despite their
impressive in vitro findings demonstrate less or negligible
in vivo activity due to following reasons:
• Poor lipid solubility.
• Improper molecular size.
• Resulting in poor absorption.
• And hence poor bioavailability.
Here, the need arises for a natural and safe solution for
combating these bioavailability problems. Trikatu fits best
to manage these bioavailability issues with allopathic and
herbal formulations. There are numerous pharmacological
findings that support the use of Piperine and Gingerols to
enhance the bioavailability.
Piperine is the biomarker of both P. longum and P. nigrum.
Piperine acts by a number of mechanisms to enhance the
bioavailability.
• Increases bioavailability of the drug across the membrane.
• Potentiates the drug molecule by conformational interactions.
• Reduction in HCl secretion and increase in gastrointestinal
tract (GIT) blood supply.[5]
• Acts as receptors for drug molecule making target cells
more receptive to drugs.
• Inhibition of gastrointestinal transit, gastric emptying
time, and intestinal motility.[6,7]
• Modifications in GIT Epithelial cell membrane
permeability.[8,9]
• Chalagogous effects.[8]
• Bioenergetics and Thermogenic properties.[8,10]
• Suppression of First Pass Metabolism and inhibition of
drug metabolizing enzymes.[10]
• Stimulation of gamma-glutamyl transpeptidase activity
which enhances uptake of amino acids.[11]
PHARMACOLOGICAL STUDIES
DEMONSTRATING BIOAVAILABILITY
ENHANCING ACTIVITY OF PIPERINE AND
GINGER
The effect of simultaneous administration of Piperine on plasma
concentration of Carbamazepine given twice daily in epileptic
patients undergoing carbamazepine therapy was evaluated,
and it was observed that piperine significantly enhanced the
bioavailability of carbamazepine. The mechanism of action
was possibly by increased absorption and reduced elimination
of the carbamazepine.[12] Antidepressant effects of curcumin
were investigated with coadministration with piperine. It was
observed that the combination of piperine with curcumin
showed significant potentiation of its anti-immobility,
neurotransmitters (serotonin and dopamine) enhancing, and
monoamine oxidase inhibitory effects as compared to curcumin
effect when taken alone.[13] Another similar study revealed that
there was potentiation of antidepressant activity of curcumin
when administered with piperine.[14] While evaluating the
effects of tiferron alone and in combination with piperine against
beryllium-induced biochemical alterations and oxidative stress,
it was found that the combination reversed all the variables
significantly toward the control.[15] In a randomized, crossover
and placebo-controlled study of the influence of piperine on the
pharmacokinetics of nevirapine (an antiretroviral drug) under
fasting conditions. The piperine or placebo was administered
to healthy adult males for 6 days. On the 7th day, Piperine or
placebo was administered with nevirapine. Post-dosing blood
samples showed enhanced bioavailability of nevirapine with
piperine.[16] Study of effect of oral curcumin with piperine on
the pain and the markers of oxidative stress in patients with
tropical pancreatitis for 6 weeks revealed that there was a
significant reduction of the erythrocyte malonyldialdehyde
levels in combination therapy as compared to placebo treatment
with significant increase in glutathione levels.[17] 1.3 times
more plasma bioavailability of epigallocatechin-3-gallate was
observed in CF-1 mice when taken with piperine as compared
to epigallocatechin-3-gallate alone. The mechanism involved
inhibition of glucouronidation and GIT transit.[18]
Ginger is one of the components of Trikatu which also possess
significant bioavailability enhancement activity. It has a
powerful effect on mucous membrane of the gastrointestinal
tract. It regulates the intestinal functions to facilitate absorption.
Ginger when used in the dose of 10–30 mg/kg body weight
acts as bioenhancer. Pharmacological studies show that it
dramatically enhanced the bioavailability of various medicines
especially antibiotics such as amoxicillin, azithromycin,
erythromycin, cephalexin, cefadroxil, and cloxacillin.[19]
Ayurvedic formulations containing Trikatu[1]
S. No. Formulation Indication
1. Sarasvata churna Epilepsy,[20] Brain
disorders
2. Astangavleha Cough and Asthma
3. Eranda paka Edema and Pain in
Urinary system
4. Panchnimba churna Skin diseases
5. Puga khanda Dyspepsia and Bleeding
haemorrhoids
6. Vyagriharitaki Cough and Rhinitis
7. Arkadi kwatha churna Lock jaw and Cold
cough
Kaushik, et al.: Trikatu - A combination of bioavailability enhancers
International Journal of Green Pharmacy • July-Sep 2018 (Suppl) • 12 (3) | S440
8. Punarnava gugglu Gout and Scrotal
swelling
9. Ashwagandhadi
churna
Tridosha
10. Dadimashtaka churna Malabsorption
syndrome
Other Pharmacological Activities of Trikatu
Different extracts and fractions of Trikatu possess
Antioxidant,[21] Antihyperlipidemic,[22] Antianorectic,[23]
Antitumor,[24] Hepatoprotective,[25] Antimicrobial,[26-28]
Anthelmintic,[29] Analgesic,[28] Antifungal,[28]
Immunomodulatory,[30,31] Antiallergic,[32] Antiarthritic,[33] and
Anti-inflammatory[34,35] activities.
Therapeutic Indication
Trikatu Churna is helpful in following health conditions.[36]
• Constipation with mucous or sticky stool.
• Loss of appetite.
• Indigestion.
• Gas or flatulence.
• Bloating.
• Abdominal distension.
• Irritable bowel syndrome.
• Common cold (acute phase during running nose).
• Cough with thin white phlegm.
• Asthma (chest congestion due to phlegm).
• Weight loss (obesity).
• Body aches with feeling of heaviness in the body.
• High cholesterol levels.
• Atherosclerosis.
• High blood pressure due to hypercholesterolemia.
• Gout.
Caution
However, Trikatu churna contains herbs and spices, which
we use in our daily kitchen, but the excess intake can cause
some unwanted effects. In the dosage <1 g/day, it is safe to
use.[36]
Side Effects
The most common side effect of Trikatu is heartburn and
acidity. The excess dosage may cause the following side
effects.[36]
• Burning aftertaste.
• Heartburn.
• Burning sensation in the throat.
• Heat sensation in the body.
• Mouth ulcer (rare).
• Sweating (rare).
• Redness in eyes or burning sensation in eyes (very rare).
Contraindications[36]
• Acid dyspepsia.
• Heartburn.
• Burning sensation in any part of the body such as in the
throat, abdomen, feet, or hands.
• Vomiting.
• Red eyes.
• Skin diseases with burning sensation as a symptom.
• Constipation with dry and hard stool or bleeding in stool.
• Bleeding disorders.
• High-risk pregnancies.
• Threatened abortion.
CONCLUSION
Trikatu being an herbal formulation will be the best
solution for bioavailability related issues with allopathic,
Ayurvedic and formulations of other traditional systems of
medicines. It has got the tremendous potential to increase the
bioavailability of drugs and nutrients. The scientific findings
further strengthen the claims of the traditional ancient texts
about Trikatu’s health benefits.
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Source of Support: Nil. Conflict of Interest: None declared.
