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PHYTOCHEMISTRY AND PHARMACOLOGY OF TRIKATU
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.
... All of these plants are utilized as spices across the world. During the time between the 7 th century B. C. and the 6 th century A. D., trikatu was one of the most often utilized medicines in ayurveda formulations for the goal of treating a variety of illness problems [10]. They are also used as significant components in folkloric medicine and Ayurvedic, Siddha, and Unani (ASU) medications. ...
Objective: The goal of this study aimed to evaluate the protective and vascular effect of the polyherbal trikatu in rats on isoproterenol (ISO) triggered myocardial infarction (MI). Methods: For a total of two days in a row at 24 h breaks (27th and 28th d), a subcutaneous (s.c.) injection of isoproterenol (85 mg/kg body weight) was used to induce myocardial infarction. The rats in Group I behaved as the normal control without pretreatment. Rats in Group II were given isoproterenol. The rats in Group III were selected as the standard, treated with vitamin E (10 mg/kg, p.o.) for 28 d and subjected to isoproterenol (ISO) toxicity. Rats of Group IV and Group V received test sample trikatu 100 mg/kg and 200 mg/kg, respectively for 28 d and were subjected to isoproterenol (ISO) toxicity. Results: Rats given isoproterenol treatment revealed a considerable elevation of serum enzyme cardiac troponin I (cTnI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), Heart creatinine kinase (CK-MB), Lactase dehydrogenase (LDH). Rats pretreated with trikatu and vitamin E+ISO showed significant different (p<0.001) for AST, ALT, LDH and CK-MB levels elevated by ISO. Histopathological tests showed that trikatu and vitamin E decreased inflammation and edema in the hearts of rats. Conclusion: The aqueous suspension of trikatu churna was found to be significantly helpful in minimizing the magnitude of myocardial damage and combating oxidative stress.
Ayurveda has an ancient heritage of traditional herbs in which Trikatu is very precious. Trikatu is a poly herbal preparation. It consists of three crude drugs namely Maricha (Piper nigrum Linn). Pippali (Piper longum Linn) and Shunthi (Zingiber officinalis Rosc) in the ratio of (1:1:1; ww). Trikatu also called as Katutrikam, Tryusnam, Vyosa. Trikatu is used as solo drug rarely, but it is an essential ingredient of numerous formulations and prescriptions of Ayurvedic medicine. Trikatu churna is considered as one of the best drugs to treat the condition of Ama (improperly digested absorbed and improperly metabolised food particles including free radicles). Trikatu is regarded as the drug of choice in cases of Agnimandya (poor digestion due to faulty digestive process). In Brihattrayi, it is recommended for various diseases due to Agni (digestive fire) vitiation such as Grahaniroga (Malabsorption syndrome), Udara roga (major diseases of abdomen surgical and medical like hepatomegaly, splenomegaly and ascites), Arsharoga (piles) etc. Its contents are dipana and pacana in their action. By virtue of these properties the drug becomes effective in managing ama. The objective of this article is to highlight classification, synonyms, pharmacological actions as described in various diseases, and different formulations of Trikatu in ancient Ayurvedic.
Herbal medicines are being used increasingly as dietary supplements to fight or prevent common disease. The dried fruits of Piper nigrum L. (Piperaceae), Piper longum L. (Piperaceae) and rhizome of Zingiber officinale Roscoe. (Zingiberaceae) were powdered and mixed together in equiproportions to get a polyherbal formulation, Trikatu churna. The aqueous, ethanol, methanol and acetone extracts of these plant's fruits and Trikatu churna were prepared and antibacterial activities were tested by disc diffusion method against enteric bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Staphylococcus epidermidis, Salmonella typhi, Salmonella typhimurium and Enterobacter aerogenes. The extracts of Piper longum, Piper nigrum and Zingiber officinale were found antibacterial to all bacterial pathogen tested. Trikatu churna exhibited potent antibacterial activity; this might be due to the multifunctional effect of all the three plant ingredients of Trikatu churna. Antibacterial activity of Trikatu churna and its ingredients was carried out in attempt to support the use of Trikatu churna for the treatment of enteric bacterial infections.
Trikatu churna is one of the commonly used Ayurvedic formulations
in the traditional system of medicine in India for the treatment of agnimandya,
i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of
Zingiber officinale Roscoe (Zingiberaceae) and fruits of Piper longum L. and
Piper nigrum L. (Piperaceae). The chief objective of the study was to determine
the antianorectic effects of three drugs individually and to compare these effects
with the effect of Trikatu. The activity of the drugs was studied after anorexia
was induced in rats by (1) physical stress arising from immobilization for 60
min; (2) intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS,
100 μg/kg body weight); and (3) 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. Corticotrophinreleasing
factor (CRF, 0.3 μg/rat) can induce anxiogenic-like behavior
and reduced food intake. This model was also studied, and the results were
compared. The components of Trikatu churna failed to individually reverse the
inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-,
fluoxetine- and CRF-induced anorexia. The study provides strong evidence
of the synergistic action of Ayurvedic formulas and also proves the ability of
Trikatu churna to reduce stress and CRF-induced anorexia.
Chemical characterization and acute and sub-acute toxicity study of Trikatu, a generic herbal formulation of Indian system of medicine, was carried out in Charles Foster (CF) rats for safety profiling. In acute toxicity experiment, Trikatu at 2,000 mg/kg body weight once orally was well tolerated by the experimental animals (both male and female) and no changes were observed in mortality, morbidity, gross pathology, gain in weight, vital organ weight, hematological (total white blood cells (WBC) and red blood cells (RBC) count), biochemical parameters such as serum creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum lipid profile and tissue biochemical parameters such as reduced glutathione and malonaldehyde content as oxidative stress markers. In sub-acute experiment, Trikatu was administered at 5, 50 and 300 mg/kg body weight once daily for 28 days in female CF rats, and non-significant changes were found in most of the parameters studied such as acute experiment except significant increase in low density lipoprotein (LDL) cholesterol level at 50 and 300 mg/kg body weight, decrease in high density lipoprotein (HDL) cholesterol level at 300 mg/kg body weight, increase in SGPT activity at 50 mg/kg body weight and decrease in WBC count at 300 mg/kg body weight on 28(th) day post treatment.
The Trikatu churna is one of the classical Ayurvedic preparations which is also called as Three pungents. It is prepared by mixing equal proportional mixture of powdered fruits of Piper nigrum L. i.e. maricha (Piperaceae), Piper longum L. i.e. pimpli (Piperaceae), & dried rhizomes of Zingiber officinale Roscoe i.e. ginger (Zingiberaceae).The present study was aimed to find out the anthelmintic activity of Trikatu churna & its individual ingredients on Pheritima postuma i.e. earthworms along with its preliminary phytochemical study. Powdered trikatu & its each component were extracted with water by the process of Maceration. The Albendazole suspension was used as standard. The time required for the paralysis & death was noted. It was found that all the samples possess good Anthelmintic activity at their highest concentrations.
Objective: To see the effect of Trikatu (piperine) on the bioavailability and pharmacokinetics of isoniazid in rabbits. Methods: In a crossover study, ten rabbits were administered either single dose (orally) of isoniazid (14 mg/kg) alone or in combination with Trikatu [piperine (10 mg/kg)]. Blood samples were collected at 0,0.5,1,1.5,2, 4,6,9 and 12 hours after drug administration and assayed for isoniazid by fluorimetric technique. A washout period of 7 days was allowed between the two treatments. Results: Coadministration of Trikatu (piperine) significantly reduced the C(max) [5.48 ± 0.75 μg/ml vs 8.42 ± 0.85 μg/ml; P <0.05] and AUCo-α [15.04 ± 3.84 μg/ml. hr vs 24.76 ± 4.03 μg/ml. hr; P<0.05] of isoniazid. Conclusion: Trikatu (piperine) reduces the bioavailability of isoniazid in rabbits.
Ethanol extract of Trikatu Churna an Ayurvedic formulation was evaluated for hepatoprotective activity in rats by inducing liver damage with carbon tetrachloride. 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 control.
Ayurvedic Medicine brings the unique theories and traditions of Ayurveda alive so that they are accessible to the complementary health practitioner of today. This book offers a clear, accessible and yet detailed guide to Ayurvedic herbalism. It encompasses a brief history of the growth of Ayurveda , a discussion of its fundamental principles, treatment strategies as well as the energetic approach of traditional Ayurvedic herbal pharmacy and pharmacology. It also emphasizes the importance of using sustainably harvested herbs in clinical practice. The introductory theoretical chapters complement the core of the book that includes over 100 plant profiles of Ayurvedic herbs and 50 traditional formulas. It is a clinical manual as well as a reference book, which relates classical Ayurvedic teachings to modern herbal medicine as well as specific bio-medical conditions. The herbalmaterial medicaof Ayurveda is discussed, along with traditional ayurvedic energetics, in way that is accessible to the western complementary practitioner. Uniquely styled plant profiles include information on over 100 herbs and 25 formulas. The Ayurvedic theory of clinical treatment is clearly presented, as well as its application. Material represents a blend of traditional medicine with modern research, combining pure Ayurveda with modern phytotherapy and bio-medicine. Coverage of each plant includes details on growing habitat and special characteristics. Practical step-by-step instructions explain how to prepare herbal medicines in the unique Ayurvedic style oils, creams, ghees, jams, etc. Photos are provided of both the freshly growing herbs and dried samples. Authored by an experienced Medical Herbalist, Ayurvedic practitioner, and passionate herb grower well-versed in the classical Ayurvedic texts and contemporary writings.
The present study was done with the aim to evaluate anthelmintic activity of Trikatu churna containing traditionally user herbs viz., Piper nigrum L. (Piperaceae), Piper longum L. (Piperaceae) and rhizome of Zingiber officinale Roscoe using adult earthworm Pheritima posthuma. All these three ingredients are spicy, commonly used in our daily diet, also well known for their tremendous therapeutic potential, since from the Vedic period. The aqueous and ethanolic extract of Trikatu churna and its ingredients were also screened for preliminary phytochemical studies. Piperazine citrate was used as standard and it was found that the TCEE activity is higher than TCAE.
Cancer is one of the most life threatening diseases and serious health problem in both developing and developed countries. Many synthetic and chemotherapeutic agents used in cancer therapy are having low bioavailability and involve the risk of life threatening host toxicity. Modern researchers are increasingly showing interest toward the improvement of bioavailability of a large number of drugs by addition of various herbs with bioenhancing properties. In oral drug delivery system, the co-administration of therapeutic agents with natural compounds possessing absorption improving activities, has also garnered great interest. Hence the present study was conducted to evaluate the anti-tumor activity of Mercaptopurine in combination with Trikatu and Gomutra. 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 (5mg/kg) and trikatu (100mg/kg) significantly restored the altered haematological and antioxidant parameters to normal values. Even Mercaptopurine (2.5mg/kg) at its sub therapeutic dose showed equivalent effects as that of therapeutic dose of Mercaptopurine (5mg/kg) when it was co administered along with trikatu compared to the positive tumor control group.
Trikatu churna is one of the traditional poly herbal preparation, formed by mixing equal quantities of three important spicy materials such as Piper longum L. (Piperaceae), Piper nigrum L. (Piperaceae) and Zingiber officinale Roscoe (Zingiberaceae). Trikatu is also known as " Three Bitters". The trikatu preparation was reported to contain alkaloids, phenols, tannins, flavanoids, steroids, lignin & saponins. The objective of study is to evaluate the antimicrobial activity of trikatu churna & its individual ingredients with their preliminary phytochemical study. The aqueous extracts of trikatu churna & its each ingredient were tested for antimicrobial activity against certain bacterial strains of Escherichia coli, Staphylococcus aureus by in vitro agar well diffusion method and the results are recorded as the zone of inhibition. Trikatu churna was found to possess higher extent of phytoconstituents with promising antimicrobial activity. INTRODUCTION: Trikatu means three herbs which are having Katu Rasa i.e. a pungent taste. It is the equiproportional mixture of Pimpli (Piper longum L.), Maricha i.e. black pepper (Piper nigrum L.) And Sunthi i.e. dried ginger (Zingiber officinale Roscoe). This combination streamlines the metabolism of the body, this is the reason it is indicated in a wide range of health problems like asthma, fever cold, cough etc. And also used as purgative, carminative, and inobesity, indigestion, high cholesterol, slow metabolism, hypothyroidism, congestion and edema.
Introduction
Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions.
Methods
All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes.
Results
There were no significant differences between treatment and reference arms on any outcome at any time of measurement.
Conclusion
Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated.
In the present study, trikatu, an herbal compound was evaluated for its immunomodulatory and anti-inflammatory properties with reference to cell mediated immune responses (delayed type hypersensitivity reaction), humoral immune response (haemagglutination titer and plaque forming assay), macrophage phagocytic index, circulating immune complex and inflammatory mediators in rats. For comparison purposes, indomethacin was used as a reference drug for anti-inflammatory studies. 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 in trikatu treated rats (1000mg/kg/b.wt.) compared to control animals implying its immunosuppressive property. In addition, significant anti-inflammatory effects were 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). Thus, in conclusion, our data suggest that trikatu could be considered as a potential anti-inflammatory agent for treating autoimmune inflammatory disorders like rheumatoid arthritis with immunosuppressive property.
Ayurveda, derives from the Sanskrit words Ayus (life) and Veda (knowledge) is the most ancient system of traditional medicine of the world. It has been practiced in Indian peninsula since 5000 BC to offer natural ways to treat diseases and to promote healthcare.
We reviewed the literature on the history, principles and current status of Ayurveda. The data have been presented systematically including the initiatives from Government of India. Several aspects of administrative management, education, teaching and related aspects for promotion and development of Ayurveda and other Indian systems of traditional medicine have been discussed.
This paper reviews on different aspects of development of Ayurveda. Presently, there are 2420 hospitals with about 42271 beds, 15017 dispensaries, 429246 registered practitioners, more than 320 educational institutions, 7699 drug-manufacturing units to promote Ayurveda into the health care delivery system in the country. Ayurvedic Pharmacopoeia of India is the official document for single Ayurvedic drugs (540 monographs) and different formulations (152 monographs). Several aspects in this regard for development of Ayurveda have been discussed.
Considering the widespread use and popularity of Ayurveda worldwide, administrative management and infrastructure facilities, indigenous practices and standards for quality control and it's evaluation have been highlighted. In India, all such efforts for integration of Ayurveda provide potential role in the health care benefits.
The evaluation of immunomodulatory potential by oral administration of Trikatu megaExt (100-200 mg/kg) evoked a significant increased carbon clearance, indicating the stimulation of reticuloendothelial system and potentiated the delayedtype 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. INTRODUCTION Modulation of immune responses to alleviate the diseases has been of interest for many years and the concept of 'Rasayana' is based on related principles (Patwardhan et al., 1990). Rasayana, listed as a class in the texts of traditional Indian medicine literature, consists of a number of plants reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. Besides, a number of medicinal plants as Rasayanas have been claimed to possess immunomodulatory activities. Some of the Rasayana drugs as immunomodulatory agents such as Withania somnifera, Tinospora cordifolia, Asparagus racemosus and Mangifera indica (Dahanukar and Thatte, 1997; Dhuley, 1997; Davis and Kuttan, 2000; Makare et al., 2001) are well known for their traditional uses. Furthermore, medicinal plants used for immunomodulation can provide potential alternatives to conventional chemotherapies for a variety of diseases, especially when the host defense mechanism has to be activated under the conditions of impaired immune response. The use of plant products in the indigenous system of medicines as immunomodulators, indeed, can modulate the body's immune system, as a variety of plant derivatives such as polysaccharides, lectins, peptides, flavonoids and tannins have been reported to modulate the immune system in various in vivo models (Shivaprasad et al., 2006). In the indigenous system there are number of herbal drugs and formulation available to withstand stress and strain of life without altering physiological functions of the body (Nirmala et al., 1999). _________________________________________ *Address for correspondence: E-mail: rnmishr@gmail.com Trikatu is a commonly used herbal preparation in Ayurvedic medicine. It consists of three crude drugs namely dried fruits of black pepper (Piper nigrum Linn.), dried fruits of long pepper (Piper longum Linn.) and dried rhizomes of ginger (Zingiber Officinalis Rosc) in the ratio of (1:1:1; w:w). Trikatu is a Sanskrit word which means "three acrids". It is an essential ingredient of numerous formulations and prescriptions of Ayurvedic medicine, used for a wide range of diseases. (Dash and Junius, 1987, Johri and Zutshi, 1992,). Trikatu have enhancement of blood levels of drugs like vasicine, sparteine, phenytoin, propanolol, theophylline, sulphadiazine and tetracycline when coadministered with trikatu or piperine (Bano et al., 1987). Trikatu is regarded as an important rasayana in ayurvedic medicine. Medicines of the rasayana group are believed to promote health, immunity, and longevity. According to Ayurveda, they strengthen all tissue of the body, prevent aging, promote intellect, and prevent disease.
The present study was undertaken to investigate the anti-inflammatory effect of piperine against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis and compared it with that of the non-steroidal anti-inflammatory drug indomethacin. Administration of heat-killed Mycobacterium tuberculosis (0. 1 ml) intradermally into the right hind paw of rats resulted in increased paw volume, lysosomal enzymes, glycoproteins and tissue marker enzymes and decreased body weight. However, these changes were reverted to near normal levels upon piperine (30 mg/kg body weight, i.p.) treatment. Histopathological analysis of joints also revealed that synovial hyperplasia and mononuclear infiltration observed in arthritic rats were alleviated by piperine. Thus, the present study clearly indicated that piperine possesses promising anti-inflammatory effect against adjuvant-induced arthritis by suppressing inflammation and cartilage destruction.
Ayurvedic herbal preparations commonly used in ayurvedic system of medicine in treatment PaCsah sahEnasdcnahbneharedicdih cichahu urcrnonalai,, ,P ASutrsajhupynhaaynl oucchgou ccrhcnuuasr, n Baaiu lwbreeaur ces,h iunErvnnetaset,r ioAgbamatelcadt e cfroh rua arennratoi,gb Geanocetkesh,r aiaPrlus ep ucohdteuonmrntoiaan,l a P bsa yna dcehirsaucsg daiiknfaofurs asci,o hnBu ramoncfeia lt,l vuhTasorr diisko auaugbtsaut ii lincinsshf,t eu bcKrtanliecoabt,ue ssArie ivaldlilapi sp aeat attpishkenoasegr ue smcnuhsocu hnsrui nacaaehs,,
cShaulmrnoan,e lAlam tlyap hcih, uSrtnaap haynlodc oPcucushs yeapniduegr mchiduirsn, aSa wlmeorne elelfaf etcytpivheim augraiuinms ta nStda Pphroytloeucos cvcuulsg aerpisid. eTrhmei dstisu,d Pyr sohteouwse dvu tlhgaatr iCs,h aSntadpahnyaldoic occhcuursn aa,u Brielubsa,
Ethsec hdeireitc bhiuat caolslio, aPnse auldteormnoantiavse aine rtuhgei ntroesaat manedn tS aanlmd ocnoenltlrao tly opfh ei.n Hteernicc eb,a ictt eisr isaul gingefesctteido nth. at these herbal preparations not only supplement of Keywords: Herbal medicine, Ayurvedic preparations, Antibacterial activities, Ayurvedic churna
In the present study, the anti-inflammatory effect of piperine was investigated on monosodium urate crystal-induced inflammation in mice, an experimental model for gouty arthritis, and compared it with that of the nonsteroidal anti-inflammatory drug, indomethacin. The levels of lysosomal enzymes, lipid peroxidation, tumor necrosis factor-α, and paw volume were increased significantly, and the activities of antioxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon piperine (30 mg/kg b.wt, i.p.) treatment. In vitro, piperine (50/100 ug/ml) suppressed the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration-dependent manner when compared to control cells. Thus, the present study clearly indicated that piperine inhibit the monosodium urate crystal-induced inflammation and can be regarded as therapeutic drug for the treatment of acute gouty arthritis.
'Trikatu' is an Ayurvedic preparation containing black pepper, long pepper and ginger, which is prescribed routinely for a variety of diseases as part of a multidrug prescription. These herbs along with piperine (alkaloid of peppers) have been shown to possess diverse biological activities in mammalian systems. A review is presented of these studies and it has been suggested that their use in the Indian system of medicine could be due to their bioavailability enhancing action on other medicaments.
The effect of piperine on the bioavailability and pharmacokinetics of propranolol and theophylline has been examined in a crossover study. Six subjects in each group received a single oral dose of propranolol 40 mg or theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7 days. An earlier tmax and a higher Cmax and AUC were observed in the subjects who received piperine and propranolol. It produced a higher Cmax, longer elimination half-life and a higher AUC with theophylline.
In clinical practice, the enhanced systemic availability of oral propranolol and theophylline could be exploited to achieve better therapeutic control and improved patient compliance.
Pharmacokinetics of phenytoin were studied in healthy subjects. In a crossover study five volunteers received either a single oral dose (300 mg) of phenytoin alone or in combination with multiple doses of piperine (20 mg × 7 days) followed by an oral dose of phenytoin. Blood samples were collected at 0.5, 1,2,3,4,8,12,24, and 48 h after drug administration and analysed for phenytoin by the enzyme multiplied immunoassay technique (EMIT). The results obtained revealed that a single daily dose of piperine for 7 days decreased the absorption halflife (P < 0.05), prolonged the elimination halflife (P < 0.01), and produced a higher area under the drug concentration curve (P < 0.05) in comparison to phenytoin alone. It is therefore concluded that piperine on multiple dose administration alters the pharmacokinetic parameters of the antiepileptic.
Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.
The effect of single and multiple doses of a herbal preparation trikatu, an Ayurvedic prescription, on the bioavailability and pharmacokinetics of rifampicin was studied in rabbits. Rabbits (n = 10) 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.). The study had a cross over design with a washout period of 7 days. In the other study, six rabbits were administered a single dose of rifampicin (24 mg/kg, p.o.) before and after multiple doses of trikatu (500 mg/kg x 7d, p.o.). 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 treated with single dose of trikatu there was a significant decrease in the peak plasma concentration (Cmax) of rifampicin (P < 0.05). 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. Our results suggest that coadministration of trikatu does not influence the extent of bioavailability (AUC0-infinity) but reduces the rate of bioavailability (Cmax) of rifampicin. And this latter effect may reduce the efficacy of rifampicin therapy.
"Trikatu"-an Ayurvedic formulation comprising of a 1:1:1 ratio of dried fruits of Piper nigrum, Piper longum and dried rhizomes of Zingiber officinale is widely used to enhance the bioavailability of drugs, like vasicine, indomethacin, etc. The enhanced biological response might lead to alteration of therapeutic regimens of commonly prescribed drugs. The present work was aimed to study the effect of concomitant administration of Trikatu on the pharmacokinetics and pharmacodynamics of diclofenac sodium, a frequently prescribed non-steroidal anti-inflammatory drug, having a poor oral bioavailability (54 +/- 2%). The effect of Trikatu on the bioavailability profile of diclofenac sodium was studied in rabbits. It was observed that Trikatu significantly decreased the serum levels of diclofenac sodium. The pharmacodynamic study was carried out to evaluate the effect of Trikatu on the anti-inflammatory activity of diclofenac sodium using carragenin-induced rat paw edema model. It was observed that the mean percent edema inhibition shown by the combination of Trikatu and diclofenac was similar to that shown by Trikatu alone but significantly less than that shown by diclofenac alone. Thus, the experimental findings indicated that Trikatu pretreatment might decrease the bioavailability of certain drugs probably through a drug-herb interaction thereby adversely affecting the therapeutic efficacy of these drugs.
Combating heart disease is one of the challenging problems of biomedical science today. Towards this goal an indigenous preparation 'Trikatu' (a herbal combination containing Piper longum (fruit), Piper nigrum (fruit) and Zingiber officinale (rhizome) dry powder) was fed to normal and cholesterol fed male Rattus norvegicus to ascertain its efficacy as a hypolipidaemic agent. Its effects on body weight, blood and tissue (aortic, cardiac and hepatic) lipids--total, free and esterified cholesterol, low density lipoprotein(LDL) and high density lipoprotein(HDL) cholesterol, triglycerides and phospholipids--and the atherogenic index 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 atherosclerosis. Hence 'Trikatu' can be used as a potent hypolipidaemic agent and it can reduce the atherosclerosis associated with a high fat diet.
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