STRATEGIES FOR ENHANCEMENT OF BIOAVAILABILITY OF MEDICINAL AGENTS WITH NATURAL PRODUCTSHTML Full Text
STRATEGIES FOR ENHANCEMENT OF BIOAVAILABILITY OF MEDICINAL AGENTS WITH NATURAL PRODUCTS
Garima Jain and Umesh K. Patil *
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh, India
ABSTRACT: In Advances drug design technologies, a large no of drug molecules are being introduced in every year but many of these molecules have problems like their solubility, stability, bioavailability and its long lasting side effects. Low bioavailability is one of the serious but curable problems in case of the drug molecule. Low bioavailability happens because a lot of molecules unable to permeation the gastrointestinal epithelia. There are some other factors also which responsible for low bioavailability i.e. low lipophilicity and zwitterionic character at physiological pH, poor water solubility or efflux by P-glycoprotein (P-gp) etc. The object of this review is to explore the concept of bioavailability to achieve better therapeutic response in appropriate dose using natural drugs and natural products like ginger, caraway, aloe, quercetin, glycyrrhizin piperine, curcumin etc. The use of natural products is the most reliable means for bioavailability enhancement because these are safe, non-toxic, economical, easily procured, non-addictive, pharmacologically inert and non-allergenic in nature etc. This review explores the natural drugs from plant and animal sources with their mechanism, in-vivo study, marketed formulation and its future prospective
Bioavailability, Bioenhancer, Natural drugs, P-glycoprotein, Piperine
INTRODUCTION: India is a country where a lot of variety of the herbs with various medicinal values is available. From past to current scenario, researchers are trying to evaluate biological activities in different plant’s parts like leaf, flower, stem, root etc for the treatment of various diseases.
In ancient time, lot of herbal drugs were used for the treatment of the diseases in individually or in the combination with many other drugs in different dosage forms e.g. black pepper was used in case of coughing, while ginger was used for coughing, flavouring etc.
Combination of long pepper (Piper longum Linn.), black pepper (Piper nigrum Linn.) and ginger (Zingiber officinale Roscoe) collectively called “Trikatu” means “three acrids”, was used for the treatment of the diseases. Combination of these drugs enhances the therapeutic efficacy by means to increase the bioavailability 1, 2.
The term bioavailability is one of the principal pharmacokinetic properties of drugs. It shows the rate and extent of the active pharmaceutical ingredients in the blood. This helps in calculating that how much amount is absorbed from blood and how much is unabsorbed and first pass metabolized.
When a drug is administered intravenously; its bioavailability is 100% means whole amount is reached into the blood circulation but when a drug is administered via. other routes such as oral, parentral, muscular, subcutaneous etc.,
due to incomplete absorption or first pass metabolism its bioavailability is decreased 3. Because of the low bioavailability, insufficient amount of drugs is reached in to the circulation and unable to produce their therapeutic effects. This problem can be overcome by the uses of bioenhancers.
In 1929, Bose introduced firstly about the concept of bioenhancer. He used long pepper along with vasaka (Adhatoda vasica Nees.) leaves and determined that the antiasthmatic activity of vasaka leaves was enhanced when long pepper was used with it 4.
Bioenhancers are the substances which increase the therapeutic effectiveness of the drug by increasing availability of the drugs in blood in combination with drugs without affecting its properties away 5, 6.
The use of bioenhancers has expanded the therapeutic effectiveness of the number of drugs that can be administered non-intravenously with improving bioavailability. This approach has been worked by alter the enzymatic system, improve GIT absorption, stimulating gamma glutamyl transpeptidase (GGT) and by drug targeting etc. Extensive research during the past decades has revealed that bioenhancing approach has attracted considerable attention as regards of its many potential advantages. It offers comfortable, convenient, and noninvasive way to administer drugs due to following advantages of it.
- Dose reduction
- Minimization of drug resistance.
- Minimization of drug (especially true in case of anticancer drug like taxol).
- Ecological benefit.
- Safety of the environment 7.
The present review highlights the current status of natural products with significant bioenhancing activities.
Ideal properties of the bioenhancers: The contribution of bioenhancers have been reviewed which states that the ideal bioenhancers 8, 9, 10.
- Should be nontoxic, non-allergenic and non-irritating.
- Should not produce own pharmacological effects.
- Should be rapid-acting with predictable and reproducible activity.
- Should be unidirectional in action.
- Should be compatible with other active pharmaceutical ingredients.
- Should be stable with time and environment.
- Should be easily formulated into a various dosage form.
- Should be easily available and cost effective.
TABLE 1: BIOEHANCING PROPERTIES OF PIPERINE IN DIFFERENT CLASSES OF DRUGS WITH THEIR EXPERIMENTAL MODEL
|S. no.||Drug||Class||Experimental model||Reference|
|1.||Rifampicin||Antituberculous||Human (in vitro)||11, 12, 13|
|2.||Phenytoin Pentobarbitone Barbiturate||Anticonvulsant||Human, Rats||14|
|4.||Nimesulide, Diclofenac sodium||NSAID||Mice, Human||17, 18|
|6.||Epigallocatechin Gallate (Green tea)||Anticancerous||In albino mice||20|
|7.||Ciprofloxacin, Oxytetracycline||Antibiotics||In vitro, WLH hens||21, 22,|
|8.||Saquinavir mesylate, Nevirapine
|Antiretroviral agents||Human Caco-2 cells line & male Sprague -Dawley rats||23,24
TABLE 2 BIOENHANCING ACTIVITY OF PIPERINE
|Boswellic acid (Boswellia serrata Triana & Planch.),
Ginsenosides (Gingko biloba Linn.), Withanaloids (Withania somnifera Linn.), Curcuminoides (Curcuma longa Linn.) and
Pycnogenol (Pinus pinaster Aiton.)
|Iodine, Calcium, Iron, Zinc, Copper, Selenium, Magnesium, Potassium and manganese||27|
|Lysine, Isoleucine, Leucine, Threonine, Valine, Tryptophan, Phenylalanine and Methionine||28|
|Water soluble: Vitamin B1, Vitamin B2, niacinamide, Vitamin B6, Vitamin B12, folic acid and Vitamin C
Fat soluble: Vitamin A, β-carotene (provitamin), Vitamin D, Vitamin E and Vitamin K
|5.||Gallic acid||A type of phenolic acid, found in gallnuts, tea leaves and oak bark||30, 31|
Classification: Bioenhancers are classified into two classes on the basis of their origin;
Bioenhancers from herbal sources:
- These bioenhancers are derived from various parts of botanicals. Secondary metabolites of various medicinal and aromatic plants are considered as rich source of bioenhancers (Table 3).
Bioenhancers from non herbal sources:
- These bioenhancers are obtained and synthesized with non herbal and synthetic chemical substances.
- Bioenhancers from herbal sources:
TABLE 3: HERBS, ITS SOURCE, MECHANISM AND THEIR DOSE AS BIOENHANCES
|S.no.||Drug||Biological source||Mechanism||Dose of drug||Drug||Ref.|
|Seeds of Piper longum Linn. and Piper nigrum Linn.
|Methylenedioxyphenyl ring in piperine helps in the inhibition of the drug metabolizing enzymes including CYP 450 enzymes and UDP glucuronyl transferase. It also inhibits P-GP and then efflux of absorbed drug from enterocytes||15 mg/kg.
|Piperine is used in combination with various drugs and increases the efficacy of these drugs
(Table 1, 2)
|Dried and fresh rhizomes of Curcuma longa Linn. Family-Zingiberaceae.||Curcumin suppresses drug metabolizing enzymes (CYP3A4) in the liver as well as inducing changes in the drug transporter P-glycoprotein, hence increase the Cmax and AUC of celiprolol and midazolam in rats||12g/day||Celiprolol and Midazolam
|32, 33, 34, 35|
|Rhizome of the perennial plant Zingiber officinale Roscoe., Family- Zingiberaceae.||Due to the presence of saponins, flavonoids, and alkaloids, Ginger acts powerfully on GIT mucous membrane. The role of ginger is to regulate intestinal function to facilitate absorption.||10-30 mg/kg||Antibiotics like Azithromycin, Erythromycin, Cephalexin, Cefadroxil, Amoxycillin and Cloxacillin||36|
|Caraway (Seeds)||Dried ripe seeds of Carum carvi Linn., Family- Apiaceae.||Due to a novel flavonoid glycoside it enhances the peak concentration (Cmax) and area under the curve (AUC) of rifampicin||1-55mg/kg||Antibiotics, antifungal, antiviral and anticancerous drugs. Therapeutic activity of Anti-TB drugs like Rifampicin, Pyrazinamide and Isoniazid||37, 38|
|5.||Glycyrrhizin||Dried root and stolon of Glycyrrhiza glabra Linn., Family- Leguminosae.||It enhances cell division inhibitory activity of anticancerous drug. It also enhances (2 to 6 fold) transport of antibiotics||1 μg/ml||Taxol and antibiotics like Rifampicin, Tetracycline, Nalidixic acid, Ampicillin and Vitamins B1 and B12 as bioenhancer||39|
|Indian aloe (Leaves)||Dried juice of the leaves of Aloe barbadensis Mill., Family-Liliaceae||Aloe in combination with vitamins, perform the absorption slower and last longer in the plasma and increases bioavailability of Vitamin C and E in human. It also capable of inhibiting the release of reactive oxygen free radicals from activated human neutrophils.||Vitamin C and E
|Quercetin||It is a flavonoid found in many fruits (apples, citrus fruits like red grapes, raspberries, and cranberries), green leafy vegetables and black and green tea||It inhibits the p-glycoprotein efflux pump and metabolizing enzyme, CYP 3A4 in the intestinal mucosa and restraint the metabolizing enzyme CYP3A4||-||Diltiazem, Digoxin, Epigallocatechin gallaate||42|
|Allicin||Aeromatic bulb of Allium sativum Linn. Family- Liliaceae||Allicin enhances AmB-induced vacuole membrane damage by inhibiting ergosterol trafficking from the plasma membrane to the vacuole membrane||120 μM allicin or a non-lethal concentration of AmB (0.5 μM)||Fungicidal activity of Amphotericin B||43, 44, 45, 46|
|Naringin||It is a flavanone-7-O-glycoside occurs naturally in citrus fruits, especially in grapefruit||It inhibits the CYP3A1/2 enzymes and p-glycoprotein is modulated in rats||3.3 and 10 mg/kg||Paclitaxel, Verapamil, Diltiazem||5, 47|
|Tea (Leaves and Buds)||Leaves and leaf buds of Thea sinensis Linn. Family- Theaceae||The thermogenic properties of tea extract shows a synergistic interaction between caffeine and catechin polyphenols that appears to prolong sympathetic stimulation of thermogenesis. Green tea also promotes fat oxidation and decreased the absorption rate of zinc while black tea increased the rate||-||Both teas promote the absorption of manganese and copper as nutrients in the blood circulation.||48|
|Niaziridin||Niaziridin a nitrile glycoside is isolated from the pods of Moringa oleifera Lam., Family- Moringaceae||Commonly act with antibiotics against gram-positive bacteria like Myobacterium smegmatis, Bacillus subtilis and gram-negative bacteria like E. coli to increase the absorption of it.||-||Vitamin B12, rifampicin, ampicillin, nalidixic acid, azole antifungal drugs such as clotrimazole||49, 50|
|Lysergol||It is isolated from higher plants like Rivea corymbosa Linn., Ipomoea violacea Linn. and Ipomoea muricata Linn.||It promotes the killing activities of different antibiotics on bacteria. lysergol enhances the transport of antibiotics across the intestinal gut and cell membrane.||10 μg/ml||Broad-spectrum antibiotics||51|
|Genistein||It is an isoflavone found in a number of dietary plants like soybean (Glycine max Linn.) and kudzu (Pueraria lobata Willd.).||Genistein is reported to be able to inhibit P-gp, BCRP and MRP-22 efflux functions.
|3.3 mg/kg or 10 mg/kg||Paclitaxel, Epigallocatechin gallate the||33, 52, 53, 54|
|Root of the climbing plant Sinomenium acutum Thunb. Family- Menispermaceae.||The mechanism underlying the increase in bioavailability of paeoniflorin is explained as sinomenine could decrease the efflux transport of paeoniflorin by P-gp in the small intestine.||90mg/kg||Paeoniflorin||55, 56, 57|
|5’ methoxy hydnocarpin (5′-MHC)||Leaves of Barberis fremontii Torr., Family- Berberidaceae.||5′-MHC has no antimicrobial activity but it inhibits the MDR-dependent efflux of berberine from S. aureus cells and effectively disabled the bacterial resistance mechanism against the berberine antimicrobial action.||100 μg/ml||Berberine||58, 59, 60|
|Seeds of Hydnocarpus wightiana Family- Achariaceae.||It acts by blocking the synthesis and coenzymatic activity of biotin.||4 µg/ml||Biotin||61|
|Leaves of Stevia rebaudiana Bertoni., Family- Asteraceae.||Components of stevia called Stevioside and steviol stimulates insulin secretion via a direct action on beta cells. Due to the activity for reducing vascular tension it is used for patients with hypertension.||30 mg/kg||Antibiotics, antiobese drugs, antidiabetic drugs, antifungal drugs, antiviral drugs, anticancer drugs, cardiovascular drugs, anti-inflammatory, antiarthritic agents, antituberculosis/ antileprosy drugs, anthelmintic/respiratory drugs, immune-modulators, antiulcer drugs, and herbal products or drugs.||62|
|Fruit of Capsicum annum Linn., Family- Solanaceae||The absorption of capsicum increases AUC of the drugs.||-||Theophylline||63, 64|
|19.||Cumin seeds||Dried seeds of Cuminum cyminum Linn., Family- Apiaceae||Possible mechanisms may be the Aquous extract of cumin seeds stimulate β-adrenoceptors and/or inhibit histamine H1 receptors. It also worked in the opening of potassium channels and inhibition of calcium channels.||0.5 to 25 mg/kg||Erythromycin, Cephalexin, Amoxycillin, Fluconazole, Ketoconazole, Zidovudine and 5-Fluorouracil
|Methanolic extract of Ammannia multiflora Roxb., Family-Lythraceae||Ammaniol have the property to increase glucose uptake and shows potent antihyperglycemic activity.||-||Antimicrobial drugs like Nalidixic acid||66, 67|
|Gallic acid is a type of phenolic acid, found in gallnuts, tea leaves and oak bark etc.||Gallic acid increases net drug absorption and decrease drug biotransformation in the gut wall by inhibiting cytochrome P450 drug metabolism preference in other locations, such as the liver, which was the primary site of drug metabolism.||-||Acetanilides, Aminoquinolines, Benzodiazepines, benzofurans, cannabinoids, digitalis glycosides, ergot alkaloids, flavonoids, imidazoles, quinolines, macrolides, naphthalenes, opiates, oxazoles, phenylalkylamines, piperidines, polycyclic aromatic hydrocarbons, pyrrolidines, pyrrolidinones, stilbenes, sulfonylureas, sulfones, triazoles, tropanes and vinca alkaloids.||68, 69|
- Bioenhancer from non herbal sources:
Source: Capmul (mono-, di- and triglyceride) are prepared by the glycerolysis of select fats and oils and/or esterification of glycerin with specific fatty acids.
Mechanism: Due to Lipophilic nature of capmul, it acts as very effective carriers and solubilizers of active compounds. Because of its mono-diglyceride medium chain esters which are recommended for the dissolution of difficult compounds such as sterols, it also exhibited bacteriostatic activity.
Drugs: Lipophilic nature of capmul is helped to increase the solubility of Ceftriaxone 70.
- Cow urine distillate: Cow urine distillate is more effective as bioenhancer than cow urine. Its Rasayana’ tatva is responsible for modulation of the immune system and act as a bioenhancer.
- It increases the effectiveness of antimicrobial, antifungal, and anticancer drugs.
- Cow urine can be used as a bioenhancer of zinc because it has antitoxic activity against the cadmium chloride toxicity 71.
- Cow urine distillate increased the activity of rifampicin against Escherichia coli and against gram-positive bacteria. It probably acts by enhancing the transport of antibiotics across the membrane of gastrointestinal tract72.
- Due to immunomodulatory properties of cow urine distillate, it is significantly enhanced the effect of gonadotropin releasing hormone on the gonadosomatic indices, sperm motility, sperm count, and sperm morphology, especially in 90- and 120-day-treated groups in male mice73.
- It also enhances the potency of taxol against MCF-7 cell lines.
- It enhances the bioavailability of ampicillin in 0.05 μ g/ml concentrations and clotrimazole in.88 μ g/ml concentration by facilitating the 0 absorption of drugs across the cell membrane 74.
Common mechanism of action of Bioenhancers:
- Alteration in the activity of the enzymatic system:
(a) Suppressors of CYP -450 enzyme and its isoenzymes: Bioenhancers inhibit CYP -450 enzyme and its isoenzymes i.e. CYP3A4 enzymes which are presented in enterocytes and hepatocytes and contribute to major extent to first-pass elimination of many drugs. This indicates that dietary bioenhancer could affect plasma concentrations of CYP3A4 substrates in humans, in particular if these drugs are administered orally. Some of the metabolizing enzymes i.e. CYP1A1, CYP1B1, CYP1B2, CYP2E1, CYP3A4 etc are inhibited or induced by bioenhancer. Most of the drugs metabolized by these enzymes are influenced by bioenhancer.
Example: Piperine 75, Naringin 76, Gallic acid 77, Quercetin78
(b)Inhibitors of P-gp efflux pumps: Efflux transporters such as P-glycoprotein play an important role in drug transporting in many organs. In the gastrointestinal track, P-glycoprotein pumps decrease the rate of absorption of the drug by taking back drug into the lumen. P-glycoprotein inducer, such as rifampicin, can reduce the bioavailability of some other drugs and inhibitors of P-glycoprotein increase the bioavailability of susceptible drugs by influencing absorption, distribution, metabolism and elimination of P-gp substrates in the process of modulating pharmacokinetics.
Example: Caraway 25, Sinomenine 25, Genistein 79
- Regulation of GIT to facilitate better absorption
Herbal drugs increase the drug absorption via paracellular route by redistribution of the cytoskeletal F-actin, causing the opening of the tight junctions.
They also increase the solubility of hydrophobic drugs in the aqueous layer and increase the fluidity of the apical and basolateral membranes. Bioavailability enhancing activity of drugs is also found to be partly due to the increase in the blood supply to the intrinsic vessels as a result of local vasodilation. Increased blood supply to the gastrointestinal tract is one of mechanism of bioenhancer.
Example: Aloes, Niaziridin, Ginger, Liquorice 80
- Cholagogous effect: Bioenhancers promote the flow of bile into the intestine by the contraction of the gallbladder.
Example: Liquorice 81, 82, 83
- Thermogenic properties: Bioenhancers, having thermogenic property, increase the rate of metabolism by increasing the temperature. In this way it also improves the gastric mobility and hinders the absorption of cholesterol.
Example: Garlic, Ginger, Turmeric 84
- Stimulation of gamma glutamyl transpeptidase (GGT) activity: Gamma glutamyl transpeptidase is a membrane-bound glycoprotein located on the outer surface of the cell membrane and used as marker for the liver, biliary system and pancreatic diseases. It is responsible for the transport of amino acids across cell membranes. Bioenhancer stimulates the activation of gamma- glutamyl transpeptidase and transport of nutrients across the intestinal cells is augmented 57.
- Alteration of gastrointestinal transit and intestinal motility: Saponins containing bioenhancers increase the permeability of intestinal mucosal cells in vitro and inhibit active mucosal transport. This facilitates uptake of those substances that are normally not absorbed. Saponins also lower transmural potential difference (TPD, the electrochemical gradient that acts as a driving force for active nutrient transport across the brush border membrane of the intestine) across the small intestine of rat.
Example: Alliums1, Tea 9, Liquorice 31
- Drug targeting: Bioenhancers helps to enhance the binding of the drug with the target sites such as receptors, proteins, DNA, RNA and in the pathogen also, increases GIT vasculature by vasodilation to increase absorption of drugs, modulation of the cell membrane dynamics to increase transport of drugs across cell membranes thus potentiate and prolong the effect lead to enhance activity of drugs 85, 86.
- Bioenhancers may also be useful in the control of diseases like cerebral infections, epilepsy and other CNS problems by promoting the transport of nutrients and the drugs across the blood brain barrier 87, 88.
Risorine: Risorine is a rifampicin containing fixed dose combination product, approved in India for the use as an antitubercular drug in place of rifampicin 450 mg and isoniazid 300 mg.
Composition: Each capsule of resorine contains:
Rifampicin 200 mg IP, Isoniazid 300 mg IP, Piperine 10 mg
Dosage: For adult, one resorine capsule to be taken once daily, one hour before or two hours after meals with a full glass of water.
Indication: It is used for treatment of all forms of tuberculosis in which organisms are susceptible to rifampicin ad isoniazid 11, 29, 31.
Problems with bioenhancers: The concept of the bioenhancer is much demanded approach now a day in the society but there are lot of problems in research and development. In large scale production, there is a need to scale up laboratory or pilot technologies for commercialization. The challenges are related to toxicity, allergy and irritation. Its compatibility and stability with other active pharmaceutical ingredients for appropriate time and duration is also a matter. 89
Its agglomeration and the chemistry process are also creating hurdles in commercialization of bioenhancers. Some national and international agencies i.e. The United States Food and Drug Administration and the European Medicines Evaluation Agency are taking the initiative steps to identify possible scientific and regulatory challenges along with their solution.
By overcoming all hurdles this concept can be used for a lot of patients with highly valuable and versatile results.
CONCLUSION: The bioenhancement technology is based on traditional system of medicine but a rapidly developing field now days. New drug development technologies are also rapidly developing field but there is concerned about the economics of drug development. Bioenhancement technique would significantly increase the number of drugs suitable for diseases in which amount of drug and doses are more and more. The researchers are now aimed at methods of reduction of drug dosage and thus drug treatment cost and making treatment available to a wider section of the society including the financially sport to the country. Bioenhancing phenomenon is helpful in various challenge and relief the society due to its side effect e.g. cancer. This review will be helpful to scientists engaged in research related to bioenhancers of herbal and non- herbal origins.
ACKNOWLEDGEMENT: The financial assistance of SERB, Department of Science and Technology (Govt. of India) under project no. SB/EMEQ-376/2014 is gratefully acknowledged.
- Grace XF, Seethalakshmi S, Chamundeeswari D, Manna PK, Shanthi S and Latha S: Bioenhancers – A new approach in modern medicine. Indo American Journal of Pharmaceutical Research 2013; 3(12):1576-1580.
- Jhanwar B and Gupta S: Biopotentiation using Herbs: Novel technique for poor bioavailable drugs. International Journal of Pharm Tech Research 2014; 6(2): 443-454.
- Thakkar H, Patel B and Thakkar S: A review on techniques for oral bioavailability enhancement of drugs. International Journal of Pharmaceutical Sciences Review and Research 2010; 4(3): 203-223.
- Madhukar S, Dama C and Varshneya MS: Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats, Journal of Veterinary Science, 2008; 9(1): 25-29.
- Kesarwani K and Gupta R: Bioavailability enhancers of herbal origin: An overview. Asian Pacific Journal of Tropical Biomedicine 2013; 3(4): 253-266.
- Johri RK and Zutshi U: An Ayurvedic formulation ‘Trikatu’ and its constituents, Journal of Ethnopharmacology 1992; 37(2): 85–91.
- Varshnaya C, Use of herbal bioenhancer in animal health care.
- Raut SV, Nemade LS, Desai MT, Bonde SD and Dongare SU: Chemical penetration enhancers: for transdermal drug delivery systems. International Journal of Pharmaceutical Review and Research 2014; 4(1): 33-40.
- Patil UK and Saraogi R: Natural products as potential drug permeation enhancer in transdermal drug delivery system. Archives of Dermatological Research 2014; 306(5): 419-426.
- Mirza ZM, Kumar A, Kalia NP, Zargar A and Khan IA: Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. Journal of Medical Microbiology 2011; 60(10): 1472–1478.
- Gurumurthy P, Vijayalatha S, Sumathy A, Asokan M and Naseema M: Hepato protective effect of aqueous extract of Piper longum and piperine when administered with antitubercular drugs. The Bioscan 2012; 7(4): 661-663.
- Balakrishnan V, Varma S and Chatterji D: Piperine augments transcription inhibitory activity of rifampicin by severalfold in Mycobacterium smegmatis. Current Science 2001; 80(10): 1302-1305.
- Zutshi RK, Singh R, Zutshi U, Johri RK and Atal CK: Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. Journal of the Association of Physicians of India 1985; 33(3): 223-224.
- Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK and Sharma SC: Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. European Journal of Clinical Pharmacolog 1991; 41(6): 615-617.
- Bano G, Amla V, Raina RK, Zutshi U and Chopra CL: The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Medica 1987; 53(6): 568-569.
- Anubala S, Sekar R, Narayana P and Nagaiah K: A validated high-performance thin-layer chromatographic method for the determination of bioenhanced first-line antituberculosis drugs in pharmaceutical formulation. Journal of Planar Chromatography 2015; 28(1): 67-73.
- Pooja S, Agrawal R, Nyati P, Savita V and Phadnis P: Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. International Journal of Pharmacology 2007; 5(1): 3.
- Gupta SK, Velpandian T, Sengupta S, Mathur P and Sapra P: Influence of piperine on nimesulide induced antinociception. Phytotherapy Research 1998; 12(4): 266-269.
- Hiwale AR, Dhuley JN and Naik SR: Effect of co administration of piperine on pharmacokinetics of β lactum antibiotics in rats. Indian Journal of Experimental Biology 2002; 40(3): 277-281.
- Lambert JD, Hong J, Kim DH, Mishin VM and Yang CS: Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3- gallate in mice. Journal of Nutrition 2004; 134(8): 1948-1952.
- Khan IA, Mirza ZM, Kumar A, Verma V and Qazi GN: Piperine, a Phytochemical Potentiator of Ciprofloxacin against Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2006; 50(2): 810–812.
- Singh M, Varshneya C, Telang RS and Srivastava AK: Alteration of pharmacokinetics of oxytetracycline following oral administration of Piper longum in hens. Journal of Veterinary Science 2005; 6(3): 197–200.
- Kasibhatta R and Naidu MUR: Influence of Piperine on the pharmacokinetics of nevirapine under fasting conditions. Drugs in R &D 2007; 8(6): 383-391.
- Basu S, Rastogi H, Patel VB and Patel H: Effect of herbal bioenhancers on saquinavir in human Caco- 2 cell monolayers and pharmacokinetics in rats. IJPMPS 2012; 2(29): 28-42.
- Patil UK, Singh A and Chakraborty AK: Role of Piperine as a bioavailability enhancer. International Journal of Recent Advances in Pharmaceutical Research 2011; 4: 16-23.
- Majeed M, Badmaev V and Rajendran R: Use of piperine to increase bioavailability of nutritional compounds. US Pat 5536506A (to Sabinsa Corp, New Jersey) 16 July, 1996.
- Randhawa GK: Cow urine distillate as bioenhancer. Journal of Ayurveda and Integrative Medicine 2010; 1(4): 240–241.
- Majeed M, Badmaev V and Rajendran R: Use of piperine as a bioavailability enhancer. US Pat 5744161A (to Sabinsa Corp, New Jersey) 28 August, 1998.
- Badmaev V, Majeed M and Norkus EP: Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14- days of oral beta-carotene supplementation. Nutrition Research 1999; 19(3): 381-388.
- Zhao J Q, Du GZ, Xiong YC, Wen YF, Bhadauria M and Nirala SK: Attenuation of beryllium induced hepatorenal dysfunction and oxidative stress in rodents by combined effect of gallic acid and piperine. Archives of Pharmacal Research 2007; 30(12): 1575-1583.
- Dudhatra GB, Mody SK, Awale M, Patel HB, Modi CM, Kumar A, Kamani DR and Chauhan BN: A comprehensive review on pharmacotherapeutics of herbal bioenhancers. The Scientific World Journal 2012; 1-33.
- Durgaprasad S, Pai CG, Vasanthkumar, Alvres JF and Namitha S: A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian Journal of Medical Research 2005; 122(4): 315-318.
- Moorthi C and Kathiresan K: Curcumin–Piperine/Curcumin–Quercetin/Curcumin–Silibinin dual drug-loaded nanoparticulate combination therapy: A novel approach to target and treat multidrug-resistant cancers. Journal of Medical Hypotheses and Ideas 2013; 7(1): 15–20.
- Anand P, Kunnumakkara AB, Newman RA and Aggarwal BB: Bioavailability of Curcumin: problems and promise. Molecular Pharmaceutics 2007; 4(6): 807–818.
- Kulkarni SK, Bhutani MK and Bishnoi M: Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 2008; 201(3): 435-442.
- Ghayur MN and Gilani AH: Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders. Digestive Diseases and Sciences 2005; 50(10): 1889-1897.
- Johri RK: Cuminum cyminum and Carum carvi: An update. Pharmacognosy Review 2011; 5(9): 63–72.
- Amin S, Mir SR, Kohli K, Ali B and Ali M: A study of the chemical composition of black cumin oil and its effect on penetration enhancement from transdermal formulations. Natural Product Research 2010; 24(12): 1151-1157.
- Khanuja SP, Kumar S, Arya JS, Shasany AK, Singh M, Awasthi S, Gupta SC, Darokar PM and Rahman LU: Composition comprising pharmaceutical/nutraceutical agent and a bio-enhancer obtained from Glycyrrhiza glabra. US Pat 6,979,471B1 (to Council of Scientific and Industrial Research, India) 27 December, 2005.
- Sahu PK, Giri DD, Singh R, Pandey P, Gupta S, Shrivastava AK, Kumar A and Pandey KD: Therapeutic and medicinal uses of Aloe vera: A review. Pharmacology Pharma, 2013; 4(8): 599-610.
- Cole L and Heard C: Skin permeation enhancement potential of Aloe Vera and a proposed mechanism of action based upon size exclusion and pull effect. International Journal of Pharmaceutics 2007; 333(1-2): 10–16.
- Hollman PC, Van trijp JM, Buysman MN, Vander Gaag MS, Mengelers MJ, Mengelers MJ, de Vries JH, Katan MB: Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS letters 1997; 418(1-2): 152–156.
- Ogita A, Fujita KI and Tanaka T: Enhancing effects on vacuole-targeting fungicidal activity of amphotericin B. Frontiers in Microbiology 2012; 3(100): 1-6.
- Davis LE, Shen J and Royer RE: In vitro synergism of concentrated Allium sativum extract and amphotericin B against Cryptococcus neoformans. Planta Medica 1994; 60(6): 546-549.
- Ogita A, Fujita K, Taniguchi M and Tanaka T: Enhancement of the fungicidal activity of amphotericin B by allicin, an allyl-sulfur compound from garlic, against the yeast Saccharomyces cerevisiae as a model system. Planta Medica 2006; 72(13): 1247–1250.
- Ankri S and Mirelman D: Antimicrobial properties of allicin from garlic. Microbes and Infection 1999; 1(2): 125–129.
- Singh R Devi S, Patel JH, Patel U, Bhavsar SK and Thaker AM: Indian herbal bioenhancers: A Review. Pharmacognosy Reviews 2009; 3(5): 80-82.
- Cooper R, Morre DJ and Morre DM: Medicinal benefits of green tea: part I. review of noncancer health benefits. Journal of Alternative and Complementary Medicine 2005; 11(3): 521–528.
- Liversidge GG and Cundy KC: Particle size reduction for improvement of oral bioavailability of hydrophobic drugs, I absolute oral bioavailavility of nanocrystalline danazol in beagle dogs. International journal of Pharmaceutics 1995; 125(1): 91–97.
- Khanuja SPS, Arya JS, Ranganathan T, Kumar S, Saikia D, Kaur H and Singh M: Nitrile glycoside useful as a bioenhancer of drugs and nutrients, process of its isolation from Moringa oleifera. US Pat 6858588B2 (to Council Of Scientific And Industrial Research, India) 22 February, 2005.
- Khanuja SPS, Arya JS, Srivastava SK, Shasany AK, Kumar S, Ranganathan T, Darokar MP and Kumar S: Antibiotic pharmaceutical composition with lysergol as bio-enhancer and method of treatment. US Pat 20070060604A1 (to Council of scientific and industrial research, India) 15 March, 2007.
- Li X and Choi JS: Effect of genistein on the pharmacokinetics of paclitaxel administered orally or intravenously in rats. International journal of Pharmaceutics 2007; 337(1-2): 188–193.
- Sparreboom A, Van AJ, Mayer U, Schinkel AH, Smit JW, Meijer DK, Borst P, Nooijen WJ, Beijnen JH and van Tellingen O: Limited oral bioavailability and active epithelial excretion of paclitaxel (taxol) caused by P-glycoproetin in the intestine. Proceeding of the National Academy of Sciences 1997; 94(5): 2031-2035.
- Huisman M, Chhatta AA, Tellingen OV, Beijnen JH and Schinkel AH: MRP2 (ABCC2) transports taxanes and confers paclitaxen resistance and both processes are stimulated by probenecid. International Journal of Cancer 2005; 116(5): 824-829.
- Takeda S, Isono T, Wakui Y, Matsuzaki Y, Sasaki H, Amagaya S andMaruno M: Absorption and excretion of paeoniflorin in rats. Journal of Pharmacy and Pharmacology 1995; 47(12A): 1036–1040.
- Liu ZQ, Zhou H, Liu L, Jiang ZH, Wong YF, Xie Y,Cai X, Xu HX and Chan K: Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats. Journal of Ethnopharmacology 2005; 99(1): 61-67.
- Drabu S, Khatri S, Babu S and Lohani P: Use of herbal bioenhancers to increase the bioavailability of drugs. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2011; 2(4): 107-119.
- Stavri M, Piddock LJV and Gibbons S: Bacterial efflux pump inhibitors from natural sources. Journal of Antimicrobial and chemotherapy 2007; 59(6): 1247-1260.
- Stermitz FR, Matsuda JT, Lorenz P, Mueller P, Zenewicz L and Lewis K: Methoxyhydnocarpin-D and Pheophorbide A: Berberis species components that potentiate berberine growth inhibition of resistant staphylococcus aureus. Journal of Natural Product 2000; 63(8): 1146-1149.
- Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA and Lewis K: Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proceeding of the National Academy of Sciences 2000; 97(4): 1433–1437.
- Peter L, Jacobsen and Levy L: Mechanism by which hydnocarpic acid inhibits mycobacterial multiplication. Antimicrobial Agents and Chemotherapy 1973; 3(3): 373-379.
- Gokaraju GR and Gokaraju RR: Bioavailability/ bioefficacy enhancing activity of Stevia rebaudiana and extracts and fractions and compounds thereof. US Pat 2010011 2101A1 (to Laila Impex, India) 6 May, 2010.
- Lopez HS, Olvera LG, Jimenez RA, Olvera CG and Gomez FJ: Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations. Arzneimittel-Forschung 2007; 57(5): 286–290.
- Bouraoui A, Toumi A, Mustapha HB and Brazier JL: Effects of capsicum fruit on theophylline absorption and bioavailability in rabbits. Drug Nutrient Interaction 1988; 5(4): 345–350.
- Qazi GN, Bedi KL, Johri RK, Tikoo MK, Tikoo AK, Sharma SC, Abdullah S T, Suri O P, Gupta BD, Suri KA, Satti NK, Khajuria RK, Singh S, Khajuria A and Kapahi BK: Bioavailability/bioefficacy enhancing activity of Cuminum cyminum and extracts and fractions thereof. US Pat 7070814 (to Council of Scientific and Industrial Research, India) 4 July, 2006.
- Upadhyay HC, Dwivedi GR, Darokar MP, Chaturvedi V and Srivastava SK: Bioenhancing and antimycobacterial agents from Ammannia multiflora. Planta Medica 2012; 78(1): 79–81.
- Upadhyay HC, Jaiswal N, Tamrakar AK, Srivastava AK, Gupta N and Srivastava SK: Antihyperglycemic agents from Ammannia multiflora. Natural Product Communication 2012; 7(7): 899-900.
- Ow YY and Stupans I: Gallic acid and gallic acid derivatives: effects on drug metabolizing enzyme. Current Drug Metabolism 2003; 4(3): 241-248.
- Wacher VJ and Benet LZ: Use of gallic acid esters to increase bioavailability of orally administered pharmaceutical compounds. US Pat 6180666B1 (to Anmax Inc, California) 30 January, 2001.
- Cho SW, Lee JS and Choi SH: Enhanced oral bioavailability of poorly absorbed drugs I Screening of absorption, carrier for the ceftriaxone complex. Journal of Pharmaceutical Sciences 2004; 93(3): 612–620.
- Randhawa GK: Cow urine distillate as bioenhancer. Journal of Ayurveda and Integrative Medicine 2010; 1(4): 240–241.
- Singla S and Garg R: Cow Urine: An Elixir. Innovare Journal of Ayurvedic Sciences 2013; 1(3): 13-15.
- Kekuda PT, Nishanth BC, Kumar SVP, Kamal D, Sandeep M and Megharaj HK: Cow urine concentrate: a potent agent with antimicrobial and anthelmintic activity. Journal of Pharma Res 2010; 3(5): 1025–1027.
- Randhawa GK and Sharma R: Chemotherapeutic potential of Cow Urine – A Review. Journal of Intercultural Ethnopharmacology 2015; 4(2):180-186.
- Brosen K: Drug Interactions and the Cytochrome P450 System. Clinical Pharmacokinetics 1995; 29(1): 20-25.
- Gescher AJ and Steward WP: Curcumin: The story so far. European Journal of Cancer 2005; 41(13): 1955–1968.
- Atal CK, Dubey RK and Singh J: Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. Journal of Pharmacology and Experimental Therapeutics 1985; 232(1): 258-262.
- Finch A and Pillans P: P-glycoprotein and its role in drug-drug interactions. Australian Prescriber 2014; 37(4): 137–139.
- Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK and Fromm MF: Piperine, a major constituent of black pepper, inhibits human p-glycoprotein and CYP3A4. Journal of Pharmacology and Experimental Therapeutics 2002; 302(2): 645–650.
- Hart LA, Nibbering PH, Barselaar MTV, Dijk HV, Burg AKV and Labadie RP: Effects of low molecular constituents from Aloe vera gel on oxidative metabolism and cytotoxic and bactericidal activities of human neutrophils. International Journal of Immunopharmacology 1990; 12(4): 427- 434.
- Szentmihalyi K, May Z, Then M, Hajdu M, Boszormenyi A, Balazs A, Lemberkovics E, Marczal G and Szoke E: Metal elements, organic agents in a herbal remedy, species Thymi Composita, and its drug-constituents. European Chemical Bulletin 2012; 1(1-2):14-21.
- Annamalai AR and Manavalan R: Effects of “Trikatu” and its individual components and piperine on gastro intestinal tracts: trikatu: a bioavailable enhancer. Indian Drugs 1990; 27(12): 595–604.
- Johri RK, Thusu N, Khajuria A and Zutshi J: Piperine mediated changes in the permeability of rat intestinal epithelial cells, The status of γ-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharmacol 1992; 43(7): 1401–1407.
- Planteng MW, Diepvens K, Joosen AMCP, Parent SB and Tremblay A: Metabolic effects of spices, teas and caffeine. Physiology and Behavior 2006; 89(1): 85–91.
- Francis G, Kerem Z, Makkar HPS and Becker K: The biological action of saponins in animal systems: a review. British Journal of Nutrition 2002; 88(6): 587–605.
- Badmaev V, Majeed M and Prakash L: Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. Journal of Nutrition Biochemistry 2000; 11(2): 109-113.
- Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Thorat SL and Naik SR: Effect of piperine on pentobarbitone induced hypnosis in rats. Indian Journal of Experimental Biology 1990; 28(5): 486-487.
- Patil UK: Natural Bioenhancers. CDACR-Natural Product Letters 2013; 13(1): 22-26.
How to cite this article:
Jain G and Patil UK: Strategies for enhancement of bioavailability of medicinal agents with natural products. Int J Pharm Sci Res 2015; 6(12): 5315-5324.doi: 10.13040/IJPSR.0975-8232.6(12). 5315-5324.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Garima Jain and Umesh K. Patil *
Division of Natural Product Research Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh, India 470003
06 July, 2015
24 October, 2015
20 November, 2015
01 December, 2015