A REVIEW ON DIVERSIFIED USE OF THE KING OF SPICES: PIPER NIGRUM (BLACK PEPPER)HTML Full Text
A REVIEW ON DIVERSIFIED USE OF THE KING OF SPICES: PIPER NIGRUM (BLACK PEPPER)
Dirgha Raj Joshi * 1, Abinash Chandra Shrestha 2 and Nisha Adhikari 3
College of Pharmacy 1, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan‑daero, Iksan, Jeolabuk‑do 54538, Republic of Korea.
Department of Pharmacy 2, College of Pharmacy, Woosuk University, 443 Samnye-ro, Samnye-eup, Wanju-gun, Jeollabuk-do Republic of Korea.
Department of Pharmacy 3, Crimson College of Technology, Butwal, Nepal.
ABSTRACT: Black pepper, the ‘King of spices’ (Piper nigrum L.), is a widely used spice, known for its pungent odour. From time immemorial, plant sources were used in traditional systems of medicine and day-to-day common use, such as in meal preparation and cosmetic purposes. This is due to their vast pharmacological potential with minimum side effects. Among the various species of the Piperaceae family, black pepper is one of the most popular due to its principle pharmacological component, piperine. Which is an alkaloid that has diverse pharmacological activities like antioxidant, anti-obesity, antitumor, antipyretic, anticonvulsant, anti-thyroid, antifungal, antibacterial, insecticidal, hepatoprotective, anti-asthmatic, larvicidal, antihypertensive, anti-inflammatory, antidiabetic, antidiarrheal, bio-availability enhancer, immunomodulator, antiepileptic, antifertility, GI stimulant, lipid metabolism accelerator, anticancer, CNS stimulant, diuretic, aphrodisiac, blood purifier and antiplatelet activities, etc. Due to some religious value of black pepper, its being popular from ancient time to modern generation. This review is aimed to provide a literature review on recent advancement of chemistry, pharmacognosy, pharmacological activities, new piperine based formulations and other general use of Piper nigrum.
Piper nigrum, Piperine, Black pepper, Piperaceae, Anti-oxidant
INTRODUCTION: Piper nigrum belongs to the family Piperaceae, it is a perennial shrub native to southern India, and has been extensively cultivated there and in other tropical regions.
As of 2013, Vietnam is the world’s largest producer, as well as exporter, of pepper, producing 34% of the global P. nigrum crop. Due to its strong pungency, it is regarded as the ‘King of spices’ and it has valuable medicinal potency.
It is one of the world most common kitchen spices and well known for its pungent chemical constituent piperine (1-peperoyl piperidine, Fig. 2), discovered in 1819 by Hans Christian, which has diverse pharmacological activities. It is commonly known as Kali mirch in Urdu and Hindi, Marich in Nepali, Pippali in Sanskrit, Milagu in Tamil, and Black Pepper, Peppercorn, Green pepper, White pepper, Madagascar pepper in English 1, 2. It is widely accepted and most used in different traditional systems of medicine, like the Unani and Ayurvedic systems 4.
FIG. 1: HARVESTED BLACK PEPPER SEEDS (L.) AND PEPPER FRUIT (GREEN AND RIPENING PINK YELLOW)
FIG. 2: SOME OF THE IMPORTANT CHEMICAL CONSTITUENT OF P. NIGRUM
It has long been used to treat many diseases, such as antihypertensive 9, antioxidant, antiplatelets, antitumor, anticonvulsant, antithyroid, analgesic 6, anti-inflammatory 20, 86, antidiarrheal, anti-spasmodic, antidepressants, immunomodulatory, antibacterial, antifungal, hepatoprotective, etc. 1, 7 This has lead scientists to think more about it, as a result there is much research going on regarding its derivative synthesis 78, SAR modification, and testing its biological activities. The traditional and modern uses (Cell, animal and human based study) are summarized in Table 1.
Piperine amount varies from 1-2% in long pepper, to 5 - 10% in commercial white and black peppers. It increases the bioavailability of many nutrients and drugs by inhibiting various metabolizing enzymes 1. Piperine inhibits adipogenesis by antagonizing PPARγ activity in 3T3-L1 Cells 3. Like in high fat diet male Wistar rats; 40 mg/kg of piperine significantly reduces body weight, levels of plasma TC (Total Cholesterol), LDL (Low Density Lipo-protein), VLDL (Very Low Density Lipoprotein), and activity of HMG CoA reductase in liver, heart, and aorta, also significantly increase the level of plasma Lecithin Cholesterol Acyl Transferase (LCAT), plasma and tissue lipoprotein lipase (LPL) 5, 10. Other summarized activities are in Table 2.
Thus, piperine is a powerful candidate in regulating obesity induced dyslipidemia, which signifies the great importance of black pepper. Researchers have isolated valuable compounds from black pepper including various lignans derivatives, phenolics, terpenes, chalcones, alkaloid, steroid, flavonoid, dihydropipericide, N-trans-feruloyltryamine, piper-amine and isobutyllocadienamide 11. They have also isolated, brachyamide B 12, benzamide group 13, (2E, 4E)-N-Eicosadienoyl pereridine 14, guineensine 15, (2E,4E)-N-isobutyldecadienamide 16, piperamide 17, piperettine 19, pipericide 18 and other sarmentine, sarmentosine, piperolein B, trichostachine, etc. More than 592 compounds have been isolated and lignans (47), alkaloid/amide (145), terpenes (89), neolignans (70) among them along with 101 novel compounds 11. Among these 14 compounds, there are biologically active and many SAR modifications going on. The main pungency of P. nigrum is due to piperine 94 and chavicine. Chavicine is an alkaloid with diastereomeric geometric isomers of piperine.
TABLE 1: TRADITIONAL USE TO SCIENTIFICALLY PROVEN MODERN USE OF P. NIGRUM 1, 3,4-6, 8-9, 15-16, 19-21
|Traditional Use||Modern Use|
|Antiseptic, antispasmodic, aroma, analgesic, anti-inflammatory, anti-toxicant, aphrodisiac, antipyretic, rheumatism, diabetes, muscular ache, diuretic, flavor, spirit, dyspepsia, increase salivary secretion and promote digestion, CNS stimulant, indigestion and flatulence, throat ache, cold, germicidal, blood purifier, antibacterial, religious value, cancer, pungency, kitchen curry, cough, as carminative, insecticide, etc||Cell Based Study||Animal Based Study||Human Based Study|
|Increase enzymatic activity, increase lipid per-oxidation, antioxidant, bioavailability enhancer, immunomodulatory effect, increase WBC count and inhibit adipogenesis||Antiepileptic, antifertility, bioavailability enhancement, anti-metastatic, stimulate enzymatic activity, inhibit mycobacterium growth, hepatoprotective, increase digestion by promoting bile secretion, synergistic effect in nimesulide, anti-amoebic activity, antifibrotic effect, antibacterial, antioxidant, reduce glutathione, antifungal, etc||Anti-asthmatic, anti-oxidant, reduce high fat diet induced oxidative stress, GI stimulant, anti-carcinogenic, lipid metabolism acceleration, anti-inflammatory, cancer, etc|
TABLE 2: NOTABLE ACTIVITIES OF PIPER NIGRUM (WHOLE) AND PIPERINE
|Enhance Bioavailability 60|
|Rat||Blood level of vasicine and sparteine increased by piperine and P. nigrum, either by promoting fast GI absorption or due to first pass metabolism in liver or both 22|
|5 mg for 14 days
|Serum level of β-Carotene increased by piperine 23
To overcome vitamin deficiency piperine enhanced β-Carotene uptake 26
|Curcumin: serum concentration, absorption, bioavailability increased by piperine 24|
|Human||2, 4, 5, 6, 7, 8h||Piperine from black pepper via oral supplementation, increases plasma levels of coenzyme Q10 25|
|20 mg; 7 days||Bioavailability of propranolol and theophylline in healthy volunteers was enhanced by piperine 36|
|Human, Mouse, Rat||20 mg/kg||Oral bioavailability of phenytoin (anti-seizure medication) was enhanced by piperine 37|
|Affect Enzyme activity and Biotransformation|
|Mice, Rats and Hamsters.||100 mg/Kg||Piperine showed acute and subacute toxicity, by potentiating CCl4 induced hepatotoxicity and increased activity of NADPH cytochrome reductase 27|
|Rat||Piperine modulate P-glycoprotein ATPase activity (stimulation at low concentration and inhibition at high concentration) 28
With direct interaction to enzyme caused impairment of cytochrome P4501A129
|Guinea-pig small intestine||piperine lowers the endogenous UDP-glucuronic acid content 30|
|Affect in Digestion|
|Human||1.5g/ meal||Via intragastrical administration of black pepper significantly increase in pepsin and parietal secretion, gastric cell exfoliation and K+ loss 31|
|20-142 mg/kg||Piperine stimulate H2 receptor and promote gastric acid secretion and was significantly antagonized by cimetidine (H₂ receptor antagonist) 32|
|Rat||20 mg %; 8 weeks||Piperine significantly enhanced intestinal lipase activity and the disaccharidases sucrase and maltase in rat; administered along with fed, thus promote digestion 33|
|20 mg/day||Significantly caused shortening of GI food transit time 34|
|12.5 or 25 mg/Kg; 4 weeks||Feeding piperine along with diet caused an increase in bile flow and decrease in bile solids, also secretion of uronic acids in bile was enhanced 35|
|Anti-inflammatory, antioxidant, and anti-obesity effects|
|Rat||20 mg/kg; 10 weeks||Piperine and P. nigrum maintained superoxide dismutase, glutathione peroxidase, catalase, glutathione-s-transferase, glutathione levels and reduced high fat diet induced oxidative stress 38|
|Piperine showed anti-inflammatory activity in rats, where acute and chronic experimental models induced by cotton pellet granuloma, rat paw edema and croton oil-induced granuloma pouch; piperine was effective and it also acted partially through stimulation of pituitary adrenal axis 40|
|Mouse||1 mg/mL||Piperine inhibit cholesterol uptake and lowered blood lipids 39|
|10 mg/kg||Nimesulide and piperine co-administration showed synergistic effects towards analgesic and anti-inflammatory activity 41|
|(Human) Murine dendritic cell||1h, 37°C||Piperine inhibited JNK and ERK pathway, so proved reputed use in arthritis and diabetes 41|
|3T3-L1 Cells||Piperine antagonized PPARγ activity in 3T3-L1 cells, thus inhibits adipogenesis 3|
|Anti-carcinogenic and Anti-mutagenic effects|
|Mouse||0.98 mg||Significantly piperine inhibited lungs metastasis-induced B16F10 melanoma cells in mice 43|
|P. nigrum, oral administration increased life span of mice with tumor
(Ehrlich ascites) 44
|50 mg/kg||Lipid peroxidation, nucleic acid content, protein carbonyl and carcinogenesis are significantly prevented due to preventing protein damage and suppressing cell proliferation by piperine 45|
|Rat||Chemical carcinogenesis was inhibited by P. nigrum through modulating glutathione-S-transferase, Cytochrome P-450, malondialdehyde levels, and acid soluble sulfhydryl content 46|
|Role in fertility and Hormonal effect|
|Rat||5-10 mg/kg||Piperine cause marked increase in serum gonadotropin, significant decrease in weight of testes and decrease in intra-testicular testosterone level without change in normal serum testosterone titres 47|
|Infusion of piperine in rat, induced catecholamine secretion from the adrenal medulla 48|
A large variety of aromatic and volatile compounds are present in P. nigrum and it possesses diverse potential for cosmetic, perfumery, medicine, and kitchen spices. Some of the categorized aromatic and volatile principles found in it are summarized in Table 3.
TABLE 3: AROMATIC AND VOLATILE COMPOUNDS PRESENT IN P. NIGRUM 21, 49
Phenyl acetic acid
The species possesses flavor, color and aroma also provides diverse therapeutic potency. Many writings of the Ayurveda describe the diversified use of P. nigrum. Day-to-day, new updates in its research for specific pharmacological action established by experimental and clinical studies signifies the traditional ethnomedicinal use of P. nigrum. Many active constituents are already being isolated from it and among them, some show significant pharmacological potency.
Some of the notable pharmacological activity showed by P. nigrum and its isolated constituents that attracts our todays research are antioxidant, antibacterial 79, antiviral, antifungal, antimicrobial, anti-adipogenesis, insecticidal, larvicidal, pesticide, anti-diarrheal, analgesic and antipyretic, anti-apoptotic, antidepressant, antimutagenic and anticancer, immunomodulatory, antispasmodic, anti-thyroid, cold extremities, gastric ailments, hepatoprotective, increase pancreatic enzymes, inhibit cytochrome, etc. which are summarized in Table 4 along with references of individual activities. Recent studies have shown that it is helpful in enhancing the absorption of Vitamins, selenium, β-carotene, and promoting body thermogenic activity naturally 56. Some physiochemical studies on pepper starch with comparison to other starch will give new application way in near future 81. Recent research is more focused to the dynamic use of piperine by formulating different dosage forms 82, 88, 92, 93.
Various patent are registered claiming novel use of piperine 40, 78, 89. Now it is not only limited to the activity but also many attempts are made to know the mechanism, biological pathway for activity shown by piperine 90, 91. An individual description below shows some of the elaborated literature review of the above potency.
Evidence Based Pharmacological Activities of P. nigrum and Piperine: Using internet search engine, accessing to different journals, this attempt has been made to collect some update research on P. nigrum or its active constituents (Piperine). Below Table 4 shows some of the summarized pharmacological activities of P. nigrum and piperine.
TABLE 4: PHARMACOLOGICAL ACTIVITIES OF P. NIGRUM
|S. no.||Activities||S. no.||Activities|
|1||Anti-diarrheal 8||15||Effects in metabolism 15, 23, 30|
|2||Antimicrobial 50,84,85||16||Effect on enzyme 16, 25, 28, 29, 33, 41|
|3||Antioxidant 9, 38, 93||17||Effects in neurodegeneration and cognitive impairment 17|
|4||Anticancer 19 and
tumor reduction activity 43, 44, 45
Bioavailability 22, 24, 26, 60
|5||Antihypertensive 9||19||Toxicity activity 27|
|6||Anti-asthmatic||20||Effects in stomach 31, 32|
|7||Anti-inflammatory 20, 40, 86||21||Decrease food transit time 34|
|8||Anti-obesity 5, 39, Antidiabetic 87||22||Effect in bile secretion 35|
|9||Hepatoprotective activity 46||23||Effect in pharmacokinetic of drugs 36, 37|
|10||Digestive activity 31, 32, 34, 35, 33||24||Synergistic effect with drugs 42|
|11||Antidepressant 16||25||Inhibition of lungs metastatis 43|
|12||Immunomodulatory activity||26||Fertility effect 47|
|13||Analgesic and Antipyretic activity 6||27||Hormonal activity 48|
|14||Anti-adipogenesis activity 3||28||Anthelmintic activity 75|
Taxonomical Classification of Piper nigrum:
Kingdom : Plantae
Subkingdom : Tracheobionta
Superdivision : Spermatophyta
Division : Magnoliophyta
Class : Magnoliopsida
Sub class : Magnoliidae
Order : Piperales
Family : Piperaceae
Genus : Piper
Species : nigrum L.
Antioxidant Activity: Free radicals are responsible for causing many diseases. Different kinds of free radicals can attack the cell membrane, and cause or alter membrane permeability, membrane damage, oxidation of lipids, loss of different enzymatic activities, and ultimately disrupt proper cell function and body physiology, which may cause cancer. There are many antioxidants in our body to scavenge the free radical generated normally during metabolism. However, it can be insufficient sometimes. When there is imbalance between the free radical generation and antioxidant activity, oxidative stress is induced; which is harmful to our body, causing many side effects from simple health problems to cancer. Antioxidant activity of our body system includes enzymes like catalase, ascorbate, peroxidase, and superoxide dismutase, which are responsible for scavenging both free radicals and related oxygen species. Plants are a potent source of antioxidant activity from ethnomedicinal practices to today’s finding.
Many scientific findings prove its great antioxidant potency 38, 56. Piperine and P. nigrum maintain superoxide dismutase, glutathione peroxidase, catalase, glutathione-s-transferase, glutathione levels and reduce high fat diet induced oxidative stress 38. Many screenings, using different solvent system for extraction of P. nigrum constituents, prove this potency 77. The ethanolic extract of P. nigrum shows high antioxidant potency with 74.61 ± 0.02% with IC50 value 14.15 ± 0.02 μg/mg 56. The methanolic extract of P. nigrum fruits showing memory enhancing and antioxidant potency at a dose of 50 and 100 mg/kg, orally for 21 days in amloid-β (1-42) were investigated in rat model of alzheimer's disease 1, 38. Research in Piper species viz. P. nigrum, P. guineense and P. umbellatum shows effects such as protecting cardiac, hepatic, and renal antioxidant status of atherogenic diet fed hamster at a dose of 1g/kg and 0.25g/kg for 12 weeks. The significant inhibition of atherogenic diet induced increased lipid profile and alteration in antioxidant enzyme activities; showed a great antioxidant protective role of the piper extract against atherogenic diet generated oxidative stress in cardiac, hepatic, and renal tissues 61. Thus, it will have important role in scavenging free radicals and delay aging process. As reported, P. nigrum has antioxidant potency that may be due to presence of flavonoids and phenolic contents 1, 77.
Antimicrobial Activity: An antimicrobial is an agent that kills micro-organism or inhibits their further growth. These antimicrobial agents can be grouped into different categories according to their primary activity, like antibacterial, antifungal, antiviral, anti-parasitic, pesticide, etc. Many plants have been used as an antimicrobial agent throughout time and will be in future. Although any modern synthetic antimicrobial agents are developed rapidly, the resistance towards them is also growing rapidly. Usually the resistant against plant source seems less when compared to modern chemical drugs, this may be due to presence of a wide variety of different chemical constituent within a single plant.
Many literature reviews have shown the antimicrobial potency of black pepper 80. Extract of black pepper using solvent viz. carbon tetrachloride, benzene, ethyl acetate, acetone, methanol, ethanol, and distilled water were tested against gram-positive and gram-negative bacteria viz. Staphylococcus albus, S. typhi, E. coli, B. megaterium, P. aeruginosa and one fungus, Pseudomonas aeruginosa 77. Against different bacteria, the strongest antibacterial and antifungal activity was shown at the concentration of 40μg/disc 50. Using P. nigrum leaf and stem extract, the silver nanoparticle was synthesized, and the antibacterial activity was examined against the agricultural plant pathogen which showed excellent activity, thus the author concluded its beneficial application in the field of agricultural nanotechnology 62. All 20 strains of K. pneumoniae were isolated from the urine culture of a hospitalized patient suffering from urinary tract infection (UTI) and alcoholic extract of P. nigrum was tested against it, which showed good activity against antibiotic resistant Klebsiella pneumonia with MIC and MBC value at 0.62 mg/ml 51.
The evaluation of essential oil from P. nigrum for repellent, developmental inhibitory, and insecticidal activity against wheat grain pest Tribolium castaneum showed that the adult of T. castaneum at 0.2% concentration (v/v) repelled it significantly. The LD50 for larva and adult was 14.022 μL and 15.262 μL respectively. The effective concentration (EC50) to decrease the larva transferred to the pupae to 50% was 6.919 μL 54. A protozoal infection, visceral leishmaniasis (VL) is a life-threatening disease in rural areas and the poor population in the tropical and sub-tropical countries. The P. nigrum hexane (PNH) and P. nigrum ethanolic extract (PNE) of seeds of black pepper showed profound leishmanicidial activity against L. donovani promastigoates and amastigoates via apoptosis 53.
The antibacterial activity of P. nigrum carried out against B. subtilis, S. aureus, P. aeruginosa, E. coli, A. niger, A. alternate, A. flavus and F. oxysporum showed zone of inhibition from 8-18 mm range. Maximum for gram positive bacteria S. aureus (18 mm) and minimum against gram negative bacteria E. coli (8 mm). Similarly, piperine maximum anti-fungal activity against Fusarium oxysporum (14 mm) and least against A. niger (38 mm) 59. The chloroform extract of black pepper showed significant damage to bacterial cell membrane of E. coli, and S. aureus followed by disruption of respiration 83. All these significant antimicrobial effects in wide variety of micro-organism signifies P. nigrum as a powerful natural antimicrobial agent.
Antidiarrhoeal Effect: Along with above described antimicrobial activity of black pepper, against some bacteria77 which are also responsible for causing diarrhea. Other research signifies its great potency in controlling diarrhea. As we know, diarrhea is a leading cause of morbidity and mortality globally, especially among the children in developing countries.
Aqueous extract of black pepper at a dose of 75, 150, 300 mg/kg, produces a significant dose-dependent antimotility, anti-secretory and anti-diarrheal effects. The author concluded that this effect is due to the presence of carbohydrates and alkaloids in black pepper 8.
Analgesic, Antipyretic and Anti-Inflammatory Activity: In-vivo analgesic activity of piperine was evaluated in mice. The analgesic activity was tested by using acetic acid-induced writhing, tail flick assay. After intraperitoneal (i.p.) injection of piperine (30, 50 and 70 mg/kg), the acetic acid-induced writhing in mice was observed and found to be significantly inhibited (P<0.01), like the effect of indomethacin- an NSAID drug (20 mg/kg, i.p.). In the tail flick assay, morphine (5 mg/kg, i.p.) and piperine (30 and 50 mg/kg, i.p.) showed a significant increase (P<0.01) in the reaction time of mice. Animals with naloxone pre-treatment (5 mg/kg i.p.), reversed the analgesic effects of both morphine and piperine. All these findings reveal that piperine exhibits analgesic effects possibly mediated via opioid pathway 63.
Analgesic activity of piperine was tested in mice (20 and 30 mg/kg, i.p.); acetic acid and hot plate reaction test was used. Indomethacin (10 mg/kg) was taken as reference standard. Piperine showed significant (p<0.5) dose dependent delayed response towards pain. The antipyretic activity of piperine was observed by using yeast-induced pyrexia in mice model. The rectal temperature was measured in piperine (20 and 30 mg/kg) treated mice as compared to the control group. Where the significant (p<0.5) increase in temperature in the control group mice was observed 6. The experiment revealed that anti-inflammatory, analgesic, and anti-arthritic activity of piperine in arthritis model of rat. For measuring in-vitro anti-inflammatory activity, the interleukin 1β stimulated synoviocytes taken from rheumatoid arthritis was used. While the anti-arthritic including analgesic potency was carried out on carrageen, an induced acute paw model or arthritis and pain in rat. The cyclo-oxygenase 2, interleukin 6, prostaglandin E2 and matrix metallo-protease levels were tested by RT-PCR and ELISA analysis method. At concentration of 10-100µg/mL, piperine treated group were found to reduce synthesis of PGE2 in a dose dependent manner. Even at 10 µg/mL it significantly inhibits the synthesis of PGE2. The expression of metallo-proteinase 13 and interleukin 6 were also inhibited 65. Which concludes the potency of piperine for the titled topic.
Anticonvulsant Effects: The mice model for anticonvulsant activity of piperine was evaluated by inducing seizure with pentylenetetrazol (PTZ)- and picrotoxin (PIC) in mice. On administering piperine (30, 50 and 70 mg/kg, i.p.) and reference standard drugs, valproic acid (200 mg/kg, i.p.), diazepam (1 mg/kg, i.p.) and carbamazepine (30 mg/kg, i.p.) which showed significantly (P<0.01) delayed onset of PTZ-and PIC-induced seizures in mice. Which indicate that piperine exhibits anticonvulsant effects possibly mediated via GABA-ergic pathways 63.
Another experiment on anticonvulsant activity of piperine in pentylenetetrazol (PTC) and maximal electroshock (MES) model of convulsion in mice showed a delay in onset of generalized chronic seizure and myoclonic jerks with administering piperine (40- 80 mg/kg) and a significant reduction of PTZ-induced Fos immune reactivity in dentata gyrus and MES-induced tonic hind limb extension after piperine administration. The capsazepine, a selective TRPV1 antagonist blocked the anti-seizure effect of piperine 64. These findings reveal the potent anti-convulsant activity of piperine.
Antitussive and Bronchodilator: Many traditional practices prove it as well. P. nigrum is widely used in many herbal cough syrups due to its potent antitussive and bronchodilator properties 60. Many old people and herbal practitioners believed that the addition of little amounts of powered peppercorn in a green tea significantly reduces asthma 4. The oral administration of piperine in different amount to mice reduced and suppressed the hyper responsiveness, infiltration of eosinophils and inflammation possibly due to suppression of production of histamine, immunoglobulin E, interleukin 4 and interleukin 5 66.
Anti-obesity Activity: Obesity is becoming a global problem, since it is a socially stigmatized health problem. The modern treatments are only effective when they are used, and the problem progresses again after stopping drug use. On the other hand, the drugs have more side effects. So, experiments are now focusing on herbal medicine and other non-pharmacological way of management of obesity like exercise, yoga, meditation, diet control etc.
There are so many plants that have anti-obesity potency among them, P. nigrum is one. In an anti-adipogenesis study of P. nigrum extract and piperine in 3T3-L1 preadipocytes both the black pepper extract and piperine strongly inhibited the adipocyte differentiation of 3T3-L1 cells, without affecting cytotoxicity. The mRNA expression of masteradipogenic transcription factor, SREBP-1c, C/EBPβ and PPARγ were significantly decreased. Piperine disrupts the rosiglitazone- dependent interaction between PPARγ and cofactor CBP in GST pull down assay.
Furthermore, in genome-wide analysis using microarray supports the potent role of piperine in gene regulation associated with lipid metabolism 3. In another experiment, supplementing piperine with high fat diet (40 mg/kg) significantly reduced not only body weight, total cholesterol, triglyceride, LDL, VLDL and fat mass but also increased the level of HDL, with no change in food intake 5. These results suggest black pepper possesses potential lipid lowering and fat reducing effects, without any change in the food appetite.
In another study, black pepper was given to a high-fat-fed rat in two different doses of 250 mg/kg and 500 mg/kg and piperine at 20 mg/kg was administered for 10 weeks and the plasma and tissue lipid profile showed significant reduction in total cholesterol, phospholipids, free fatty acids, and triglycerides in both groups. Thus, these all results suggest that dietary intake of black pepper or piperine reduces the risk of arthrosclerosis via hypolipidemic and antiatherogenic effects 58.
Antimutagenic, Antitumor and Anticancer Activity: Cancer is becoming global challenge in today’s health system. Although enormous efforts are done and going on to find new technology, drugs, research, surgery, it is still insufficient. So, we need to search such systems where negligible side effect with high therapeutic outcomes. Chemo-therapy is very painful to a patient and has other serious adverse effects. Many herbal medicines are used in different systems of medicine, such as Ayurveda, Chinese, Homeopathy, and so on. Plant sources are believed having no/negligible side effects. We should use herbal medicine in our daily life along with food to avoid cancer and tumors in our lives. To signify this potency, black pepper has been used as an anticancer and antitumor agent. P. nigrum has been reported in many literatures as having the potency to inhibit tumor formation in different experimental models 1.
Ethanolic extract of peppercorn and piperine showed effective immunomodulatory and antitumor activity 1. As we know, angiogenesis plays a key role in tumor progression and cancer. Research findings show that piperine inhibits proliferation and G1/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death, and also inhibits migration of HUVEC and in-vitro tubule formation and angiogenesis induced by collagen and breast cancer cell in embryo of chick.
Moreover, the phosphorylation is an essential controller in angiogenesis process and function of endothelial cells. Interestingly, piperine also inhibits phosphorylation of Thr 308 residues of Akt of protein kinas B and Ser 473 too. Thus, piperine can be a good agent for controlling angiogenesis in cancer treatment 67. Prostate cancer is a big problem for men, causing thousands of deaths a year. Research has shown that piperine has good anticancer activity against prostatic cancer cells of both androgens dependent and independent. A dose dependent inhibition of the proliferation of 22RV1, DU-145, PC-3 and LNCaP prostate cancer cells by piperine was investigated 68. Piperine from black pepper modulate lipid peroxidation and activation of antioxidative protection enzyme, thus reduced lung cancer 69, 70.
Anticancer and cancer prevention potency of piperine free P. nigrum extract (PFPE) against the N-nitrosomethyllurea (NMU)-induced mammary tumorigenesis in rat and on breast cancer cells was carried out and the result showed potent inhibition in growth of luminal like breast cancer cells via induction of apoptosis. Moreover, PFPE showed a higher selectivity against breast cancer cells than lungs cancer, neuroblastoma cells and colorectal cancer. In an acute toxicity test, a dose of 5g/kg single dose for 14 days observation period showed no mortality and morbidity. The mechanism of action and cytotoxicity effect in breast cancer cells was measured by Western blot analysis and MTT assay respectively 57. Piperine inhibited growth of 4T1 cells at a dose of 35-280 μmole/L in dose and time dependent manner with IC50 were 105 ± 1.08 and 78.52 ± 1.06 μmole/L respectively at 48 and 72h. At 70-280 μmole/L dose dependently induced apoptosis of 4T1 cells via activation of caspase 3. Piperine injection (5 mg/kg) significantly inhibited lung metastasis and at injection dose (2.5 and 5mg/kg) cause marked suppression of 4T1 tumor growth dose-dependently 52.
Anxiolytic and Antidepressant Activity: In this globalized world, people are more stressed. Suicide and mental sub-activity is a big problem in today’s society. Many herbs are used as a memory enhancer. Among which, black pepper has been used for a long time in herbal and ethnomedicinal practice 22, 76. Today’s more scientific experimental model findings prove it is useful. Anxiolytic and antidepressant activity of the methanolic extract of P. nigrum fruits in beta-amyloid (1-42) treated rat model of Alzheimer’s disease showed increase in immobility and decrease in swimming time within forced swimming test. Whereas decreases in % of time spent, exploratory activity and number of entries in open arm within elevated plus-maze test.
This showed the methanolic extract significantly exhibited antidepressant and anxiolytic effects by attenuation of oxidative stress 55. Another study was done in corticosteroid induced depression model of mice. After 3-week corticosterone injection mice showed depression like behavior observed by tail suspension test and immobility time in forced swim test. These depression behaviors are significantly diminished after piperine administration 71. Those finding proves the potent anxiolytic and antidepressant activity of black pepper.
Digestive and Hepatoprotective Activity: Many experimental findings show the hepatoprotective effect of P. nigrum in animal and human model 4. The methanolic extract from black pepper (MEPN) fruits (100 and 200 mg/kg, p.o. for 15 days) and piperine (50 mg/kg, p.o. for 15 days) were tested against ethanol-CCl4 induced hepatotoxicity Wistar rats, which reveals the significant activity of black pepper in decreasing the hepatic biomarker level like TG, AST, ALT, ALP and bilirubin, which were increased on ethanol-CCl4 administration. The significantly decreased level of SOD, GSH and CAT after ethanol-CCl4 administration were restored with MEPN and piperine. These results were like the reference standard Liv 52 (1ml/kg, p.o., 15 days) 72.
Another study where liver toxicity in mice was induced with D-galactosamine and exposed to dose dependent piperine, which inhibited increase in serum GOT and GPT levels and suggested that this effect dependend on hepatocytes reduced sensitivity towards tumor necrosis factor-α 73. Those study reveals that the P. nigrum possesses potent hepatoprotective properties which can be used as therapeutic potential in liver disorder.
The pungent properties of P. nigrum specially the piperine increases production of the saliva, activate salivary amylase, and promote gastric secretion, more over decrease GI transit time 74. The use of black pepper as spicy is more. Black pepper 1.5g/meal administration in healthy human volunteer via intragastrical administration significantly increases pepsin and parietal secretion, gastric cell exfoliation and potassium loss 31. In rat model administration of piperine 20 mg% for 8 weeks along with fed significantly enhanced intestinal lipase activity and disaccharidases the maltase and sucrose, thus promote digestion 33.
Other Pharmacological Activities and Use: P. nigrum (Black pepper) exhibits many pharmacological actions like antiplatelets, anti-hypertensive, antispasmodic, antiprotozoal, bioavailability enhancer 60, memory enhancer, antimutagenic, insecticidal, immunomodulator, antithyroid, anti-asthmatic, anxiolytic activities etc. 1, 47, 52, 55.
CONCLUSION: Black pepper is a very rich source of a wide variety of chemical constituents, most of which are biologically active. The long practice of using pepper in different traditional systems of medicine made its scope from the kitchen, to drugs, to cosmetics. Modern experimental research on the different biological activities reveals the significance of its use in traditional systems of medicine. Many scientific elaborations about its volatile constituents, monoterpenes, sesquiterpenes, and specially piperine have increased the scope in the field of further activity testing its medicinal and other uses.
Moreover, the synthetic modifications to make a more potent drug candidate with minimum toxicity and great significance. New researches are going on, using different formulation, method of use, linked with other delivery technology where the pepper is the main constituent. The pepper’s use in treating cancer, obesity, hypertension, diabetes, diarrhea, and its bioavailability signifies its attraction in the future. Furthermore, specific research studies are needed to signify the black pepper is miraculously really the King of species.
ACKNOWLEDGEMENT: Great thanks to College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, for providing all services during this review writing. Special thanks to Mr. Tyler Reimer for helping in proof checking.
CONFLICT OF INTEREST: The authors have no conflicts of interest to declare that are directly relevant to the content of this manuscript.
- Damanhouri ZA and Ahmad A: A review on therapeutic potential of Piper nigrum (Black Pepper): The King of Species. Medicinal and Aromatic Plants. 2014; 3(3): 1-6.
- Meghwal M and Goswami TK: Piper nigrum and piperine: An Update. Phytotherapy Research. 2013; 27:1121-1130.
- Park UH, Jeong HS, Jo EY, Park T, Yoon SK, Kim EJ, Jeong JC and Um SJ: Piperine, a component of Black Pepper, inhibits adipogenesis by antagonizing PPARγ activity in 3T3-L1 Cells. J. Agrc. Food Chem. 2012; 60: 3853-3860.
- Ahmad N, Fazal H, Abbasi BH, Farooq S, Ali M and Khan MA: Biological role of Piper nigrum (Black pepper): A review. Asian Pacific Journal of Tropical Biomedicine. 2012; 1945-1953.
- Shah SS, Shah GB, Singh SD, Gohil PV, Chauhan K, Shah KA and Chorawala M: Effect of piperine in the regulation of obesity-induced dyslipidemia in high-fat diet rats. Indian J. of Pharmacology. 2011; 43(3): 296-299.
- Sabina EP, Nasreen A, Vedi M and Rasool M: Analgesic, antipyretic and ulcerogenic effects of piperine: An active ingredient of pepper. J. pharm. Sci. and Res. 2013; 5(10): 203-206.
- Vasavirama K and Upender M: Piperine- A valuable alkaloid from piper species. Int. J. of Ph. and Phr. Sci. 2014; 6(4): 34-38.
- Shamkuwar PB, Shahi SR and Jadhav ST: Evaluation of anti-diarrheal effect of Black pepper ( nigrum L). Asian Journal of Plant Science and Research. 2012; 2: 48-53.
- JS Swathy, Mishra P, Thomas J, Mukherjee A and Chandrasekaran N: Antimicrobial potency of high-energy emulsified black pepper oil nanoemulsion against aquaculture pathogen. Aquaculture. 2018; 491: 210-220. https://doi.org/10.1016/j.aquaculture.2018.03.045.
- Rolls BJ et al.: Sibutramine reduces food intake in non-dieting women with obesity. Obes. Res. 1998; 6(1): 1-11.
- Parmar VS, Jain SC, Bisht KS, Jain R, Taneja P, Jha A and Tyagi OD: Phytochemistry of genus Piper. Phyto-chemistry. 1997; 46: 597-673.
- Cotinguiba F, Manke K, Furlan M and Vogt T: Molecular investigation of Piper nigrum (black piper) fruits in search for natural products biosynthetic target genes. Congresso Brasileiro de Genetica. 2011; 30: 16.
- Wei K, Li w, Koike K, Pei Y, Chen Y and Nikaido T: New amide alkaloid from the root of Piper nigrum. J. Nat. Prod. 2004; 67: 1005-1009.
- Anh TT, Linh TB, Phong NV, Bien TLT, Tram THN and Don LD: Expression of proteins related to phytophthora capsici tolerance in black pepper (Piper nigrum). International Journal of Agriculture Innovations and Research. 2018; 6(4): 2319-1473.
- Lee CS, Han ES, and Kim YK: Piperine inhibition of 1-methyl- 4- phenylpyridinium - induced mitochondrial dysfunction and cell death in PC12 cells. Europ. J. Pharma. 2006; 537: 37-44.
- Lee SA, Hong SS, Han XH, Hwang JS, Oh GJ, Lee KS, Lee MK, Hwang BY and Ro JS: Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant like activity. Chem. Pharma. Bull. 2005; 53: 832-835.
- Chonpathompikunlert P, Wattanathorn J and Muchimapura S: Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food. Chem. Toxicol. 2010; 48: 798-802.
- Kolhe SR, Borole P and Patel U: Extraction and evaluation of piperine from Piper nigrumlinn. Inter. J. Appl. Biol. Pharma. Tech. 2011; 2: 144-149.
- Ramji MT, Deepthi K, Lakshmi KA and Uma P: In silico docking analysis of piperine amino acid analogues against carcinogenic activating enzymes. Biotechnology. 2011; doi:10.4172/jpb.1000240.
- Wang B, Zhang Y, Huang J, Dong L, Li T and Fu X: Anti-inflammatory activity and chemical composition of dichloromethane extract from Piper nigrum and longum on permanent focal cerebral ischemia injury in rats. Revista Brasileira de Farmacognosia. 2017; 27: 369-374.
- Chen WX, Dou HG, Ge C and Li C: Comparison of volatile compounds in pepper (Piper nigrum) by Simultaneous Distillation Extraction (SDE) and GC-MS. Advanced Materials Research. 2011; 236-238: 2643-2646.
- Mohapatra SS, Sarma J, Roy RK, Panigrahi S and Ganguly S: Ethnomedicinal plants used in Balasore District of Odisha: A Comprehensive Report. Int. J. Curr. Microbiol. App. Sci. 2018; 7(1): 1959-1963.https://doi.org/10.20546/ijcmas.2018.701.237.
- Badmaev V, Majeed M and Norkus EP: Piperine, an alkaloid derived from black pepper increases serum response of β-carotene during 14 days of oral β-carotene supplementation. Nutr Res.1999; 19(3): 381-388.
- Shoba G, Joy D and Joseph T: Influence of piperine on the pharmacokinetics of curcumin shows activity against Aedes aegypti mosquito larvae. J Agr Food Chem. 1998; 50: 3765-3767.
- Badmaev V, Majeed M and Prakash L: Piperine derived from black pepper increases plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000; 11: 109-113.
- Veda S and Srinivasan K: Influence of dietary spices-black pepper, red pepper, and ginger on the uptake of β-carotene by rat intestines. J Funct Foods. 2009; 1(4): 394–398.
- Piyachaturawat P, Glinsukon T and Toskulkao C: Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicology Letters. 1983; 16: 351-359.
- Najar AI, Sachin BS and Sharma SC: Modulation of P-glycoprotein ATPase activity by some phytoconstituents. Phytother Res. 2010; 24: 454–458.
- Reen RK, Roesch SF and Kiefer F: Piperine impairs cytochrome P4501A1 activity by direct interaction with the enzyme and not by down regulation of CYP1A1 gene expression in rat hepatoma 5L cell line. Biochem Biophys Res Commun. 1996; 218: 562-569.
- Singh J, Dubey RK and Atal CK: Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content. J Pharmacol Exp Ther. 1986; 236: 488-493.
- Myers BM, Smith JL and Graham DY: Effect of red pepper and black pepper on the stomach. Am J Gastroenterol. 1987; 82: 211-214.
- Ononiwu IM, Ibeneme CE and Ebong OO: Effects of piperine on gastric acid secretion in albino rats. Afr J Med Sci. 2002; 31: 293-295.
- Platel K, and Srinivasan K: Influence of dietary spices or their active principles on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci Nutr. 1996; 47: 55–59.
- Platel K and Srinivasan K: Studies on the influence of dietary spices on food transit time in experimental rats. Nutr. Res. 2001; 21: 1309-1314.
- Bhat GB and Chandrasekhara N: Effect of black pepper and piperine on bile secretion and composition in rats. Nahrung. 1987; 31: 913-916.
- Bano G, Raina RK and Zutshi U: Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol. 1991; 41: 615-617.
- Pattanaik S, Hota D and Prabhakar S: Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy. Phytother Res. 2006; 20: 683-686.
- Vijayakumar RS, Surya D and Nalini N: Antioxidant efficacy of black pepper (Piper nigrum) and piperine in rats with high fat diet induced oxidative stress. Redox Rep. 2004; 9: 105-110.
- Duangjai A, Ingkaninan K, Praputbut S and Limpeanchob N: Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J Nat Med. 2013; 67: 303-310.
- Cavallaro A and FL M: Pine bark extract and black pepper essential oil with anti-inflammatory and anti-arthritic action and method of preparing same. 2017; Patent No.: US 9,669,099 B2.
- Bae GS, Kim JJ and Park KC: Piperine inhibits lipopolysaccharide- induced maturation of bone-marrow-derived dendritic cells through inhibition of ERK and JNK activation. Phytother Res. 2012; 26: 1893-1897.
- Gupta SK, Velpandian T and Sengupta S: Influence of piperine on nimesulide induced antinociception. Phytother Res. 1998; 12: 266-269.
- Pradeep CR and Kuttan G: Effect of piperine on the inhibition of lung metastasis induced B16F-10 melanoma cells in mice. Clin Exp Metastas. 2002; 19: 703-708.
- Irshad S, Ashfaq A, Muazzam A and Yasmeen A: Antimicrobial and anti-prostate cancer activity of turmeric (Curcuma longa) and Black Pepper (Piper nigrum L.) used in Typical Pakistani Cuisine Pakistan. J. Zool. 2017; 49(5): 1665-1669.
- Selvendiran K and Sakthisekaran D: Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo(a)pyrene induced lung carcinogenesis. Biomedicine and Pharmacotherapy. 2004; 58: 264-267.
- Sarfaz M, Khaliq T, Khan JA and Aslam B: Effect of aqueous extract of black pepper and ajwa seed on liver enzymes in alloxan-induced diabetic Wister albino rats. Saudi Pharmaceutical Journal. 2017; 25(4): 449-452. https://doi.org/10.1016/j.jsps.2017.04.004.
- Malini T, Manimaran RR and Arunakaranet J: Effects of piperine on testis of albino rats. J Ethnopharmacol. 1999; 64: 219-225.
- Kawada T, Sakabe S and Watanabe T: Some pungent principles of spices cause adrenal medulla to secrete catecholamine in anesthetized rats. Proc Soc Exp Biol Med. 1988; 188: 229-233.
- Plessi M, Bertelli D and Miglietta F: Effect of microwaves on volatile compounds in white and black pepper. LWT- Food Sci Technol. 2002; 35(3): 260-264.
- Zang J, Ye KP, Zang X, Pan DD, Sun YY and Cao JX: Antibacterial activity and mechanism of action of black pepper essential oil on meat-borne Escherichia coli. Front. Microbiol. 2017; 7: Article- 2094.https://doi.org/10.3389/fmicb.2016.02094.
- Sepehri Z, Bagheri G, Mohasseli T, Javadian F, Anbari M, Nasiri A, Kiani Z, Shahi Z and Baigi GS: Antibacterial activity of Cuminum cyminum and Piper nigrum against antibiotic resistant Klebsiella pneumonia. Bull. Env. Pharmacol. Life Sci. 2014; 3: 17-19.
- Lai LH, Fu QH, Liu Y, Jiang K, Gou QM, Chen QY, Yan B, Wang QQ and Shen JG: Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model. Acta Pharmacologica Sinica. 2012; 33: 523-530.
- Chouhan G, Islamuddin M, Want MY, Ozbak HA, Hemeg HA, Sahal D and Afrin F: Leishmanicidal activity of Piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by Th1 immuno-stimulatory potential in vivo. Frontiers in Microbiology. 2015; 6: 1-19.
- Upadhyay RK and Jaiswal G: Evaluation of biological activities of Piper nigrum oil against Tribolium castaneum. Bulletin of Insectology. 2007; 60(1): 57-61.
- Hritcu L, Noumedem JA, Cioanca O, Hancianu M, Postu P and Mihasan M: Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer’s disease. Behavioral and Brain Function. 2015; 11(13): 1-13.
- Nahak G and Sahu RK: Phytochemical evaluation and antioxidant activity of Piper cubeba and Piper nigrum. J Applied Phr. Sci. 2011; 1(8): 153-157.
- Sriwiriyanjan S, Tedasen A, Lailerd N, Boonyaphiphat P, Nitiruangjarat A, Deng Y and Graidist P: Anticancer and cancer prevention effects of piperine- free Piper nigrum extract on N-nitrosomethylurea- induced mammary tumorigenesis in rats. Cancer Prev. Res. 2016; 9(1): 74-82.
- Vijayakumar RS, Surya D, Senthilkumar R and Nalini N: Hypolipidemic effect of Black Pepper (Piper nigrum) in Rats Fed High Fat Diet. J. Clin. Biochem. Nutr. 2002; 32: 31-42.
- Rani SKS, Saxena N and Udaysree: Antimicrobial activity of Black Pepper (Piper nigrum). Global J. Pharmacology. 2013; 7 (1): 87-90.
- Majeed M, Badmeev V and Rajendran R: Use of piperine as a bioavailability enhancer. United State Patent. 1999; (5): 972, 382.
- Agbor GA, Akinfiresoye L, Sortino J, Johnson R and Vinson JA: Piper species protect cardiac, hepatic, and renal antioxidant status of atherogenic diet fed hamster. Food chem. 2012; 134: 1354-1359.
- Paulkumar P, Gnanajobitha G, Vanaja M, Kumar SR, Malarkodi C, Pandian K and Annaduria G: Piper nigrum leaf and stem assisted green synthesis of silver nanoparticles and evaluation of its antibacterial activity against agricultural plant pathogens. Scientific World Journal. 2014; Article id: 829894.http://dx.doi.org/10.1155/2014/829894.
- Bukhari IA, Pivac N, Alhumayyd MS, Mahesar AL and Gilani AH: The analgesic and anticonvulsant effects of piperine in mice. J. Physiol. Pharmacol. 2013; 64: 789-794.
- Chen CY, Li W, Qu KP and Chen CR: Piperine exerts antiseizure effect via the TRPV1 receptor in mice. Eup. J Pharmaco. 2013; 714: 288-294.
- Bang JS, Ohda H, Choi HM, Sur BJ and Lim SJ: Anti-inflammatory and antarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Research and Therapy. 2009; 11: R49.
- Kim SH, Lee YC: Piperine inhibits eosinophil infiltration and airway hyper responsiveness by suppressing T cell activity and Th2 cytokine production in ovalbumin-induced asthma model. J Pharm Pharmacol. 2009; 61: 353-359.
- Doucette CD, Hilchie AL, Liwiski R and Hoskin DW: Piperine, a dietary phytochemical, inhibits angiogenesis. The Journal of Nutritional Biochemistry. 2013; 24: 231-239.
- Samykutty A, Shetty AV, Dakshinamoorthy G, Bartik MM, Johnson GL, Webb B, Zheng G, Chen A, Kalyanasundaram R and Munirathinam G: Piperine, a bioactive component of pepper spice exerts Therapeutic effects on Androgen dependent and Androgen Independent Prostate cancer cells. 2013; https://doi.org/10.1371/ journal.pone.0065889.
- Selvendiran K and Sakthisekaran D: Chemprotective effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo (a) pyrene induced lung carcinogenesis. Biomedicine and Pharmacotherapy. 2004; 58: 264-267.
- Mona AM, Abo Z and Ayman A: The anti-mutagenic activity of piperine against mitomycin C induced sister chromatid exchange and chromosomal aberration in mice. Nature and Sci. 2009; 7: 72-78.
- Mao QQ, Huang Z, Zhong XM, Xian YF and Ip SP: Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Neuro Chem Int. 2014; 74: 36-41.
- Nirwane AM and Bapat AR: Effect of methanolic extract of Piper nigrum fruits in Ethanol-CCl4 induced hepatotoxicity in Wistar rats. Der. Pharmacia. Lettre. 2012; 4: 795-802.
- Singh A and Duggal S: Piperine- Review of advances in Pharmacology. Int. J. Pharm. Sci. Nanotech. 2009; 2: 615-620.
- Srinivasan K: Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Crit. Rev. Food Sci. Nutr. 2007; 47: 735-748.
- George ES: Anthelmintic activity of the alcoholic extract of the dried fruits of Piper nigrum Indian J. Sci. Res. 2018; 19(2): 62-64.
- Matthew C: Black Pepper consumption in the Roman Empire. Journal of the Economic and Social History of the Orient. 2018. http://repository.uwtsd.ac.uk/id/eprint/848.
- Sapam R, Kalita PP, Sarma MP, Talukdar N and Das H: Screening of phytochemicals and determination of total phenolic content, anti-oxidant, and antimicrobial activity of methanolic extract of Piper nigrum Indo American Journal of Pharmaceutical Research. 2018; 8(2): 1354-1360.
- Park TS and Jeong NS: Piperine derivatives and uses thereof. 2016. US Patent: US 9,321,751 B2.
- Lopez KJF, Mayorga JLC, Mahecha MMA, Cabedo L and Lagaron JM: Antibacterial and barrier properties of gelatin coated by electrospun polycaprolactone ultrathin fibers containing black pepper oleoresin of interest in active food biopackaging applications. Nanomaterials. 2018; 8(4): 199. doi:10.3390/nano8040199.
- MošovskáS,Medvecká V, Halászová N, Ďurina P, Valík L, Mikulajová A and Zahoranová A: Cold atmospheric pressure ambient air plasma inhibition of pathogenic bacteria on the surface of black pepper. Food Research International. 2018; 106: 862-869. https://doi.org/10.1016/ j.foodres.2018.01.066.
- Zhu F, Mojel R and Li G: Physicochemical properties of black pepper (Piper nigrum) starch. Carbohydrate Polymers. 2017; 181: 986-993. https://doi.org/10.1016/ j.carbpol.2017.11.051
- Moghaddasi F, Housaindokht MR, Darroudi M, Bozorgmehr R and Sadeghi A: Synthesis of nano curcumin using black pepper oil by O/W Nanoemulsion Technique and investigation of their biological activities. LWT - Food Science and Technology. 2018; 92: 92-100. https://doi.org/ 10.1016/j.lwt.2018.02.023
- Chen W, Zou L, Chen W, Hu Y and Chem H: effects of black pepper (Piper nigrum) chloroform extract on the enzymatic activity and metabolism of Escherichia coli and Staphylococcus aureus. Journal of Food Quality. 2018; Article ID 9635184, 9 pages. https://doi.org/10.1155/2018/ 9635184
- Umadevi P, Soumya M, George JK and Anandaraj M: Proteomics assisted profiling of antimicrobial peptide signatures from black pepper (Piper nigrum). Physiol. Mol. Biol. Plants. 2018; 1-9. https://doi.org/10.1007/ s12298-018-0524-5
- Tang H, Chen W, Bou ZM, Chen R, HU Y, Chen W and Chen H: Antimicrobial effect of black pepper petroleum ether extract for the morphology of Listeria monocytogenes and Salmonella typhimurium. Journal of Food Science and Technology. 2017; 54(7): 2067-2076.
- Moreno IR, Guerrero IN, Escareno N, Soto MEF, Gertsch J and Paredes JMV: An Endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice. J. Agric. Food Chem. 2017; 65 (43): 9435-9442. DOI: 10.1021/acs.jafc.7b02979
- Vazhacharickal PJ, Mathew JJ and Babu A: Phytochemical and anti-diabetic activities of different plant part extracts among black pepper (Piper nigrum) varieties in comparison with Piper longum and Piper betel. Scientific Study. 2017.
- Jin Z, Kwon M, Lee AR, Ro DK, Wungsintaweekul J and Kim SU: Molecular cloning and functional characterization of three terpene synthases from unripe fruit of black pepper (Piper nigrum). Archives of Biochemistry and Biophysics. 2018; 638: 35-40. https:// doi.org/10.1016/j.abb.2017.12.011.
- Park TS: Novel Use of Piperine. 2011. US Patent: US 2011/0288125 A1.
- Kim DY, Kim EJ and Jang WG: Piperine induces osteoblast differentiation through AMPK-dependent Runx2 expression. Biochemical and Biophysical Research Communications. 2018; 495(1): 1497-1502. https:// doi.org/10.1016/j.bbrc.2017.11.200.
- Soutar DA, Doucette CD, Liwski RS and Hoskin DW: Piperine, a pungent alkaloid from black pepper, inhibits B lymphocyte activation and effect or functions. Phytotherapy Research. 2017; 31(3). https://doi.org/ 10.1002/ptr.5772.
- Gorgain L, Mohammadi M, Najafpour GD and Nikzad M: Piperine-The bioactive compound of black pepper: From isolation to medicinal formulations. Comprehensive Reviews in Food Science and Food Safety. 2016; 16(1). https://doi.org/10.1111/1541-4337.12246.
- Ozdemir N, Pola CC, Teixeira BN, Hill LE, Bayrak A and Gomes CL: Preparation of black pepper oleoresin inclusion complexes based on beta-cyclodextrin for antioxidant and antimicrobial delivery applications using kneading and freeze-drying methods: A comparative study. LWT - Food Science and Technology. 2018; 91. 439-445. https://doi.org/10.1016/j.lwt.2018.01.046.
- Khan ZR, Moni F, Sharmin S, Mansur MAA, Gafur A, Rahman O and Afroz F: Isolation of bulk amount of piperine as Active Pharmaceutical Ingredient (API) from black pepper and white pepper (Piper nigrum). Pharmacology and Pharmacy. 2017; 8: 253-262.
How to cite this article:
Joshi DR, Shrestha AC and Adhikari N: A review on diversified use of the King of Spices: Piper nigrum (Black Pepper). Int J Pharm Sci & Res 2018; 9(10): 4089-01. doi: 10.13040/IJPSR.0975-8232.9(10).4089-01.
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.
D. R. Joshi *, A. C. Shrestha and N. Adhikari
College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan daero, Iksan, Jeolabuk do 54538, Republic of Korea.
19 January, 2018
19 April, 2018
11 June, 2018
01 October, 2018