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Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1945

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Document heading doi: 2012 by the Asian Pacific Journal of Tropical Biomedicine. All rights reserved. 襃 Biological role of nigrum L. (): A review

Nisar Ahmad1, Hina Fazal2, Bilal Haider Abbasi1, Shahid Farooq2, Mohammad Ali1 and Mubarak Ali Khan1

1Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan 2Pakistan Council of Scientific and Industrial Research (PCSIR) Laboratories Complex, Peshawar 25100, Pakistan

ARTICLE INFO ABSTRACT

Article history: Piper nigrum L. is considered the king of throughout the world due to its pungent principle 13 2012 Piper nigrum Received September . Peppercorn of as a whole or its active components are used in most of 7 2012 Piper nigrum Received in revised form October the food items. Different parts of including secondary metabolites are also used A 12 N 2012 Piper nigrum ccepted ovember as drug, preservative, insecticidal and larvicidal control agents. Biologically is Available online 28 December 2012 very important specie. The biological role of thisPiper spec inigrume is explained in different experiments that peppercorn and secondary metabolites of can be used as Antiapoptotic, Keywords: Antibacterial, Anti-Colon toxin, Antidepressant, Antifungal, Antidiarrhoeal, Anti-inflammatory, Piper nigrum Antimutagenic, Anti-metastatic activity, Antioxidative, Antiriyretic, Antispasmodic, Black-pepper Antispermatogenic, Antitumor, Antithyroid, Ciprofloxacin potentiator, Cold extremities, Gastric Peppercorn ailments, Hepatoprotective, Insecticidal activity, Intermittent fever and Larvisidal activity. Other Piperine roles of this specie includes protection against diabetes induced oxidative stress; Piperine protect Biological activities oxidation of various chemicals, decreased mitochondrial lipid peroxidation, inhibition of aryl hydroxylation, increased bioavailability of vaccine and sparteine, increase the bioavailability of active compounds, delayed elimination of antiepileptic drug, increased orocecal transit time, piperine influenced and activate the biomembrane to absorb variety of active agents, increased serum concentration, reducing mutational events, tumour inhibitory activity, Piperine inhibite mitochondrial oxidative phosphorylation, grPiperowth nigrumstimulatory activity and chemopreventive effect. This review based on the biological role of can provide that the peppercorn or other parts can be used as crude drug for various diseases while the secondary metabolites such as piperine can be used for specific diseases.

1. Introduction administrated[7]. Some reports have been demonstrated that black pepper consumption in humans increased orocecal Piper nigrum [10-11] isPiper fam onigrumus as thP.nigrume spices king due to its transit time . Piperine prevents and minimize diarrhea pungent quality[1]. ( ) L. is a member produced by various oil and chemicals and also reduce [2-4] [11] of . The piper has mP.nigrumore than intestinal fluid aP.cc unigrummo- in mouse intestine . The 1P.longum000 buP.betlet the most well known sp.pe nigrumcies are , active agents of activates the epithelial cells and ; 51 of have been in rat jejunum to permeates the uptake of various amino repoP.nigrumrted from the tropical and subtropical regions of acids through the activation of membranes, enhance the [5]. are also used to produce white pepper production of proteins which are later used for the formation and green pepper and are valued due the presence of of cytoskeleton system due to surface adsorption property. piperine including its different isomers[6]. Black pepper This valuable specie also has the power to minimize can be used for different purposes such as human dietaries, different mutations like ethylcarbamte induced mutation as medicine, as preservatives, as biocontrol agents[1, in Drosophila. As compare to mutation, black pepper also 8, 9]. This and its active component piperine can reduced tumor formation in mice such as Ehrlich ascites stimulate the digestive enzymes of pancreas and intestines tumour and Doltons lymphoma cells[12-14]. and also increases biliary bile acid secretion when orally Other related activities included Anti-inflammatory activity, thermogenic action, growth stimulatory activity, *Corresponding author: Nisar Ahmad, PhD Scholar, Department of Biotechnology, anti-thyroid activity and chemopreventive[15]. Secondary Quaid-i-Azam University, Islamabad-45320, Pakistan. P. nigrum Tel: +92-332-9959234 metabolites from play defensive role against [16-17] E-mail: [email protected] infections by microbes, insects and animals . Nisar Ahmad et al./Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1946 P. nigrum Piperamides extracted from had shown isolated which includes alkaloides/amides (145), lignans (47), insecticidal activities[18-19].毬- showed neolignans (70), (89) and 101 noval compounds has [20] anesthetic actiP.vit ynigrum. Nerolidol is very famous secondary also been extracted, 14 of which shown different biological metabolite of , used to control mites. Another activities[25, 41, 42, 43]. important component of pepper volatile oil is pipene, which [21] is a famous odorants . 2. Biological value of P. nigrum Black pepper is important for its medicinal value[22]. Medicinally black pepper can be used for digestive disorders like large intestine toxins, different gastric problems, Most of the plant species including piper produced diarrhea, and indigestion and also can be used against secondary metabolites which help in body metabolism and [23, 24, 26] respiratory disorders including coldP., feguineensever, asthma . also used as defense system against various agents such as The West African Black pepper, ( ), important insect feeding and animals.[16]. Recently scientists as flavorant and its different parts are used as internal from different biological fields screen plants for various medicine for curing bronchitis, gastric ulcer, rheumatism secondary metabolites which can be used for preparation of and as antiviral agent[25]. Recently, an interesting study has medicines and biocontrol agents[45]. shown effects of piperine on mood and cognitive disorder[27]. Piperaceae family has provided many past and present Notwithstanding, it has been shown that enhances the civilizations with a source of medicines and food spices; the bioavailability of various including vitamins; 毬 secondary metabolites of different species in the genus piper -carotene and [28]. Different field investigators have been used for various biological activities including isolated valuable compound from this specie including insect repellent activities. The active compounds having Phenolics, various derivatives of lignans, terpenes, insecticidal activity are the piperaPipermide snigrum extracted from chalcones, flavonoid, and steroid[25]. Brachyamide B different species of piper including [46]. Black [29], Dihydropipericide[25], benzamide group[30], (2E, 4E)-N- pepper is the main food stuff and Piperine is a pungent Eicosadienoyl pereridine[31], N-trans-Feruloyltryamine,[25], alkaloid of black pepper. Two important sesquiterpens, 毬 Guineensine[32], pentadienoyl as , (2E, 4E)-N- -caryophyllene and nerolidol, the first having anaesthetic isobutyldecadienamide[33], isobutyl-eicosatrienamide[34], activity[20]and second used for flavouring agent, it is also isobutyloctadienamide[25], Piperamide[35], Piperamine[25], been reported that the piperine enhances the trans-dermal Piperettine[36], Pipericide[37], Piperine[3,38], Piperolein B, delivery of active drugs through skin membrane. A natural Trichostachine, Sarmentine, Sarmentosine,[39,25,4,40]. Only compound isolated from piper species known as nerolidol 12% plant species of Piperaceae family has been investigated having pesticidal activity against various mites. Another for analysis. 592 compounds has been active agent isolated from volatile oil of peppercorn known Table 1 et al P. nigrum Mathew [44] reported 51 cultivars of in various districts of India. No Locality District No Cultivar Locality District 1 Ampirian Kulathupuzha 27 Kanjiramkodan Kalpetta Wayanad 2 Angamali Kodolippuram 28 Kareelanchi Kulathupuzha Kollam 3 Arakulammundy Pulpally Wayanad 29 Karimkottavalli Kalpetta Wayanad 4 Areepadappan Kulathupuzha Kollam 30 Karimunda Peruvanthanam Idukki 5 Arivally Kodolippuram Kannur 31 Karimundy Pulpally Wayanad 6 Balankotta Kalpetta Wayanadu 32 Karivally Porora Kannur 7 Cheriyakaniyakadan Veliyambra Kannur 33 Kottanadan Peringamala Trivandrum 8 Cheriyauthiran Naiketty Wayanad 34 Kuruvantherivally Kodolippuram Kannur 9 Cherumany Naiketty Wayanad 35 Kuthiravaaly Kodolippuram Kannur 10 Chombala Mattannoor Kannur 36 Maniyamcode Kalpetta Wayanad 11 Jeerakamundy Idukki 37 Manjavallypadappan Peringamala Trivandrum 12 Kallubalancotta Kodolippuram Kannur 38 Menonvally Kodolippuram Kannur 13 Kallumany Periya Wayanad 39 Mundy Aralam Kannur 14 Kalluvally Periya Wayanad 40 Murithothan Kulathupuzha Trivandrum 15 Kalyanamandiram Kalpetta Wayanad 41 Narayakodi Pathamuttom Kottayam 16 Kaniyakadan Kulathupuzha Kollam 42 Neelamundi Vandiperiyar Idukki 17 Muttiyaramundy Pulpally Wayanad 43 Orumaniyan Vallakkadavu Idukki 18 Pala Palode Trivandrum 44 Peringamala Peringamala Trivandrum 19 Panickaruvally Naiketty Wayanad 45 Perumkodi Pulpally Wayanad 20 Panniyur-I Palode Trivandrum 46 Poonjarmunda Kodolippuram Kannur 21 Thevanmundy Peermade Idukki 47 Uthirankotta Kodolipuram Kannur 22 Thirimuriyan Kalpetta Wayanad 48 Vadakkan Vandiperiyar ldukki 23 Uthiran Kalpetta Wayanad 49 Valiyauthiran Naiketty Wayanad 24 Valiyapadappan Kulathupuzha Trivandrum 50 Vattamundy Upputhara Idukki 25 Vellamundy Vallakkadavu Idukki 51 Veluthauthiri Porora Kannur 26 Wayanadan Chandanathod Wayanad Nisar Ahmad et al./Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1947

A B C D

Figure 1. P. nigrum P. nigrum P. Adopted from internet (A) Climbing of ; (B) Green mature of ; (C) Black, white and green fruits of nigrum ; (D) Processed peppercorn. P. nigrum as pipene which is important odorants[21]. Black pepper The pungent compound of especially piperine stimulates rat gastric acid secretion and its active agent increases the production of saliva and gastric secretions piperine decreases the secretion of small intestine activated [1]. Furthermore, the ingestion of peppercorn increases [43] by castor oil. This plant also increases rat pancreatic the production and activation of salivary amylasP.e nigrum. The enzymes activity[47]. Black pepper is antimicrobial[48], digestive enzymes production by the ingestion of same antimicrobial activities also reported from Piper probably the stimulate liver to secrete bile, which further betle, antimutagenic[12], antioxidant & radical scavenging digests food substances. Researchers[9]examined various [49-50] properties , improve reflexive swallowing movement animal modelsP. f onigrumr bile secretion after the ingestion of [51]. Black pepper and peppercorn are used to cure various piperine from . These workers further observed digestive disorders, fevers, obesity and respiratory tract that orally administrated piperine can significantly diseases caused by different pathogenic agents such as increases bile acid secretion from liver. The effect of intake bacteria, viruses and fungal strains. Peppercorns extract of peppercorn in food items and oral administration of active con+t2ain such active spasmolytic compounds which block the compounds of genus piper such as piperine, piperamides, Ca influx and explain its traditional medicinal use in the piperamines and pipene on the enzymes activation of curing various digestive disorders[52,23]. Aqueous decoction pancreas, liver and the terminal digestive enzymes of the Staphylococcus [7-8] oaureusf black pepper has maximum effect against small intestinal mucosa has been reported . Addition [53]; also inhibit the growth of meat spoilage bacteria of piperine to food substances as food additives increases [54] [19] . Black pepper μalso P.ha vnigrume insecticidal activities , lipase activity, pancreatic amylase activity, chymotrypsin concentration of 0.2 l of oil significant repellent activation and protease activity[1]. T. castaneum[55] of , also show anti-spermatogenic and O O [56] O O infertility effect in mice , anti-diarrheal & antispasmodic O N 4 O P T P R activities of iperine. he natuPiperral li pnigrumophilic iperine and n piperiline were isolated from , Piperine was hydrolyzed into piperic acid which was converted into 16 (a) Piperamide (b) Piperamine amides having insecticidal activity[25,57]. The larvicidal O activity of Piper nigru, was also reported, larvicidal effects O O O of crude extracts of dried ripened fruits of pepper against O N R Culex quinquifasciatus 4 H n larval instars. Piperine displays O antipyretic, analgesic, insecticidal, anti-inflamatory[57-58], immuno-modulatory, antitumar[14]and antidepressant (c) Pipericide (d) Piperine [59] [60] activities , anti-apoptotic activity .Piperine derivatives O P.nigrum P.longum O O from and having anti-metastatic O [61] [15] [62] N N activity , antithyroid activity , Hepatoprotective and 2 4 immunostimulating activity[14]. Antiplatelets, anxiolytic activities. It is anti-oxidant and its anti-apoptotic potential (e) Sarmentosine (f) Sarmentine has also been reported[63-64]. Piperine inhibits several Cytochrome P450-mediated pathways in animals[22,65]. O N Piperine significantly increased plasma concentration O O (g) Trichosta of refampin, phenytoin, propranolol and theophylline in Figure 2: P. nigrum humans[66-68], a potentiator of Ciprofloxacin Some important derivatives of . agaP.in nigrumst Stapyloccocus aureus. The dichloroC.me masulatusthane extracts of has pesticidal activity against and [69] P. nigrum 4. Antioxidant activity of P. nigrum S. zeamais . Aspergillus inhibit thparaiticuse transcription of toxin biosynthesis genes in [70]. Antifungal [71] ’ activity of this plant also reported against bean rust . Plants a’re more important in human s life and fulfill his every day s needs[74]. In recent developments free radicals [40] 3. Effects of P. nigrum on digestion are involved in many diseases . Different free radicals produced in the body attack on membranes causing oxidation of lipids, reduced the fluidity of biomembranes, Nisar Ahmad et al./Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1948 6. Antimutagenic and antitumor activity of P. nigrum loss of different enzyme activities, loss of receptor activities and causing cell inactivation by damaging the proteins P.nigrum present in membrane[75,78]. Some Free radicals are the not only used in perfumery and food industry causing agent of cancer, first the free radicals attacks but also very effectietv eal against fatal diseases caused by on cell DNA, the DNA causes mutational changes which mutations. El Hamss .[12] observed that when Drosophila [76, 79] finally induced cancer . Due to such diseases natural melanogaster was exposed to mutation through proP.m unigrumtagen- antioxidant are of interest for scientist to cure cellular ethyl carbamate, in such induced situationP. th enigrum degeneration[77, 80]. Antioxidants are such type of agents is effective to reduce mutational events. and which completely stop or delay the process of oxidation. its active derivatives especially peppercorn extract has The antioxidant compounds blocked the chain reaction of been reported to inhibit tumors formation in experimental oxidation. Natural and synthetic antioxidants are the two models[90]. Such reduced antitumor activity by the oral group of antioxidant but the synthetic antioxidants are administration was also reported[3]. The alcoholic extract of [75, 81] carcinogenic . The interest in natural antioxidants have peppercorn and piperine was ef’fective in immunomodulatory, been increased considerably, especially to the antioxidant antitumor activity and Dalton s lymphoma[14]. [61]Observed compounds present in plants which is consider non toxic that piperine are involved in antimetastatic activity, in his and environmental friendly[75-76]. The antioxidants of plants experiment he documented that mice models when exposed origin are recently used as food additives[77, 82]. Reactive to melanoma cells (B16F-10), the active agent piperine secondary metabolites and reactive oxygen species (ROS) prevent and inhibit lung metastasis and finally concluded produced during metabolism causes carcinogenesis and that piperine dramaticallyP.nigrum reduced tumor nodule formation. cell damage[1]. To protect themselves from reactive oxygen Moreover, piperine from reduced lung cancer by species such oxidative damage, plants developed a complex modulating lipid peroxidation and through the activation of antioxidant system [75]. Antioxidant protection system antioxidative protection enzymes[91-92]. Table 2 includes enzyme like Peroxidase (POD), Catalase (CAT) P. nigrum Superoxide dismutase (SOD) and Ascorbate (ASC), which Different biological activities of . scavenge both radicals and their associPiperated nnigrumon-radical S.NO Activity References oxygen insp evitrocies. Regenerated inti svitrosues of like 1 Anti-apoptotic [63-64] callus, shoots, roots, plantlets, peppercorn 2 Antibacterial [71] and acclimated plantlets possesses antioxidant activity 3 Anti-Colon toxin [52] which is probably due to the preetse alnce of flavonoids and 4 Antidepressant [59] phenolic contents[3]. Vijayakumar [84]reported the effect P. nigrum 5 Antifungal [17] of intake of on membrane lipid peroxidation, 6 Analgesic [25] enzymic, and nPiperon-e nnigrumzymic antioxidants in rats and [58] documented that prevent induced stress such 7 Antidiarrhoeal Piper nigrum [25-58] as oxidative stress. also prevent the intestine 8 Anti-inflammatory [12] induced oxidative stress, inhibit lipid peroxidation, arresting 9 Antimutagenic [61] different radicals such as hydroxyl and super oxides 10 Anti-metastatic activity radicals, decrease induced lung carcinogenesis and inhibit 11 Antioxidative [3,63,64] human lipoxygenase[83, 84, 85, 86, 87, 92]. 12 Antiriyretic [25] 13 Immuno-modulatory [14] [58] 5. Antidiarrhoeal property P. nigrum 14 Antispasmodic 15 Asthma, obesity, sinus [52] [56] P. nigrum 16 Antispermatogenic is important due it pungent piperine[3]. Several 17 Antithyroid [15] workers reported the antidiarrhoeal property of this plant. 18 Antitumor [14] Interestingly in most of the developing countries local 19 Ciprofloxacin potentiator [67,68] peoples, herbal practioners and herbal industries specially 20 Colic [23] [88] formulate the peppercorn for diarrhea for all ages . The 21 Cold extremities [23] antidiarrhoeal activity in experimental mice has already 22 Gastric ailments [23] [11] been reported . Furthermore, the piperine profile of piper 23 Hepatoprotective [62] species minimizes the antidiarrheal activity induced by 24 Increase plasma [66] the supplementation of ’various chemical activators and oil 25 Increase pancreatic enzymes [47] [89] S in experimental animal s model . ome reports has been 26 Inhibit cytochrome [10,65-71] published on the effects of piperine in mice small intestine 27 Inhibit transcription [70] fluid accumulation activated by castor oil. In such induced 28 Insecticidal activity [46] situation piperine sequentially prevent the small intestine 29 I [23] fluid accumulation. Furthermore, the reduction in fluid ntermittent fever 30 Larvisidal activity [52] secretion and accumulation was control by - [69] sensitive neurons, but comparatively the - 31 Pesticidal activity sensitive vanilloid receptors was less effective during castor [88] oil induced situation . 7. Antidepressant activity of P. nigrum Nisar Ahmad et al./Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1949 Table 3 P. nigrum Some important role of fruits and isolated piperine [1] P. nigrum Different effect of and Piperine References Piperine inhibit ascorbate-Fe++-induced lipid peroxidation [100] Piperine protected against oxidative stress induced carcinogenesis [85] Protection against diabetes induced oxidative stress [101] Inhibition / quenching of super oxides and hydroxyl radicals by piperine [86] Piperine protects Cu++-induced lipid per-oxidation [92] Decreased mitochondrial lipid peroxidation [84] Dietary black pepper/piperine reduces high fat diet induced oxidative stress [87] Inhibition of aryl hydroxylation [102] Decreased UDP-glucuronic acid concentration [65] Inhibition of O-deethylase activities in pulmonary microsomes [103] Inhibition of UDP- dehydrogenase and UDP- glucuronyl transferase [104] Increased bioavailability of vaccine and sparteine [73] Enhanced systemic availability of propranolol and theo-phylline [68] Increased serum concentration [105] Delayed elimination of anti-epileptic drug [106] Enhanced bioavailability of 毬-lactam [107] Increased plasma levels and delayed excretion of epigallo-catechin-3-gallate [108] Stimulation of digestive enzymes of Pancreas by dietary piperine [8] Increased orocecal transit time [109] Black pepper increased gastric acid secretion [110] Piperine modulated the membrane dynamics and permea-tion characteristics, [85] Reducing mutational events [12] Tumour inhibitory activity [13] Anti-metastatic activity of piperine on lung metastasis [61] Chemopreventive effect [91] Thermogenic action of piperine via adrenal catecholamine secretion [111] Growth stimulatory activity [112] Anti-thyroid activity [15] Piperine inhibited mitochondrial oxidative phosphorylation [113] Piperine exerted protection against t-butyl hydroperoxide [62] α Piperine promoted cytotoxicity induced by benzo( )pyrene [114] Piperine potentiated hepatotoxicity of carbon tetrachloride in rats [115] et al et al 9. Anti inflammatory activity of P. nigrum Li .[93]and Song .[94]demonstrated the effect of piperine on antidepressant activity in experimental mice [88] through chronic mild stress procedure. Dose dependant Singh and DuP.g gnigrumal in their review reported that piperine intake of piperine for 15 consecutive days reverse the chronic isolated from inhibits adhesion of endothelial mild stress and changes in consumption of and also monolayer to neutrophils anαd due such inhibitory activity plasma corticosterone level. Furthermore, the level of brain- the tumor necrosis factor- induced expression of cell derived neurotrophic factor in hippocampus of chronic adhesion molecules was blocked i.e. intercellular adhesion stressed mice was up-regulated by piperine treatment[88]. molecule-1, vascular cell and E-selectin. Vijayakumar [84] et al [27] Wattanathorn . also observed the antidepressant also reported another blocking system thκatα piperine blocks activity by the administration of piperine to Wister male the phosphorylation and dαegradation ofκ I B by attenuating rats in different doses for 28 days and finally documented tumor necrosis factor- induced I B kinase activity. that piperine possessed anti-depression like activity and Piperine in various concentrations, dose-dependently cognitive enhancing effect during entire treatment duration. inhibited the collagen matrix invasion of melanoma cells [61] [88] (B16F-10) . Singαh and Duggal also documented that GM- 8. Anti-platelet activity of P. nigrum CSF, IL-6, TNF- and IL-1毬 which was pro-inflammatory cytokines was dramatically reduced by the administration of piperine. The valuable component of different piper species is piperine. Piperine is mostly responsible for various activitieets 10. Antihypertensive effect of P. nigrum [1-3]. Piperine also possesses anti-platelet activity. Park al[95] observed the toxic effect of piperine on aggression of P. nigrum platelet in experimental rabbit induced by different factors are mostly administrated orally as food which activate platelets, by collagen and thrombin. additives. For more specification the isolated components like piperine are administrated by different means. Piperine in dose-dependent manner when administrated Nisar Ahmad et al./Asian Pacific Journal of Tropical Biomedicine (2012)S1945-S1953 S1950 intravenously, it induced to decreased pressure in ainrt evitrories BioPerine in small amount with beta-carotene increased in normotensive anesthetized rats[96]. Piperine, in two fold the blood levels of beta carotene in human[118]. study on rabbit heart causes a partial reduction of force, BioPerine also enhanced the bioavailability of drugs. The contraction of tissues and blood flow in coronary vessels. In therapeutic effectiveness of is limited due to its rabbit aortic ring, piper+ine partially inhibited phenylephrine poor absorption from the GI tract, therefore the BioPerine and2+ inhibited high 2+K pre-contractions due to blockade significantly improved the uptake of Curcumin. Ca channel. In Ca -free medium, piperine in low doses [88] exhibited vasoconstrictor effect . 15. Cosmoperine from P. nigrum fruits

11. Hepatoprotective effect of P. nigrum Cosmoperine prepared from piperine used in cosmetics, a natural bio-enhancer which improve the permeability P. [116] nigrum After Silybum marianum as main hepatoprotector, of active compounds through skin . Cosmoperine ’ also possess hepatoprotective effectset i nal experimental activate and stimulate the natural power of skin to absorb animal s models and in humans. Matsuda .[97]observed nutrients[119-120]. Cosmoperine isolated from piperine are that when experimental mice with D-galactosamine non-irritant, interacts with the skin quantitatively and induced liver toxicity were exposed to dose-dependent qualitatively in various means. Furthermore, Cosmoperine piperine, it inhibited increase in serum GPT and GOT levels are pain relieving and causes skin reddening due to vascular and suggested that this inhibitory effect depended on the engorgement as well as a slight skin tingling sensation. reduced sensitivity of hepatocytes to tumor necrosis factor α[88] - . References

12. Antithyroid activity of P. nigrum [1] S rinivasan K. Black pepper and its pungent principle-piperine. Crit. Rev. Food Sci. A review of diverse physiological effects. P. nigrum Nutr 47 and its active piperine alone can be used for a 2007; : 735-748. [2] N air RR, Gupta SD. Somatic embryogenesis and plant variety of diseases. But when piperine in combination with Piper nigrum carbimazole was administrated, it has been observed that regeneration in black pepper ( L.). Direct somatic embryogenesis from tissue of germinating and ontogeny the combination dramatically reduced the lipoproteins and J. Hortic. Sci. Biotchnol 78 plasma lipids, furthermore such combination increases the of somatic embryos. 2003; : 416-421. high density lipoproteins level[98]. Singh and Duggal[88] also [3] A hmad N, Fazal H, Abbasi BH, Rashid M, Mahmood T, Fatima N. Efficient regeneration and antioxidant potential in reported that piperine supplementation significantly reduced Piper nigrum Tissue and regenerated-tissues of L. Plant Cell, TSH and apo B, however the testosterone, apo A-I, T4 and T3 Organ Culture 102 level were increased. Panda and Kar[15]administrated Swiss 2010; : 129-134. [4] A bbasi BH, Ahmad N, Fazal H, Mahmood T. Conventional and albino mice with piperine and recorded lowered thyroxin Piper nigrum J. Med. Plant modern propagation techniques in . and triiodothyronine, serum levels of both the thyroid Res 4 2010; : 007-012. hormones and as well as glucose’ concentrations with a [5] K han S, Mirza KJ, Anwar F, Zainul Abdin M. Development of concomitant decrease in hepatic 5 D enzyme and glucose- Piper nigrum Environ. RAPD markers for authentication of (L.). 6-phospatase activity. We Int. J. Sci. Tech 5 2010; : 47-56. [6] Z averi M, Khandhar A, Patel S, Patel A. and 13. P. nigrum as antiasthmatic J. Pharma. Sci. Rev. pharmacology of Piper longum L. Inter. Res 5 . 2010; : 67-76. Most of the herbal practioners and old people believed [7] T iwari P, Singh D. Antitrichomonas activity of sapindus saponins, a candidate for development as microbicidal that addition of poetw aldered peppercorn to green tea reduced J. Antimicrob. Chemother 62 asthma[3-4]. Kim .[99]reported that oral administration contraceptive. 2008; : 526-534. of piperine in different proportion to mice suppressed and [8] A wen BZ, Ganapati S, Chandu BR. Influence of sapindus mukorossi on the permeability of ethyl cellulose free film for reduced the infiltration of eosinophil, hyper responsiveness Res. J. Pharma. Biol. Chem. Sci 1 and inflammation due the suppression of the production transedermal use. 2010; : 35- of histamine, interleukin- 5, immunoglobulin E and 38. [9] H ussain A, Naz S, Nazir H, Shinwari ZK. Tissue culture of interleukin-4. Piper nigrum Pak. J. Bot 43 Black pepper ( L.) in Pakistan. 2011; : 1069-1078. 14. 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