Chapter

Piperine: Sources, Properties, Applications, and Biotechnological Production

Authors:
  • GURU GHASIDAS VISHWAVIDYALAYA (A CENTRAL UNIVERSITY),
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Abstract

From ancient times, phytopharmaceuticals have played an important role in the management of human health. Piperine, an alkaloid with the piperidine nucleus was discovered and isolated by Hans Christian Ørsted, from the fruits of Piper nigrum. Piperine forms is slightly water soluble and forms monoclinic needles and possess a strong pungent taste. Piperine contains plentiful established health effects and beneficial therapeutic properties. Cells and enzymes are key elements in biotechnological processes to carry out a wide variety of very specific reactions under judicious conditions to produce piperine and their products. Piperine also serves as bio-enhancers in conjunction with drugs to stimulate drug molecules’ activity across different routes by improving the drug's bioavailability across the membrane, raising the drug's effect across conformational interaction, and working as a drug receptor. In recent years, there has been significant interest in the use of piperine to treat many illnesses, its health-beneficial effects, and its work as bio-enhancers. Due to their biological activity, piperine has the potential to be used in health and medicine.

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Piperine is an attractive therapeutic alkaloid from black pepper that exhibits a broad spectrum of pharmacological properties over various pathological disorders including cancer. Voltage gated K ⁺ (K V ) channels play an important role in regulating cancer cell proliferation and are considered as potential target for cancer treatment. However, the implication of piperine in K V associated anticancer activities on human prostate cancer cells LNCaP and PC-3 remains unrevealed. The electrophysiological and pharmacological data identifies that both androgen sensitive (LNCaP) and insensitive (PC-3) prostate cancer cells typically expressed voltage gated K ⁺ current (I K ). This current was significantly blocked by piperine in a concentration-dependent manner with an IC 50 value 39.91 μM in LNCaP and 49.45 μM in PC-3 cells. Analysis of voltage-dependence of activation kinetics showed that piperine induces a positive shift in the relative activation curve in both the cells. Piperine also depolarized the resting membrane potential by an average of 10.2 mV and 8.3 mV in LNCaP and PC-3 cells, respectively. The anticancer studies showed that, treatment with piperine concentration dependently induced G 1 phase cell cycle arrest and apoptosis in LNCaP and PC-3 cells. These results unravel that the I K inhibition might be responsible for the anticancer effect of piperine on androgen sensitive and insensitive human prostate cancer cells.
Article
Aims: The first-line anti-epileptic agent carbamazepine has narrow therapeutic index and can potentially interact with piperine, the major component from black pepper. The present study aimed to delineate the mechanism of such interaction for safe usage of carbamazepine during epilepsy control. Materials and methods: The effect of piperine on carbamazepine hepatic metabolism was examined using rat or human liver microsomes. Mechanistic static model was applied to predict the extent of interaction. In addition, liver microsomal activities, mRNAs and protein expressions of genes regulating carbamazepine metabolism were evaluated after two weeks oral administrations of 3.5 and 35 mg/kg piperine in rats. Moreover, the effect of piperine on the xenobiotic receptor constitutive androstane receptor (CAR) was further accessed. Key findings: Time-dependent inhibitory effect of piperine on carbamazepine metabolism was observed, with kinact and KI of 0.0153 min⁻¹ and 18.34 μM for rat, and 0.0093 min⁻¹ and 9.45 μM for human. Based on such in-vitro metabolic parameters, further estimation using mechanistic static model indicated that piperine could increase the AUC of CBZ by 7% and 11% in rat and human, respectively. Significant inhibition on rat liver microsomal activity, Cyp3a2 mRNA and protein expression, CAR mRNA were demonstrated with piperine at 35 mg/kg. Yet, no direct effect on the activity of CAR for piperine was found. Significance: We have demonstrated the time-dependent inhibition by piperine on carbamazepine metabolism as the interaction mechanism. Prolonged use of piperine at high dose could increase carbamazepine concentrations through inhibiting metabolic enzyme activities and their related genes expressions.
Article
Piperine has several well-documented anti-inflammatory properties; however, little is known regarding its effect on humoral immunity. In this study, we describe the immunosuppressive effect of piperine on B lymphocytes, which are integral to the humoral immune response. Mouse B cells were cultured in the absence or presence of non-cytotoxic concentrations (25, 50, and 100 μM) of piperine during T-dependent or T-independent stimulation. Piperine inhibited B cell proliferation by causing G0/G1 phase cell cycle arrest in association with reduced expression of cyclin D2 and D3. The inhibitory effect of piperine was not mediated through transient receptor potential vanilloid-1 ion channel (TRPV1) because piperine also inhibited the proliferation of B cells from TRPV1-deficient mice. Expression of class II major histocompatibility complex molecules and costimulatory CD40 and CD86 on B lymphocytes was reduced in the presence of piperine, as was B cell-mediated antigen presentation to syngeneic T cells. In addition, piperine inhibited B cell synthesis of interleukin (IL)-6 and IL-10 cytokines, as well as IgM, IgG2b, and IgG3 immunoglobulins. The inhibitory effect of piperine on B lymphocyte activation and effector function warrants further investigation for possible application in the treatment of pathologies related to inappropriate humoral immune responses. Copyright
Chapter
Alkaloids include a family of naturally occurring chemical compounds containing mostly basic nitrogen atoms. Piperine is an alkaloid present in black pepper (Piper nigrum), one of the most widely used spices, in long pepper (Piper longum), and other Piper species fruits belonging to the family of Piperaceae. Piperine is responsible for the black pepper distinct biting quality. Piperine has many pharmacological effects and several health benefits, especially against chronic diseases, such as reduction of insulin-resistance, anti-inflammatory effects, and improvement of hepatic steatosis. The aim of this chapter is to summarize the effects of piperine, alone or in combination with other drugs and phytochemicals, in chronic diseases.
Article
Objective: The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology. Methods: Piperine 10-40% w/w and Eudragit(®) EPO/Kollidon(®) VA 64 or Soluplus(®) were mixed, and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus(®) , and pure piperine to study the permeability characteristics. Key findings: Dissolution studies demonstrated enhancement in piperine per cent release of 10% and 20% w/w piperine/Soluplus(®) extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus(®) increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus(®) extrudates up to 158.9 μg/5 ml compared with pure piperine at 1.3 μg/5 ml within 20 min. Conclusion: These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.
Article
Ajmodadi churna (AJC) is an Ayurvedic formulation containing Piper species (Piper longum in both form root and fruit and Piper nigrum) as main ingredients. It is a traditional Ayurvedic oral Herbal formulation, available as a popular proprietary, from most manufacturers of ayurvedic drugs. A selective, precise and accurate High Performance Thin Layer Chromatography (HPTLC) method has been developed for the simultaneous quantification of Piperine in Ajmodadi churna as well as its bulk drug. The method employed TLC aluminum plate precoated with silica gel 60 F254 as a stationary phase. The solvent system consists of Toluene: Ethyl acetate( 7 : 3 % v/v). This system was found to give compact spot for Piperine. Densiometric analysis was carried out in the absorbance mode at 254 nm. The linear regression analysis data for the calibration plot showed good linear relation with r2 = 0.992 and with respect to peak area for Piperine, in concentration range 0.5-20 μg/spot. The method was validated for precision (0.173), recovery (99.43%), Limit of Detection (0.063mg/ml) and Limit of Quantification (0.071mg/ml). The proposed HPTLC method can be used for the quality control of the raw materials as well as formulations. Piperine in Piper longum and Piper nigrum are reported to be the active components in the formulation AJC and can be considered as marker compounds. Therefore, HPTLC method has been developed for the estimation of these marker compounds 11, and also to develop finger print profile for the standard formulation of Ajmodadi churna so that these parameters can be compared with any marketed formulation for evaluating its purity and quality. The proposed method has been validated as per ICH guidelines.12-13
Article
Background: Community oncologists need a simplified methodology for assessing the value of anticancer drugs. In the United States and Europe, costs of anticancer drug were previously estimated at US$50,000 to >US$100,000 per quality adjusted lifeyear (QALY). The National Institute for Health and Care Excellence in the United Kingdom states that the average cost-effectiveness ratios intervention of >US$50,000 per QALY must be questioned. Objectives: To design a drug model to estimate the amount in United States dollars (US$) paid for life-year gain (LYG) and QALY, and to apply that model in the treatment of chemo-naïve and chemo-treated patients with castrate-resistant metastatic prostate cancer (mCRPC). Methods: Cost per LYG (cost/LYG) was compared with cost per probability of survival (cost/PoS) calculated as [1.0 minus HR]. Results were expressed in relative values (RV) calculated as US$50,000 or US$100,000 per cost/outcome. Results: In patients with mCRPC, generic docetaxel demonstrated the lowest cost/LYG (US$26,330), lowest cost/ PoS (US$21,942), and the highest RV (3.80-4.56). Cost/LYG of sipuleucel-T was US$272,195, with an RV of 0.37. Significant variation between cost/LYG and cost/PoS was noted among drugs with borderline survival and HR. In previously treated patients, the cost/LYG of cabazitaxel was US$207,240; of abiraterone, US$194,087; enzalutamide, US$223,500; and radium-223 dichloride, US$230,000, all with RVs <0.5. Conclusions: A simplified drug model to weigh cost, survival, and HR with imposed limits on cost/outcome was proposed and applied to patients with mCRPC. The results among that patient population suggested that generic docetaxel had the lowest costs, cost/outcome and the highest RV. Sipuleucel-T, abiraterone, enzalutamide, radium-223 dichloride, and cabazitaxel were overpriced for their values. Drugs with RVs of <0.5 should be scrutinized, costs negotiated, or other drugs considered, and those with RVs of <0.25, rejected.
Article
The in vitro antioxidant activity of aerial parts of Cynodon dactylon has been investigated by estimating degree of non-enzymatic haemoglobin glycosylation measured colorimetrically at 520 nm. The ethyl acetate extract of aerial parts of C. dactylon showed higher antioxidant activity than other extracts of it. The antioxidant activity of the extracts is close and identical in magnitude and comparable to that of standard antioxidant compounds used.
Article
Objective: To see the effect of Trikatu (piperine) on the bioavailability and pharmacokinetics of isoniazid in rabbits. Methods: In a crossover study, ten rabbits were administered either single dose (orally) of isoniazid (14 mg/kg) alone or in combination with Trikatu [piperine (10 mg/kg)]. Blood samples were collected at 0,0.5,1,1.5,2, 4,6,9 and 12 hours after drug administration and assayed for isoniazid by fluorimetric technique. A washout period of 7 days was allowed between the two treatments. Results: Coadministration of Trikatu (piperine) significantly reduced the C(max) [5.48 ± 0.75 μg/ml vs 8.42 ± 0.85 μg/ml; P <0.05] and AUCo-α [15.04 ± 3.84 μg/ml. hr vs 24.76 ± 4.03 μg/ml. hr; P<0.05] of isoniazid. Conclusion: Trikatu (piperine) reduces the bioavailability of isoniazid in rabbits.
Article
Piperine, a major alkaloid found in the fruits of black and long pepper plants, has anti-inflammatory properties; however, piperine's effect on dendritic cell (DC) migration and T cell-activating function has not been investigated. Bone marrow-derived mouse DC that were matured in the presence of 100μM piperine showed reduced in vitro migration in response to CCL21, as well as reduced in vivo migration to lymph nodes. In addition, piperine-treated DC had reduced CCR7 expression and elevated CCR5 expression, as well as reduced expression of CD40 and class II major histocompatibility complex molecules and decreased nuclear accumulation of RelB. DC production of interleukin (IL)-6, tumor necrosis factor, and monocyte chemoattractant protein-1 in response to lipopolysaccharide stimulation was also reduced following piperine treatment. Exposure to piperine during maturation therefore caused DC to retain an immature phenotype, which was associated with a reduced capacity to promote T cell activation since co-culture of ovalbumin (OVA323-339)-specific T cells with OVA323-339-pulsed DC that were previously matured in the presence of piperine showed reduced interferon-γ and IL-2 expression. OVA323-339-specific T cell proliferation was also reduced in vivo in the presence of piperine-treated DC. Inhibition of DC migration and function by piperine may therefore be a useful strategy to down-regulate potentially harmful DC-driven T cell responses to self-antigens and transplantation antigens.
Article
A radical is any molecule that contains one or more unpaired electrons. Radicals are normal products of many metabolic pathways. Some exist in a controlled (caged) form as they perform essential functions. Others exist in a free form and interact with various tissue components. Such interactions can cause both acute and chronic dysfunction, but can also provide essential control of redox regulated signaling pathways. The potential roles of endogenous or xenobiotic-derived free radicals in several human pathologies have stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. In recent years, improvements in analytical methodologies, as well as the realization that subtle effects induced by free radicals and oxidants are important in modulating cellular signaling, have greatly improved our understanding of the roles of these reactive species in toxic mechanisms and disease processes. However, because free radical-mediated changes are pervasive, and a consequence as well as a cause of injury, whether such species are a major cause of tissue injury and human disease remains unclear. This concern is supported by the fact that the bulk of antioxidant defenses are enzymatic and the findings of numerous studies showing that exogenously administered small molecule antioxidants are unable to affect the course of most toxicities and diseases purported to have a free radical mechanism. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents, and provides examples of selected disease processes that may have a free radical component.
Article
Introduction: Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied and piperine-like derivatives have shown an interesting range of pharmacological activities. In this context, significant advances have been made in the discovery of new chemical entities, based on the piperine scaffold, endowed with therapeutic potential. Areas covered: The aim of this review is to provide a thorough inquiry on the therapeutic potential of piperine and related derivatives. It provides an overview of recent developments in patented processes and applications thereof between 2000 and 2015. Expert opinion: Cumulative evidence shows that piperine is currently paving its way to become a privileged scaffold for the development of bioactive compounds with therapeutic application in multiple human diseases. In particular, piperine derivatives were shown to modulate the activity of several targets related to neurological disorders, including epilepsy, Parkinson's disease, depression and pain related disorders. Moreover, the efflux pump inhibitory ability of piperine and its analogues tackles important drug resistance mechanisms and may improve the clinical efficacy of antibiotic and anticancer drugs. Although the use of piperine as a scaffold for bioactive compounds is still in its early stages, the continuous exploration of this structure may lead to remarkable advances in drug discovery programs.
Article
Purpose: To assess the gastroprotective potential of the stem bark ethanol extract of Delonix regia (EDR) on ethanol and cold restrain stress-induced ulcer in experimental rats. Methods: EDR (100, 200 and 400 mg/kg doses, orally) was evaluated on ethanol and cold restrain stress-induced ulcer in experimental rats. In ethanol induced ulcer model, ulcer index, percent protection, reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), cytokines and nitric oxide (NO) levels in stomach tissue were evaluated. In the cold restrain stress model, ulcer index, percent protection, and GSH levels were evaluated. 2,2-Diphenyl-1-picryl hydrazyl (DPPH) radical scavenging assay of EDR was also performed. Results: EDR caused a significant (p < 0.05-0.001) decreased ulcer index in ethanol (61.33-76.00%) and cold restrain stress (47.34-84.28%) models. The EDR caused a significant (p < 0.05 - 0.001) increase in SOD (0.20 - 0.27 U/mg protein, CAT (200 - 270 µmole H2O2/mg of protein/minute), GSH (1.63 - 1.17 µg/mg protein) and reduction in nitric oxide (NO) level, pro-inflammatory cytokine (TNF-α and IL-6) levels and inhibition in neutrophil accumulation (p < 0.001) in ethanol-induced model. EDR exhibited significant antioxidant activity with IC50 value of 45.23 ± 3.23 µg/ml. Conclusion: The results suggest that EDR has gastroprotective effect in the two ulcer models and this may be due to its antioxidant effect. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
Article
The present study was to develop the fingerprint method for Trikatu churna by simple highperformance thin layer chromatography (HPTLC) determination using piperine as a standard, which is as an important and major content in formulation. HPTLC methods for determination of piperine from the Trikatu churna along with its raw materials have been developed. The method was validated for linearity, accuracy, limit of detection, limit of quantification, inter-day and intra - day assay precision, repeatability of measurement, and repeatability of sample application. The concentration of piperine present in raw materials was found to be 4.2%± 0.43w/w in Piper nigrum (Marica), and 2.15% ± 0.68w/ w in Piper longum (Pipali) respectively and in three identical laboratory batch of Trikatu churna name TK-I, TK-II, TK-III, was 2.13%±0.62, 2.42%±0.67, 2.18%±0.41 w/w respectively with mean value 2.24%±0.48 w/w. The piperine content of all the three batches is found to be in close proximities with each other. Obtained results were compared with marketed formulations.
Article
Eladi Gutika is a polyherbal formulation official in Ayurvedic formulary of India and used for dry cough and throat infection. A simple, specific and precise high-performance thin-layer chromatography (HPTLC) method has been developed for quantification of piperine and 18-β glycyrrhetinic acid in Eladi Gutika. We report the extraction and estimation of these compounds in a laboratory prepared sample of Eladi Gutika and two of its marketed formulations. The compounds were chromatographed on precoated silica gel G 60254 plates in the mobile phase comprising of toluene, ethyl acetate, and glacial acetic acid. Under the optimized chromatographic conditions, the calibration plot was found to be linear in the range of 0.2-1 g mL-1 with a correlation coefficient R2 = 0.9902 for piperine and 0.9904 for 18-β glycyrrhetinic acid. Mean recovery for piperine was 99.75% w/w and for 18-β glycyrrhetinic acid was 101.36% w/w.
Article
Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.
Article
The antioxidant and antidiabetic activity of aerial parts of Aerva sanguinolenta (L) Blume and leaves of Mikania scandens (L.) Willd were investigated by three in vitro and one in vivo assays i.e., by estimating degree of non-enzymatic haemoglobin glycosylation measured colorimetrically at 520 nm; by assaying DPPH free radical scavenging activity; by reduction of phosphomolybdenum complex and by estimating blood glucose levels in alloxan-induced diabetic mice. From the analysis, it was found that the ethyl acetate and chloroform extract of both aerial parts of A. sanguinolenta and leaves of Mikania scandens had higher antioxidant potential than that of other extracts of the plant(s). Among the examined plants, it was also observed that M. scandens L. extracts had better antioxidant and antihyperglycemic action than that of A. sanguinolenta. The antioxidant activity of the extracts was close, identical in magnitude, concentration dependent and comparable to that of standard antioxidant compounds used. Flavonoids and tannins present in the selected extracts may be responsible for such antioxidant and antidiabetic activities.
Article
Pippali churna (PC) is well known ayurvedic formulation is official in Ayurvedic Formulary of India, traditionally used for cough and cold, spleen disorders, fever, diabetes, piles, tuberculosis, abdominal disease ,thrust warms, leprosy, pain (colic-spasmodic) and digestive impairments. Pipali churna possesses bioavailability enhancing properties. Three batches of pippali churna(PC) were prepared according to the method given in the ayurvedic formulary and another three different formulations were procured from the market.In present study a spectrophotometric method was devloped for the estimation of piperine in laboratory and marketed preprations. The concentration of piperine present in raw material of PC was found to be 1.45±0.014 w/w in piper longum fruits. The content of piperine in different laboratory preprations were found PC-I (1.35±0.002), PC-II(1.38±0.004), PC-III(1.37±0.001)w/w respetively and for marketed formulations were found to be PC-A (1.14±0.004), PC-B(1.15±0.002), PC-C(1.17±0.006)w/w respetively. In order to maintain precision and accuracy the recovery study was performed and result obtained with mean value 99.49, which prove reproducibility of the result. The mean of %RSD value was found to be 0.17 with the mean standard error were 0.24. A result of statistical analysis show present spectrophotometric method for determination of piperine is simple, precise, accurate and suitable for routine analysis of piperine in pippali churna. The devloped fingerprints can be used as a standard and piperine can be used as a possible marker compound for fingerprinting of the formulation.
Article
Efforts were made to enhance the yield of piperine using ultrasound assisted extraction (UAE) from fruit of Piper longum. The effects of various factors such as solvent, extraction time, solid to solvent ratio, duty cycle, ultrasound frequency, ultrasound power and temperature on the yield of piperine were investigated and optimized. The maximum yield of piperine (5.8 mg/g) from Piper longum powder was obtained at optimal UAE conditions such as, ethanol as extracting solvent, extraction time 18 min, solid to solvent ratio 1:10, ultrasound power 125 W, 80% duty cycle, ultrasound frequency 25 kHz and temperature 50 °C. The experimental results revealed the advantage of UAE over traditional method of batch extraction and solvent extraction. The extraction time is reduced from 8 h of batch solvent extraction and 4 h of Soxhlet to 18 min in UAE with enhanced extraction yield of piperine. Extraction yields of piperine obtained from Soxhlet extraction and batch extraction methods were found to be 1.67 mg/g and 0.98 mg/g, respectively, which were much lower than UAE optimized results. Hence, ultrasound assisted extraction of natural phytoconstituents will diminish the problem of lower extractability and higher extraction time over traditional methods.
Article
Abstract The main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed Cmax1, Cmax2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p < 0.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.
Article
B-lymphocytes are integral to host defense against microbial pathogens and are associated with many autoimmune diseases. The B-cell receptor implements B-cell self-tolerance based on the antigen specificity, and B-cell-activating factor receptor (BAFF-R) imposes homeostatic control. While shaping the repertoire, the immune tolerance process also culls mature B cells into distinct populations. The activation response of B cells is tailored to the type of pathogen attack and is facilitated by T-cell help via CD40/CD40L interaction and/or innate cell help via toll-like receptors in conjunction with BAFF receptors and ligands. Activated effector B cells not only produce antibodies, but also produce a variety of cytokines to enhance and suppress the immune response. Not surprisingly, B cells play multiple roles in both humoral and cellular immune responses during infection and autoimmune pathogenesis. Here, we discuss how gene expression and signaling networks regulate peripheral B-cell tolerance, B-cell effector functions and emerging therapies targeting B-cell signaling in autoimmune diseases.
Article
The mechanisms involved in the anti-seizure property of piperine (1-[5-(1, 3-benzodioxol-5-yl)-1-oxo-2, 4-pentadienyl]-(E, E)-piperidine, C17H19NO3) are still unclear. Piperine could activate transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, and the rapid activation of whole-cell currents is antagonized by the competitive TRPV1 antagonist capsazepine. Interestingly, recent studies have reported that TRPV1 may be a novel anti-epileptogenic target which led us to hypothesize that the anti-seizure property of piperine involves the TRPV1 receptor. To test this hypothesis, we examined the effect of piperine on seizures induced in mice and identified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) models. Piperine, administered at doses of 40 and 80mg/kg, significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with the vehicle-treated animals. Piperine also significantly reduced the incidence of MES-induced tonic hindlimb extension (THE) and PTZ-induced Fos immunoreactivity in the dentate gyrus. The anti-seizure effects of piperine were blocked by a TRPV1-selective antagonist capsazepine. Taken together, these data support the further investigation of piperine as a TRPV1 agonist for anti-seizure therapy.
Article
Effect of piperine which is an alkaloid present in plants such as Piper nigrum and Piper longum on the production of nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α) level was analyzed using in vitro as well as in vivo systems. The level of nitrite in the LPS stimulated Balb/C mice (95.3 µM) was reduced in the piperine treated animals (25 µM) significantly. Nitrite level in the Concanavalin‐A (Con‐A) treated control animals (83.1 µM) was also significantly reduced to 18.5 µM in the piperine treated mice. The drastically elevated levels of TNF‐α in the lipopolysaccharide (LPS) stimulated animals (625.8 pg/mL) was lowered in the piperine treated animals (105.8 pg/mL). Piperine also inhibited the Con‐A induced TNF‐α production. Piperine could inhibit the nitrite production by in vitro activated macrophages (116.25 µM) to the normal level (15.67 µM) at concentration of 5 µg/mL. In vitro L929 bioassay also revealed the inhibition of TNF‐α production by the piperine treatment.
Article
A simple, sensitive, and rapid high-performance thin layer chromatographic (HPTLC) method has been established for estimation of piperine in commercial Ayurvedic formulations and in the fruits of Piper nigrum Linn, and Piper longum Linn. Chromatography was performed on aluminum foil HPTLC plates coated with 0.2 mm layers of silica gel F-254, with hexane-acetone 6.5:3.5 (v/v) as mobile phase. The development distance was 76 mm, the temperature 25 +/- 51 degrees C, and the chamber was saturated for 5 min. Piperine was quantified at 340 nm, its wavelength of maximum absorbance. Under the conditions used the R-F of piperine was 0.33 and the limit of detection (LOD) was 4 ng per zone. The calibration plot was linear in the range of 10 to 60 ng per zone with a correlation coefficient of 0.9996. Recovery was in the range 98.76 to 100.70%. This HPTLC method was found to be reproducible, accurate, and precise and could be used to detect piperine at nanogram levels. The method is a very simple and cost-effective means of quantitative estimation of piperine in Ayurvedic formulations.