Piperine

CAS# 94-62-2

Piperine

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Quality Control of Piperine

Number of papers citing our products

Chemical structure

Piperine

3D structure

Chemical Properties of Piperine

Cas No. 94-62-2 SDF Download SDF
PubChem ID 638024 Appearance White powder
Formula C17H19NO3 M.Wt 285.34
Type of Compound Alkaloids Storage Desiccate at -20°C
Synonyms Bioperine; 1-Piperoylpiperidine
Solubility DMSO : 50 mg/mL (175.23 mM; Need ultrasonic)
Chemical Name (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one
SMILES C1CCN(CC1)C(=O)C=CC=CC2=CC3=C(C=C2)OCO3
Standard InChIKey MXXWOMGUGJBKIW-YPCIICBESA-N
Standard InChI InChI=1S/C17H19NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h2-3,6-9,12H,1,4-5,10-11,13H2/b6-2+,7-3+
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Source of Piperine

The fruits of Piper nigrum L.

Biological Activity of Piperine

DescriptionPiperine, an inhibitor of human P-glycoprotein and/or CYP3A4, which has antinociceptive, antiarthritic, antidepressant, hepatoprotective, immunomodulatory , antitumor, anti-oxidative, anti-apoptotic, chemo-protective, and anti-inflammatoryactivities. Administration of piperine appears to reverse preexisting high-fat diet (HFD)-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling.
TargetsP-gp | P450 (e.g. CYP17) | TNF-α | IL Receptor | CCR | CDK | Akt | IkB | Caspase | AMPK | AP-1 | PGE | MMP(e.g.TIMP) | NF-kB | IKK
In vitro

Immunomodulatory and antitumor activity of Piper longum Linn. and piperine.[Pubmed: 15013199]

J Ethnopharmacol. 2004 Feb;90(2-3):339-46.

Alcoholic extract of the fruits of the plant Piper longum and its component Piperine was studied for their immunomodulatory and antitumor activity.
METHODS AND RESULTS:
Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and Piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as Piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and Piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and Piperine (71.4%) on 5th day after immunization.
CONCLUSIONS:
Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and Piperine.

In vivo

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.[Pubmed: 25907981]

J Ethnopharmacol. 2015 Apr 21.

Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of Piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated.
METHODS AND RESULTS:
LS174T cells and C57BL/6J mice were treated by the Piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. Data indicated that treatment of LS174T cells with Piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via Piperine was PXR-dependent. Data show that pre-administration of Piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with Piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA).
CONCLUSIONS:
Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that Piperine may contribute to prevention or reduction of colonic inflammation.

Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice.[Pubmed: 23993530 ]

Food Chem. 2013 Dec 15;141(4):3627-35.


METHODS AND RESULTS:
This study examined the effect of Piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of Piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered Piperine. However, Piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice.
CONCLUSIONS:
Administration of Piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.

Protocol of Piperine

Kinase Assay

Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4.[Pubmed: 12130727]

J Pharmacol Exp Ther. 2002 Aug;302(2):645-50.

Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that Piperine, a major component of black pepper, inhibits drug-metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans. However, there are no direct data whether Piperine is an inhibitor of human P-glycoprotein and/or CYP3A4.
METHODS AND RESULTS:
We therefore investigated the influence of Piperine on P-glycoprotein-mediated, polarized transport of digoxin and cyclosporine in monolayers of Caco-2 cells. Moreover, by using human liver microsomes we determined the effect of Piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC(50) values of 15.5 and 74.1 microM, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K(i) values of 36 +/- 8 (liver 1)/49 +/- 6 (liver 2) and 44 +/- 10 (liver 1)/77 +/- 10 microM (liver 2), respectively.
CONCLUSIONS:
In summary, we showed that Piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary Piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.

Cell Research

Piperine from Black Pepper Inhibits Activation-Induced Proliferation and Effector Function of T Lymphocytes.[Pubmed: 25900378]

J Cell Biochem. 2015 Apr 21.

Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice.
METHODS AND RESULTS:
Here, we investigated the effect of Piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, Piperine inhibited CD25 expression, synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of Piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of κBα, but not ZAP-70.
CONCLUSIONS:
The ability of Piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that Piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders..

Animal Research

Evaluation of the liver protective potential of piperine, an active principle of black and long peppers.[Pubmed: 8255933 ]

Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms.[Pubmed: 17289085 ]

Life Sci. 2007 Mar 20;80(15):1373-81.


METHODS AND RESULTS:
In this study, we investigated the antidepressant-like effect of Piperine in mice exposed to chronic mild stress (CMS) procedure. Repeated administration of Piperine for 14 days at the doses of 2.5, 5 and 10 mg/kg reversed the CMS-induced changes in sucrose consumption, plasma corticosterone level and open field activity. Furthermore, the decreased proliferation of hippocampal progenitor cells was ameliorated and the level of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS stressed mice was up-regulated by Piperine treatment in the same time course. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that Piperine (6.25-25 microM) or fluoxetine (FLU, 1 microM) dose-dependently protected primary cultured hippocampal neurons from the lesion induced by 10 microM corticosterone (CORT). Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger ribonucleic acid (mRNA) level of BDNF in cultured neurons. Treatment with Piperine (6.25-25 microM) for 72 h reversed the CORT-induced reduction of BDNF mRNA expression in cultured hippocampal neurons.
CONCLUSIONS:
In summary, up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity might be mechanisms involved in the antidepressant-like effect of Piperine, which may be closely related to the elevation of hippocampal BDNF level.

Planta Med. 1993 Oct;59(5):413-7.

Piperine, an active alkaloidal constituent of the extract obtained from Piper longum and Piper nigrum, was evaluated for its antihepatotoxic potential in order to validate its use in traditional therapeutic formulations.
METHODS AND RESULTS:
This plant principle exerted a significant protection against tert-butyl hydroperoxide and carbon tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion of GSH and total thiols in the intoxicated mice. Silymarin, a known hepatoprotective drug was tested simultaneously for comparison.
CONCLUSIONS:
Piperine showed a lower hepatoprotective potency than silymarin.

Piperine Dilution Calculator

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Piperine Molarity Calculator

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Preparing Stock Solutions of Piperine

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.5046 mL 17.523 mL 35.0459 mL 70.0918 mL 87.6148 mL
5 mM 0.7009 mL 3.5046 mL 7.0092 mL 14.0184 mL 17.523 mL
10 mM 0.3505 mL 1.7523 mL 3.5046 mL 7.0092 mL 8.7615 mL
50 mM 0.0701 mL 0.3505 mL 0.7009 mL 1.4018 mL 1.7523 mL
100 mM 0.035 mL 0.1752 mL 0.3505 mL 0.7009 mL 0.8761 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Piperine

Piperine, a natural alkaloid isolated from Piper nigrum L, inhibits P-glycoprotein and CYP3A4 activities with an IC50 value of 61.94±0.054 μg/mL in HeLa cell.

In Vitro:Piperine has shown to possess in vitro cytotoxic activity and in silico studies. The IC50 value is found to be 61.94±0.054 μg/mL and in silico studies, it has more number of hydrogen bonds with minimum binding and docking energy and may be considered as inhibitor of EGFR tyrosine kinase[1]. Piperine has been found to have immunomodulatory, anti-oxidant, anti-asthmatic, anti-carcinogenic, anti-inflammatory, anti-ulcer, and anti-amoebic properties[2]. Piperine could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity[3].

In Vivo:At the dose of 3.5 mg/kg, the bioavailability of piperine is calculated to be 25.36%. Its AUC0→t is unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of piperine. It is found that the AUC0→t and C0 of docetaxel and t1/2of piperine are significantly increased after their combination use, suggesting potential enhanced bioavailability of not only docetaxel but also piperine, which may lead to the overall enhanced pharmacological effects[3]. The phosphorylation of I-κB, p65, p38, ERK, and JNK is inhibited by piperine in a dose-dependent manner, indicating that piperine may be a potential anti-inflammatory drug both in endometritis and in other S. aureus-induced diseases[4].

References:
[1]. Paarakh PM, et al. In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn. In Silico Pharmacol. 2015 Dec;3(1):9. Epub 2015 Oct 29. [2]. Meghwal M,et al. Piper nigrum and piperine: an update. Phytother Res. 2013 Aug;27(8):1121-30. [3]. Li C, et al. Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats. J Pharm Biomed Anal. 2016 Sep 5;128:286-93. [4]. Zhai WJ, et al. Piperine Plays an Anti-Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice. Evid Based Complement Alternat Med. 2016;2016:8597208.

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References on Piperine

Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms.[Pubmed:17289085]

Life Sci. 2007 Mar 20;80(15):1373-81.

In this study, we investigated the antidepressant-like effect of Piperine in mice exposed to chronic mild stress (CMS) procedure. Repeated administration of Piperine for 14 days at the doses of 2.5, 5 and 10 mg/kg reversed the CMS-induced changes in sucrose consumption, plasma corticosterone level and open field activity. Furthermore, the decreased proliferation of hippocampal progenitor cells was ameliorated and the level of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS stressed mice was up-regulated by Piperine treatment in the same time course. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that Piperine (6.25-25 microM) or fluoxetine (FLU, 1 microM) dose-dependently protected primary cultured hippocampal neurons from the lesion induced by 10 microM corticosterone (CORT). Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger ribonucleic acid (mRNA) level of BDNF in cultured neurons. Treatment with Piperine (6.25-25 microM) for 72 h reversed the CORT-induced reduction of BDNF mRNA expression in cultured hippocampal neurons. In summary, up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity might be mechanisms involved in the antidepressant-like effect of Piperine, which may be closely related to the elevation of hippocampal BDNF level.

Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4.[Pubmed:12130727]

J Pharmacol Exp Ther. 2002 Aug;302(2):645-50.

Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that Piperine, a major component of black pepper, inhibits drug-metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans. However, there are no direct data whether Piperine is an inhibitor of human P-glycoprotein and/or CYP3A4. We therefore investigated the influence of Piperine on P-glycoprotein-mediated, polarized transport of digoxin and cyclosporine in monolayers of Caco-2 cells. Moreover, by using human liver microsomes we determined the effect of Piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC(50) values of 15.5 and 74.1 microM, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K(i) values of 36 +/- 8 (liver 1)/49 +/- 6 (liver 2) and 44 +/- 10 (liver 1)/77 +/- 10 microM (liver 2), respectively. In summary, we showed that Piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary Piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.

Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes.[Pubmed:25900378]

J Cell Biochem. 2015 Nov;116(11):2577-88.

Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice. Here, we investigated the effect of Piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, Piperine inhibited CD25 expression, synthesis of interferon-gamma, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of Piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of kappaBalpha, but not ZAP-70. The ability of Piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that Piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders.

Immunomodulatory and antitumor activity of Piper longum Linn. and piperine.[Pubmed:15013199]

J Ethnopharmacol. 2004 Feb;90(2-3):339-46.

Alcoholic extract of the fruits of the plant Piper longum and its component Piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and Piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as Piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and Piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and Piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and Piperine.

Comparative efficacy of piperine and curcumin in deltamethrin induced splenic apoptosis and altered immune functions.[Pubmed:25868812]

Pestic Biochem Physiol. 2015 Mar;119:16-27.

Deltamethrin (DLM) being a potent immunotoxicant affects both humoral and cell mediated immunity. Thus, for the amelioration of its effects, two different bioactive herbal extracts Piperine and curcumin are evaluated and their efficacy has been compared. The docking results demonstrated that curcumin has good binding affinity towards CD28 and CD45 receptors as compared to Piperine but in vitro studies revealed that Piperine is more effective. DLM induced apoptotic markers such as oxidative stress and caspase 3 have been attenuated more significantly by Piperine as compared to curcumin. Phenotypic and cytokine changes have also been mitigated best with Piperine. Thus, these findings strongly demonstrate that Piperine displays the more anti-oxidative, anti-apoptotic and chemo-protective properties in the DLM induced splenic apoptosis as compared to curcumin. So, Piperine can be considered the drug of choice under immunocompromised conditions.

Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice.[Pubmed:23993530]

Food Chem. 2013 Dec 15;141(4):3627-35.

This study examined the effect of Piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of Piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered Piperine. However, Piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of Piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.[Pubmed:25907981]

J Ethnopharmacol. 2015 Jul 1;169:109-23.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of Piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated. MATERIALS AND METHODS: LS174T cells and C57BL/6J mice were treated by the Piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. RESULTS: Data indicated that treatment of LS174T cells with Piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via Piperine was PXR-dependent. Data show that pre-administration of Piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1beta, IL-6, IL-10, iNOS, MCP-1, and TNFalpha) after DSS treatment were significantly decreased in mice pretreated with Piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA). CONCLUSION: Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that Piperine may contribute to prevention or reduction of colonic inflammation.

Description

Piperine, a natural alkaloid isolated from Piper nigrum L, inhibits P-glycoprotein and CYP3A4 activities with an IC50 value of 61.94±0.054 μg/mL in HeLa cell.

Keywords:

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