The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders....The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.展开更多
Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was condu...Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was conducted to evaluate the binding affinity of diclofenac with piperine and D-limonene against p53,Bax,and Bcl-2.The MTT assay was used to determine IC50,and the Chou-Talay method was used to determine the synergistic concentration of the combination treatment of diclofenac plus piperine and diclofenac plus D-limonene.Apoptosis detection,cell cycle arrest,reactive oxygen species production,and mitochondrial membrane potential were also investigated.Results:Diclofenac,piperine,and D-limonene showed potent binding affinity for p53,Bax,and Bcl-2.Diclofenac plus piperine and diclofenac plus D-limonene enhanced the formation of reactive oxygen species,which also had an effect on the mitochondrial membrane’s integrity and caused DNA fragmentation.Diclofenac plus piperine and diclofenac plus D-limonene arrested the cells in the sub-G0phase while drastically lowering the percentage of cells in the G2/M phase.Furthermore,the elevated apoptosis in the combined therapy was confirmed by annexin V/propidium iodide staining.Conclusions:The combined therapy prominently enhanced the antiproliferative and apoptotic effects on MCF-7 cells compared with treatment with diclofenac,piperine,and D-limonene alone.展开更多
Piperine is a member of the lipids family commonly found in peppercorn, ginger and other natural sources and is grouped as an alkaloid. The solubility of piperine has been determined in carbon dioxide at near critical...Piperine is a member of the lipids family commonly found in peppercorn, ginger and other natural sources and is grouped as an alkaloid. The solubility of piperine has been determined in carbon dioxide at near critical and supercritical conditions in a dynamic extraction apparatus. The conditions studied were at pressures ranging from 10 to 20 MPa and temperatures at 293, 300, 313, 323 and 333 K. The results showed that piperine solubility increased with increasing pressure at all temperatures studied. The solubility of plperme in near critical conditions was slightly higher than that at supercritical conditions only at the low-pressure range. Two semi-empirical density dependent correlations, namely the Chrastil model and the Dilute Solution model, were also used to estimate the solubility data. Although both models showed good correlation with the solubility data, the Dilute Solution model performed better prediction than the Chrastil model.展开更多
1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents.Quercetin(QC)i...1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents.Quercetin(QC)is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability.Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants(e.g.,Quercetin).Therefore,the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats.MPTP(100μg/μL/rat,bilaterally)was injected intranigrally on days 1,4 and 7 using a digital stereotaxic apparatus.QC(25 and 50 mg/kg,intragastrically)and QC(25 mg/kg,intragastrically)in combination with piperine(2.5 mg/kg,intragastrically)were administered daily for 14 days starting from day 8 after the 3^(rd) injection of MPTP.On day 22,animals were sacrificed and the striatum was isolated for oxidative stress parameter(thiobarbituric acid reactive substances,nitrite and glutathione),neuroinflammatory cytokine(interleukin-1β,interleukin-6,and tumor necrosis factor-α)and neurotransmitter(dopamine,norepinephrine,serotonin,gamma-aminobutyric acid,glutamate,3,4-dihydroxyphenylacetic acid,homovanillic acid,and 5-hydroxyindoleacetic acid)evaluations.Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance.Both QC(25 and 50 mg/kg)and QC(25 mg/kg)in combination with piperine(2.5 mg/kg),in particular the combination therapy,significantly improved MPTP-induced behavioral abnormalities in rats,reversed the abnormal alterations of neurotransmitters in the striatum,and alleviated oxidative stress and inflammatory response in the striatum.These findings indicate that piperine can enhance the antioxidant and anti-inflammatory properties of QC,and QC in combination with piperine exhibits strong neuroprotective effects against MPTP-induced neurotoxicity.展开更多
Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation o...Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.Methods:Cu-Pi nanoparticles were prepared by thin film hydration method,solid dispersion method,emulsion polymerization method and Fessi method.Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles.Results:Out of four methods,Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV.Change of organic solvent(acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles.However,increase in sonication time,stirring speed,viscosity,use of 1:10:10 ratio of drag/polymer/surfactant,and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles.Conclusions:Cu-Pi nanoparticles coated with PEC containing copolymer produced by Fessi method had a minimum average particle size,excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study.This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.展开更多
Aim: To study the effect of piperine on the epididymal antioxidant system of adult male rats. Methods: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each d...Aim: To study the effect of piperine on the epididymal antioxidant system of adult male rats. Methods: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30 consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation. Results: Body weight of the piperine-treated rats remained unchanged. The weights of the caput, corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg. Conclusion: Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.展开更多
AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,th...AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.展开更多
Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colon...Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colony formation assays,wound healing assays,Matrigel migration assays,flow cytometry,RT-qPCR,and Western blotting assays.Results:Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation.Cell reduction at the G_(0)/G_(1) phase and cell arrest at the G_(2)/M phase were observed in breast cancer cells.However,the significant effect was only demonstrated in MDA-MB-231 cells.Moreover,cancer cell migration was suppressed by piperine at low concentration.RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression.Conclusions:Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.展开更多
A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed and validated for the determination of piperine (PPR) on dried blood spots (DBS). DBS samples were prepared by spiking the...A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed and validated for the determination of piperine (PPR) on dried blood spots (DBS). DBS samples were prepared by spiking the whole blood with analyte to produce 30 μL of blood spots on specimen collection cards. Chromatographic separation was achieved on an Atlantis dC18 column using acetonitrile and water (0.1% formic acid) (85:15, v/v) as mobile phase in an isocratic mode of elution at a flow rate of 0.75 mL/min. MS detection was carried out in electrospray positive ion mode for the target ions and monitored at m/z 286.1465 for PPR and 272.1303 for the internal standard (IS). The developed method exhibited a linear dynamic range over 0.01-2000 ng/mL for PPR on DBS. The overall extraction recovery of PPR from DBS was 92.5%. Influence of hematocrit and spot volume on DBS was also evaluated and found to be well within the acceptable limits. The method was successfully applied to pharmacokinetic studies of PPR in rats.展开更多
Antidepressant and cognitive effects of piperine -encapsulated liposomes (PL) were investigated in male Wistar rats. Oral piperine (5 mg/kg body weight/day) and intranasal PL (7.2 μg/day) were randomly assigned to da...Antidepressant and cognitive effects of piperine -encapsulated liposomes (PL) were investigated in male Wistar rats. Oral piperine (5 mg/kg body weight/day) and intranasal PL (7.2 μg/day) were randomly assigned to daily administer for 14 days to rats which were subjected to forced swimming, Mor-ris water maze and spontaneous motor behavior tests. PL significantly exhibited anti-depression like activity and cognitive enhancing effects, in comparison to the control groups after the first dose (p < 0.01) and the effects could be maintained throughout the period of study. Quantitative analysis of the brain homogenates by HPLC indicated that piperine, delivered either orally or nasally, distributed to the hippocampus at a higher extent than the cortex and that the time to peak concentration of nasal PL was shorter than for the oral piperine. Intranasal PL was, thus, potential in delivery of piperine, at a low dose, to exert its an-tidepressant and cognitive enhancing activities.展开更多
Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lower...Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering a- gent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation in- duced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogen- ic or chow diets for 10 weeks, with or without PA ( 15, 30 and 60 mg ~ kg-1 ) or ursodeoxycholic acid ( UDCA, 60 mg ~ kg-1) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological chan- ges and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol poten- cy and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein / low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/ 8 ) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation.展开更多
In order to clarify the insecticidal active ingredients of Piper sarmentosum,one active ingredient was isolated from ethanol extract of P. sarmentosum by bioassay-guided fractionation method. Its chemical structures w...In order to clarify the insecticidal active ingredients of Piper sarmentosum,one active ingredient was isolated from ethanol extract of P. sarmentosum by bioassay-guided fractionation method. Its chemical structures were identified to be piperine by MS,1H NMR,13C NMR. The insecticidal activity of piperine and ethanol extract of P. sarmentosum against Aleurodicus dispels Russell were tested by leaf dip method. The results showed that piperine and ethanol extract of P. sarmentosum exhibited strong insecticidal activity against adults and nymphs of A. dispels; LC50values against adults were 28. 59 and 224. 31 mg/L,and LC50values against nymphs were 65. 91 and 336. 68 mg/L,respectively. There was no significant difference between piperine and azadirachtin against adults and nymphs of A.dispels. Therefore,piperine might be one of the main insecticidal ingredients of P. sarmentosum. In addition,piperine and ethanol extract showed ovicidal activity with different mode of action,piperine reduced the survival rate of newly hatched nymphs while ethanol extract impacted hatch of eggs.展开更多
In the pharmaceutical world the majority of the active pharmaceutical ingredients (API) have been obtained from the natural products. Piperine is such naturally occurring alkaloid which can be considered as major bioa...In the pharmaceutical world the majority of the active pharmaceutical ingredients (API) have been obtained from the natural products. Piperine is such naturally occurring alkaloid which can be considered as major bioactive phytochemical having broad spectrum of pharmacological activities. It is obtained from the most valuable ethnomedicinal spices peppercorns i.e. black pepper and white pepper, which are the fruits of the Asian vine Piper nigrum L. Because of the widespread traditional uses of this medicinal compound, present article reveals a simple and effective isolation method of bulk piperine. The novelty of this investigation is to provide an idea for utilizing such natural method of large scale commercial piperine production as API drug in spite of chemical synthesis. Piperine was isolated in a pure crystal form and characterized by its melting point, X-Ray diffraction (XRD) studies and spectral data, including two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy. Chromatographic techniques like Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography (HPLC) were applied to determine the purity of the yielded piperine. It was found that piperine yield from black pepper was within 2.5% - 3.0% and from white pepper within 4.0% - 4.5% and the purity of the yielded piperine was found to be up to 98.5% for black pepper and 98.2% for white pepper. Considering this yield value and purity it is indicated that, such effective isolation method can be successfully utilized for industrial large-scale production commercially. According to the result, it can be claimed that, as a natural product the isolated piperine can also be utilized as API drug like other expensive chemically synthesized piperine in different drug formulation.展开更多
Objective:To explore the mechanism of Piperine of Piperis Longi Fructus in the treatment of vitiligo based on network pharmacology and transcriptome.Methods:Piperine,the active component of Piperis Longi Fructus,was s...Objective:To explore the mechanism of Piperine of Piperis Longi Fructus in the treatment of vitiligo based on network pharmacology and transcriptome.Methods:Piperine,the active component of Piperis Longi Fructus,was screened from Traditional Chinese Medicine Systems Pharmacology,and the target network and protein interaction network of piperine-vitiligo were constructed.PPI analyzed the cross targets,GO function,and KEGG pathway analysis.In the GEO database,vitiligo gene expression profile chips GSE65127 and GSE75819 were selected for differential gene screening and gene set enrichment analysis.The potential key signal pathways of piperine in the treatment of vitiligo were identified by transcriptome microarray data verification.Results:31 potential targets of piperine in the treatment of vitiligo were found,of which 9 targets such as ESR1,AKT1,and IGF1 were closely related to the treatment of vitiligo.Enrichment analysis showed that signal pathways such as PI3K-Akt,MAPK,and Melanogenesis were related to piperine's mechanism in treating vitiligo.The cross-validation of chip analysis results confirmed that Melanogenesis is a potential key signal pathway for piperine in vitiligo treatment.Conclusion:This study discusses the potential targets and signal pathways of piperine in the treatment of vitiligo,which helps clarify the mechanism of piperine in the treatment of vitiligo and provides a theoretical basis for the clinical treatment of vitiligo.It also provides direction for the research and development of new drugs for vitiligo.展开更多
Multidrug resistance (MDR) in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein (P-gp) is an ATP-binding cassette transporter fre...Multidrug resistance (MDR) in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein (P-gp) is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and (R)-(+)-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and (R)-(+)-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and (R)-(+)-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while (R)-(+)-citronellal had no effect on the MDR1 expression. Therefore, piperine and (R)-(+)-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.展开更多
Ginsenoside Rh2(Rh2)is one of the major bioactive ginsenosides in Panax ginseng.However,the oral bioavailability of Rh2 is low,with P-glycoprotein(P-gp)and CYP3A4 being reported to be the main factors.The purpose of t...Ginsenoside Rh2(Rh2)is one of the major bioactive ginsenosides in Panax ginseng.However,the oral bioavailability of Rh2 is low,with P-glycoprotein(P-gp)and CYP3A4 being reported to be the main factors.The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2.The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system,respectively.The pharmacokinetics of oral Rh2(10 mg·kg^(-1))administered alone or in combination with piperine(10 and 20 mg·kg^(-1))was performed in rats.The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine.The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2.The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose(20 mg·kg^(-1))when compared to the control group,with relative bioavailability of 196.8%.The increase of Rh2 exposure led to increased serum levels of IL-12.In conclusion,piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.展开更多
Although the etiology of sciatica remains uncertain,there is increasing evidence that the disease process of sciatica is associated with the levels of inflammatory factors.Piperine,an alkaloid isolated from Piper nigr...Although the etiology of sciatica remains uncertain,there is increasing evidence that the disease process of sciatica is associated with the levels of inflammatory factors.Piperine,an alkaloid isolated from Piper nigrum,has previously been demonstrated to inhibit inflammation and analgesic effects.The purpose of this study is to verify the regulatory relationship between miR-520a and p65 and to explore how miR-520a/P65 affects the level of cytokines under the action of piperine,so as to play a therapeutic role in sciatica.Through ELISA experiment,we confirmed that four inflammatory factors(IL-1β,TNF-α,IL-10,TGF-β1)can be used as evaluation indexes of sciatica.The differentially expressed miRNA was screened as miR-520a,by microarray technology,and the downstream target of miR-520a was P65 by bioinformatics.Real-time fluorescence quantitative PCR confirmed that the expression of miR-520a was negatively correlated with pro-inflammatory cytokines,positively correlated with anti-inflammatory cytokines and negatively correlated with p65 expression at mRNA level.The expression of p65 was positively correlated with pro-inflammatory cytokines and negatively correlated with anti-inflammatory cytokines at the protein level verified by ELISA and Western blot.HE staining analysis showed that the nerve fibers were repaired by piprine,the vacuoles were significantly reduced,and the degree of nerve fiber damage was also improved.Immunohistochemical analysis showed that the expression of p65 decreased after administration of piperine.Dual-luciferase reporter gene assay confirmed that the luciferase signal decreased significantly after cotransfection of miR-520a mimics and p653'UTR recombinant plasmid.To sum up,in the rat model of non-compressed lumbar disc herniation,piperine plays a significant role in analgesia.MiR-520a can specifically and directly target P65,and piperine can promote the expression of miR-520a,then inhibit the expression of p65,down-regulate the pro-inflammatory factors IL-1βand TNF-α,and up-regulate the effects of anti-inflammatory factors IL-10 and TGF-β1,so as to treat sciatica.展开更多
Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characte...Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.展开更多
Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine ...Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.展开更多
The second derivative differential pulse polarography was developed for the quantitative determination of active principles in medicinal herbs (baicalin in Scutellaria baicalensis Georgi, indigo in Baphicacanthus cusi...The second derivative differential pulse polarography was developed for the quantitative determination of active principles in medicinal herbs (baicalin in Scutellaria baicalensis Georgi, indigo in Baphicacanthus cusia (Nees) Bremek, paeonol in Paeonia suffruticosa Andr and piperine in Piper longum L ) The C O group in baicalin, indigo, paeonol and piperine could be reduced to CH OH in acidic solution at the dropping mercury electrode, and showed very good second derivative differential pulse polarographic peak at 1 550V, 1 300V, 1 630V and 0 860V (vs Ag/AgCl) respectively The linear relationship between concentration of baicalin, indigo, paeonol, piperine and peak height was obtained in the concentration range of 4 5×10 5 ~ 2 7×10 4 mol·L 1 , 3 8×10 5 ~ 4 2×10 4 mol·L 1 , 1 0~6 0×10 4 mol·L 1 and 7 0×10 5 ~2 5×10 4 mol·L 1 and the determination limits were 9 0×10 8 mol·L 1 , 8 4×10 9 mol·L 1 , 9 2×10 9 mol·L 1 and 8 7×10 9 mol·L 1 respectively This method is simple, rapid and sensitive, and the results are accurate展开更多
基金financially supported by the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019ZT08N291)the National Natural Science Foundation of China (31901689)the Natural Science Foundation of Guangdong Province,China (2021A1515012124)。
文摘The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.
文摘Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was conducted to evaluate the binding affinity of diclofenac with piperine and D-limonene against p53,Bax,and Bcl-2.The MTT assay was used to determine IC50,and the Chou-Talay method was used to determine the synergistic concentration of the combination treatment of diclofenac plus piperine and diclofenac plus D-limonene.Apoptosis detection,cell cycle arrest,reactive oxygen species production,and mitochondrial membrane potential were also investigated.Results:Diclofenac,piperine,and D-limonene showed potent binding affinity for p53,Bax,and Bcl-2.Diclofenac plus piperine and diclofenac plus D-limonene enhanced the formation of reactive oxygen species,which also had an effect on the mitochondrial membrane’s integrity and caused DNA fragmentation.Diclofenac plus piperine and diclofenac plus D-limonene arrested the cells in the sub-G0phase while drastically lowering the percentage of cells in the G2/M phase.Furthermore,the elevated apoptosis in the combined therapy was confirmed by annexin V/propidium iodide staining.Conclusions:The combined therapy prominently enhanced the antiproliferative and apoptotic effects on MCF-7 cells compared with treatment with diclofenac,piperine,and D-limonene alone.
基金Supported by the IRPA Project of the Ministry of Science,Technology and Innovation,Malaysia (09-02-03-0101-EA0001)Fundamental Research Grant 2009 Directorate General of Higher Education,Ministry of National Education,the Republic of Indonesia
文摘Piperine is a member of the lipids family commonly found in peppercorn, ginger and other natural sources and is grouped as an alkaloid. The solubility of piperine has been determined in carbon dioxide at near critical and supercritical conditions in a dynamic extraction apparatus. The conditions studied were at pressures ranging from 10 to 20 MPa and temperatures at 293, 300, 313, 323 and 333 K. The results showed that piperine solubility increased with increasing pressure at all temperatures studied. The solubility of plperme in near critical conditions was slightly higher than that at supercritical conditions only at the low-pressure range. Two semi-empirical density dependent correlations, namely the Chrastil model and the Dilute Solution model, were also used to estimate the solubility data. Although both models showed good correlation with the solubility data, the Dilute Solution model performed better prediction than the Chrastil model.
基金Science and Engineering Board(SERB),Department of Science and Technology,Government of India,New Delhi for providing financial assistance under Fast Track Scheme(DST-SERB-FTYS)(SB/FT/LS-139/2012) to Dr.PK
文摘1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents.Quercetin(QC)is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability.Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants(e.g.,Quercetin).Therefore,the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats.MPTP(100μg/μL/rat,bilaterally)was injected intranigrally on days 1,4 and 7 using a digital stereotaxic apparatus.QC(25 and 50 mg/kg,intragastrically)and QC(25 mg/kg,intragastrically)in combination with piperine(2.5 mg/kg,intragastrically)were administered daily for 14 days starting from day 8 after the 3^(rd) injection of MPTP.On day 22,animals were sacrificed and the striatum was isolated for oxidative stress parameter(thiobarbituric acid reactive substances,nitrite and glutathione),neuroinflammatory cytokine(interleukin-1β,interleukin-6,and tumor necrosis factor-α)and neurotransmitter(dopamine,norepinephrine,serotonin,gamma-aminobutyric acid,glutamate,3,4-dihydroxyphenylacetic acid,homovanillic acid,and 5-hydroxyindoleacetic acid)evaluations.Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance.Both QC(25 and 50 mg/kg)and QC(25 mg/kg)in combination with piperine(2.5 mg/kg),in particular the combination therapy,significantly improved MPTP-induced behavioral abnormalities in rats,reversed the abnormal alterations of neurotransmitters in the striatum,and alleviated oxidative stress and inflammatory response in the striatum.These findings indicate that piperine can enhance the antioxidant and anti-inflammatory properties of QC,and QC in combination with piperine exhibits strong neuroprotective effects against MPTP-induced neurotoxicity.
基金financially supported by UGC Sanction order No.F.4-1/2006(BSR)/7-269/2009(BSR)
文摘Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.Methods:Cu-Pi nanoparticles were prepared by thin film hydration method,solid dispersion method,emulsion polymerization method and Fessi method.Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles.Results:Out of four methods,Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV.Change of organic solvent(acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles.However,increase in sonication time,stirring speed,viscosity,use of 1:10:10 ratio of drag/polymer/surfactant,and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles.Conclusions:Cu-Pi nanoparticles coated with PEC containing copolymer produced by Fessi method had a minimum average particle size,excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study.This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.
文摘Aim: To study the effect of piperine on the epididymal antioxidant system of adult male rats. Methods: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30 consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation. Results: Body weight of the piperine-treated rats remained unchanged. The weights of the caput, corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg. Conclusion: Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.
基金Supported by the National Natural Science Foundation of China(No.81072221)Projects of Research and Development in Key Areas of Hunan Province(No.2017SK2020+1 种基金No.2020SK2133)the Natural Science Foundation of Hunan Province(No.2020JJ5005)。
文摘AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.
基金financially supported by Mahasarakham University 2021(MSU2021).
文摘Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colony formation assays,wound healing assays,Matrigel migration assays,flow cytometry,RT-qPCR,and Western blotting assays.Results:Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation.Cell reduction at the G_(0)/G_(1) phase and cell arrest at the G_(2)/M phase were observed in breast cancer cells.However,the significant effect was only demonstrated in MDA-MB-231 cells.Moreover,cancer cell migration was suppressed by piperine at low concentration.RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression.Conclusions:Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.
文摘A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed and validated for the determination of piperine (PPR) on dried blood spots (DBS). DBS samples were prepared by spiking the whole blood with analyte to produce 30 μL of blood spots on specimen collection cards. Chromatographic separation was achieved on an Atlantis dC18 column using acetonitrile and water (0.1% formic acid) (85:15, v/v) as mobile phase in an isocratic mode of elution at a flow rate of 0.75 mL/min. MS detection was carried out in electrospray positive ion mode for the target ions and monitored at m/z 286.1465 for PPR and 272.1303 for the internal standard (IS). The developed method exhibited a linear dynamic range over 0.01-2000 ng/mL for PPR on DBS. The overall extraction recovery of PPR from DBS was 92.5%. Influence of hematocrit and spot volume on DBS was also evaluated and found to be well within the acceptable limits. The method was successfully applied to pharmacokinetic studies of PPR in rats.
文摘Antidepressant and cognitive effects of piperine -encapsulated liposomes (PL) were investigated in male Wistar rats. Oral piperine (5 mg/kg body weight/day) and intranasal PL (7.2 μg/day) were randomly assigned to daily administer for 14 days to rats which were subjected to forced swimming, Mor-ris water maze and spontaneous motor behavior tests. PL significantly exhibited anti-depression like activity and cognitive enhancing effects, in comparison to the control groups after the first dose (p < 0.01) and the effects could be maintained throughout the period of study. Quantitative analysis of the brain homogenates by HPLC indicated that piperine, delivered either orally or nasally, distributed to the hippocampus at a higher extent than the cortex and that the time to peak concentration of nasal PL was shorter than for the oral piperine. Intranasal PL was, thus, potential in delivery of piperine, at a low dose, to exert its an-tidepressant and cognitive enhancing activities.
文摘Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering a- gent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation in- duced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogen- ic or chow diets for 10 weeks, with or without PA ( 15, 30 and 60 mg ~ kg-1 ) or ursodeoxycholic acid ( UDCA, 60 mg ~ kg-1) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological chan- ges and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol poten- cy and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein / low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/ 8 ) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation.
基金Supported by Fundamental Research Fund of Chinese Academy of Tropical Agricultural Science(1630042013017)Special Fund for Agro-scientific Research in the Public Interest(201103026-1)+2 种基金Fundamental Research Fund for Central-level Nonprofit Research Institutes(Young Talents in Tropical Agriculture)(2013hzs1J002)Natural Science Foundation of Hainan Province of China(310086,313083)Natural Science Foundation of China(31101465)
文摘In order to clarify the insecticidal active ingredients of Piper sarmentosum,one active ingredient was isolated from ethanol extract of P. sarmentosum by bioassay-guided fractionation method. Its chemical structures were identified to be piperine by MS,1H NMR,13C NMR. The insecticidal activity of piperine and ethanol extract of P. sarmentosum against Aleurodicus dispels Russell were tested by leaf dip method. The results showed that piperine and ethanol extract of P. sarmentosum exhibited strong insecticidal activity against adults and nymphs of A. dispels; LC50values against adults were 28. 59 and 224. 31 mg/L,and LC50values against nymphs were 65. 91 and 336. 68 mg/L,respectively. There was no significant difference between piperine and azadirachtin against adults and nymphs of A.dispels. Therefore,piperine might be one of the main insecticidal ingredients of P. sarmentosum. In addition,piperine and ethanol extract showed ovicidal activity with different mode of action,piperine reduced the survival rate of newly hatched nymphs while ethanol extract impacted hatch of eggs.
文摘In the pharmaceutical world the majority of the active pharmaceutical ingredients (API) have been obtained from the natural products. Piperine is such naturally occurring alkaloid which can be considered as major bioactive phytochemical having broad spectrum of pharmacological activities. It is obtained from the most valuable ethnomedicinal spices peppercorns i.e. black pepper and white pepper, which are the fruits of the Asian vine Piper nigrum L. Because of the widespread traditional uses of this medicinal compound, present article reveals a simple and effective isolation method of bulk piperine. The novelty of this investigation is to provide an idea for utilizing such natural method of large scale commercial piperine production as API drug in spite of chemical synthesis. Piperine was isolated in a pure crystal form and characterized by its melting point, X-Ray diffraction (XRD) studies and spectral data, including two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy. Chromatographic techniques like Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography (HPLC) were applied to determine the purity of the yielded piperine. It was found that piperine yield from black pepper was within 2.5% - 3.0% and from white pepper within 4.0% - 4.5% and the purity of the yielded piperine was found to be up to 98.5% for black pepper and 98.2% for white pepper. Considering this yield value and purity it is indicated that, such effective isolation method can be successfully utilized for industrial large-scale production commercially. According to the result, it can be claimed that, as a natural product the isolated piperine can also be utilized as API drug like other expensive chemically synthesized piperine in different drug formulation.
文摘Objective:To explore the mechanism of Piperine of Piperis Longi Fructus in the treatment of vitiligo based on network pharmacology and transcriptome.Methods:Piperine,the active component of Piperis Longi Fructus,was screened from Traditional Chinese Medicine Systems Pharmacology,and the target network and protein interaction network of piperine-vitiligo were constructed.PPI analyzed the cross targets,GO function,and KEGG pathway analysis.In the GEO database,vitiligo gene expression profile chips GSE65127 and GSE75819 were selected for differential gene screening and gene set enrichment analysis.The potential key signal pathways of piperine in the treatment of vitiligo were identified by transcriptome microarray data verification.Results:31 potential targets of piperine in the treatment of vitiligo were found,of which 9 targets such as ESR1,AKT1,and IGF1 were closely related to the treatment of vitiligo.Enrichment analysis showed that signal pathways such as PI3K-Akt,MAPK,and Melanogenesis were related to piperine's mechanism in treating vitiligo.The cross-validation of chip analysis results confirmed that Melanogenesis is a potential key signal pathway for piperine in vitiligo treatment.Conclusion:This study discusses the potential targets and signal pathways of piperine in the treatment of vitiligo,which helps clarify the mechanism of piperine in the treatment of vitiligo and provides a theoretical basis for the clinical treatment of vitiligo.It also provides direction for the research and development of new drugs for vitiligo.
文摘Multidrug resistance (MDR) in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein (P-gp) is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and (R)-(+)-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and (R)-(+)-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and (R)-(+)-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while (R)-(+)-citronellal had no effect on the MDR1 expression. Therefore, piperine and (R)-(+)-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.
基金supported by the National Natural Science Foundation of China(No.81573789)
文摘Ginsenoside Rh2(Rh2)is one of the major bioactive ginsenosides in Panax ginseng.However,the oral bioavailability of Rh2 is low,with P-glycoprotein(P-gp)and CYP3A4 being reported to be the main factors.The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2.The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system,respectively.The pharmacokinetics of oral Rh2(10 mg·kg^(-1))administered alone or in combination with piperine(10 and 20 mg·kg^(-1))was performed in rats.The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine.The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2.The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose(20 mg·kg^(-1))when compared to the control group,with relative bioavailability of 196.8%.The increase of Rh2 exposure led to increased serum levels of IL-12.In conclusion,piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.
基金supported by the National Natural Science Foundation of China(Nos.81760748,81550047)the Natural Science Foundation of Inner Mongolia Autonomous Region(Nos.2018LH08032,2017MS0831)Inner Mongolia Autonomous Region"Prairie Excellence"Project,West Light Foundation of the Chinese Academy of Sciences,the Major Science Foundation of Affiliated Hospital of Inner Mongolia Medical University(No.NY-FY ZD010).
文摘Although the etiology of sciatica remains uncertain,there is increasing evidence that the disease process of sciatica is associated with the levels of inflammatory factors.Piperine,an alkaloid isolated from Piper nigrum,has previously been demonstrated to inhibit inflammation and analgesic effects.The purpose of this study is to verify the regulatory relationship between miR-520a and p65 and to explore how miR-520a/P65 affects the level of cytokines under the action of piperine,so as to play a therapeutic role in sciatica.Through ELISA experiment,we confirmed that four inflammatory factors(IL-1β,TNF-α,IL-10,TGF-β1)can be used as evaluation indexes of sciatica.The differentially expressed miRNA was screened as miR-520a,by microarray technology,and the downstream target of miR-520a was P65 by bioinformatics.Real-time fluorescence quantitative PCR confirmed that the expression of miR-520a was negatively correlated with pro-inflammatory cytokines,positively correlated with anti-inflammatory cytokines and negatively correlated with p65 expression at mRNA level.The expression of p65 was positively correlated with pro-inflammatory cytokines and negatively correlated with anti-inflammatory cytokines at the protein level verified by ELISA and Western blot.HE staining analysis showed that the nerve fibers were repaired by piprine,the vacuoles were significantly reduced,and the degree of nerve fiber damage was also improved.Immunohistochemical analysis showed that the expression of p65 decreased after administration of piperine.Dual-luciferase reporter gene assay confirmed that the luciferase signal decreased significantly after cotransfection of miR-520a mimics and p653'UTR recombinant plasmid.To sum up,in the rat model of non-compressed lumbar disc herniation,piperine plays a significant role in analgesia.MiR-520a can specifically and directly target P65,and piperine can promote the expression of miR-520a,then inhibit the expression of p65,down-regulate the pro-inflammatory factors IL-1βand TNF-α,and up-regulate the effects of anti-inflammatory factors IL-10 and TGF-β1,so as to treat sciatica.
文摘Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.
文摘Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.
文摘The second derivative differential pulse polarography was developed for the quantitative determination of active principles in medicinal herbs (baicalin in Scutellaria baicalensis Georgi, indigo in Baphicacanthus cusia (Nees) Bremek, paeonol in Paeonia suffruticosa Andr and piperine in Piper longum L ) The C O group in baicalin, indigo, paeonol and piperine could be reduced to CH OH in acidic solution at the dropping mercury electrode, and showed very good second derivative differential pulse polarographic peak at 1 550V, 1 300V, 1 630V and 0 860V (vs Ag/AgCl) respectively The linear relationship between concentration of baicalin, indigo, paeonol, piperine and peak height was obtained in the concentration range of 4 5×10 5 ~ 2 7×10 4 mol·L 1 , 3 8×10 5 ~ 4 2×10 4 mol·L 1 , 1 0~6 0×10 4 mol·L 1 and 7 0×10 5 ~2 5×10 4 mol·L 1 and the determination limits were 9 0×10 8 mol·L 1 , 8 4×10 9 mol·L 1 , 9 2×10 9 mol·L 1 and 8 7×10 9 mol·L 1 respectively This method is simple, rapid and sensitive, and the results are accurate