nsc-4347 and Disease-Models--Animal

Eighty percent (80%) aqueous acetone extract from fruit of Piper chaba (Piperaceae) was found to have a hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: i) the amide moiety was essential for strong activity; ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effect at a dose of 5 mg/kg, p.o. and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.

Topics: Alkaloids; Amides; Animals; Benzodioxoles; Cells, Cultured; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Dose-Response Relationship, Drug; Galactosamine; Hepatocytes; Lipopolysaccharides; Mice; Piper; Piperidines; Polyunsaturated Alkamides; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

Piper wallichii (family: Piperaceae), a folk herbal medicine with anti-inflammatory and anti-thrombotic properties, has been traditionally used to treat rheumatic arthralgia, lumbocrural pain, gastrointestinal flatulence, and other intestinal diseases in China, Thailand, and India. However, there is no scientific report on the efficacy and potential mechanisms of Piper wallichii for ulcerative colitis (UC).. The study aims to investigate the therapeutic effect and possible molecular mechanisms of the ethanol extract of Piper wallichii (EEPW) on DSS-induced UC in BALB/c mice.. The main components in EEPW were characterized by UPLC-QE-Orbitrap-MS. Subsequently, the anti-inflammatory effect of EEPW in vitro was preliminarily evaluated in RAW264.7 cells stimulated with LPS. UC model mice were triggered by free access to 4% DSS aqueous solution for 12 consecutive days, and simultaneously, EEPW (25, 50, and 100 mg/kg) and tofacitinib (positive control, 30 mg/kg) were orally administrated, respectively. The therapeutic efficacy of EEPW on UC was assessed by body weight, DAI, colon length, and pathological morphology. Besides, we investigated the effects of EEPW on intestinal barrier function, inflammatory factors, and immune systems of UC mice through immunohistochemistry (IHC), flow cytometry, and other techniques. Moreover, the expression of related proteins in the TLR4/NF-κB/COX-2 pathway was analyzed by Western blot.. A total of 14 components were identified in the positive and negative modes, including isofutoquinol A (11), hancinone C (12), and futoquinol (14) which characterized by references. In the RAW264.7 cells experiments, the extract significantly suppressed the levels of TNF-α and IL-6. More importantly, EEPW distinctly improved the symptoms of DSS-induced UC mice as reflected by a significant recovery from body weight, colon length, pathological injuries of the colon, and so on. Further research found that EEPW remarkably restored the levels of occludin, promoted proliferation, and inhibited apoptosis in colon to maintain the integrity of intestinal barrier. In addition, the down-regulation of TNF-α and IL-1β in colon, Th1 and Th17 cells in spleen, as well as the up-regulation of IL-10 in colon and Th2 cells in spleen were distinctly observed in EEPW-treated groups. Furthermore, the protein expression of TLR4, p-IκB-α, p-p65, and COX-2 were significantly inhibited by EEPW.. This study confirmed for the first time that EEPW effectively ameliorated DSS-induced UC in mice, which might be related to improving intestinal barrier function, maintaining the levels of inflammatory factors, and regulating the immune system. In addition, we found that the anti-inflammatory effect of EEPW on UC mice was involved in the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, Piper wallichii can be used as a candidate for the treatment of UC.

Topics: Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Colon; Cyclooxygenase 2; Dextran Sulfate; Disease Models, Animal; Mice; Mice, Inbred C57BL; NF-kappa B; Piper; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Fruit; Guanosine Triphosphate; Mice; MicroRNAs; NF-kappa B; Piper; Tea

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6-8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour.

Topics: Animals; Disease Models, Animal; Dysmenorrhea; Female; Ibuprofen; Inflammation; Mast Cells; Mice; Neutrophils; Oxytocin; Piper; Plant Extracts

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antigens, Surface; Antineoplastic Agents; Antioxidants; Antiviral Agents; Aporphines; Atherosclerosis; Benzoyl Peroxide; beta Catenin; Biofilms; Biomarkers; Brain; Cannabis; Carcinoma, Squamous Cell; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child; China; Chlorides; Chlorophyll; Cholesterol, LDL; Coinfection; Corylus; Cross-Sectional Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Developmental Disabilities; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electroencephalography; Environmental Exposure; Enzyme Inhibitors; Epilepsy, Generalized; Ethnicity; Female; Fertilization in Vitro; Fluorescent Dyes; Follow-Up Studies; Forecasting; Glutamate Carboxypeptidase II; Glycine; Half-Life; Head and Neck Neoplasms; Health Communication; Heart Ventricles; Hepacivirus; Hepatitis C; Heterosexuality; HIV Infections; Humans; Hypercholesterolemia; Immunoassay; Inhalation Exposure; Isocitrate Dehydrogenase; Laryngeal Neoplasms; Ligands; Light; Lipopolysaccharide Receptors; Liver Cirrhosis; Lung; Lung Neoplasms; Magnetic Resonance Imaging, Cine; Male; Maternal Age; Mechanical Phenomena; Mice; Mice, Nude; Mice, SCID; Microglia; MicroRNAs; Microscopy, Fluorescence; Microsomes, Liver; Middle Aged; Minority Groups; Mitochondrial Membrane Transport Proteins; Models, Biological; Molecular Structure; Molecular Weight; Monte Carlo Method; Muscle Hypotonia; Mutagenesis, Site-Directed; Mutation, Missense; Natriuretic Peptide, Brain; Neoplasms; Nickel; Nitric Oxide; Optical Imaging; Oxides; Particle Size; Particulate Matter; PCSK9 Inhibitors; Peptide Fragments; Phenotype; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Piper; Placenta Growth Factor; Plant Extracts; Plant Leaves; Plant Stems; Platinum; Point-of-Care Testing; Population Surveillance; Postpartum Period; Pregnancy; Pregnancy, Twin; Prevalence; Prospective Studies; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyridines; Pyridones; Racial Groups; Rats; Respiratory Physiological Phenomena; Retrospective Studies; Risk Factors; RNA, Long Noncoding; Semiconductors; Sexual and Gender Minorities; Sexual Behavior; Social Media; Sodium; Solubility; Stereoisomerism; Stochastic Processes; Structure-Activity Relationship; Substance-Related Disorders; Sustained Virologic Response; Sweat; Temperature; Time Factors; Tissue Distribution; Titanium; Transplantation, Heterologous; Tumor Cells, Cultured; Tungsten; Tyramine; United States; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Veterans; Xenograft Model Antitumor Assays; Young Adult

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Schistosomiasis is one of the most important parasitic infections in terms of its negative effects on public health and economics. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new anthelmintic agents. Piplartine, also known as piperlongumine, is a biologically active alkaloid/amide from peppers that can be detected in high amounts in the roots of Piper tuberculatum. Previously, it has been shown to have in vitro schistosomicidal effects. However, its anthelmintic activity in an animal host has not been reported. In the present work, in vivo antischistosomal properties of isolated piplartine were evaluated in a mouse model of schistosomiasis infected with either adult (patent infection) or juvenile (pre-patent infection) stages of Schistosoma mansoni. A single dose of piplartine (100, 200 or 400 mg/kg) or daily doses for five consecutive days (100 mg/kg/day) administered orally to mice infected with schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest piplartine dose (400 mg/kg) caused a significant reduction in a total worm burden of 60.4% (P < 0.001) in mice harbouring adult parasites. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also significantly inhibited by piplartine. Studies using scanning electron microscopy revealed substantial tegumental alterations in parasites recovered from mice. Since piplartine has well-characterized mechanisms of toxicity, is easily available, and is cost-effective, our results indicate that this bioactive molecule derived from medicinal plants could be a potential lead compound for novel antischistosomal agents.

Topics: Animals; Disease Models, Animal; Female; Mice; Piper; Piperidones; Schistosomiasis mansoni; Schistosomicides

Inflammation processes are implicated in many degenerative diseases. Piper guineense, a West African spice belonging to the Piperaceae family has been reported to contain anti-inflammatory agents.. This study determined the modulatory effects of methanolic extracts of Piper guineense leaves and seeds on egg albumin-induced inflammation in rats.. Inflammation in the hind paw was induced by injecting 0.1ml egg albumin subcutaneously. Treatments including diclofenac were given orally. Rectal temperature and paw size were monitored hourly for the first 3 h' post-induction of inflammation and then at the 6th and 24th hour. Serum levels of CRP, MDA, LDH and GGT activities were determined at these hours.. Results showed that egg albumin-induced inflammation caused a significant (p < 0.05) increase in paw size and rectal temperature. It further showed that treatment with the leaves and seed extracts reversed the effect of inflammation on serum levels of CRP and MDA, and on LDH and GGT activities similar to diclofenac in rats.. Extracts of the Piper guineense seed and leaves have potentials of being used as an anti-inflammatory agent but further studies need to be done to determine their toxicity and effects on immunological markers of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Carrier Proteins; Disease Models, Animal; gamma-Glutamyltransferase; Inflammation; L-Lactate Dehydrogenase; Male; Malondialdehyde; Ovalbumin; Piper; Plant Extracts; Plant Leaves; Rats; Seeds

Piper nigrum L. and Piper longum L. consist a classic formula in traditional Chinese Hui medicine and are widely used in treatment of stroke. To examine the therapeutic effect of neuron injury after apoplexy, we used a permanent middle cerebral artery occlusion model in rats to investigate the effects of dichloromethane fraction (DF) of Piper nigrum L. and Piper longum L.. DF alleviated neurological deficits and markedly prevented ischemia-induced cellular damage. Immunohistochemical micrographs revealed that PSD-95 and syn-I proteins increased, and α-syn presented reduced expression in brain samples from the sham group. Western blot analyses revealed that the model group exhibited a noticeable reduction in PSD-95, p-CaMK II, CaM, and NR2B. The DF-treated model group exhibited increased PSD-95, p-CaMK II, CaM, and NR2B. UPLC-Q-TOF/MS analysis revealed eight main components of DF, of which piperine accounted for the largest proportion.

Topics: alpha-Synuclein; Animals; Behavior, Animal; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calmodulin; Disease Models, Animal; Disks Large Homolog 4 Protein; Infarction, Middle Cerebral Artery; Male; Methylene Chloride; Motor Activity; Neurons; Neuroprotective Agents; Phosphorylation; Piper; Piper nigrum; Plant Extracts; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Solvents; Synapsins

Amyloidogenesis is known to cause Alzheimer's disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF-κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i.p.) injection of LPS (0.25 mg/kg/day, i.p.). We then injected PL (1.5 or 3.0 mg/kg/day, i.p.) for 7 days in three groups of mice to observe effects on memory. We also conducted an in vitro study with astrocytes and microglial BV-2 cells, which were treated with LPS (1 µg/mL) or PL (0.5 or 1.0 or 2.5 µM). Results from our behavioral tests showed that PL inhibited LPS-induced memory. PL also prevented LPS-induced beta-amyloid (Aβ) accumulation and inhibited the activities of β- and γ-secretases. The expression of inflammatory proteins also was decreased in PL-treated mice, cultured BV-2, and primary astrocyte cells. These effects were associated with the inhibition of NF-κB activity. A docking model analysis and pull-down assay showed that PL binds to p50. Taken together, our findings suggest that PL diminishes LPS-induced amyloidogenesis and neuroinflammation by inhibiting NF-κB signaling; PL therefore demonstrates potential for the treatment of Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Astrocytes; Cell Death; Cells, Cultured; Cytokines; Dioxolanes; Disease Models, Animal; Inflammation; Lipopolysaccharides; Male; Memory; Mice; Microglia; NF-kappa B p50 Subunit; Piper

Although some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited.. This study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice.. The acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws.. These results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hyperalgesia; Male; Mice; Oils, Volatile; Piper; Plant Extracts; Plant Leaves; Toxicity Tests, Acute; Toxicity Tests, Subacute

Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed.. The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA. HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity.. The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is independent of anti-H. pylori activity, with substances probably responsible for the pharmacological activity being flavonoids, quercetin and rutin. These results support the popular use of P. umbellatum leaves in the treatment of peptic ulcers.

Topics: Acetic Acid; Acute Disease; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Catalase; Chronic Disease; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Glutathione; Helicobacter pylori; Inflammation Mediators; Male; Malondialdehyde; Mice; Phytotherapy; Piper; Plant Extracts; Plant Leaves; Plants, Medicinal; Solvents; Stomach; Stomach Ulcer; Wound Healing

Alkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by inhibiting microglial activation using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model.. The animal behaviors of rotational behavior, rotarod test and open-field test were investigated. The survival ratio of dopaminergic neurons and microglial activation were examined. The dopamine (DA) and its metabolite were detected by high performance liquid chromatography (HPLC). The effects of PLA on the expression of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and nitric oxide (NO) were also estimated.. We showed that the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were reduced after a single intranigral dose of LPS (10 μg) treatment. The survival rate of TH-ir neurons in the SNpc and DA levels in the striatum were significantly improved after treatment with PLA for 6 weeks. The over-activated microglial cells were suppressed by PLA treatment. We also observed that the levels of inflammatory cytokines, including TNF-α, IL-6 and IL-1β were decreased and the excessive production of ROS and NO were abolished after PLA treatment. Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment.. This study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.

Topics: Alkaloids; Animals; Disease Models, Animal; Dopaminergic Neurons; Inflammation; Lipopolysaccharides; Male; Parkinson Disease; Piper; Plant Extracts; Rats; Rats, Sprague-Dawley

Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness of Piper cubeba fruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT, γ-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNFα, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene.

Topics: Animals; Antioxidants; Biphenyl Compounds; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Cytokines; Disease Models, Animal; Ethanol; Free Radical Scavengers; Lignans; Liver; Male; Malondialdehyde; Oxidative Stress; Phytochemicals; Picrates; Piper; Plant Extracts; Protective Agents; Rats, Wistar; RNA, Messenger; Sulfhydryl Compounds

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Carrageenan; Chemotaxis, Leukocyte; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Erythrocytes; Female; Lethal Dose 50; Male; Mice; Micronucleus Tests; Oils, Volatile; Phytotherapy; Piper; Plant Extracts; Plant Leaves; Plant Oils; Plants, Medicinal; Pleurisy; Rats; Rats, Wistar; Risk Assessment; Time Factors

Endothelial cell protein C receptor (EPCR) plays an important role in coagulation and inflammation. EPCR can be shed from the cell surface, and this is mediated by tumor necrosis factor-α-converting enzyme (TACE). Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit antihyperlipidemic, antiplatelet, and antimelanogenesis activities. However, little is known about the effects of PL on EPCR shedding. Here, we investigated this issue by monitoring the effects of PL on phorbol-12-myristate 13-acetate (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. PL induced potent inhibition of PMA, and CLP induced EPCR shedding through suppression of TACE expression. And treatment with PL resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, PL might have potential as an anti-sEPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.

Topics: ADAM Proteins; ADAM17 Protein; Animals; Anti-Inflammatory Agents; Antigens, CD; Cells, Cultured; Dioxolanes; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelial Protein C Receptor; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Fruit; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Phytotherapy; Piper; Plant Extracts; Plants, Medicinal; Receptors, Cell Surface; Sepsis; Tetradecanoylphorbol Acetate; Time Factors; Tumor Necrosis Factor-alpha

In this study, we identified the antinociceptive and anti-inflammatory effects of two flavonoids (PMT1 and PMT2) from Piper montealegreanum. The antinociceptive effect was evaluated using the classical tests: acetic acid-induced writhing, formalin and hot plate test. PMT1 and PMT2 (0.1, 1, 30 and 100 μmol/kg, i.p.) reduced the writhings, with an ID50 of 0.58 and 0.44 μmol/kg, respectively. Moreover, these flavonoids (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin test, but only PMT2 was active in the inflammatory phase. However, PMT1 and PMT2 (100 μmol/kg, i.p.) did not increase the latency time of the animals in the hot plate. In order to evaluate the anti-inflammatory effect of these flavonoids, capsaicin-induced ear oedema was carried out. Both flavonoids (100 μmol/kg, i.p.) were active in this model. These results suggest that PMT1 and PMT2 have antinociceptive and anti-inflammatory activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Capsaicin; Disease Models, Animal; Edema; Flavonoids; Formaldehyde; Male; Mice; Molecular Structure; Pain; Pain Measurement; Piper

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone.. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy.. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group.. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adrenalectomy; Animals; Anti-Obesity Agents; Disease Models, Animal; Glycyrrhizic Acid; Intra-Abdominal Fat; Male; Obesity; Phytotherapy; Piper; Plant Extracts; Rats; Rats, Sprague-Dawley; Treatment Outcome

Chandraprabha Vati (CV) is an Indian polyherbal Siddha drug, traditionally used as an anti-inflammatory agent for arthritis and urinary ailments. This study explores its effect on mice with urinary tract infection.. The in-organic constituents of CV were determined by atomic absorption spectroscopy and phytochemical analysis was carried out. The supplementing dose of CV to infected experimental mice was determined by in vitro antimicrobial assay. Transurethrally infected animals were supplemented with CV extract for 20 days after confirmation of UTI. The animals were euthanized as per the guidelines and the tissues were harvested from the control and infected mice for histopathological examination the antimicrobial peptide Tamm-Horsfall protein (THP) and inflammatory markers (tumor necrosis factor-α and nuclear factor kappa-light-chain-enhancer of activated B cells) to ascertain the modulatory effects of CV. Indicators for oxidative stress and protein levels were also quantified to validate the efficacy of CV.. Terpenoids and flavanoids were majorly found to constitute CV along with zinc and iron as in-organic content. Histological and immunohistochemical studies confirmed the pronounced infection in the kidney of the uropathogenic Escherichia coli-infected animals. Supplementation of CV significantly restored the increased levels of the antimicrobial proteins, THP, and inflammatory markers.. This study explored the efficacy of the aqueous extract of CV as an alternative medication for the synthetic analogues administered for UTI. This study also provides information on the possible role of THP as an antimicrobial protein in the kidney in preventing infection due to uropathogenic E coli.

Topics: Animals; Coriandrum; Curcuma; Cyperus; Disease Models, Animal; Female; Kidney; Medicine, Ayurvedic; Mice; NF-kappa B; Phyllanthus emblica; Piper; Plant Preparations; Tumor Necrosis Factor-alpha; Urinary Bladder; Urinary Tract Infections; Uromodulin; Uropathogenic Escherichia coli; Zingiber officinale

Atherogenic diet is known to induce high plasma lipid concentration, oxidative stress and early atherosclerosis. Antioxidants have potentials to counter the effect of atherogenic diet. The present research aims at evaluating the antioxidant and anti-atherosclerotic activities of three Piper species (Piper guineense, Piper nigrum and Piper umbellatum) on atherogenic diet fed hamsters. Hamsters divided into 8 groups: normal control, atherosclerotic control and six test groups. The normal animals fed normal rodent chow, the atherosclerotic control animals fed the same rodent chow supplemented with 0.2% cholesterol and 10% coconut oil (high cholesterol diet). The 6 test groups' animals fed same diet as the atherosclerotic control group but with additional supplementation of 2 graded doses (1 and 0.25 mg/kg body weight, o.p.) of plant extracts for 12 weeks. The atherogenic diet induced a collapse of the erythrocyte antioxidant defense system (significant decrease in superoxide dismutase, catalase and glutathione peroxidase activities). Atherogenic diet also induced an increase in plasma total cholesterol, triglyceride, thiobarbituric acid reactive substances (TBARS), oxidation of low density lipoprotein cholesterol (LDL) and accumulation of foam cells in the aorta a hall mark for atherosclerosis. Administration of the Piper species prevented the collapse of the antioxidant system and the increase of plasma parameters maintaining them towards normality. The Piper species also prevented LDL oxidation by increasing the time (lag time) for its oxidation. The results suggest that these Piper species have significant antioxidant and anti-atherogenic effect against atherogenic diet intoxication.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta; Arteriosclerosis; Cricetinae; Dietary Fats; Disease Models, Animal; Foam Cells; Lipid Peroxidation; Lipoproteins, LDL; Male; Mesocricetus; Oxidation-Reduction; Oxidative Stress; Piper; Plant Extracts; Plant Leaves; Species Specificity

Argulus are common aquatic ectoparasites that create one of the major threats to aquaculture due to absence of suitable therapy. Piperine, a bioactive component of Piper longum, has medicinal properties and acts as anti-inflammatory, antibacterial, and antifungal, considering eco-friendliness and cost-effectiveness. The present study aimed to evaluate antiparasitic effect of piperine against an ectoparasite Argulus spp. on Carassius auratus. Artificial Argulus infection was carried out by cohabitation method, and the fishes were selected for in vivo study when intensity of Argulus infestation was observed to be 15-20 Argulus per fish. In vitro and in vivo studies were performed at different concentration 1.0 (T (1)), 3.0 (T (2)), 5.0 (T (3)), 7.0 (T (4)), and 9.0 mg l(-1) (T (5)) of piperine solution to treat Argulus for 3 and 72 h, respectively. The acute toxicity test for piperine EC 97 % against goldfish was performed for 96 h. The 96 h median lethal concentration (LC(50)) for piperine was found to be 52.64 mg l(-1). In vitro effect of piperine solution led to 100 % mortality of Argulus at 9.0 mg l(-1) in 3 h whereas, under in vivo test, the 100 % antiparasitic efficacy of piperine solution was found at 9.0 mg l(-1) in 48 h. The EC(50) for 48 h was 9.0 mg l(-1), and thus, therapeutic index is 5.8. The results revealed that piperine at a concentration of 9.0 mg l(-1) can be used as a potential natural agent for controlling Argulus parasite.

Topics: Alkaloids; Animals; Antiparasitic Agents; Arguloida; Benzodioxoles; Disease Models, Animal; Ectoparasitic Infestations; Goldfish; Piper; Piperidines; Polyunsaturated Alkamides; Survival Analysis; Treatment Outcome

4-Nerolidylcatechol (4-NC) isolated from Piper peltatum L. (Piperaceae) was evaluated for in vitro antiplasmodial activity against Plasmodium falciparum (cultures of both standard CQR (K1) and CQS (3D7) strains and two Amazonian field isolates) and for in vivo antimalarial activity using the Plasmodium berghei-murine model. 4-NC exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-NC administered orally and subcutaneously at doses of 200, 400 and 600 mg/kg/day suppressed the growth of P. berghei by up to 63% after four daily treatments (days 1-4). Also, 4-NC exhibited important in vitro antiplasmodial activity against both standard and field P. falciparum strains in which 50% inhibition of parasite growth (IC(50) ) was produced at concentrations of 0.05-2.11 μg/mL and depended upon the parasite strain. Interestingly, healthy (non-infected) mice that received 4-NC orally presented (denatured) blood plasma which exhibited significant in vitro activity against P. falciparum. This is evidence that mouse metabolism allows 4-NC or active metabolites to enter the blood. Further chemical and pharmacological studies are necessary to confirm the potential of 4-NC as a new antimalarial prototype.

Topics: Animals; Antimalarials; Brazil; Catechols; Disease Models, Animal; Female; Malaria; Malaria, Falciparum; Mice; Piper; Plasmodium berghei; Plasmodium falciparum

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity.. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy.. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model.. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin.. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

Topics: Allyl Compounds; Animals; Anti-Inflammatory Agents; Carrageenan; Chromatography; Dioxoles; Disease Models, Animal; Female; Indomethacin; Inflammation; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Piper; Plant Leaves; Plant Oils; Plants, Medicinal; Rats; Rats, Wistar; Structure-Activity Relationship

Piper sarmentosum (P.s) has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically.. The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits.. Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study.. Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 + or - 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 + or - 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups.. Administration of P.s extract has protective effect against atheroscleros.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Atherosclerosis; Cholesterol; Disease Models, Animal; Flavonoids; Foam Cells; Male; Microscopy, Electron, Transmission; Phytotherapy; Piper; Plant Extracts; Rabbits; Treatment Outcome

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg(-1) day(-1) intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3% for piplartine and 55.1 and 56.8% for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Benzodioxoles; Cell Proliferation; Disease Models, Animal; Female; Kidney; Liver; Mice; Neoplasm Transplantation; Piper; Piperidines; Piperidones; Plant Extracts; Plant Roots; Polyunsaturated Alkamides; Sarcoma 180; Spleen

In this study, the furofuran lignan (+)-diayangambin [tetrahydro-1,4-bis(3,4,5-trimethoxyphenyl)-(1 R)-1alpha,3abeta,4alpha,6abeta-1 H,3 H-furo [3,4- c]furan] was evaluated in vitro and in vivo for its immunomodulatory and anti-inflammatory efficacy. Human mononuclear cell proliferation was inhibited by diayangambin with an IC 50 value of 1.5 (0.5 - 2.8) microM. In addition, the compound reduced for 40.8 % prostaglandin E 2 generation in stimulated RAW 264.7 macrophage cell line at 10 microM. In vivo, a clear reduction of ear swelling was observed when diayangambin (40 mg/kg) was administered orally to 2,4-dinitrofluorobenzene-treated mice. The inhibition of swelling was associated with a reduction of leukocyte infiltration determined as myeloperoxidase activity. In the carrageenan mouse paw edema model, diayangambin significantly suppressed inflamed paw volume and prostaglandin E 2 levels. Our findings indicate the potential interest of diayangambin in the treatment of immune and inflammatory responses.

Topics: Animals; Anisoles; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Dexamethasone; Dinoprostone; Disease Models, Animal; Edema; Furans; Immunosuppressive Agents; Inflammation; Lymphocyte Activation; Macrophages; Mice; Molecular Structure; Phytotherapy; Piper; Plant Extracts