ABSTRACT
P2X7 receptor promotes inflammatory response and neuropathic pain. New drugs capable of impairing inflammation and pain-reducing adverse effects extracted from plant extracts have been studied. Physalis angulate L. possesses traditional uses and exhibits antiparasitic, anti-inflammatory, antimicrobial, antinociceptive, antimalarial, antileishmanial, immunosuppressive, antiasthmatic. diuretic, and antitumor activities. The most representative phytochemical constituents identified with medicinal importance are the physalins and withanolides. However, the mechanism of anti-inflammatory action is scarce. Although some physalins and withanolides subtypes have anti-inflammatory activity, only four physalins subtypes (B, D, F, and G) have further studies. Therefore, we evaluated the crude ethanolic extract enriched with physalins B, D, F, and G from P. angulata leaves, a pool containing the physalins B, D, F, G, and the physalins individually, as P2X7 receptor antagonists. For this purpose, we evaluated ATP-induced dye uptake, macroscopic currents, and interleukin 1-ß (IL-1ß) in vitro. The crude extract and pool dose-dependently inhibited P2X7 receptor function. Thus, physalin B, D, F, and G individually evaluated for 5'-triphosphate (ATP)-induced dye uptake assay, whole-cell patch-clamp, and cytokine release showed distinct antagonist levels. Physalin D displayed higher potency and efficacy than physalin B, F, and G for all these parameters. In vivo mice model as ATP-induced paw edema was potently inhibited for physalin D, in contrast to physalin B, F, and G. ATP and lipopolysaccharide (LPS)-induced pleurisy in mice were reversed for physalin D treatment. Molecular modeling and computational simulation predicted the intermolecular interactions between the P2X7 receptor and physalin derivatives. In silico results indicated physalin D and F as a potent allosteric P2X7 receptor antagonist. These data confirm physalin D as a promisor source for developing a new P2X7 receptor antagonist with anti-inflammatory action.
Subject(s)
Acute Lung Injury/drug therapy , Physalis/chemistry , Plant Extracts/pharmacology , Secosteroids/pharmacology , Acute Lung Injury/physiopathology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Computer Simulation , Disease Models, Animal , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Male , Mice , Models, Molecular , Plant Extracts/administration & dosage , Plant Leaves , Purinergic P2X Receptor Antagonists/administration & dosage , Purinergic P2X Receptor Antagonists/isolation & purification , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic P2X7/drug effects , Secosteroids/isolation & purificationABSTRACT
OBJECTIVE: We investigated the antiinflammatory properties of a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet. MATERIAL AND METHODS: Zymosan-induced arthritis and pleurisy in Swiss and C57/Bl6 mice (n = 10 per group). Western blot analysis was performed to analyze nuclear factor-kappaB (NFkappaB) translocation in mice peritoneal macrophages stimulated in vitro with zymosan (500 microg/ml). ELISA was performed to evaluate cytokine levels in knee joints. Values of p
Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/drug therapy , Limonins/pharmacology , Meliaceae , Plant Preparations/pharmacology , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/metabolism , Cytokines/metabolism , Dose-Response Relationship, Drug , Knee Joint/metabolism , Knee Joint/pathology , Macrophages, Peritoneal , Male , Mice , Mice, Inbred C57BL , NF-kappa B/drug effects , NF-kappa B/metabolism , Phytotherapy/methods , Seeds , Synaptotagmin I/metabolism , Synovial Membrane/metabolism , Synovial Membrane/pathology , ZymosanABSTRACT
Uncaria guianensis (Aublet) J. F. Gmelin is an herbal medicine from tropical areas of South and Central America. We investigated the anti-inflammatory and anti-allergic properties of an ethanolic extract of U. guianensis leaves, containing alkaloids, flavonoids and phenol carboxylic acids, as revealed by thin layer chromatography (TLC). Oral pre-treatment with U. guianensis inhibited zymosan-induced paw oedema (500 mg/paw) and pleural exudation (100 mg/kg) within 4 h (25-200 mg/kg). U. guianensis (100 mg/kg) inhibited total leukocyte and neutrophil numbers in the pleural cavity 4 h after zymosan stimulation. Pre-treatment with U. guianensis (100 mg/kg, p.o.) inhibited total leukocyte, neutrophil and eosinophil recruitment into the pleural cavity 24 h after LPS (250 ng/cavity, i.t.). Pre-treatment with U. guianensis inhibited paw oedema (25-200 mg/kg) induced by ovalbumin (OVA) within 1 h, and neutrophil and eosinophil recruitment into the mice pleural cavity 24 h after OVA (100 mg/kg). In vitro data revealed that U. guianensis impaired LPS-induced nitric oxide and CXCL8 generation by murine peritoneal macrophages, as well as OVA-induced interleukin-5 synthesis by previously sensitized spleen cells. These results demonstrate that U. guianensis leaves provide effective anti-inflammatory and anti-allergic activities.
Subject(s)
Anti-Allergic Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Edema/drug therapy , Macrophages, Peritoneal/drug effects , Pleurisy/drug therapy , Uncaria/chemistry , Animals , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Survival/drug effects , Cells, Cultured , Chemokine CXCL1 , Chemokines, CXC/metabolism , Chemotaxis, Leukocyte/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/immunology , Intercellular Signaling Peptides and Proteins/metabolism , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Pleurisy/immunology , Tumor Necrosis Factor-alpha/metabolism , ZymosanABSTRACT
In the present work, the anti-inflammatory and gastroprotective properties of ethanolic extracts of Stachytarpheta cayennesis (L.C. Rich) Vahl (Verbenaceae) were assessed. Chromatographic analysis of the crude ethanolic extract, SC01, revealed high concentrations of the iridoid ipolamiide, whereas the SC02, the second ethanolic extract, presented the arylpropanoid verbacoside as a major constituent. The oral administration of SC01 (100 mg/kg) into Swiss mice failed to inhibit paw oedema and pleural exudation induced by carrageenan and zymosan, whereas SC02 (100 mg/kg, p.o.) inhibited oedema and protein extravasation in all instances. Both extracts inhibited total leukocyte accumulation into the pleural cavity 4 and 24h after the intrathoracic (i.t.) injection of carrageenan, due to the inhibition of neutrophil and mononuclear cell influx, whereas only SC02 was able to inhibit leukocyte mobilization induced by zymosan (100 microg/cavity, i.t.). SC02 inhibited LPS (250 ng/cavity)-induced total leukocyte, neutrophil and eosinophil accumulation in the pleural cavity, whereas SC01 selectively inhibited neutrophil influx. In addition, our data indicates that the extract SC02 presents an important anti-ulcerogenic activity, since it inhibited diclofenac-induced (100 mg/kg, p.o.) gastric ulcera. Overall, these data provide evidence for the anti-inflammatory and gastroprotective properties of Stachytarpheta cayennensis, supporting its use in folk medicine for such purposes.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Ulcer Agents/therapeutic use , Stomach Ulcer/drug therapy , Verbenaceae , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Edema/drug therapy , Edema/pathology , Male , Mice , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Structures , Stomach Ulcer/pathologyABSTRACT
OBJECTIVE: We investigated the anti-allergic and analgesic properties of an oil and a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet. MATERIALS AND METHODS: Pleurisy, paw and ear edema were induced in Swiss and C57/Bl10 mice mice, whereas thermal hyperalgesia was assessed in Wistar rats (n = 6-10 per group). Values of p < 0.05 were regarded as significant. RESULTS: C. guianensis oil (100 to 400 mg/kg, p.o.) and TNTP (12.5 to 100 mg/kg, p.o.) inhibited pleural exudation, paw and ear edema induced by ovalbumin (OVA) in sensitized mice. TNTP (12.5 to 100 mg/kg, p.o.) also inhibited paw edema induced by histamine, PAF and bradykinin. TNTP (100 mg/kg, p.o.) inhibited prostaglandin E(2) generation in the pleural cavity in response to antigenic challenge. Moreover, C. guianensis oil (100 to 400 mg/kg) and TNTP (12.5 to 100 mg/kg) decreased OVA- and histamine-induced hyperalgesia. CONCLUSION: Taken together, these findings demonstrate the anti-edematogenic and analgesic effects of C. guianensis oil, and points out TNTP as the responsible bioactive compounds.