stigmasterol and Edema

Stigmasterol is a phytosterol that presents pharmacologic properties. However, its anti-inflammatory mechanism and antinociceptive effect are not yet elucidated. Thus, the present study aimed to investigate the anti-inflammatory and antinociceptive activities of stigmasterol and its mechanism of action in mice. The antinociceptive activity was assessed by the acetic acid-induced writhing test, formalin test, and hot plate test. The anti-inflammatory activity was investigated by carrageenan-induced peritonitis and paw edema induced by arachidonic acid. The involvement of glucocorticoid receptors in the mechanism of stigmasterol anti-inflammatory action was investigated by molecular docking, also by pretreating mice with RU-486 (glucocorticoid receptor antagonist) in the acetic acid-induced writhing test. Mice motor coordination was evaluated by the rota-rod test and the locomotor activity by the open field test. The lowest effective dose of stigmasterol was standardized at 10 mg/kg (p.o.). It prevented abdominal writhes and paw licking, but it did not increase the latency time in the hot plate test, suggesting that stigmasterol does not show an antinociceptive effect in response to a thermal stimulus. Stigmasterol decreased leukocyte infiltration in peritonitis assay and reduced paw edema elicited by arachidonic acid. Molecular docking suggested that stigmasterol interacts with the glucocorticoid receptor. Also, RU-486 prevented the effect of stigmasterol in the acetic-acid abdominal writhing test, which might indicate the contribution of glucocorticoid receptors in the mechanism of stigmasterol action. Stigmasterol reduced the number of crossings but did not impair mice's motor coordination. Our results show that stigmasterol presents anti-inflammatory effects probably mediated by glucocorticoid receptors.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Inflammation; Male; Mice; Mifepristone; Molecular Docking Simulation; Pain; Peritonitis; Receptors, Glucocorticoid; Stigmasterol

Critonia aromatisans (Asteraceae), commonly known as "Chiople", is a cultivated species that is used in Mayan traditional medicine to treat inflammation, joint pain and rheumatism.. To evaluate the in vivo and in vitro anti-inflammatory and immunomodulatory properties of aqueous and organic extracts prepared from Critonia aromatisans leaves.. Methanol, ethyl acetate, methylene chloride, hexanic, and aqueous extracts were obtained from the leaves of C. aromatisans. The anti-inflammatory properties of the extracts were tested in vivo to evaluate their ability to reduce the inflammatory response in the carrageenan-induced hind paw edema model in NIH mice. In addition, to explore the immunomodulatory effects of C. aromatisans, in vitro testing was performed to determine whether C. aromatisans leaf extracts are capable of decreasing macrophage production of nitric oxide (NO), tumour necrosis factor alpha (TNF-α), and cytokines IL-1β, IL-6, and cyclooxygenase 2 (COX-2) without affecting macrophage viability.. Single orally administered doses (100mg/kg or 200mg/kg) of a hexanic extract of C. aromatisans leaves significantly reduced carrageenan-induced paw edema in mice (P<0.001) by 76% and 84%, respectively. The effect of the extract in this model was generally comparable to those of the standard drugs used. In the in vitro determination, the extracts reduced the amount of NO mainly at 500 and 1000μg/mL. Hexanic extract and subfractions C, D, E, and F at 50 and 100μg/mL produced the lowest concentration of mediators in culture supernatants (protein) and at the mRNA/gene level by the significant down-regulation of cytokines. These findings explain some of the anti-inflammatory activity of this species. Purification of fractions C and D allowed the complete identification of cyclocolorenone, stigmasterol and stigmasterol derivatives as some of their main components.. A hexanic extract of C. aromatisans displayed anti-inflammatory effects, validating the traditional practice of Mayan communities wherein an ointment with a petrolatum base, a non-polar substance, is used to treat inflammation. Additionally, C. aromatisans showed strong in vivo and in vitro activity, and one of the mechanisms of its anti-inflammatory response was shown to be inhibition of the production of NO and pro-inflammatory cytokines. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders. The presence of stigmasterol and cyclocolorenone could be the responsibles of the anti-inflammatory activity of this specie. Further studies should be done on the antioxidant and anti-inflammatory properties of cyclocolorenone. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents; Asteraceae; Carrageenan; Cell Line; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Edema; Female; Gas Chromatography-Mass Spectrometry; Immunologic Factors; Inflammation Mediators; Macrophages, Peritoneal; Magnetic Resonance Spectroscopy; Male; Mice; Nitric Oxide; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; RNA, Messenger; Sesquiterpenes; Solvents; Stigmasterol

Chemical investigation of the Red Sea sponge Dragmacidon coccinea led to the isolation of a new nucleoside, dragmacidoside (1), along with eight known compounds: adenosine (2), inosine (3), deoxycytidine (4), methyl-α-d-glucopyranoside (5), clionasterol (6), stigmasterol (7), campesterol (8) and brassicasterol (9). The compounds were isolated from chloroform and ethyl acetate fractions of the methanolic extract of the sponge, and their structures were established based on various spectroscopic data including MS, 1D and 2D NMR (COSY, HSQC and HMBC). Biological testing revealed that the chloroform fraction possesses significant anti-inflammatory activity in the carrageenan-induced hind paw oedema in rats.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Indian Ocean; Marine Biology; Molecular Structure; Nucleosides; Porifera; Rats; Sitosterols; Stigmasterol

Leaves and branches of Machaerium hirtum Vell. (Fabaceae), native to South America, were subjected to phytopharmacological investigation in order to identify its major chemical constituents and evaluate its extracts, fractions and isolated compounds in assays for anti-inflammatory activities. These were performed using mouse ear edema model, pleurisy and myeloperoxidase activity assays. Six compounds were isolated and identified as the flavanones swertisin and isovitexin, the alkaloid 4-hydroxy-N-methylproline, the triterpenes friedelin and lupeol, and the steroids sitosterol and stigmasterol. These compounds were identified by nuclear magnetic resonance of (1)H and (13)C data, in comparison with literature.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Edema; Fabaceae; Magnetic Resonance Spectroscopy; Mice; Pentacyclic Triterpenes; Plant Extracts; Plant Leaves; Proline; Sitosterols; Stigmasterol; Triterpenes

The transient receptor potential vanilloid 1 (TRPV1) receptor is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction also had antioedematogenic effect. Among the compounds isolated from the dichloromethane fraction, only α-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, α-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. α-Spinasterol was able to displace [3H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and α-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with α-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, α-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and α-spinasterol did not affect body temperature or locomotor activity. In conclusion, α-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.

Topics: Analgesics; Animals; Binding, Competitive; Body Temperature; Calcium; Capsaicin; Chromatography, High Pressure Liquid; Diterpenes; Edema; Freund's Adjuvant; Hot Temperature; Male; Mice; Nociceptors; Pain; Pain Measurement; Plant Extracts; Plant Leaves; Stigmasterol; Tissue Distribution; TRPV Cation Channels; Vernonia

The roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the N-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1 β-treated SW1353 cells, a human chondrosarcoma cell line, at 50-200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), β-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1 β-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20-200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders.

Topics: Acetates; Alkynes; Amaranthaceae; Animals; Carrageenan; Cartilage; Cell Line, Tumor; Chondrocytes; Chondrosarcoma; Disease Models, Animal; Dopamine; Down-Regulation; Edema; Humans; Hypolipidemic Agents; Interleukin-1beta; Lactones; Male; Matrix Metalloproteinase 13; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Roots; Sesquiterpenes; Sitosterols; Stigmasterol

Two new lupanes, 2 alpha-acetoxy-3 beta-hydroxy-19 beta-hydrogen-lup-20(29)-en-28-oic acid (2-acetoxyalphitolic acid) ( 1) and 2 alpha-hydroxy-3 beta-acetoxy-19 beta-hydrogen-lup-20(29)-en-28-oic acid (3-acetoxyalphitolic acid) ( 2), together with the known betulinic acid ( 3), betulin ( 4), and stimasterol-3- O- beta- D-glucopyranoside ( 5), were isolated from the leaves and twigs of GARCINIA HANBURYI. Compounds 1- 3 were also isolated from the resin of this plant. The structure of 2 was confirmed by single-crystal X-ray diffraction analysis. All of the lupanes ( 1- 4) displayed anti-HIV-1 activities in the anti-HIV-1 reverse transcriptase (IC (50) values 16.3-116.9 microg/mL) and syncytium assays (EC (50) 5.6-73.6 microg/mL, SI 1.7-3.3). Moreover compounds 1- 4 exhibited anti-inflammatory activity in an ethyl phenylpropiolate (EPP)-induced ear edema model.

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Disease Models, Animal; Edema; Garcinia; Giant Cells; Glucosides; HIV-1; Inflammation; Inhibitory Concentration 50; Molecular Structure; Phytotherapy; Plant Extracts; Plant Leaves; Plant Stems; Resins, Plant; RNA-Directed DNA Polymerase; Stigmasterol; Triterpenes; X-Ray Diffraction

ETHNOPHARMACOLOGYCAL RELEVANCE: The tea from the leaves of Baccharis illinita DC (Asteraceae family) is commonly used by the population as anti-inflammatory (including topically), protective gastric and anti-infectious. However, no studies have been done with this species to confirm its topical anti-inflammatory action.. This study evaluated he topical effects of crude extract of leaves (CE) and its active constituents in 12-O-tetradecanoylphorbol acetate (TPA)-induced ear oedema.. CE and compounds effects were tested in commonly used models of TPA-, arachidonic acid (AA)- and capsaicin-ear oedema. Polymorphonuclear (PMN) cell migration was evaluated by mieloperoxidase and analyzed histologically.. CE (0.1-1 mg/ear) caused a dose-related inhibition of TPA-induced ear oedema and PMN influx similarly to that produced by topical application of the steroidal anti-inflammatory drug dexamethasone. The active constituents of the AcOEt fraction kaurenoic acid, alpha-spinasterol, oleanolic acid and baurenol also inhibited TPA-induced ear edema. Histological analysis of the ear of CE-treated animals confirmed the reduction of edema and of PMN infiltration. Both CE and the nosteroidal anti-inflammatory drug indomethacin inhibited the AA-induced ear oedema, but did not change capsaicin-induced oedema.. These results indicate that the CE and the active constituents have a topical anti-inflammatory effect and the possible mechanisms for the pharmacological effects are discussed.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Baccharis; Capsaicin; Dermatitis, Contact; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Ear; Edema; Male; Mice; Neutrophil Infiltration; Oleanolic Acid; Plant Leaves; Plant Preparations; Stigmasterol; Tetradecanoylphorbol Acetate

A sesquiterpenoid Bakkenolide (1), and two steroids, (3beta, 22E)-Stigmasta-5, 22-diène-3-ol (Stigmasterol) (2) and stigmasterol 3beta-glucoside (3), isolated from the Hertia cheirifolia (L.) chloroform extract, were evaluated respectively for their spasmolytic and anti-inflammatory activities. We note that these natural products were isolated and purified for the first time from the specie Hertia cheirifolia. Their structures have been established by spectroscopy (1 and 2D NMR experiences) and mass spectrometry. Chloroform-, ethyl acetate- and methanol-extracts were also tested for their spasmolytic and anti-inflammatory activities. Spasmolytic and anti-inflammatory screening were based respectively on the contractile response effects on rat isolated smooth muscles and on the dose-related carrageenan induced paw edema in rats. screening of the crude extracts showed spasmolytic and anti-inflammatory positive results. The antispasmodic effect of Bakkenolide was found in the same range as that of Alverine, a standard musculotropic spasmolytic agent.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents; Asteraceae; Carrageenan; Edema; Female; Male; Molecular Structure; Muscle, Smooth; Parasympatholytics; Phytotherapy; Plant Components, Aerial; Plant Extracts; Propylamines; Rats; Rats, Wistar; Sesquiterpenes; Stigmasterol

The analgesic activity of the methanol and acetone extracts of Leucas inflata L. (family Labiatae) was evaluated in mice using different experimental models. The effect of the two extracts on pentobarbitone-sleeping time, motor activity, sensorimotor coordination, carrageen induced inflammation, and brewer's yeast-induced pyrexia has also been investigated. The two crude extracts have been phytochemically analyzed and some constituents isolated and characterized. These included stigmasterols, a chromone and coumarins. Extracts of L. inflata L., given at single oral doses of 0.25, 0.5, 1.0 or 2.0 g/kg, significantly and dose-dependently, reduced formalin-induced pain, acetic acid induced abdominal constrictions and increased the reaction time in the hot-plate test. Both extracts caused significant and dose-related impairment in the sensorimotor control and ambulatory and total motor activity of treated mice. Both extracts exhibited anti-inflammatory action by reducing paw edema of treated mice. The extracts did not significantly affect the rectal temperature of normothermic mice. However, they were effective in preventing Brewers yeast induced pyrexia. It is concluded that the crude methanol and acetone extract of L. inflata has CNS depressant properties, manifested as antinociception and sedation. Both extracts have anti-inflammatory and antipyretic actions.

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Carrageenan; Central Nervous System Agents; Coumarins; Dose-Response Relationship, Drug; Edema; Inflammation; Lamiaceae; Male; Mice; Motor Activity; Phytotherapy; Plant Extracts; Psychomotor Performance; Stigmasterol; Toxicity Tests, Acute

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Chloroform; Chronic Disease; Dexamethasone; Disease Models, Animal; Ear; Edema; Indomethacin; Mice; Peroxidase; Plant Extracts; Plants, Medicinal; Sitosterols; Stigmasterol; Tetradecanoylphorbol Acetate

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Edema; Female; Foot Diseases; Male; Mice; Phytosterols; Rats; Stigmasterol