stigmasterol and Inflammation

Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.. The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.. The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 μg/mL and 20 μg/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 μM WIN62577 (NK1-R specific antagonist), and 1 μM recombinant human NK1-R protein were applied.. NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 μg/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted anti-inflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL-13-induced BEAS-2B. Meanwhile,. The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Humans; Inflammation; Interleukin-13; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Neurokinin-1; Respiratory Hypersensitivity; Stigmasterol

Topics: Animals; Inflammation; Mice; Molecular Docking Simulation; Phytosterols; Psoriasis; Sitosterols; Stigmasterol; Swine

Osteoarthritis (OA) is the most prevalent joint disease predominantly characterized by inflammation which drives cartilage destruction. Mesenchymal stem cells-condition medium (MSC-CM) or the secretome is enriched with bioactive factors and possesses anti-inflammatory and regenerative effects. The present study aimed at evaluating the effects of combining MSC-conditioned medium with stigmasterol compared with the individual treatments in alleviating interleukin-1 beta (IL-1β)-induced inflammation in rat chondrocytes. Stigmasterol is a phytosterol exhibiting anti-inflammatory effects. IL-1β (10 ng/ml) was used to induce inflammation and mimic OA in-vitro in primary rat articular chondrocytes. The IL-1β-stimulated chondrocytes were treated with MSC-CM, stigmasterol, and a combination of MSC-CM and stigmasterol for 24 h. Cell viability was measured using MTT assay. Protein expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), collagen II (COL2A1) and matrix metalloproteinase (MMP)-13 were evaluated by immunofluorescence. Gene expression levels of MMP-3, MMP-13 and A Disintegrin-like and Metalloproteinases with Thrombospondin Motifs (ADAMTS)-5 were measured using qRT-PCR. NF-κB signaling pathway was studied using western blotting. A significant reduction in the expression of iNOS, IL-6, MMP-3, MMP-13 and ADAMTS-5, and a significant increase in COL2A1 expression was observed in the rat chondrocytes across all the treatment groups. However, the combination treatment of MSC-CM and stigmasterol remarkably reversed the IL-1β-induced pro-inflammatory/pro-catabolic responses to near normal levels comparable to the control group. The combination treatment (MSC-CM + stigmasterol) elicited a superior anti-inflammatory/anti-catabolic effect by inhibiting the IL-1β-induced NF-κB activation evidenced by the negligible phosphorylation of p65 and IκBα subunits, thereby emphasizing the benefit of the combination therapy over the individual treatments.

Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Combined Modality Therapy; Disease Models, Animal; Female; Inflammation; Interleukin-1beta; Mesenchymal Stem Cells; NF-kappa B; Osteoarthritis; Rats; Rats, Wistar; Secretome; Stigmasterol

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

Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.

Topics: Animals; Diabetes Mellitus; Gene Expression; Hypothalamus; Inflammation; Linoleic Acid; Male; Mice; Nervous System Diseases; Obesity; Oxytocin; Soybean Oil; Stigmasterol

A new peroxy fatty acid, tagetnoic acid (

Topics: Fatty Acids; Humans; Inflammation; Lipoxygenase Inhibitors; Molecular Docking Simulation; Plant Extracts; Protein Binding; Saudi Arabia; Stigmasterol; Tagetes; Thiophenes

Particulate matter (PM) air pollution has gradually become a widespread problem in East Asia. PM may cause unfamiliar inflammatory responses, oxidative stress, and pulmonary tissue damage, and a comprehensive understanding of the underlying mechanisms is required in order to develop effective anti-inflammatory agents. In this study, fine dust collected from Beijing, China (CPM) (size < PM13 with majority < PM2.5) was evaluated for its oxidative stress- and inflammation-inducing effects, which cause cell damage, in A459 human lung epithelial cells. Oxidative stress was marked by an increase in intracellular ROS levels and the production of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1). Upon induction of oxidative stress, a marked increase was observed in the expression of key inflammatory mediators such as COX-2 and PGE

Topics: A549 Cells; Air Pollutants; Anti-Inflammatory Agents; Beijing; China; Epithelial Cells; Humans; Inflammation; Lung; Lung Diseases; Lung Injury; Oxidative Stress; Particulate Matter; Sargassum; Stigmasterol

Increased levels of particulate matter (PM) air pollutants in East Asia have resulted in detrimental health impacts increasing morbidity and mortality. Epidemiological studies suggest a possible relation between the cutaneous exposure of PM and increased oxidative stress and inflammation which lead to skin lesions. The present study utilizes an integrated cell culture model of keratinocytes and fibroblasts to mimic viable skin layers and investigate the possible effects of PM exposure after penetration through corneocytes. The skin perfection is upheld by homeostatic functionality of epidermal cells and the integrity of connective tissues. Exposure to xenobiotics could alter the skin cell homeostasis aggravating premature skin aging. Stimulation of HaCaT keratinocytes by PM collected from Beijing, China (CPM) increased the intracellular ROS levels triggering a cascade of events aggravating inflammatory responses and connective tissue degradation. In HDF fibroblasts, treatment with preconditioned keratinocyte culture media augmented inflammatory responses, cellular differentiation, and connective tissue degradation. Above events were marked by the increased intracellular ROS, inflammatory mediators, pro-inflammatory cytokines, matrix metalloproteinases (MMP)-1 and -2 levels, collagenase, and elastase activity. Fucosterol treatment of keratinocytes dose-dependently attenuated the detrimental effects both in keratinocytes and fibroblasts restoring the conditions near to physiological levels. Further evaluations could be advanced on developing fucosterol, in forms such as rejuvenating cosmeceuticals which could attenuate detrimental responses of CPM exposure.

Topics: Air Pollutants; Cells, Cultured; Coculture Techniques; Cytokines; Fibroblasts; Humans; Inflammation; Keratinocytes; NF-kappa B; Oxidative Stress; Particulate Matter; Reactive Oxygen Species; Skin; Skin Diseases; Stigmasterol

Topics: Analgesics; Anti-Inflammatory Agents; Apocynaceae; Cytokines; Fatty Acids, Unsaturated; Glucosides; Humans; Inflammation; Interleukin-6; Leukocytes, Mononuclear; Lipopolysaccharides; Macrophages; Molecular Docking Simulation; Nociceptive Pain; Pain Perception; Plant Extracts; Plant Roots; Sitosterols; Steroids; Stigmasterol; Tumor Necrosis Factor-alpha

We explored the potential benefits of stigmasterol in the treatment of asthma, an airway disorder characterized by immune pathophysiology and with an ever-increasing worldwide prevalence. We assessed the modulatory effect of the intraperitoneal administration of stigmasterol on experimentally induced airway inflammation in guinea pigs. The effect of stigmasterol on inflammatory cell proliferation, oxidative stress, lung histopathology, and remodeling was investigated. The results showed significant suppressive effects on ovalbumin-induced airway inflammatory damage. Stigmasterol at 10-100 mg/kg reduced proliferation of eosinophils, lymphocytes, and monocytes while reducing peribronchiolar, perivascular, and alveolar infiltration of inflammatory cells. Histopathology revealed stigmasterol maintained lung architecture and reversed collagen deposition, an index of lung remodeling. Overexpression of serum vascular cell adhesion molecule-1 (VCAM-1) and ovalbumin-specific immunoglobulin E (OVA sIgE) elicited by ovalbumin sensitization and challenge was significantly controlled with stigmasterol. Taken together, stigmasterol possessed significant antiasthmatic properties and had suppressive effects on key features of allergen-induced asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Catalase; Cell Movement; Disease Models, Animal; Eosinophils; Female; Glutathione; Guinea Pigs; Immunoglobulin E; Inflammation; Leukocyte Count; Lung; Male; Malondialdehyde; Ovalbumin; Oxidative Stress; Stigmasterol; Superoxide Dismutase; Vascular Cell Adhesion Molecule-1

Stigmasterol is a naturally occurring steroid alcohol which occurs in vegetables, soya and a large variety of medicinal plants. Stigmasterol and other phytosterols have been documented as immunomodulators with huge therapeutic potential. We assessed the mitigating effect of stigmasterol on non-fatal and fatal innate immune responses in murine models after intraperitoneal challenge with an endotoxin, lipopolysaccharide, LPS. The effect of stigmasterol on LPS-induced febrile response, inflammatory cell proliferation, multiple organ damage and mortality were respectively investigated. Pretreatment with stigmasterol 10, 50 and 100mg/kg reduced total LPS-induced fever response by 39.93±10.52%, 53.05±5.84% and 77.27±6.25% respectively. Neutrophil proliferation both in blood and recovered peritoneal fluid was significantly reversed by stigmasterol at 50 and 100mg/kg. Lung and liver histopathology showed stigmasterol effectively controlled organ damage. The lung inflammation score of 9.20±0.73 for the polyethylene glycol, PEG-treated disease control mice was reduced respectively to 6.50±0.54, 4.60±0.40 and 4.10±0.42 with 10, 50 and 100mg/kg of stigmasterol. Serum levels of liver enzyme markers, alanine transaminase, ALT and aspartate transaminase, AST were consistent with the observed histological changes. Stigmasterol at 50 and 100mg/kg significantly protected mice from LPS-induced mortality with 40% survival. Overall, stigmasterol inhibits LPS-induced innate immune responses in murine models.

Topics: Alanine Transaminase; Animals; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Female; Fever; Humans; Immunity, Innate; Inflammation; Injections, Intraperitoneal; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; Neutrophils; Rats; Rats, Wistar; Stigmasterol

Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported.. We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions.. Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03).. Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholesterol; Female; gamma-Glutamyltransferase; Humans; Infant; Inflammation; Intestinal Diseases; Liver; Male; Parenteral Nutrition; Phytosterols; Plant Oils; Portal Vein; Sitosterols; Stigmasterol; Triglycerides

Fucosterol is a phytosterol commonly extracted from algae. It has been proved that fucosterol possesses antioxidant activity that is capable of scavenging the free radicals causing skin damages. In this study, we investigated the protective mechanisms of fucosterol on cobalt chloride (CoCl2) induced hypoxia damages to keratinocytes (HaCaT). We found that fucosterol inhibited CoCl2 induced cytotoxicity and inflammation in a dose-dependent manner. Furthermore, fucosterol attenuated CoCl2 induced excess expression of IL-6, IL-1β and TNF-α in HaCaT cells. In addition, fucosterol surpressed the phosphorylation of PI3K and Akt and accumulation of HIF1-α simulated by CoCl2. Taken together, these results suggested that fucosterol executed its protective effects against CoCl2 induced cytotoxicity and inflammation by the inhibition of hypoxia inducible factor through PI3K/Akt pathway.

Topics: Cell Line; Chromones; Cobalt; Cytokines; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Keratinocytes; Morpholines; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Stigmasterol

To investigate the active chloroform fraction of the ethanol extract of Ipomoea carnea flowers on hematological changes in toluene diisocyanate-induced inflammation in Wistar rats.. Except for the control group, all of the rats were sensitized with intranasal application of 5 μL of 10% toluene diisocyanate (TDI) for 7 days. One week after second sensitization, all of the rats were provoked with 5 μL of 5% TDI to induce airway hypersensitivity. After the last challenge, blood and bronchoalvelor lavage (BAL) fluid were collected and subjected to total and differential leucocytes count. Flash chromatography was performed on the most active chloroform fraction to isolate an individual component.. Treatment with the ethanolic extract and its chloroform fraction at an oral dose of 200 mg·kg⁻¹ showed a significant decrease in circulating neutrophil and eosinophil in blood and BAL as compared with standard dexamethasone (DEXA). The structure of the compound obtained from chloroform fraction of Ipomea carnea was elucidated as stigmast-5, 22-dien-3β-ol on the basis of spectral data analysis.. The chloroform fraction was found to be more effective to suppress airway hyper reactivity symptoms, and decreased count of both total and differential inflammatory cells.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Eosinophils; Female; Flowers; Hematology; Inflammation; Ipomoea; Leukocyte Count; Male; Molecular Structure; Neutrophils; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Stigmasterol; Toluene 2,4-Diisocyanate

Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Cell Line; Chlorocebus aethiops; Cholestanones; Epithelial Cells; Herpesvirus 1, Human; Humans; Inflammation; Interferon-gamma; Interleukin-6; Mice; Stigmasterol; Vero Cells; Virus Replication

Human diets contain sterol oxidation products that can induce cytotoxic effects, mainly caused by cholesterol oxides. However, phytosterol oxides effects have been less extensively investigated. This study evaluates the production of inflammatory biomarkers (IL-1β, IL-8, IL-10, TNFα) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells. These effects were linked to intracellular signaling pathways by using several inhibitors. Results showed 7-ketostigmasterol to have a greater proinflammatory potential than 7-ketocholesterol. In non-pre-treated cells, only efflux transporters were down-regulated by 7-ketosterols, showing a greater influence upon ABCG5 expression. Cell-pre-incubation with bradykinin induced changes in ABCG expression levels after 7-ketostigmasterol-incubation; however, the energetic metabolism inhibition reduced NPC1L1 expression only in 7-ketocholesterol-incubated cells. In non-pre-treated cells, HMG-CoA was up-regulated by both 7-ketosterols. However, exposure to inhibitors down-regulated the expression levels, mainly in 7-ketocholesterol-incubated cells. While ACAT expression values in non-pre-treated cells were unchanged, exposure to inhibitors caused down-regulation of mRNA levels. These results suggest that internalization and excretion of 7-ketostigmasterol is probably influenced by [Ca]i, which also could mediate HMGCoA activity in POPs metabolism. However, energetic metabolism and reducing equivalents exert different influences upon the 7-ketosterol internalization.

Topics: Acetyl-CoA C-Acetyltransferase; Acyl Coenzyme A; Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP-Binding Cassette Transporters; Biological Transport; Biomarkers; Bradykinin; Caco-2 Cells; Down-Regulation; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-8; Ketocholesterols; Lipoproteins; Membrane Proteins; Membrane Transport Proteins; RNA, Messenger; Stigmasterol; Tumor Necrosis Factor-alpha; Up-Regulation

Polygala cyparissias, used in folk medicine as an anaesthetic, has already demonstrated antinociceptive activity against acute pain. In this study, we investigated the antihyperalgesic activity of the P. cyparissias methanol extract (PCME) from which the following compounds were isolated: α-spinasterol (PC1), 1,3-dihydroxy-7-methoxyxanthone (PC2), 1,7-dihydroxy-2,3-methylenedioxyxanthone (PC3) and 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (PC4). The antihyperalgesic effect was evaluated using experimental models of persistent pain induced by carrageenan, lipopolysaccharide (LPS), Freund's Complete Adjuvant (CFA), PGE(2) or epinephrine. The partial ligation of the sciatic nerve (PLSN) model was also used. In inflammatory hyperalgesia induced by carrageenan, LPS, CFA or PGE(2), the inhibition values obtained with the PCME treatment were 68 ± 3%, 89 ± 5%, 43 ± 3% and 40 ± 4%, respectively. In epinephrine-induced hyperalgesia, the extract was effective, reducing 99 ± 11% of response frequency, while in PLSN, 54 ± 4% of inhibition was obtained. These results allow to suggest that the antihyperalgesic activity of PCME is, at least in part, related to its capability to inhibit the hypersensitization induced by pro-inflammatory mediators, such as LPS, carrageenan and CFA, without interfering with locomotor activity or motor performance. Furthermore, compounds PC1, PC3 and PC4 inhibited the carrageenan-induced hyperalgesia with inhibition of 42 ± 6%, 48 ± 5% and 64 ± 4%, respectively. In summary, our data demonstrate that PCME has relevant antihyperalgesic activity and that the isolated PC1, PC3 and PC4 seem to be responsible, at least in part, for this important effect.

Topics: Analgesics; Animals; Carrageenan; Disease Models, Animal; Drug Evaluation, Preclinical; Epinephrine; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Lipopolysaccharides; Medicine, Traditional; Methanol; Mice; Neuralgia; Pain; Plant Extracts; Polygala; Sciatic Nerve; Stigmasterol; Xanthones

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

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