gamma-sitosterol and Asthma

In most asthma patients, symptoms are controlled by treatment with glucocorticoid, but long-term or high-dose use can produce adverse effects. Therefore, it is crucial to find new therapeutic strategies. β-sitosterol could suppress type Ⅱ inflammation in ovalbumin (OVA)-induced mice, but its mechanisms have remained unclear.. A binding activity of β-sitosterol with glucocorticoid receptor (GR) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) and human bronchial smooth muscle cells (HBSMC) were treated with different concentrations (0, 1, 5, 10, 20, and 50 μg/mL) of β-sitosterol for suitable concentration selection. In transforming growth factor (TGF)-β1 treated BEAS-2B and HBSMC, cells were treated with 20 μg/mL β-sitosterol or dexamethasone (Dex) to analyze its possible mechanism. In OVA-induced mice, 2.5 mg/kg β-sitosterol or Dex administration was performed to analyze the therapeutic mechanism of β-sitosterol. A GR antagonist RU486 was used to confirm the mechanism of β-sitosterol in the treatment of asthma.. A good binding of β-sitosterol to GR (score = -8.2 kcal/mol) was found, and the GR expression was upregulated with β-sitosterol dose increase in BEAS-2B and HBSMC. Interleukin (IL)-25 and IL-33 secretion was significantly decreased by β-sitosterol in the TGF-β1-induced BEAS-2B, and the levels of collagen 1A and α-smooth muscle actin (SMA) were reduced in the TGF-β1-induced HBSMC. In the OVA-challenged mice, β-sitosterol treatment improved airway inflammation and remodeling through suppressing type Ⅱ immune response and collagen deposition. The therapeutic effects of β-sitosterol were similar to Dex treatment in vitro and in vivo. RU486 treatment clearly hampered the therapeutic effects of β-sitosterol in the TGF-β1-induced cells and OVA-induced mice.. This study identified that β-sitosterol binds GR to perform its functions in asthma treatment. β-sitosterol represent a potential therapeutic drug for allergic asthma.

Topics: Airway Remodeling; Animals; Asthma; Collagen; Disease Models, Animal; Humans; Inflammation; Lung; Mice; Mice, Inbred BALB C; Mifepristone; Molecular Docking Simulation; Ovalbumin; Receptors, Glucocorticoid; Sitosterols; Transforming Growth Factor beta1

To investigate the effects of β-sitosterol (B-SIT) and the underlying mechanisms of action in an ovalbumin-induced rat model of asthma.. The pathological and morphological changes in lung and tracheal tissues were observed by H&E, PAS, and Masson's staining. The levels of IgE, TNF-. B-SIT improved the injury in OVA-induced pathology, decreased the levels of inflammatory factors of IgE, TNF-. B-SIT improved symptoms in a rat model of asthma likely

Topics: Animals; Asthma; Dendritic Cells; Interleukin-10; Interleukin-13; Interleukin-5; Interleukin-6; Ovalbumin; Rats; Sitosterols; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

In the present study, the efficacy of β-sitosterol isolated from an n-butanol extract of the seeds of the plant Moringa oleifera (Moringaceae) was examined against ovalbumin-induced airway inflammation in guinea pigs. All animals (except group I) were sensitized subcutaneously and challenged with aerosolized 0.5% ovalbumin. The test drugs, β-sitosterol (2.5mg/kg) or dexamethasone (2.5mg/kg), were administered to the animals (p.o.) prior to challenge with ovalbumin. During the experimental period (on days 18, 21, 24 and 29), a bronchoconstriction test (0.25% acetylcholine for 30s) was performed and lung function parameters (tidal volume and respiration rate) were measured for each animal. On day 30, blood and bronchoalveolar lavaged fluid were collected to assess cellular content, and serum was collected for cytokine assays. Lung tissue was utilized for a histamine assay and for histopathology. β-sitosterol significantly increased the tidal volume (V(t)) and decreased the respiration rate (f) of sensitized and challenged guinea pigs to the level of non-sensitized control guinea pigs and lowered both the total and differential cell counts, particularly eosinophils and neutrophils, in blood and bronchoalveolar lavaged fluid. Furthermore, β-sitosterol treatment suppressed the increase in cytokine levels (TNFα, IL-4 and IL-5), with the exception of IL-6, in serum and in bronchoalveolar lavaged fluid detected in model control animals. Moreover, treatment with β-sitosterol protected against airway inflammation in lung tissue histopathology. β-sitosterol possesses anti-asthmatic actions that might be mediated by inhibiting the cellular responses and subsequent release/synthesis of Th2 cytokines. This compound may have therapeutic potential in allergic asthma.

Topics: Acetylcholine; Animals; Anti-Asthmatic Agents; Asthma; Body Weight; Bronchial Spasm; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cell Count; Cytokines; Disease Models, Animal; Guinea Pigs; Histamine; Inflammation; Lung; Male; Ovalbumin; Respiratory System; Sitosterols; Th2 Cells

Asthma is a disease marked by chronic lung inflammation and the number of patients suffering from asthma increases annually. Both beta-sitosterol (BS) and beta-sitosterol glucoside exist in a variety of plants and have anti-tumor, anti-microbial, and immunomodulatory activities. However, the precise role of BS and beta-sitosterol glucoside in asthma has not been well understood. The aim of this study was to investigate the inhibitory effects of BS and lactose-BS (L-BS) on the pathophysiological process in ovalbumin-induced asthmatic mice. The total cells and eosinophils in the bronchoalveolar lavage (BAL) fluid markedly decreased (p<0.05) after L-BS or BS administration (1 mg/kg; i.p.), and the ROS production also decreased in comparison to the asthma control. Histopathological features were detected by performing histochemistry, including H&E and alcian blue & P.A.S staining. Both L-BS and BS mitigated the inflammation by eosinophil infiltration and mucus hypersecretion by goblet hyperplasia. These effects of L-BS were superior to those of BS. L-BS and BS inhibited the increased mRNA and protein expression of IL-4 and IL-5 in the lung tissue and BAL fluid, respectively. The IgE concentration in the BAL fluid and serum was measured by performing ELISA and the ovalbumin-specific IgE in the BAL fluid was uniquely inhibited by L-BS (p<0.05). The splenocytes were isolated from the normal and asthmatic mice and incubated in the absence and presence of 100 microg/ml ovalbumin, respectively. L-BS blocked the survival rate of the splenocytes of the mice (p<0.01). This finding indicates the possibility of L-BS and BS as potential therapeutic molecules in asthma and may contribute to the need to improve current therapeutic drugs.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cell Survival; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; Gene Expression; Glycosides; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Lactose; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Molecular Structure; Ovalbumin; Pneumonia; Reverse Transcriptase Polymerase Chain Reaction; Sitosterols; Vaccination