chrysoeriol and Disease-Models--Animal

Asthma is a hackneyed chronic inflammatory disease of the airway. Chryseriol (CSR) is a kind of flavonoid, and has the effect of bronchiectasis, indicating its potential application for treating respiratory diseases. However, the functions of CSR in asthma have not been reported till now.. The histopathologic changes of the lung tissues were assessed by hematoxylin and eosin staining. The cell apoptosis was identified through terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Total numbers of eosinophils, neutrophils, and macrophages were assessed under microscope. The levels of interleukin (IL)-1β, IL-4, IL-5, and IL-13 were detected by enzyme-linked-immunosorbent serologic assay. The airway hyper-responsiveness (AHR) was evaluated by the whole body plethysmography. The levels of methane dicarboxylic aldehyde, superoxide dismutase, glutathione S-transferase, and glutathione in lung homogenates were confirmed by using corresponding commercial kits. The protein expressions were examined by Western blot analysis.. The ovalbumin (OVA) was utilized to establish asthma mouse model. At first, it was revealed that CSR treatment reduced lung injury in OVA-stimulated mice. Moreover, cell apoptosis was enhanced after OVA stimulation but was attenuated by CSR treatment. In addition, CSR treatment decreased the infiltration of inflammatory cells and the production of inflammatory factors in OVA-treated mice. Further investigations demonstrated that CSR treatment relieved AHR in OVA-stimulated mice. The oxidative stress was strengthened in OVA-treated mice, but these effects were relieved by CSR treatment. Lastly, it was discovered that CSR treatment retarded nuclear factor kappa B (NF-κB)/hypoxia-inducible factor 1 alpha (HIF-1α) and p38 mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 1 (STAT1) pathways in OVA-triggered asthma mice.. Our findings proved that CSR attenuated the progression of OVA-induced asthma in mice through inhibiting NF-κB/HIF-1α and MAPK/STAT1 pathways. This work might highlight the functions of CSR in the treatment of asthma.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Flavones; Lung; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Ovalbumin; Respiratory Hypersensitivity; STAT1 Transcription Factor

Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells.. This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects.. A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues.. In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1β and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model.. We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Disease Models, Animal; Drug Eruptions; Flavones; Gene Expression Regulation; I-kappa B Proteins; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; NF-kappa B; Nitric Oxide Synthase Type II; RAW 264.7 Cells; STAT3 Transcription Factor; Tetradecanoylphorbol Acetate

Rooibos tea has been widely used for abdominal spasm and diarrhoea. The aim of the present study was to explore the possible mechanism for its use in such ailments. Its aqueous extract (RT) at 0.3-10 mg/ml produced relaxation of spontaneous and low K(+) (25 mM)-induced contractions of rabbit jejunum, with weak effect on high K(+) (80 mM)-induced contractions. In the presence of glibenclamide, relaxation of low K(+)-induced contractions was prevented. Cromakalim inhibited contractions induced by low K(+), but not high K(+), while verapamil did not differentiate in its inhibitory effect on contractions produced by the two concentrations of K(+). RT also exhibited antidiarrhoeal and antisecretory activities in mice. The spasmolytic effect was concentrated in organic fractions. Its constituents, chrysoeriol, orientin and vitexin showed a similar pattern of spasmolytic effects to the extract, while rutin was more like verapamil. So Rooibos tea possesses a combination of dominant K(ATP) channel activation and weak Ca(++) antagonist mechanisms and hence justifies its use in hyperactive gastrointestinal disorders.

Topics: Animals; Apigenin; Aspalathus; Beverages; Diarrhea; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Female; Flavones; Flavonoids; Glucosides; Glyburide; Jejunum; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Parasympatholytics; Plant Extracts; Potassium Channel Blockers; Potassium Channels; Rabbits; Toxicity Tests, Acute

Rooibos tea (Aspalathus linearis) is commonly used for hyperactive gastrointestinal, respiratory and cardiovascular disorders.. The aqueous extract of Rooibos tea (RT) was studied for the possible bronchodilator, antispasmodic and blood pressure lowering activities in an attempt to rationalize some of its medicinal uses.. Isolated tissue preparations, such as rabbit jejunum, aorta and guinea-pig trachea and atria were set up in appropriate physiological salt solutions and aerated with carbogen. For in vivo studies rats were anesthetized with pentothal sodium and blood pressure was measured through carotid artery cannulation.. In jejunum, RT caused a concentration-dependent relaxation of low K(+) (25 mM)-induced contractions, with mild effect on the contractions induced by high K(+) (80 mM). In presence of glibenclamide, the relaxation of low K(+)-induced contractions was prevented. Similarly, cromakalim caused glibenclamide-sensitive inhibition of low K(+), but not of high K(+), while verapamil did not differentiate in its inhibitory effect on contractions produced by the two concentrations of K(+). Like in jejunum, RT caused glibenclamide-sensitive relaxation of low K(+)-induced contractions in trachea and aorta, but with a 20 times higher potency in trachea. In atria, RT was least potent with weak inhibitory effect on atrial force and rate of contractions. RT caused a dose-dependent fall in arterial blood pressure in rats under anesthesia. Among the tested pure compounds of Rooibos, chrysoeriol showed selective bronchodilator effect. Chrysoeriol (luteolin 3'-methyl ether) is a bioactive flavonoid known for antioxidant, antiinflammatory, antitumor, antimicrobial, antiviral, and free radical scavenging activities.. These results indicate that the bronchodilator, antispasmodic and blood pressure lowering effects of Rooibos tea are mediated predominantly through K(ATP) channel activation with the selective bronchodilatory effect. This study provides a sound mechanistic basis for the wide medicinal use of Rooibos tea, with the therapeutic potential to be developed for congestive respiratory ailments.

Topics: Animals; Antihypertensive Agents; Aorta; Aspalathus; Bronchodilator Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flavones; Flavonoids; Glyburide; Guinea Pigs; Jejunum; Male; Muscle Contraction; Plant Extracts; Potassium Channels; Rabbits; Rats; Rats, Sprague-Dawley; Tea; Tissue Culture Techniques; Trachea