orientin and Disease-Models--Animal

Oxidative stress and inflammatory responses are nearly involved in the pathogenesis of various diseases, including acute lung injury (ALI). Orientin (Ori), a flavonoid component extracted from natural plants, displayed anti-inflammatory and antioxidant properties in our previous studies. In the current study, we aimed to investigate the amelioration effect of Ori on lipopolysaccharide (LPS)-induced ALI, and we further explored the potential molecular mechanisms. The present results indicated that Ori effectively alleviated LPS-induced ALI by improving the histological changes of lung; decreasing the lung W/D ratio and protein levels, the release of inflammatory cells and cytokines into the bronchoalveolar lavage fluid (BALF); inhibiting nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and high mobility group box 1 (HMGB1) protein expression; reducing malondialdehyde (MDA) formation and reactive oxygen species (ROS) generation; and increasing the content of glutathione (GSH) and superoxide dismutase (SOD) contents. Moreover, Ori treatment not only significantly suppressed the LPS-induced nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, and nuclear factor-kappa B (NF-κB) signaling pathway activation, but also obviously restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD (P) H: quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic (GCLC), and heme oxygenase 1 (HO-1) expression in the lung; all of which are reduced by LPS. Taken together, these data suggested that Ori plays an important role in the protection against ALI by suppressing inflammation and oxidative stress which may be strongly related to the suppression of NLRP3 inflammasome and NF-κB activation, as well as the upregulation of the Nrf2 signaling pathway.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Disease Models, Animal; Flavonoids; Glucosides; Inflammasomes; Lipopolysaccharides; Lung; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pneumonia; Signal Transduction

Neuropathic pain affects patients worldwide. The therapeutic effects of current methods are still poor. This study was performed to investigate the neuro-protective effect of orientin in rats with spinal nerve ligation (SNL). In this study, the paw mechanical withdrawal threshold (PWT) and the paw thermal withdrawal latency (PWL) behavioral assays indicated that orientin alleviated the warm and mechanical allodynia in rats with SNL. The enzyme-linked immunosorbent assay (ELISA) showed that orientin suppressed the levels of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) and increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10). Malondialdehyde (MDA) levels were down-regulated while superoxide dismutase (SOD) and glutathione (GSH) levels were up-regulated by orientin. OX42 and GFAP immune fluorescent staining results demonstrated that orientin inhibited the activation of microglia and astrocytes in rats with SNL. Western blot analysis indicated that the neuroprotective effect of orientin was mediated by inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappa B) signaling pathway. This study suggested that orientin is a promising neuroprotective agent suitable for therapy for neuropathic pain.

Topics: Animals; Astrocytes; Behavior, Animal; Cytokines; Disease Models, Animal; Flavonoids; Glucosides; Humans; Inflammation Mediators; Ligation; Microglia; Neuralgia; Neuroprotective Agents; NF-kappa B; Poaceae; Postoperative Complications; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Nerves; Toll-Like Receptor 4

Thrombocytopenia or chronic depletion of platelets in blood, could create life-threatening conditions in patients who receive aggressive systemic radiation and chemotherapy. Currently there are no approved agents for the rapid treatment of thrombocytopenia. In the present study, we demonstrate that administration of Orientin, a glycosidic flavonoid or dietary administration of Orientin containing Tulsi (Holy Basil) leaves, results in a significant increase in circulating platelets in a clinically relevant mouse model. No noticeable effects were observed on red blood cells, white blood cells or other hematologic parameters in treated animals indicating that Orientin specificity enhances platelet formation. The gene expression and immunophenotyping of bone marrow revealed that Orientin stimulates megakaryopoiesis specific transcriptional program. A significant increase in colony formation in bone marrow cells from Orientin pretreated mice further complemented the effect of Orientin on progenitor cells. The ex-vivo differentiation of irradiated human peripheral blood CD34

Topics: Animals; Blood Platelets; Bone Marrow Cells; Cell Differentiation; Dietary Supplements; Disease Models, Animal; Flavonoids; Gene Expression Regulation; Glucosides; Humans; Mice; Ocimum sanctum; Phytochemicals; Thrombocytopenia; Thrombopoiesis

Orientin has been reported to have extensive pharmaceutical effects of antioxidant, anti-inflammatory, antithrombosis, antiapoptosis, and so on. In the present study, we tried to investigate the protective effects of orientin on cerebral ischemia-reperfusion (I/R) injury and explored the possible mechanisms.. Middle cerebral artery occlusion rat model was established and then treated with low, middle, and high concentrations of orientin, respectively, with edaravone as a positive control. The treatment effect of orientin was evaluated by measuring the neurological deficit score, cerebral infarction, brain edema, oxidative stress, excitatory amino acids release, the expression levels of aquaporin-4 (AQP-4), and related inflammatory molecules using different methods including immunohistochemistry, enzyme-linked immunosorbent assay, real-time PCR, and western blot. Moreover, morphological and structural changes were also observed by hematoxylin-eosin staining and transmission electron microscope.. Orientin provided a significant reduction on neurological deficits, cerebral infarction, cerebral edema, oxidative damage, and neurotoxicity of excitatory amino acids compared to model group (P < .05) in a dose-dependent manner. In addition, orientin substantially downregulated AQP-4 and inflammatory factors expression (P < .05) and improved cell morphology and structure in rats following I/R injury.. Orientin was able to mediate noticeable protection against cerebral I/R injury through the attenuation of oxidative stress and neurotoxicity of amino acids and inhibiting the upregulation of AQP-4 and inflammatory cytokines.

Topics: Animals; Aquaporin 4; Brain; Brain Edema; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids; Glucosides; Male; Neuroprotective Agents; NF-kappa B; Oxidative Stress; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Oxidative stress is involved in chronic stress-induced depression and the disruption of neurotransmission and neuroplasticity. Recently, orientin, a phenolic compound abundant in some fruits, millet, and herbs, has been shown to have antioxidant properties. This study investigated the potential antidepressant effects of orientin against chronic stress and its underlying mechanisms.. The chronic unpredictable mild stress (CUMS) model was used to investigate the effects of orientin on behavior and biochemical alterations in mice. After 2 weeks of the CUMS protocol, the mice were treated with orientin (20 mg/kg and 40 mg/kg, oral gavage) for 3 weeks. Administration of orientin significantly alleviated the CUMS-induced depression-like behavior, including sucrose preference reduction, locomotor activity decline, and hypomotility. Orientin treatment attenuated the oxidative stress markers and increased the concentrations of serotonin and norepinephrine in the hippocampus and prefrontal cortex of CUMS mice. Orientin treatment also increased the brain-derived neurotrophic factor and synapse-associated proteins (synaptophysin and postsynaptic density protein 95) of CUMS mice.. Orientin exerts antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity. Therefore, supplementation with orientin-enriched food or fruit could be beneficial as a preventive strategy for chronic stress-induced depression.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain-Derived Neurotrophic Factor; Depression; Disease Models, Animal; Flavonoids; Glucosides; Hippocampus; Male; Mice; Neuronal Plasticity; Norepinephrine; Oxidative Stress; Serotonin; Stress, Psychological; Synaptic Transmission

Lagenaria siceraria (Molina) Standl. (Cucurbitacae) (LS) has been reported to possess cardioprotective, antihyperlipidemic, and diuretic activities.. To evaluate antihypertensive and cardioprotective effects of the Lagenaria siceraria fruit powder in N(G)-nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats.. Male Wistar rats were divided in four groups. Control 2% gum acacia p.o., L-NAME (40 mg/kg p.o.), LS (500 mg/kg p.o.) + L-NAME (40 mg/kg p.o.), L-arginine (100 mg/kg p.o.) + L-NAME (40 mg/kg p.o.). Treatment period was 4 weeks. On day 29 serum marker enzymes, cholesterol and heamodynamic parameters were measured. Histology of heart was performed. LS powder was characterized by HPLC.. Systolic blood pressures were increased by L-NAME (p < 0.001). In both drug treated groups systolic and diastolic blood pressures were reduced significantly (p < 0.001) compared to L-NAME. In L-NAME group significantly (p < 0.01) elevated cholesterol which was reduced (p < 0.05) by LS treatment. In L-NAME group inflammation and necrosis (0-35%) was present in heart whereas there was no change in myocardium of LS and L-arginine treated rats. Vitexin, orientin and isoorientin were detected in methanol extract of LS powder.. L-NAME induced hypertension in rats was reduced by treatment with LS. The absence of necrosis, inflammation in the heart and significant reduction in serum cholesterol in LS and L-arginine treated rats indicated cardioprotective activity. Antioxidant activity of orientin and isoorientin appears to reduce the L-NAME induced damage. It is concluded that LS fruit possess antihypertensive and cardioprotective activity.

Topics: Animals; Antihypertensive Agents; Antioxidants; Apigenin; Blood Pressure; Cardiotonic Agents; Cholesterol; Chromatography, High Pressure Liquid; Cucurbitaceae; Disease Models, Animal; Flavonoids; Fruit; Glucosides; Hypertension; Inflammation; Luteolin; Male; NG-Nitroarginine Methyl Ester; Plant Extracts; Rats; Rats, Wistar

To study the protective effects of orientin against myocardial ischemia and hypoxia in rats.. The protective effect of orientin against myocardial ischemia and hypoxia was observed in mice by recording their survival time under closed normobaric hypoxia and time of cardiac electric disappearance due to trachea clamping, in rabbits by evaluating arachidonic acid (AA)-induced blood platelet aggregation, in guinea pigs by measuring the coronal flow in the isolated heart and in SD rats with myocardial ischemia induced by pituitrin injection.. Orientin (1, 2, 4 mg/kg) significantly prolonged the survival time of mice under closed normobaric hypoxia and the gasping duration induced by decapitation. Orientin at concentrations of 3, 10, and 30 micromol/L also inhibited AA-induced blood platelet aggregation in rabbits and increased coronal flow in the isolated heart of guinea pigs. At 0.75, 1.5, and 3.0 mg/kg, orientin significantly antagonized pituitrin-induced ECG changes.. Orientin may offer protection against myocardial ischemia and hypoxia in animal models in dose-dependent fashions.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Female; Flavonoids; Glucosides; Guinea Pigs; Hypoxia; Male; Mice; Myocardial Ischemia; Platelet Aggregation; Rabbits; Rats; Survival Rate

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