sophoricoside and Disease-Models--Animal

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Administration, Oral; Animals; Disease Models, Animal; Dopaminergic Neurons; Mammals; Mice; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; Neuroprotective Agents; NF-kappa B; Parkinson Disease

Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1β and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.

Topics: Acute Lung Injury; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Benzopyrans; Cytokines; Disease Models, Animal; Inflammation Mediators; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase Type II; Pneumonia; RAW 264.7 Cells; Signal Transduction

Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4

Topics: Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Benzopyrans; CD4-Positive T-Lymphocytes; Cell Degranulation; Cell Differentiation; Cells, Cultured; Cytokines; Disease Models, Animal; Histamine Release; Immunoglobulins; Inflammation Mediators; Lung; Mast Cells; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Sophora

Abnormal immune responses, specifically excessive differentiation of Th2 cells, are associated with the development of atopic dermatitis (AD). Sophoricoside, the genistein-4'-β-D-glucoside isolated from Styphnolobium japonicum, has previously demonstrated anti-inflammatory and immunosuppressive effects along with IL-3 and IL-5 inhibitory activities. Therefore, we speculated that sophoricoside could regulate AD by regulating abnormal immune responses.. To investigate the role of sophoricoside on AD-like allergic skin inflammation induced by ovalbumin (OVA) or 2,4,6-trinitrochlorobenzene (TNCB) in mouse models.. Sophoricoside was isolated from the 70% ethanol extract of S. japonicum dried mature seeds. After being submitted to a purification process, its purity was assessed by high-performance liquid chromatography (HPLC). The effects of sophoricoside were determined in vivo by OVA- and TNCB-induced AD-like allergic skin inflammation in mice. Skin tissues were subjected with hematoxylin-eosin (H&E), Giemsa and toluidine blue staining. In vitro CD4. Topical application of sophoricoside decreased the symptoms of AD-like allergic skin inflammation, including elevated hypertrophic scars with spongiotic epidermis, epidermal hyperplasia, hyperkeratosis, infiltration of immune, and mast cells, dermal thickness, amounts of immunoglobulins, and pro-inflammatory cytokines, and the mast cell population in the skin. Sophoricoside also decreased T cell antigen receptor (TCR)-mediated immune responses. In particular, sophoricoside suppressed the differentiation of naïve CD4. Sophoricoside can improve AD-like allergic skin diseases mainly by inhibiting pathogenic CD4

Topics: Animals; Benzopyrans; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Fabaceae; Female; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Picryl Chloride; Skin; T-Lymphocytes, Helper-Inducer; Th2 Cells

The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure.. Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination.. Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy.. Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.

Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Benzopyrans; Cardiomegaly; Cell Size; Cells, Cultured; Disease Models, Animal; Enzyme Activation; Enzyme Activators; Fibrosis; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Myocytes, Cardiac; Rats, Sprague-Dawley; Signal Transduction