forsythoside-b and Disease-Models--Animal

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl

Topics: Animals; Caffeic Acids; Carbon Tetrachloride; Cells, Cultured; Disease Models, Animal; Gene Knockdown Techniques; Glucosides; Hepatic Stellate Cells; Humans; Immunohistochemistry; Liver Cirrhosis; Liver Cirrhosis, Experimental; Male; Mice; Mice, Inbred C57BL; Phenylacetates; RNA, Messenger; RNA, Small Interfering; TRPV Cation Channels; Up-Regulation

Acute lung injury (ALI), which is mainly triggered by infection, pneumonia, vasculitis, and sepsis, has no specific and effective therapy except for primary supportive treatment or bedside care. Excessive inflammation caused by innate immune cells is the major characteristic of ALI. Forsythoside B, a phenylethanoside compound, possesses good antioxidant and anti-bacterial properties in vivo and in vitro. In this study, the therapeutic potential of forsythoside B and its mechanism of action were investigated in a lipopolysaccharide (LPS)-induced ALI mouse model. The results showed that LPS-induced edema exudation and lung pathological changes in mice were significantly suppressed by forsythoside B pre-treatment. Furthermore, it also attenuated lung inflammation caused by LPS stimulation, evidenced by decreased inflammatory cell infiltration and down-regulated expression of cytokines, chemokines, and inducible enzymes. The anti-inflammation property of forsythoside B was confirmed in vitro using LPS-stimulated RAW 264.7 macrophages. Moreover, it alleviated LPS-induced inflammation by inhibiting the activation of TLR4/NF-κB signaling pathway in vivo and in vitro. In conclusion, the results demonstrated that forsythoside B protects against LPS-induced ALI by attenuating inflammatory cell infiltration and suppressing TLR4/NF-κB-mediated lung inflammation. Therefore, it might be a potential therapeutic agent for ALI caused by sepsis.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Caffeic Acids; Cytokines; Disease Models, Animal; Female; Glucosides; Inflammation; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Mice, Inbred BALB C; NF-kappa B; RAW 264.7 Cells; Signal Transduction; Toll-Like Receptor 4

The present study was to investigate the neuroprotective efficacy and mechanism of Forsythoside B. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 1 h followed by reperfusion for 23 h. Rats received an intravenous bolus injection of Forsythoside B at 15 min after reperfusion. The results showed that Forsythoside B at doses higher than 8 mg/kg produced a significant neuroprotective potential in cerebral ischemia and reperfusion rats. Forsythoside B (20 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 5 h after cerebral ischemia and reperfusion. Forsythoside B 20 mg/kg attenuated histopathological damage as demonstrated by smaller brain infarct size and brain edema, decreased cerebral Evans blue extravasation and myeloperoxidase (MPO) activity, inhibited cerebral phosphor-IkappaB-alpha and nuclear transcription factors kappaB (NF-kappaB) expression. Meanwhile, NF-kappaB expression with immunohistochemical staining was reduced, while circulating polymorphonuclear leukocytes was increased. All of these findings suggested that Forsythoside B exerted potent neuroprotective effects with a favorable therapeutic time-window, reduce of cerebral ischemia and reperfusion injury degree, attenuating blood-brain barrier (BBB) breakdown, and its protective effects may be due to inhibition of inflammatory response.

Topics: Animals; Anti-Inflammatory Agents; Antigens, Nuclear; Brain Infarction; Brain Ischemia; Caffeic Acids; Disease Models, Animal; Evans Blue; Extravasation of Diagnostic and Therapeutic Materials; Glucosides; Glycosides; Leukocytes; Male; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; NF-kappa B; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury