Yang Zhengtao

The effect of magnolol on the toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced acute lung injury in mice

Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of magnolol on acute lung injury induced by lipopolysaccharide in mice. Male BALB/c mice were pretreated with dexamethasone or magnolol 1 h before intranasal instillation of lipopolysaccharide (LPS). 7 h after LPS administration, the myeloperoxidase in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). The extent of phosphorylation of nuclear factor of inhibitory kappa B alpha (IκB-α), nuclear factor kappa-B (NF-κB) p65 and the expression of Toll-like receptor-4 (TLR4) were detected by western blot. The results showed that magnolol markedly attenuated the histological alterations in the lung; reduced the number of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid; decreased the wet/dry weight ratio of lungs in the bronchoalveolar lavage fluid; down-regulated the level of pro-inflammatory mediators, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. Taken together, our results suggest that anti-inflammatory effects of magnolol against the LPS-induced acute lung injury may be due to its ability of inhibition TLR4 mediated NF-κB signaling pathways. Magnolol may be a promising potential therapeutic reagent for acute lung injury treatment.

Stevioside Suppressed Inflammatory Cytokine Secretion by Downregulation of NF-κB and MAPK Signaling Pathways in LPS-Stimulated RAW264.7 Cells

Stevioside, a diterpene glycoside isolated from Stevia rebaudiana, has been reported to have anti-inflammatory properties. However, the underlying molecular mechanisms are not well understood. The objective of this study was to investigate the molecular mechanism of stevioside in modifying lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 cells. RAW264.7 cells were stimulated with LPS in the presence or absence of stevioside. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) were determined by western blot. The results showed that stevioside dose-dependently inhibited the expression of tumor necrosis factor-α, interleukin-6, and interleukin-1β in LPS-stimulated RAW264.7 cells. Western blot analysis showed that stevioside suppressed LPS-induced NF-κB activation, IκBa degradation, phosphorylation of ERK, JNK, and P38. Our results suggest that stevioside exerts an anti-inflammatory property by inhibiting the activation of NF-κB and mitogen-activated protein kinase signaling and the release of proinflammatory cytokines. These findings suggest that stevioside may be a therapeutic agent against inflammatory diseases.

Chlorogenic acid attenuates lipopolysaccharide-induced mice mastitis by suppressing TLR4-mediated NF-κB signaling pathway

Chlorogenic acid (CGA), one of the most abundant polyphenols in the diet, has been reported to have potent anti-inflammatory properties. However, the effect of CGA on lipopolysaccharide (LPS)-induced mice mastitis has not been investigated. The purpose of the present study was to elucidate whether CGA could ameliorate the inflammation response in LPS-induced mice mastitis and to clarify the possible mechanism. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. CGA was administered intraperitoneally with the dose of 12.5, 25, and 50mg/kg respectively 1h before and 12h after induction of LPS. In this study, the effect of CGA on LPS-induced mice mastitis was assessed through histopathological examination, ELISA assay, and western blot analysis. The results showed that CGA significantly reduced TNF-α, IL-1β, and IL-6 production compared with LPS group. Besides, western blot analysis showed that CGA could inhibit the expression of TLR4 and the phosphorylation of NF-κB and IκB induced by LPS. These results suggested that anti-inflammatory effects of CGA against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathway. Therefore, CGA may be a potent therapeutic reagent for the prevention of the immunopathology encountered during Escherichia coli elicited mastitis.

Magnolol Inhibits the Inflammatory Response in Mouse Mammary Epithelial Cells and a Mouse Mastitis Model

Mastitis comprises an inflammation of the mammary gland, which is almost always linked with bacterial infection. The treatment of mastitis concerns antimicrobial substances, but not very successful. On the other hand, anti-inflammatory therapy with Chinese traditional medicine becomes an effective way for treating mastitis. Magnolol is a polyphenolic binaphthalene compound extracted from the stem bark of Magnolia sp., which has been shown to exert a potential for anti-inflammatory activity. The purpose of this study was to investigate the protective effects of magnolol on inflammation in lipopolysaccharide (LPS)-induced mastitis mouse model in vivo and the mechanism of this protective effects in LPS-stimulated mouse mammary epithelial cells (MMECs) in vitro. The damage of tissues was determined by histopathology and myeloperoxidase (MPO) assay. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and Toll-like receptor 4 (TLR4) were determined by Western blot. The results showed that magnolol significantly inhibit the LPS-induced TNF-α, IL-6, and IL-1β production both in vivo and vitro. Magnolol declined the phosphorylation of IκBα, p65, p38, ERK, and JNK in LPS-stimulated MMECs. Furthermore, magnolol inhibited the expression of TLR4 in LPS-stimulated MMECs. In vivo study, it was also observed that magnolol attenuated the damage of mastitis tissues in the mouse models. These findings demonstrated that magnolol attenuate LPS-stimulated inflammatory response by suppressing TLR4/NF-κB/mitogen-activated protein kinase (MAPK) signaling system. Thereby, magnolol may be a therapeutic agent against mastitis.