Lanan Wassy Soromou

Regulation of Inflammatory Cytokines in Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage by 7-O-Methyl-naringenin

7-O-Methylnaringenin, extracted from Rhododendron speciferum, belongs to the flavanone class of polyphenols. In the present study, we investigated the anti-inflammatory effects of 7-O-methylnaringenin on cytokine production by lipopoly-saccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. The results showed that pretreatment with 10, 20 or 40 μg/mL of 7-O-methylnaringenin could downregulate tumour necrosis factor (TNF-α), interleukin (IL-6) and interleukin (IL-1β) in a dose-dependent manner. Furthermore, we investigated the signal transduction mechanisms to determine how 7-O-methylnaringenin affects RAW 264.7 macrophages. The activation of mitogen-activated protein kinases (MAPK) and IκBα were measured by Western blotting. The data showed that 7-O-methylnaringenin could downregulate LPS-induced levels of phosphorylation of ERK1/2, JNK and IκBα. These observations indicated that 7-O-methylnaringenin modulated inflammatory cytokine responses by blocking NF-қB, ERK1/2 and JNK/MAPKs activation.

Astragalin attenuates lipopolysaccharide-induced inflammatory responses by down-regulating NF-κB signaling pathway.

Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The present study aimed to determine the protective effects and the underlying mechanisms of astragalin on lipopolysaccharide-induced endotoxemia and lung injury in mice. Mice were injected intraperitoneally (i.p.) with lipopolysaccharide (LPS) (dose range: 5-40 mg/kg). We observed mice on mortality for 7 days twice a day and recorded survival rates. In drug testing, we examined the therapeutic effects of astragalin (25, 50 or 75 mg/kg) on LPS- induced endotoxemia by dosing orally astragalin 1 hour before LPS challenge. Using an experimental model of LPS-induced acute lung injury (ALI), we examined the effect of astragalin in resolving lung injury. The investigations revealed that pretreatment with astragalin can improve survival during lethal endotoxemia and attenuate inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury. The mechanisms by which Astragalin exerts its anti-inflammatory effect are correlated with inhibition of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) production via inactivation of NF-κB.

In vitro and in vivo protection provided by pinocembrin against lipopolysaccharide-induced inflammatory responses

Pinocembrin or 5, 7-dihydroxyflavanone is a flavanone, a type of flavonoid. In the present study, we first assessed the anti-inflammatory effects of pinocembrin in RAW macrophage cells; and based on these effects, we investigated the therapeutic effects of pinocembrin in murine model of endotoxin-induced acute lung injury. We found that in vitro pretreatment with pinocembrin remarkably regulated the production of TNF-α, IL-1β, IL-6 and IL-10 via inhibiting the phosphorylation of IκBα, ERK1/2, JNK and p38MAPK. In the mouse model of LPS-induced acute lung injury, pinocembrin (20 or 50 mg/kg, i.p.) attenuated the development of pulmonary edema, histological severities, as well as neutrophil, lymphocyte and macrophage infiltration, which were increased by LPS administration. Additionally, TNF-α, IL-1β and IL-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after pinocembrin pretreatment. Our results also showed that pinocembrin attenuated LPS-induced lung injury through suppression of IκBα, JNK and p38MAPK activation. These findings suggest that pinocembrin may represent a novel candidate for the modulation of inflammatory responses.

Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice

Zingerone, one of the active components of ginger, is a phenolic alkanone with antioxidant and anti-inflammatory properties. In the present study, we analyzed the role of zingerone against RAW 264.7 cells and acute lung injury induced by lipopolysaccharide (LPS) in mice. RAW cells or BALB/c mice were pretreated with zingerone one hour before stimulated with LPS. We found that zingerone significantly inhibited the production of LPS-induced proinflammatory cytokines in vitro and in vivo. When pretreated with zingerone, pulmonary histopathologic changes, as well as alveolar hemorrhage and neutrophil infiltration were substantially suppressed in lung tissues, with evidence of reduced myeloperoxidase (MPO) activity in murine acute lung injury model. The lung wet-to-dry weight (W/D) ratios, as the index of pulmonary edema, were markedly decreased by zingerone pretreatment. Furthermore, we demonstrated that zingerone attenuates the mitogen-activated protein kinases (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways through blocking the phosphorylation of ERK, p38/MAPK and IκBα, NF-κB/P65. These results suggest that zingerone may provide protective effects against LPS-induced ALI.

Traditional medicine alpinetin inhibits the inflammatory response in Raw 264.7 cells and mouse models

Alpinetin, one of the main constituents of the seeds of Alpinia katsumadai Hayata, belonging to flavonoids, has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The purpose of this study was to investigate the protection of alpinetin on inflammation in Lipopolysaccharide (LPS) stimulated Raw 264.7 cells and LPS induced vivo lung injury model. The effects of alpinetin on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay and Western blot. The results showed that alpinetin markedly inhibited the LPS- induced TNF-α, IL-6 and IL-1β production both in vitro and vivo. Furthermore, alpinetin blocked the phosphorylation of IκBα protein, p65, p38 and extracellular signal-regulated kinase (ERK) in LPS stimulated RAW 264.7 cells. From in vivo study, it was also observed that alpinetin attenuated lung histopathologic changes in mouse models. These results suggest that alpinetin potentially decreases the inflammation in vitro and vivo, and might be a therapeutic agent against inflammatory diseases.

Paeonol suppresses lipopolysaccharide-induced inflammatory cytokines in macrophage cells and protects mice from lethal endotoxin shock

Paeonol (2′‐hydroxy‐4′‐methoxyacetophenone) is the main phenolic compound of the radix of Paeonia suffruticosa which has been used as traditional Chinese medicine. In this study, we primarily investigated the anti‐inflammatory effects and the underlying mechanisms of paeonol in RAW macrophage cells; and based on these effects, we assessed the protective effects of paeonol on lipopolysaccharide‐induced endotoxemia in mice. The in vitro study showed that paeonol regulated the production of TNF‐α, IL‐1β, IL‐6, and IL‐10 via inactivation of IκBα, ERK1/2, JNK, and p38 MAPK. In mouse model of lipopolysaccharide‐induced endotoxemia, pro‐ and anti‐inflammatory cytokines are significantly regulated, and thus the survival rates of lipolysaccharide‐challenged mice are improved by paeonol (150, 200, or 250 mg/kg). Therefore, paeonol has a beneficial activity against lipopolysaccharide‐induced inflammation in RAW 264.7 cell and mouse models.

Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice

Abstract Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin–eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway.

p-Cymene Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammatory Cell Activation

The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.

Preventive effect of Imperatorin on acute lung injury induced by lipopolysaccharide in mice

Imperatorin, a linear furanocoumarin, has many pharmacological effects such as antibacterial, anti-inflammatory and antiviral effects. The purpose of this study was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1h before LPS challenge. We found that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level of interleukin-10 (IL-10) was up-regulated 8h after Imperatorin treatment. Pretreatment with Imperatorin (15 or 30 mg/kg) decreased lung wet-to-dry weight (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO) activities. Additionally, Imperatorin attenuated lung histopathological changes and significantly inhibited the phosphorylation of IκB, JNK, ERK and p38/MAPK. These findings demonstrate that Imperatorin protects against LPS-induced ALI in mice.

Suppression of LPS-induced inflammatory responses by gossypol in RAW 264.7 cells and mouse models

Gossypol, a yellowish polyphenolic compound originally from cotton plant, has been known to exert a potential for anti-cancer, anti-inflammatory and other important therapeutic activities. The purpose of this investigation was to determine the protection of gossypol on inflammation in Lipopolysaccharide (LPS) stimulated RAW 264.7 cells and LPS induced in vivo lung injury model. The effects of gossypol on pro-inflammatory cytokines and signaling pathways were evaluated by enzyme-linked immunosorbent assay and Western blot. The results showed that gossypol significantly inhibited the production of LPS-induced TNF-α, IL-6 and IL-1β both in vitro and vivo. Furthermore, gossypol blocked the phosphorylation of IκBα protein, p65, p38, c-Junterminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in LPS stimulated RAW 264.7 cells. From the in vivo study, it was observed that gossypol attenuated lung histopathologic changes in mouse models. The present data suggest that gossypol suppresses the inflammation in vitro and vivo, and may be a potential therapeutic candidate for the treatment of inflammatory disorders.