Protective effects of ethyl acetate extracts of Rimulus Cinnamon on systemic inflammation and lung injury in endotoxin-poisoned mice.

Rimulus cinnamon is the dried twig of Cinnamomum cassia Presl. It is widely used in China for the treatment of inflammatory processes, amenorrhea, and other diseases. We aimed to study the protective effects of ethyl acetate extracts of R. cinnamon (EAE) on systemic inflammation and lung injury in endotoxin-poisoned mice. EAE was administered 5 d prior to lipopolysaccharide (LPS) challenge with 15 mg/kg LPS. The administration of EAE increased the levels of interferon-γ (IFN-γ) and decreased the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the serum. Additionally, EAE relieved the pathological changes in the tissues of the lungs and spleen, and significantly reduced the number of neutrophils in the lung tissues. In addition, treatment with EAE decreased the mRNA expression of the NLR family, pyrin domain-containing protein 3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) in the lungs, as well as the expression of NLRP3, caspase-1 (p20), and pro-IL-1ß proteins. These results demonstrated the promising anti-inflammatory effects of EAE in endotoxin-poisoned mice. Furthermore, EAE could alleviate the lung injury of endotoxin-poisoned mice by antagonizing the activation of the NLRP3 inflammasome.

Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice.

Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated. Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated. Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group. Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1ß (IL-1ß), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1ß (MIP-1ß), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups. Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.

Protective effect of cinnamic acid in endotoxin-poisoned mice.

In this work, we aimed to evaluate the protective effect of cinnamic acid (CD) on lipopolysaccharide (LPS; Escherichia coli 055:B5)-induced endotoxin-poisoned mice and clarify the underlying mechanisms. The mice were administrated CD 5 d before 15 mg/kg LPS challenge. 12 hr later, thymus was separated for determination of thymus indexes. Lung and spleen tissues were collected for histologic examination and the wet/dry weight ratio of lung was calculated, and serum was acquired for tumor necrosis factor-α (TNF-α), interleukin (IL)-18, and IL-1ß measurement. Moreover, the expression of NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome was determined in lung. CD increased the thymus indexes and decreased lung wet/dry weight ratio. In addition, CD improved the lung and spleen histopathological changes induced by LPS and decreased the number of neutrophils in lung tissues. CD also inhibited the pro-inflammatory cytokines (TNF-α, IL-18, and IL-1ß) production in serum. Furthermore, CD suppressed the LPS-induced NLRP3, Caspase-1, and IL-1ß mRNA expression in lung, as well as the expression of NLRP3 and Caspase-1 (p20) protein. CD may have protective effects in endotoxin-poisoned mice via inhibiting the activation of NLRP3 inflammasome, and can be considered as a potential therapeutic candidate for diseases involved in endotoxin poisoning such as sepsis.

Inhibition of NLRP3 inflammasome: a new protective mechanism of cinnamaldehyde in endotoxin poisoning of mice.

CONTEXT: Cinnamaldehyde (CA) has a protective effect in endotoxin poisoning of mice, but there is no direct evidence for the protective effect of CA through inhibition of NLRP3 inflammasome activation in endotoxin poisoning of mice. OBJECTIVE: We aimed to investigate the protective mechanism of CA in endotoxin poisoned mice through NLRP3 inflammasome. MATERIALS AND METHODS: First, we evaluated the anti-inflammatory effect of CA in phorbol-12-myristate acetate-differentiated THP-1 cells through the NLRP3 inflammasome. Second, in a mouse model of lipopolysaccharide (LPS)-induced endotoxin poisoning, CA was administrated for 5 d (once a day) before the 15 mg/kg LPS challenge. Then, the levels of IL-1ß in serum were measured, and the effect of CA on the NLRP3 inflammasome activation and the expression of cathepsin B and P2X7R proteins in lung were explored. RESULTS: In vitro, CA decreased the levels of p20, pro-IL-1ß and IL-1ß in cell culture supernatants, as well as the expression of NLRP3 and IL-1ß mRNA in cells. In vivo, CA decreased IL-1ß production in serum. Furthermore, CA suppressed LPS-induced NLRP3, p20, Pro-IL-1ß, P2X7 receptor (P2X7R) and cathepsin B protein expression in lung, as well as the expression of NLRP3 and IL-1ß mRNA. CONCLUSIONS: CA has a protective effect in the endotoxin poisoned mice through the inhibition of NLRP3 inflammasome activation. Furthermore, CA suppresses the NLRP3 inflammasome activation by inhibiting the expression of cathepsin B and P2X7R protein expression. CA can be considered as a potential therapeutic candidate for diseases involved in endotoxin poisoning such as sepsis.

Protective effect of cinnamicaldehyde in endotoxin poisoning mice.

CONTEXT: Several pharmacological studies have shown that cinnamicaldehyde (CA) has anti-inflammatory and anti-tumor effects, but no data show the effects of CA on the endotoxin poisoning. OBJECTIVE: In this work, the protective effect of CA in LPS-induced endotoxin poisoning mice was investigated. MATERIALS AND METHODS: Mice were randomly divided into normal, LPS, LPS +5 mg/kg dexamethasone (DEX), LPS +0.132 g/kg CA, and LPS +0.264 g/kg CA group. Pretreated with CA (0.132 and 0.264 g/kg/day, respectively) for 5 consecutive days before LPS injection. Except the normal group, the other animals were intraperitoneally injected with LPS (15 mg/kg). RESULTS: Twelve hours after LPS injection, CA significantly reduced the production of pro-inflammatory cytokines (interleukin-18, interleukin-1ß, and interleukin-5) and chemokines (macrophage colony stimulating factor, macrophage inflammatory protein-1ß) in serum. In addition, the histopathological study indicated that CA attenuates lung injury induced by LPS. Moreover, the numbers of neutrophils were significant decreased and the NF-κB (p65) mRNA level was reduced in lung after treated with CA. CONCLUSION: The present data suggest that cinnamicaldehyde can be considered as potential therapeutic candidates for the endotoxin-poisoning-related diseases such as sepsis via its anti-inflammation effects.

[Protective effects of Schizonepeta volatile oil on endotoxin poisoning induced by lipopolysaccharide in mice].

In order to study the protective effects of Schizonepeta volatile oil (Sto）on endotoxin poisoning mice, and the relatively content of each chemical osubstance in Schizonepeta volatile oil was measured using GC-MS. The mare C57BL/6J mice were randomly divided into five groups including the normal group, model group, dexamethasone group (5 mg•kg⁻¹), and Sto (0.226 and 0.452 g•kg⁻¹, respectively) groups. The dexamethasone group was given the drugs once time by intraperitoneal injection on the 5th day, while the other mice were given drugs by oral administration once a day for 5 days. Then, the normal group was injected with the saline and the other groups were injected LPS (15 mg•kg-1) after 30 minutes of the last administration. After LPS injection twelve hours, the blood, serum, and lung tissue of mice were collected. The IL-18, IL-1ß, IL-5, TNF-α, MCP-1, MIP-1ß, M-CSF, and GM-CSF were measured in serum by ELISA and Luminex Magpix. The white cell (WBC) and platelet (PLT) in blood were counted and lung, spleen, and thymus index were calculated. The lung histopathology was performed at the same time. The GC-MS results showed that the relative content of menthone and pulegone are 46.67% and 33.92%, respectively. The Sto (0.452 and 0.226 g•kg⁻¹, respectively) reduced the levels of IL-1ß, IL-5, TNF-α, MCP-1, MIP-1ß, and M-CSF in serum (P<0.01 or P<0.05). The 0.452 g•kg⁻¹ Sto also reduced the levels of IL-18 and GM-CSF in the serum (P<0.01 or P<0.05). And the 0.226 g•kg⁻¹ Sto showed good anti-inflammatory effects by reducing neutrophil infiltration in the lung tissue. But the Sto had no effect on the increasing of WBC, spleen and lung index as well as decreasing of PLT and thymus index. The results showed that Sto has a protective effect in LPS-induced exdotoxin poisoning mice, its mechanism is related to inhibit the release of varies of inflammatory cytokines and reduce the inflammation reaction.

Protective effects of essential oils from Rimulus cinnamon on endotoxin poisoning mice.

The essential oils from Rimulus cinnamon (EORC) have anti-inflammation activities, but the effects of EORC on endotoxin poisoning mice remain to be explored, the mechanism is still unclear. This study was designed to investigate the protective effects and mechanism of EORC on lipopolysaccharide (LPS)-induced endotoxin poisoning mice. Pre-treatment with EORC decreased the production of pro-inflammatory cytokines (Interleukin-1ß, Interleukin-18, Interleukin-5, and Interferon-γ) and chemokines (Monocyte chemotactic protein-1, Macrophage colony-stimulating factor, and Macrophage inflammatory protein-1ß) in serum of endotoxin poisoning mice. The histopathological study showed that the lung injury was improved and EORC decreased the numbers of neutrophils and Nitric oxide (NO) levels in lung. EORC could reduce the mRNA expression of NLR family, pyrin domain-containing 3 (NLRP3), Interleukin (IL)-1ß, and nitric oxide synthase (iNOS). In addition, EORC decreased the protein expression of NLRP3, Caspase-1 (p20), Pro-IL-1ß, and purinergic P2 × 7 receptor (P2 × 7R) in the lung tissues. The results above indicated that the EORC may have protective effects on LPS-induced endotoxin poisoning mice via inhibiting the activation of P2 × 7R/NLRP3 inflammasome.