Artesunate Inhibits Renal Ischemia Reperfusion-Stimulated Lung Inflammation in Rats by Activating HO-1 Pathway

Artesunate (AS), a semi-synthetic derivative of Artemisia, has been shown to exert a wide range of pharmacological effects, such as anti-inflammatory and antioxidant functions. However, the protective functions of AS on renal ischemia reperfusion injury (RIR)-stimulated lung inflammation remain unclear. In this research, acute lung injury (ALI) was stimulated by renal ischemia reperfusion injury (RIR). AS (15 mg/kg) was intraperitoneal administrated to rat 1 h before RIR stimulation. Serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, arterial blood gas and biochemistry, lung wet/dry weight ratio and MPO activity, total cell number and protein concentration in BALF, tissue histology, and NF-κB expression were determined. The results indicated that serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF enhanced after RIR stimulation. These alterations were mitigated by AS. AS attenuated lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF. AS attenuated RIR-stimulated pulmonary NF-κB phosphorylation. In addition, these previously mentioned actions of AS were antagonized by suppressing HO-1 pathway. However, RIR-stimulated arterial blood gas and biochemistry and lung histopathology were also attenuated by AS. In summary, AS inhibited RIR-stimulated lung inflammation by activating HO-1 pathway.     

Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway

The present study was to evaluate the effect of ergosterol (ER) on CS (cigarette smoke)-induced chronic obstructive pulmonary disease (COPD) in mice. Fifty male ICR mice were randomly assigned to five groups: control group, CS group, CS + dexamethasone (Dex, 2 mg/kg) group, CS + ER (ER, 25 mg/kg) group, CS + ER (ER, 50 mg/kg). H&E staining demonstrated that ER inhibited CS-induced pathological injury in lung tissue. Besides, ER could restore the activities of superoxide dismutase (SOD) in serum and in the lung, catalase (CAT) in serum and reduce the content of malondialdehyde (MDA) in serum and in the lung. ER also inhibited pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and the lung. Furthermore, ER significantly inhibited the protein expression of JAK3/STAT3/NF-κB pathway in CS-induced mice. Our findings suggested that ER might effectively ameliorate the progression of COPD via JAK3/STAT3/NF-κB pathway in mice.     

Suppression of MAPK and NF-κB Pathways by Limonene Contributes to Attenuation of Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury

The present study aimed to investigate the protective role of limonene in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and limonene (25, 50, and 75 mg/kg) was injected intraperitoneally 1 h prior to LPS administration. After 12 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Limonene pretreatment at doses of 25, 50, and 75 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with limonene inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that limonene blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase in LPS-induced ALI. The results presented here suggest that the protective mechanism of limonene may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of NF-κB and MAPK activation.     

Systemic Administration of FC-77 Dampens Ischemia–Reperfusion-Induced Acute Lung Injury in Rats

Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia–reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-α and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-κB activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-κB activation and attenuation of subsequent inflammatory response.     

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury <Emphasis Type="Italic">via</Emphasis> NF-κB Signaling Pathway <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.     

Protective Effect of p-Cymene on Lipopolysaccharide-Induced Acute Lung Injury in Mice

In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor alpha (TNF-α), IL-1β, and IL-6 were assayed by enzyme-linked immunosorbent assay method. The pathological changes of the lung tissues were observed by hematoxylin and eosin staining. The inflammatory signal pathway-related protein levels of NF-κB were measured using Western blotting. The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice.     

Stevioside Protects LPS-Induced Acute Lung Injury in Mice

Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known to exhibit anti-inflammatory properties. To evaluate the effect and the possible mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury, male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before intranasal instillation of LPS. Seven hours later, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were also determined. The right lung was excised for histological examination and analysis of myeloperoxidase activity and nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), nuclear factor-kappa B (NF-κB), inhibitory kappa B protein were detected by western blot. The results showed that stevioside markedly attenuated the LPS-induced histological alterations in the lung. Stevioside inhibited the production of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue significantly decreased, the number of total cells, neutrophils, and macrophages in the BALF were also significantly reduced after treatment with stevioside. Moreover, western blotting showed that stevioside inhibited the phosphorylation of IκB-α and NF-κB caused by LPS. Taken together, our results suggest that anti-inflammatory effect of stevioside against the LPS-induced acute lung injury may be due to its ability of inhibition of the NF-κB signaling pathway. Stevioside may be a promising potential therapeutic reagent for acute lung injury treatment.     

Anti-inflammatory Role of Pilose Antler Peptide in LPS-Induced Lung Injury

The present study was designed to investigate the effects of pilose antler peptide (PAP) on lipopolysaccharide (LPS)-induced lung injury. BalB/c mice intraperitoneally received PAP (10 and 20 mg/kg) or dexamethasone (2 mg/kg) 1 h prior to intratracheal instillation of LPS. PAP significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and restored LPS-induced lung histopathological changes. PAP also increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content and levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that PAP inhibited Rho/NF-κB pathway in LPS-induced mice. Our experimental results indicated that the protective mechanism of PAP might be attributed partly to the inhibition of Rho/NF-κB pathway.     

盐酸戊乙奎醚抑制脂多糖致急性肺损伤大鼠肺组织中PMN扣押和NF-κB活化

目的：观察盐酸戊乙奎醚(PHC)对脂多糖(LPS)致急性肺损伤(ALI)大鼠中性粒细胞(PMN)肺内扣押及对肺组织核因子κB（NF-κB）活化的影响。方法： SD大鼠随机分为对照组、LPS模型组（静脉注射5 mg/kg LPS）、LPS+PHC高、中和低(3.0、1.0和0.3 mg/kg)3个剂量组，每组8只，用比色法测定肺组织髓过氧化物酶(MPO)活性，进行支气管肺泡灌洗液(BALF)PMN计数，蛋白免疫印迹法检测肺组织NF-κB的表达。结果： PHC显著降低ALI大鼠肺组织MPO活性、BALF中PMN计数比例（均P＜0.05)；ALI组大鼠肺组织磷酸化NF-κB的表达显著高于正常对照组（P＜0.05)；PHC高、中剂量组能显著抑制大鼠肺组织磷酸化NF-κB表达高于ALI模型组（均P＜0.05)；在造模后不同的时点观察，PHC对磷酸化NF-κB表达的作用有差别，以造模后6 h时最能有效抑制磷酸化NF-κB上调。结论： PHC能抑制LPS诱导ALI大鼠PMN在肺内扣押和肺组织NF-κB活化，PHC抑制LPS诱导PMN肺内扣押可能与抑制NF-κB活化有关，后者有待进一步验证。     

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.     

Protective Effect of Amygdalin on LPS-Induced Acute Lung Injury by Inhibiting NF-κB and NLRP3 Signaling Pathways

The acute lung injury (ALI) is a leading cause of morbidity and mortality in critically ill patients. Amygdalin is derived from the bitter apricot kernel, an efficacious Chinese herbal medicine. Although amygdalin is used by many cancer patients as an antitumor agent, there is no report about the effect of amygdalin on acute lung injury. Here we explored the protective effect of amygdalin on ALI using lipopolysaccharide (LPS)-induced murine model by detecting the lung wet/dry ratio, the myeloperoxidase (MPO) in lung tissues, inflammatory cells in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines production, as well as NLRP3 and NF-κB signaling pathways. The results showed that amygdalin significantly reduced LPS-induced infiltration of inflammatory cells and the production of TNF-α, IL-1β, and IL-6 in the BALF. The activity of MPO and lung wet/dry ratio were also attenuated by amygdalin. Furthermore, the western blotting analysis showed that amygdalin remarkably inhibited LPS-induced NF-κB and NLRP3 activation. These findings indicate that amygdalin has a protective effect on LPS-induced ALI in mice. The mechanism may be related to the inhibition of NF-κB and NLRP3 signaling pathways.     

1,8-Cineol Attenuates LPS-Induced Acute Pulmonary Inflammation in Mice

Eucalyptol, also known as 1,8-cineol, is a monoterpene and has been shown to exert anti-inflammatory and antioxidant effect. It is traditionally used to treat respiratory disorders due to its secretolytic properties. In the present study, we evaluated the effect of 1,8-cineol on pulmonary inflammation in a mouse model of acute lung injury. We found that 1,8-cineol significantly decreased the level of TNF-α and IL-1β, and increased the level of IL-10 in lung tissues after acute lung injury induced by lipopolysaccharide (LPS). It also reduced the expression of nuclear factor kappa B (NF-κB) p65 and toll-like receptor 4 (TLR4), and myeloperoxidase activity in lung tissues. In addition, 1,8-cineol reduced the amounts of inflammatory cells in bronchoalveolar lavage fluid (BALF), including neutrophils and macrophages, and significantly decreased the protein content in BALF and the lung wet/dry weight (W/D) ratio. Its effect on LPS-induced pulmonary inflammation was associated with suppression of TLR4 and NF-κB expressions. Our results provide evidence that 1,8-cineol inhibits acute pulmonary inflammation, indicating its potential for the treatment of acute lung injury.     

Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice

Objective

Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods

Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were detected by western blot.

Results

Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS.

Conclusion

The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment.     

薯蓣皂苷减轻卵清蛋白诱导的过敏性哮喘小鼠的气道炎症

目的探讨薯蓣皂苷对卵清蛋白(ovalbumin,OVA)诱导的过敏性哮喘小鼠中过敏性支气管炎的影响及机制。方法24只小鼠随机分为对照组、OVA组、OVA+30 mg/kg薯蓣皂苷组和OVA+60 mg/kg薯蓣皂苷组,每组纳入6只小鼠。全自动生化仪检测各组支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中嗜中性粒细胞、嗜酸性粒细胞和单核细胞的数量;ELISA法检测BALF中促炎因子IL-1β、IL-4、IL-5和TNF-α的含量;PAS染色法观察肺组织黏液分泌情况并对黏液分泌程度进行评分;免疫组化法观察肺组织p-NF-κB p65的表达和分布情况;Western blotting法检测肺组织中p-IκB和NF-κB p65的蛋白表达水平。结果薯蓣皂苷可降低过敏性哮喘小鼠BALF中炎性细胞数量,同时降低BALF中促炎因子IL-1β、IL-4、IL-5和TNF-α的水平以及肺部黏液的分泌和NF-κB的活化水平。结论薯蓣皂苷能减轻过敏性哮喘小鼠的气道炎症,且其抗炎作用与抑制NF-κB活化有关。     

Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation

Artesunate, a derivative of artemisinin, has been reported to have anti-inflammatory property. However, few studies showed the protective effects of artesunate on lung injury. In this study, we aimed to investigate the effects of artesunate on LPS-induced lung injury in mice. The mice were treated with artesunate 1 h before or after LPS treatment. The effects of artesunate on lung MPO activity and malondialdehyde (MDA) content were detected. The lung wet/dry radio and the numbers of inflammatory cells in BALF were also measured. ELISA was used to evaluate the levels of TNF-α, IL-1β, and IL-6 in BALF. Western blot analysis was adapted to detect TLR4 and Nrf2 signaling pathways. The results showed that artesunate protected against LPS-induced ALI by decreasing the numbers of inflammatory cells, lung edema, MPO activity, and MDA content. Furthermore, artesunate significantly inhibited the levels of TNF-α, IL-1β, and IL-6. Artesunate also inhibited LPS-induced IL-6 and IL-8 production in the A549 cells. In addition, artesunate dose-dependently suppressed LPS-induced TLR4 expression and NF-κB activation. The expression of Nrf2 and HO-1 were also up-regulated by artesunate. The data suggest that artesunate possesses anti-inflammatory and anti-oxidant properties against LPS-induced ALI via inhibiting TLR4 signaling pathway and activating Nrf2 signaling pathway.     

Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine

CORM-released CO has been shown to be beneficial in resolution of acute inflammation. The acute phase of intestinal ischemia-reperfusion (I/R) injury is characterized by oxidative stress-related inflammation and leukocyte recruitment. In this study, we assessed the effects and potential mechanisms of CORM-2-released CO in modulation of inflammatory response in the small intestine following I/R-challenge. To this end mice (C57Bl/6) small intestine were challenged with ischemia by occluding superior mesenteric artery (SMA) for 45 min. CORM-2 (8 mg/kg; i.v.) was administered immediately before SMA occlusion. Sham operated mice were injected with vehicle (0.25% DMSO). Inflammatory response in the small intestine (jejunum) was assessed 4 h following reperfusion by measuring tissue levels of TNF-α protein (ELISA), adhesion molecules E-selectin and ICAM-1 (Western blot), NF-κB activation (EMSA), along with PMN tissue accumulation (MPO assay) and leukocyte rolling/adhesion in the microcirculation of jejunum (intravital microscopy). The obtained results indicate that tissue levels of TNF-α, E-selectin and ICAM-1 protein expression, activation of NF-κB, and subsequent accumulation of PMN were elevated in I/R-challenged jejunum. The above changes were significantly attenuated in CORM-2-treated mice. Taken together these findings indicate that CORM-2-released CO confers anti-inflammatory effects by interfering with NF-κB activation and subsequent up-regulation of vascular pro-adhesive phenotype in I/R-challenged small intestine.     

Elevated GDF-15 contributes to pulmonary inflammation upon cigarette smoke exposure

The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-β superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-β superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice. Next, we exposed GDF-15 KO and control mice to air or CS and evaluated pulmonary inflammation. GDF-15 levels were higher in sputum supernatant and lung tissue of patients with COPD and smokers without COPD compared with never smokers. Immunohistochemistry revealed GDF-15 staining in the airway epithelium. Increased expression and secretion of GDF-15 was confirmed in vitro in CS-exposed pHBECs compared with air-exposed pHBECs. Similarly, GDF-15 levels were increased in lungs of CS-exposed mice. Importantly, GDF-15 deficiency attenuated the CS-induced pulmonary inflammation. These results suggest that increased GDF-15—as observed in lungs of smokers and patients with COPD—contributes to CS-induced pulmonary inflammation.     

Modulation of LPS-Stimulated Pulmonary Inflammation by Borneol in Murine Acute Lung Injury Model

The object of our study is to investigate the protective effects of Borneol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To determine the effects of Borneol on the histopathological changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective effects on ALI, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways were investigated. In the present study, Borneol obviously alleviated pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed phosphorylation of NF-κB/P65, IκBa, p38, JNK, and ERK. Taken together, our results suggest that Borneol suppressed inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-κB and MAPKs signaling pathways. Borneol may be a promising potential preventive agent for acute lung injury treatment.     

Anti-inflammatory Effects of Triptolide in LPS-Induced Acute Lung Injury in Mice

Triptolide is one of the main active components of Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to have anti-inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to clarify the possible mechanisms. Mice were administered intranasally with LPS to induce lung injury. Triptolide was administered intraperitoneally 1 h before LPS challenge. Triptolide-treated mice exhibited significantly reduced leukocyte, myeloperoxidase (MPO) activity, edema of the lung, as well as TNF-α, IL-1β, and IL-6 production in the bronchoalveolar lavage fluid compared with LPS-treated mice. Additionally, Western blot analysis showed that triptolide inhibited the phosphorylation of inhibitor-kappa B kinase-alpha (IκB-α), p65, nuclear factor kappa B (NF-κB), p38, extracellular receptor kinase (ERK), and Jun N-terminal kinase (JNK) and the expression of Toll-like receptor 4 (TLR4) caused by LPS. In conclusion, our results suggested that the promising anti-inflammatory mechanism of triptolide may be that triptolide activates peroxisome proliferation-activated receptor gamma (PPAR-γ), thereby attenuating an LPS-induced inflammatory response. Triptolide may be a promising potential therapeutic reagent for ALI treatment.     

Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression

High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of HMGB1 in a rat model of LPS-induced ALI. Rats underwent intraperitoneal injection of LPS to mimic sepsis-induced ALI. Propofol bolus (1, 5, or 10 mg/kg) was infused continuously 30 min after LPS administration, followed by infusion at 5 mg/(kg?·?h) through the left femoral vein cannula. LPS increased wet to dry weight ratio and myeloperoxidase activity in lung tissues and caused the elevation of total protein and cells, neutrophils, macrophages, and neutrophils in bronchoalveolar lavage fluid (BALF). Moreover, HMGB1 and other cytokine levels were increased in BALF and lung tissues and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. Propofol inhibited all the above effects. It also inhibited LPS-induced toll-like receptor (TLR)2/4 protein upexpression and NF-κB activation in lung tissues and human alveolar epithelial cells. Propofol protects rats and human alveolar epithelial cells against HMGB1 expression in a rat model of LPS-induced ALI. These effects may partially result from reductions in TLR2/4 and NF-κB activation.