The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways.

The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state.

Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway.

The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), glutathione, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured after the rats were killed. iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway proteins were detected by Western blot. In vitro, we evaluated the protective effect of Sal on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Reactive oxygen species (ROS) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT, SOD, GSH-px, glutathione-S-transferase, TNF-α, IL-6 and IL-1β in cellular supernatant were measured. PI3K/Akt/mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway in vivo. Furthermore, the pharmacological effect of Sal associated with the ROS-mediated PI3K/Akt/mTOR pathway was proved by the use of ROS scavenger, N-acetyl-l-cysteine, in LPS-stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.12871

Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo.

Acute lung injury (ALI) is a critical clinical condition with a high mortality rate, characterized with excessive uncontrolled inflammation and apoptosis. Recently, microRNAs (miRNAs) have been found to play crucial roles in the amelioration of various inflammation-induced diseases, including ALI. However, it remains unknown the biological function and regulatory mechanisms of miRNAs in the regulation of inﬂammation and apoptosis in ALI. The aim of this study is to identify and evaluate the potential role of miRNAs in ALI and reveal the underlying molecular mechanisms of their effects. Here, we analyzed microRNA expression profiles in lung tissues from LPS-challenged mice using miRNA microarray. Because microRNA-27a (miR-27a) was one of the miRNAs being most significantly downregulated, which has an important role in regulation of inflammation, we investigated its function. Overexpression of miR-27a by agomir-27a improved lung injury, as evidenced by the reduced histopathological changes, lung wet/dry (W/D) ratio, lung microvascular permeability and apoptosis in the lung tissues, as well as ameliorative survival of ALI mice. This was accompanied by the alleviating of inflammation, such as the reduced total BALF cell and neutrophil counts, decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-6) interleukin-1β (IL-1β) and myeloperoxidase (MPO) activity in BAL fluid. Toll-like receptor 4 (TLR4), an important regulator of the nuclear factor kappa-B (NF-κB) signaling pathway, was identified as a novel target of miR-27a in RAW264.7 cells. Furthermore, our results showed that LPS stimulation increased the expression of MyD88 and NF-κB p65 (p-p65), but inhibited the expression of inhibitor of nuclear factor-κB-α (IκB-α), suggesting the activation of NF-κB signaling pathway. Further investigations revealed that agomir-miR-27a reversed the promoting effect of LPS on NF-κB signaling pathway. The results here suggested that miR-27a alleviates LPS-induced ALI in mice via reducing inﬂammation and apoptosis through blocking TLR4/MyD88/NF-κB activation.

https://www.tandfonline.com/doi/pdf/10.1080/15384101.2018.1509635

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inﬂammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway.

Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro

Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway.

In this study, we investigated anti-inflammatory effects of esculin (ESC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS, and ESC (20 and 40 mg/kg) was given orally 1 h prior to LPS administration. After 6 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. ESC pretreatment decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with ESC inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that ESC inhibited the Toll-like receptor-2 (TLR2), Toll-like receptor-4 (TLR4), myeloid differentiation primary response gene-88 (MyD88), and nuclear factor-κB (NF-κB) p65 in LPS-induced ALI. The results indicated that the ESC had a protective effect on LPS-induced ALI in mice.

Esculin Inhibits the Inflammation of LPS-Induced Acute Lung Injury in Mice Via Regulation of TLR/NF-κB Pathways

In this work, the anti-asthma potential of platycodin D (PLD) was studied by investigation of its effect to suppress airway inflammation, a murine model of asthma and the possible mechanisms. A total of 50 mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+dexamethasone (2 mg/kg) and OVA+PLD (40, 80 mg/kg). Airway resistance (Raw) were measured; airway histological studies were evaluated by the hematoxylin and eosin (HE) staining; interleukin-4 (IL-4), interleukin-5(IL-5), and interleukin-13 in bronchoalveolar lavage fluid (BALF) were evaluated by enzyme-linked immunosorbent assay (ELISA); NF-κBp65, p-NF-κBp65, p-IKKα, IKKα, p-IKKβ, p-IкBα, and IкBα of airway were measured by Western blotting. Our study demonstrated that PLD inhibited OVA-induced increases in Raw and eosinophil count in airway; IL-4, IL-5, and IL-13 were recovered in BALF. Histological studies demonstrated that PLD substantially inhibited OVA-induced eosinophilia in airway tissue. Western blotting studies demonstrated that PLD substantially inhibited NF-κB pathway. These findings suggest that PLD may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Platycodin D Attenuates Airway Inflammation in a Mouse Model of Allergic Asthma by Regulation 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.

Wang Shumin

Papers

Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro

Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway.

Esculin Inhibits the Inflammation of LPS-Induced Acute Lung Injury in Mice Via Regulation of TLR/NF-κB Pathways

Platycodin D Attenuates Airway Inflammation in a Mouse Model of Allergic Asthma by Regulation NF-κB Pathway

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