The protective effects of Mai-Luo-Ning injection against LPS-induced acute lung injury via the TLR4/NF-κB signalling pathway.

BACKGROUND: Acute lung injury (ALI) is a severe inflammatory disorder associated with high morbidity and mortality rates. Various therapeutic strategies for ALI have been proposed over the last few decades; however, the treatment options remain limited. Mai-Luo-Ning injection (MLN), a traditional Chinese medical formulation, has been extensively used for the treatment of respiratory diseases. Nevertheless, the effects of MLN on ALI remain unclear. PURPOSE: This study aimed to investigate the protective and therapeutic effects of MLN on lipopolysaccharide-induced ALI mouse models and RAW 264.7 cells, and further explore the underlying mechanism of these effects. METHODS: The therapeutic activity of MLN was evaluated using an in vivo ALI model and an in vitro model of RAW 264.7 macrophages. UHPLC-ESI-Q-TOF-MS/MS was used to investigate the chemical constituents of the MLN. The material basis and potential protective mechanism of MLN were analyzed using network pharmacology. The roles of MLN in inhibiting the Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signalling pathway were investigated via western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. RESULTS: In vivo experiments demonstrated that MLN ameliorated LPS-induced histological changes in lung tissues and reduced lung wet/dry weight ratio, total protein concentration in the bronchoalveolar lavage fluid and myeloperoxidase activity. Furthermore, MLN downregulated the in vivo and in vitro expression of pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-6, and interleukin-1ß. Network pharmacology analysis revealed that MLN could act synergistically through multiple targets and pathways and exert a protective effect, possibly through inhibiting TLR4/ NF-κB signalling pathways. Western blotting and immunofluorescence experiments further confirmed that MLN could regulate the expression of TLR4, MyD88, phospho-IκB-α, and phospho-NF-κB p65 in the TLR4/NF-κB signalling pathway and decrease the translocation of phospho-NF-κB p65 into the nucleus. CONCLUSION: This study suggests that MLN has a potential protective effect against LPS-induced ALI, which might be associated with the inhibition of the TLR4/NF-κB signalling pathway. Therefore, MLN is worthy of further investigation as a potential candidate for the treatment of ALI in the future.

The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products.

Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.

Composite films of lecithin and heme proteins with electrochemical and electrocatalytic activities.

Functional composite films made from lecithin micelles and the two heme proteins of met-myoglobin (Mb) and met-hemoglobin (Hb) are reported in this paper. Proteins in functional composite films have much higher rates of electron transfer than proteins in solutions on carbon paste (CP) electrodes. Cyclic voltammograms (CVs) all give a pair of well-defined and quasi-reversible peaks, corresponding to the heme FeIII/FeII redox couple of proteins. Differential pulse voltammograms (DPVs) also show the same formal potential (E0') values of proteins under identical conditions. Electronic and vibrational spectra indicate that proteins in these films are not denatured, but their conformational differences from native states may exist. The E0' value for Mb in the lecithin film is found to be pH dependent. The Mb lecithin film can catalytically reduce O2 and H2O2, and its analytical application to H2O2 determination is established.