Improving Anti-Inflammatory Effect of Luteolin with Nano-Micelles in the Bacteria-Induced Lung Infection

Abstract

The effective therapy for lung infectious diseases became more and more difficult since the severe antibiotic resistance of pathogenic microorganisms, it is urgent to develop new antimicrobial agents. Luteolin has been reported to play a crucial part in host immune responses. However, the clinical use of luteolin is impeded due to its hydrophobicity and low oral bioavailability. In this study, we formulated luteolin-loaded Methoxy poly(ethylene glycol)-poly(lactide) micelles (luteolin/MPEG-PLA), to improve the bioavailability of luteolin in lung infectious diseases. The results showed that luteolin/MPEG-PLA treatment could reduce the adhesion of Klebsiella pneumoniae (K. pneumoniae) to lung epithelial cells and enhance the germicidal ability of macrophages against K. pneumoniae compared to untreated group. Meanwhile, luteolin/MPEG-PLA showed stronger adhesion resistance of epithelial cells and germicidal ability of macrophages compared with free luteolin. In vivo study, luteolin/MPEG-PLA administration significantly promoted the clearance of bacteria and reduced inflammatory infiltration of lung tissue in K. pneumoniae induced lung infectious mice model. Further studies showed that treatment with luteolin/MPEG-PLA reduced the mRNA expression of LPS-induced inflammatory cytokines and chemokines in macrophages significantly. In general, luteolin/MPEG-PLA can enhance the anti-bacterial ability of lung epithelial cells and macrophages, and has a stronger therapeutic effect than free luteolin in bacterial-induced lung infection. Luteolin/MPEG-PLA may be an excellent potential drug for bacterial-induced lung infectious diseases treatment.

Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan–indocyanine green/luteolin nanocomposites for wound healing

“…Although the quorum sensing inhibitor agent has evolved as a promising weapon against infections, LUT suffers from inadequate bactericidal effect and poor solubility [ 26 ]. To address these limitations, nanoscale carriers were applied to improve their bioavailability toward achieving the bacteria-killing efficiency of LUT [ 27 , 28 ]. Compared with free drugs, this nanoplatform could assist in biofilm eradication due to reducing drug absorption rate to extracellular polymeric substances, avoiding drug degradation in the biofilm and achieving sustained release of drug [ 29 ].…”

Luteolin Binds Streptolysin O Toxin and Inhibits Its Hemolytic Effects and Cytotoxicity

“…At present, luteolin has been used in food packaging films to exert long-term antioxidant and antibacterial activities during food storage ( Bi et al, 2021 ). Scientists are constantly trying various methods to increase the bioavailability of luteolin, one example is the use of luteolin-loaded Methoxy poly(ethylene glycol)-poly(lactide) micelles that can significantly promote bacterial clearance while reducing inflammatory infiltration in a mouse model of pulmonary infection caused by Klebsiella pneumoniae ( Miao et al, 2021 ). Recent studies have demonstrated that luteolin can alleviate olfactory dysfunction after COVID-19, which provides further support for the clinical application of luteolin ( D'Ascanio et al, 2021 ).…”

Antibacterial Modes of Herbal Flavonoids Combat Resistant Bacteria

“…HAC AO flavonoids are able to combat bacterial infection with their antioxidation function, by reducing the free radicals and lipid peroxidation to inhibit oxygen-derived radicals or nitrogen-derived radicals to avoid oxidative damage ( Kamdi et al, 2021 ; Palierse et al, 2021 ) In addition, this antibacterial activity mainly relies on the phenolic hydroxy group of flavonoid compounds, such as quercetin and hyperoside ( Figures 3C , 4A ) ( Xie et al, 2015 ). For the HAC AI flavonoids, the major anti-inflammatory modes of flavonoid compounds are inhibition of protein kinases (COX, cyclooxygenase, LOX, lipoxygenase and PLA2, phospholipase A2), inflammatory factors (IL-1, IL-4, IL-10, and IL-13) and related transcription factors (NF-κB, GATA-3, and STAT-6) ( Park et al, 2018 ; Ren et al, 2019 ; Kamdi et al, 2021 ; Miao et al, 2021 ). The anti-inflammatory flavonoid compounds include apigenin, baicalein, baicalin, luteolin, lonicerin, tamarixetin, rutin, phloridzin, isoliguirtigentin, puerarin, and catechin ( Table 1 ).…”