Baicalin Protects Mice From Staphylococcus aureus Pneumonia Via Inhibition of the Cytolytic Activity of α-Hemolysin

Qiu, Jiazhang; Niu, Xiaodi; Dong, Jing; Wang, Dacheng; Wang, Jianfeng; Li, Hongen; Luo, Mingjing; Li, Shentao; Feng, Hailan; Deng, Xuming

doi:10.1093/infdis/jis336

Cited by 130 publications

(122 citation statements)

References 36 publications

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“…Bronchoalveolar lavage (BAL) fluid collections were administered twice by intratracheal instillation of 500 ml of sterile PBS. The clear surface liquid obtained after centrifugation was collected, and the lavage fluid supernatants were used for cytokine detection (Qiu et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers

Zhao

Wang

et al. 2015

Mol Pharmacol

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Pneumolysin (PLY), an essential virulence factor of Streptococcus pneumoniae (pneumococcus), can penetrate the physical defenses of the host and possesses inflammatory properties. The vital role PLY plays in pneumococcus pathogenesis makes this virulence factor one of the most promising targets for the treatment of pneumococcal infection. Verbascoside (VBS) is an agent that does not exhibit bacteriostatic activity but has been shown to inhibit PLY-mediated cytotoxicity. The results from molecular dynamics simulations and mutational analysis indicated that VBS binds to the cleft between domains 3 and 4 of PLY, thereby blocking PLY's oligomerization and counteracting its hemolytic activity. Moreover, VBS can effectively alleviate PLY-mediated human alveolar epithelial (A549) cell injury, and treatment with VBS provides significant protection against lung damage and reduces mortality in a pneumococcal pneumonia murine model. Our results demonstrate that VBS is a strong candidate as a novel therapeutic in the treatment of Streptococcus pneumoniae infection.

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Section: Methodsmentioning

confidence: 99%

Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers

Zhao

Wang

et al. 2015

Mol Pharmacol

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“…Increasing evidence indicated that certain natural products protect mice from S. aureus pneumonia (26)(27)(28). A previous study demonstrated that resveratrol had obvious anti-bacterial activities against clinical isolates of methicillin-resistant S. aureus (29).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol alleviates Staphylococcusï¿½aureus pneumonia by inhibition of the NLRP3 inflammasome

Su-xia

Huang

2017

Exp Ther Med

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Abstract. Staphylococcus aureus (S. aureus) causes a wide variety of infections, including S. aureus pneumonia. Resveratrol, a natural polyphenolic compound contained in several plant species, exerts various activities, including anti-bacterial and pulmonary protective activities. The aim of the present study was to evaluate the protective effect of resveratrol on a murine model of S. aureus pneumonia and to elucidate the underlying mechanisms. It was found that resveratrol significantly reduced S. aureus-induced mortality, ameliorated lung injury and decreased cytokine levels in the bronchoalveolar lavage fluid and lung tissue of S. aureus infected-mice. In addition, reverse-transcription quantitative polymerase chain reaction and western blot assays showed that resveratrol markedly decreased the mRNA and protein expression of nucleotide-binding domain and leucine-rich repeat containing gene family pyrin domain containing 3 protein (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain and caspase-1. These results demonstrated that resveratrol significantly alleviates S. aureus pneumonia in mice, the possible underlying mechanism of which is associated with the inhibition of the NLRP3 inflammasome. The present study suggested that resveratrol is a potentially useful agent for the treatment of S. aureus pneumonia and S. aureus-induced infectious diseases.

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“…21,[28][29][30] Qiu et al previously reported that baicalin, a kind of flavonoid, inhibited the cytolytic activity of alpha-hemolysin by blocking the assembly of the alpha-hemolysin monomer to a heptamer and also had a protective effect against S. aureus pneumonia in a mouse model. 21) In the present study, we determined whether baicalin inhibited the activity of ALH. Our results showed that baicalin did not inhibit the activity of ALH, but was effective against that of alpha-hemolysin.…”

Section: Discussionmentioning

confidence: 99%

“…21) We tested the effect of baicalin to the hemolytic activity of ALH. However, baicalin did not inhibit the activity of ALH (Fig.…”

Section: Synthesis Of Indolo[32-b]quinoline Derivativesmentioning

confidence: 99%

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Indolo[3,2-b]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by Aeromonas sobria and Alpha-Hemolysin Produced by Staphylococcus aureus

Takahashi

Fujinami

Kuroda

et al. 2016

Biological & Pharmaceutical Bulletin

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In an attempt to discover inhibitory compounds against pore-forming toxins, some of the major toxins produced by bacteria, we herein examined the effects of four kinds of indolo[3,2-b]quinoline derivatives on hemolysis induced by the aerolysin-like hemolysin (ALH) of Aeromonas sobria and also by the alphahemolysin of Staphylococcus aureus. The results showed that hemolysis induced by ALH was significantly reduced by every derivative, while that induced by alpha-hemolysis was significantly reduced by three out of the four derivatives. However, the degrees of reduction induced by these derivatives were not uniform. Each derivative exhibited its own activity to inhibit the respective hemolysin. Compounds 1 and 2, which possessed the amino group bonding the naphthalene moiety at the C-11 position of indolo[3,2-b]quinoline, had strong inhibitory effects on the activity of ALH. Compound 4 which consisted of benzofuran and quinoline had strong inhibitory effects on the activity of alpha-hemolysin. These results indicated that the amino group bonding the naphthalene moiety of compounds 1 and 2 assisted in their ability to inhibit ALH activity, while the oxygen atom at the 10 position of compound 4 strengthened its interaction with alpha-hemolysin. These compounds also suppressed the hemolytic activity of the supernatant of A. sobria or A. hydrophila, suggesting that these compounds were effective at the site of infection of these bacteria.

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Baicalin Protects Mice From Staphylococcus aureus Pneumonia Via Inhibition of the Cytolytic Activity of α-Hemolysin

Cited by 130 publications

References 36 publications

Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers

Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers

Resveratrol alleviates Staphylococcusï¿½aureus pneumonia by inhibition of the NLRP3 inflammasome

Indolo[3,2-<i>b</i>]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by <i>Aeromonas sobria</i> and Alpha-Hemolysin Produced by <i>Staphylococcus aureus</i>

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