The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin

Guo, Tingting; Guo, Yinan; Liu, Qingbing; Xu, Yan; Wei, Lian-Qiang; Wang, Zhongtian; Chen, Si; Wang, Caiwen; Tian, Yange; Cui, Jie; Wang, Yijie; Li, Han; Sun, Liping

doi:10.1016/j.jep.2021.114133

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…Ephedrine hydrochloride and Pseudoephedrine hydrochloride are phenethylamines from Ephedra sinica granules [ 86 ] and MXSGT (Ma-xing-shi-gan-tang) [ 87 ] are compounds obtained from plants used in traditional Chinese medicine. All of them seem to inhibit the oligomerization of the toxin, although more studies are necessary to specify which residues of PLY are involved.…”

Section: Resultsmentioning

confidence: 99%

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

et al. 2023

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Background This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction. Methods The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework. Results Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability. Discussion Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis. Conclusion A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.

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Section: Resultsmentioning

confidence: 99%

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

et al. 2023

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“…The ability of S. pneumoniae to spread and colonize in a host is a key aspect of pneumococcal population biology and a prerequisite for invasion. 10,36 PLY is an intracellular protein expressed in traditional Chinese medicine extracts and main compounds 14,37,38 can effectively inhibit the synthesis of the PLY protein. In this experiment, we found that wogonin could significantly decrease the haemolytic activity of PLY.…”

Section: Discussionmentioning

confidence: 99%

“…Only when autolysin A of S. pneumoniae is activated and self‐cleavage occurs is PLY released into the extracellular environment in large quantities. Recent research shows that some traditional Chinese medicine extracts and main compounds 14 , 37 , 38 can effectively inhibit the synthesis of the PLY protein. In this experiment, we found that wogonin could significantly decrease the haemolytic activity of PLY.…”

Section: Discussionmentioning

confidence: 99%

Wogonin attenuates the pathogenicity of Streptococcus pneumoniae by double‐target inhibition of Pneumolysin and Sortase A

Ding

Wang

et al. 2023

J Cellular Molecular Medi

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Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore‐forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface‐associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY‐mediated cell damage and reduced SrtA‐mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony‐forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF‐α, IL‐6 and IL‐1β in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection.

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“…31,32 Maxing Shigan decoction (MXSGT), a TCM formula first documented in Shang Han Lun, which was compiled by Zhong Jing Zhang over 2000 years ago, has been widely used to treat various diseases such as cough, fever, and pneumonia. 33 It consists of Gypsum Fibrosum (Shi gao), Ephedrae herba (Ma huang), Armeniacae Semen Amarum (Ku xing ren), and Glycyrrhizae Radix Et Rhizoma (Gan cao). However, despite its well-known heat-removing and detoxifying properties, the mechanism underlying the antipyretic effect of MXSGT is yet to be fully understood.…”

Section: Introductionmentioning

confidence: 99%

Study on the Nanoaggregate Formation Mechanism and Antipyretic Effect of Maxing Shigan Decoction

Zhao,

Zhang,

Fan

et al. 2024

ACS Omega

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Traditional Chinese medicine (TCM) formula decoctions easily form nanoaggregates due to self-assembly during the decoction process. However, research on nanoaggregates in TCM is still in its infancy with limited systematic studies. Maxing Shigan Decoction (MXSGT), a TCM formula, has been commonly used for the treatment of fever for thousands of years in China. This study used MXSGT as an example to investigate the antipyretic effects of MXSGT nanoaggregates (MXSGT-NAs) in its decoction, shedding light on the compatibility mechanisms of Chinese medicine. MXSGT-NAs were isolated by using high-speed centrifugation and dialysis techniques. The morphology, particle size distribution, and electrical potential of MXSGT-NAs were characterized. High-performance liquid chromatography (HPLC) was used to detect ephedrine and pseudoephedrine in MXSGT-NAs. The self-assembly mechanism of MXSGT-NAs was investigated by deconstructing the prescription. In pharmacodynamic experiments, a rat fever model was established through the subcutaneous injection of dry yeast to investigate the antipyretic effects of MXSGT-NAs. The results showed the presence of regularly shaped spherical nanoaggregates in MXSGT. It contains carbon, oxygen (O), sulfur (S), sodium, aluminum (Al), calcium (Ca), iron, magnesium, bismuth (Bi), etc. MXSGT-NAs exerted substantial antipyretic effects on febrile rats. Furthermore, we found micrometer-sized particles composed of Ca, O, S, potassium, and Bi in Shi gao decoctions. This study is the first to provide evidence for the self-assembling property of Shi gao, elucidate the scientific connotation of dispensing Shi gao in MXSGT, and provide a novel perspective for the study of TCM decoctions.

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The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin

Cited by 12 publications

References 25 publications

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

Wogonin attenuates the pathogenicity of Streptococcus pneumoniae by double‐target inhibition of Pneumolysin and Sortase A

Study on the Nanoaggregate Formation Mechanism and Antipyretic Effect of Maxing Shigan Decoction

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