Inhibitory Effect of the Traditional Chinese Medicine <i>Ephedra sinica granules</i> on <i>Streptococcus pneumoniae</i> Pneumolysin

Abstract

Streptococcus pneumoniae (S. pneumoniae) is an opportunistic pathogen that causes pneumonia, meningitis and bacteremia in humans and animals. Pneumolysin (PLY), a major pore-forming toxin that is important for S. pneumoniae pathogenicity, is a promising target for the development of anti-infective agents. Ephedra sinica granules (ESG) is one of the oldest medical preparation with multiple biological activities (such as a divergent wind and cold effect); however, the detailed mechanism remains unknown. In this study, we found that ESG treatment significantly inhibited the oligomerization of PLY and then reduced the activity of PLY without affecting S. pneumoniae growth and PLY production. In a PLY and A549 cell coincubation system, the addition of ESG resulted in significant protection against PLY-mediated cell injury. Furthermore, S. pneumoniae-infected mice showed decreased mortality, and alleviated tissue damage and inflammatory reactions following treatment with ESG. Our results indicate that ESG is a potential candidate treatment for S. pneumoniae infection that targets PLY. This finding partially elucidates the mechanism of the Chinese herbal formula ESG in the treatment of pneumococcal disease.

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

“…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.…”

Pneumolysin: Pathogenesis and Therapeutic Target

“…Investigation of other natural compounds have identified chemical moieties important to blocking of PLY hemolytic activity and perhaps to the design of future inhibitors of PLY (Li et al, 2017). Similar studies have also reported prevention and attenuation of pneumococcal infection using compounds that prohibit PLY oligomerization (Li et al, 2020;Lv et al, 2020;Xu et al, 2020). These compounds potentially show promise as tools for developing small molecule adjuvant therapies in the prevention or treatment pneumococcal infection and studying PLY interactions.…”

Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption

“…Artemisinin, an active molecule isolated from Artemisia annua Linn., has saved the lives of millions of people suffering from malaria [12] , [13] . Compared to the existing antibiotics, antimicrobial compounds from traditional Chinese medicine have better bactericidal activity and can reverse multidrug resistance in bacteria [14] , [15] . For example, Scutellaria baicalensis extracts may be effective against inflammation and Salmonella enteritidis infection [16] .…”