Dibenzocyclooctadiene lignans from Schisandra spp. selectively inhibit the growth of the intracellular bacteria Chlamydia pneumoniae and Chlamydia trachomatis

Abstract

Lignans from Schisandra chinensis berries show various pharmacological activities, of which their antioxidative and cytoprotective properties are among the most studied ones. Here, the first report on antibacterial properties of six dibenzocyclooctadiene lignans found in Schisandra spp. is presented. The activity was shown on two related intracellular Gram-negative bacteria Chlamydia pneumoniae and Chlamydia trachomatis upon their infection in human epithelial cells. All six lignans inhibited C. pneumoniae inclusion formation and infectious progeny production. Schisandrin B inhibited C. pneumoniae inclusion formation even when administered 8 h post infection, indicating a target that occurs relatively late within the infection cycle. Upon infection, lignan-pretreated C. pneumoniae elementary bodies had impaired inclusion formation capacity. The presence and substitution pattern of methylenedioxy, methoxy and hydroxyl groups of the lignans had a profound impact on the antichlamydial activity. In addition our data suggest that the antichlamydial activity is not caused only by the antioxidative properties of the lignans. None of the compounds showed inhibition on seven other bacteria, suggesting a degree of selectivity of the antibacterial effect. Taken together, the data presented support a role of the studied lignans as interesting antichlamydial lead compounds.

Antimicrobial Resistance and the Alternative Resources with Special Emphasis on Plant-Based Antimicrobials—A Review

“…Lignans isolated from Pseudolarix kaempferi were reported to have antimicrobial activity against Candida albican and S. aureus [43]. Dibenzocyclooctadiene lignin isolated from Schissandra chinensis inhibits the growth of Chlamydia trachomatis and C. pneumonia [44]. …”

Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies

“…The essential oil, and also an extract from schisandra berry showed antibacterial effects against Gram positive ( Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis ) and Gram negative ( Chlamydia pneumoniae, C. trachomatis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris ) bacteria (Chen et al 2011; Hakala et al 2015). …”

Assaying Chlamydia pneumoniae persistence in monocyte-derived macrophages identifies schisandrin lignans as phenotypic switchers

“…Despite their similar effects on cellular ROS and GSH levels, schisandrin and schisandrin C show differential activity on the C. pneumoniae infection in THP-1 macrophages. This may reflect two separate aspects of their biological activities: a redox-dependent phenotypic switch by C. pneumoniae from persister to active replication and a dual mode of antichlamydial action by schisandrin C. While schisandrin C exhibits chlamydiocidal activity in the acute infection model, schisandrin does not affect actively dividing bacteria at 25 μM concentration 29 . Based on these observations, we propose that depleting cellular GSH stimulates chlamydial growth, and persistent infection is converted to active state.…”

“…We have recently identified the antichlamydial activity of dibenzocyclooctadiene lignans isolated from a medicinal plant Schisandra chinensis against the actively replicating bacteria in respiratory epithelial cells 28, 29 . Within the validation process on the current assay, three of these lignans, schisandrin, schisandrin B and schisandrin C were evaluated for their efficacy against C. pneumoniae in the THP-1 macrophage model at concentrations determined based on cell viability assays (Supplementary Tables 1 and 2).…”