Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells

Kortesoja, Maarit; Karhu, Elina; Ólafsdóttir, Elín Soffia; Freysdóttir, Jona; Hanski, Leena

doi:10.1016/j.freeradbiomed.2018.12.019

Cited by 19 publications

(16 citation statements)

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“…Our previous studies in monocytic THP-1 cells showed that the lignans affect cellular glutathione metabolism by causing a decrease in total GSH pools [25]. Similar to monocytic THP-1 cells, THP-1 macrophages exhibited remarkably lowered GSH pools after lignan treatment ( Figure 5B), and a drastic decrease in GSH levels was also observed in C. pneumoniae-infected THP-1 macrophages after lignan exposure ( Figure 5C).…”

Section: Role Of Cellular Redox Status In the Effects Of Schisandrin supporting

confidence: 57%

“…Similar to monocytic THP-1 cells, THP-1 macrophages exhibited remarkably lowered GSH pools after lignan treatment ( Figure 5B), and a drastic decrease in GSH levels was also observed in C. pneumoniae-infected THP-1 macrophages after lignan exposure ( Figure 5C). Our previous studies in monocytic THP-1 cells showed that the lignans affect cellular glutathione metabolism by causing a decrease in total GSH pools [25]. Similar to monocytic THP-1 cells, THP-1 macrophages exhibited remarkably lowered GSH pools after lignan treatment ( Figure 5B), and a drastic decrease in GSH levels was also observed in C. pneumoniae-infected THP-1 macrophages after lignan exposure ( Figure 5C).…”

Section: Role Of Cellular Redox Status In the Effects Of Schisandrin supporting

confidence: 57%

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Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

et al. 2020

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Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia–host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.

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Section: Role Of Cellular Redox Status In the Effects Of Schisandrin supporting

confidence: 57%

Section: Role Of Cellular Redox Status In the Effects Of Schisandrin supporting

confidence: 57%

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

et al. 2020

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“…Based on rodent bioavailability studies, micromolar plasma concentrations of the lignans can be achieved after a single oral dose 56 , indicating the potential of the lignans as leads for orally administered drugs. Furthermore, our in vitro cell viability data (Supplementary information, 29, 42 and the numerous in vivo studies on these compounds 45 indicate the lack of acute or subacute toxicity of the lignans.…”

Section: Resultsmentioning

confidence: 78%

“…The promotion of redox activities is linked to their ability to modulate mitochondrial functions 46, 47 . In addition, our previous studies in monocytic THP-1 cells showed that the lignans affect cellular glutathione metabolism by causing a decrease in total GSH pools 42 . Similar to monocytic THP-1 cells, THP-1 macrophages exhibit remarkably lowered GSH pools after lignan treatment (Fig.…”

Section: Resultsmentioning

confidence: 96%

“…Previous work has highlighted the role of NO and inducible nitric oxide synthase (iNOS) as a trigger for chlamydial persistence in murine RAW264.7 macrophages 17, 37 . NO production in in PBMCs and macrophages involves, however, remarkable inter-species differences 40, 41 and based on data published by us and other research groups, the human THP-1 cell line produces NO neither in its monocytic nor macrophage like phenotype 42–44 . The lack of iNOS induction after chlamydial trigger can be speculated to enable the productive C. pneumoniae infection in THP-1 macrophages, yet more comprehensive picture on host cell redox status is necessary in order to draw conclusions in this respect.…”

Section: Resultsmentioning

confidence: 97%

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

Taavitsainen

Kortesoja

Hanski

2019

Preprint

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23Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need 24 for extended antibiotic treatment. Taking persisters into account in susceptibility assays is thus an essential 25 success factor in antibacterial drug discovery. The virulence of the obligate intracellular bacterium 26Chlamydia pneumoniae is tightly linked to its propensity for persistence, but current susceptibility 27 screening on this gram-negative respiratory pathogen relies on permissive epithelial cells. To establish an 28 improved antichlamydial susceptibility assay allowing the analysis of both actively growing and persister 29 bacteria, we studied C. pneumoniae clinical isolate CV-6 infection kinetics in THP-1 macrophages by qPCR 30 and quantitative culture. Indicated by the steady increase of chlamydial genome copy numbers and 31 infectious progeny as well as the failure of azithromycin to eradicate the intracellular forms of the 32 bacterium, the macrophages were found to harbor a subpopulation of persister C. pneumoniae cells. The 33 potential of the assay for the discovery of anti-persister molecules against intracellular bacteria was 34 demonstrated by the identification of the differential effects of two dibenzocyclooctadiene lignans on C. 35 pneumoniae infection. While schisandrin reverted C. pneumoniae persistence and promoted productive 36 infection, schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection. The 37 phenotypic switch was associated with the suppression of cellular glutathione pools, implying that targeting 38 glutathione homeostasis may provide a novel means for intracellular bacteria resuscitation. In conclusion, 39 these data highlight the value of macrophages over permissive cell lines in anti-persister agent discovery on 40 intracellular bacteria and targeting host cell redox status to fight persistent infections. 41 42 43 Keywords: persistent infection, antibiotic persistence, dormancy, phenotypic switch, glutathione, 44 antibacterial agent 45 46 47 48 49 50 51 52Owing to redundant mechanisms, these phenotypical variants are able to survive under antibiotic pressure 58 and revert back to metabolically more active phenotype when stressful conditions are cleared off. 59In clinical settings, bacterial dormancy is associated with hard-to-treat infections via two mechanistically 60 overlapping phenomena, persistent infections evading host immune responses and antibiotic persistence 61 defined based on the presence of drug-tolerant subpopulations of bacteria. Both of these features are 62 typical to infections caused by Chlamydia pneumoniae, a gram-negative obligate intracellular human 63 pathogen that causes respiratory infections from dry cough to pneumonia. While a majority of C. 64 pneumoniae infections are subclinical, nearly everyone getting infected during their lifetime, the bacterium 65 is also responsible for 5-10% of community-acquired pneumonia cases worldwide 3, 4 . C. pneumoniae has a 66 unique biphasic development cycle, whe...

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A Review of Extraction and Purification, Biological Properties, Structure–Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis

Xu,

Wang,

et al. 2023

Chemistry & Biodiversity

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Since ancient times, China has used natural medicine as the primary way to combat diseases and has a rich arsenal of natural medicines. With the progress of the times, the extraction of bioactive molecules from natural drugs has become the new development direction for natural medicines. Among the numerous natural drugs, Schisandrin C (Sch C), derived from Schisandra Chinensis (Turcz.) Baill. It has excellent potential for development and has been shown to possess various pharmacological properties, including hepatoprotective, antitumor and anti‐inflammatory activities. Based on the biological properties of hepatoprotection, scholars have explored Sch C and its synthetic products in depth; some studies have shown that pentosidine has the effect of improving the symptoms of liver fibrosis and reducing the concentration of alanine transaminase (ALT) and aspartate aminotransferase (AST) in the serum of rats, which is an essential inspiration for the development of anti‐liver fibrosis drugs. But more in vivo and ex vivo studies still need to be included. This paper focuses on Sch C′s extraction and synthesis, biological activities and drug development progress. The future application prospects of Sch C are discussed to perfect its development work further.

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Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells

Cited by 19 publications

References 76 publications

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

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

A Review of Extraction and Purification, Biological Properties, Structure–Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis

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