Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro : implications for COVID-19 treatment

  1. Kurt Lucas
  2. Maximilian Ackermann
  3. Anna Lena Leifke
  4. William W. Li
  5. Ulrich Pöschl
  6. Janine Fröhlich-Nowoisky

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Abstract

Overshooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate inflammatory signaling in vitro . Cinnamaldehyde interferes with the dimerization of toll-like receptor 4 (TLR4), which can be activated by DAMPs like HSP60 and HMGB1. Our results suggest that supplementary treatment with Ceylon cinnamon may allow administration of lower doses of dexamethasone to avoid high dose steroid side effects. Moreover, preliminary results indicate that Ceylon cinnamon modulates angiogenesis, which is a reactive phenomenon in COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.06.16.448642: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The THP-1 cells were seeded in 96-well V-bottom cell culture plates (Greiner Bio-One GmbH, Frickenhausen, Germany) at a density of 4×104 cells in 100 μL growth medium per well and allowed to settle for 1 h.
    THP-1
    suggested: None
    Cultivation of HUVEC Cells: HUVEC cells (Lonza) were cultivated in endothelial cell medium (EGM-2; Lonza) containing 2% fetal bovine serum (FBS) and vascular endothelial growth factor (VEGF) for rapid proliferation.
    HUVEC
    suggested: KCB Cat# KCB 200648YJ, RRID:CVCL_2959)
    Experimental Models: Organisms/Strains
    SentencesResources
    CCE was diluted 1:10 in Dulbecco’s Phosphate Buffered Saline (DPBS -/-) (Thermo Fisher Scientific Inc.
    DPBS -/-
    suggested: None
    Software and Algorithms
    SentencesResources
    Using Gen5 software (Biotek), the reference wavelength values were subtracted from the absorbance wavelength values.
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    Statistical analysis and corresponding graphs were generated with Prism 9 software (GraphPad Software, San Diego, USA)
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Single-strand cDNA was synthesized from 500 ng RNA per sample using the High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific) following the standard protocol. cDNA (2.1 ng) served as template for a qPCR reaction using SsoAdvanced™ Universal SYBR® Green Supermix (Bio-Rad Laboratories, Hercules, USA) and forward and reverse primers in a final concentration of 333 nM each.
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Primer sequences were designed with Primer-BLAST software (NCBI) (Table 1)
    Primer-BLAST
    suggested: (Primer-BLAST, RRID:SCR_003095)
    Data analysis was performed with CFX Manager software 3.1 (Bio-Rad) using the 2-ΔΔCT method to calculate gene expression.
    CFX Manager
    suggested: (CFX Manager, RRID:SCR_017251)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.06.16.448642v1 on bioRxiv