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Semisynthetic Abietic and Dehydroabietic Acid Derivatives and Triptoquinone Epimers Interfere with LPS-Triggered Activation of Dendritic Cells. | LitMetric

AI Article Synopsis

  • Abietic acid (AA), dehydroabietic acid (DHA), and triptoquinones (TQs) are plant-derived compounds known for their health benefits, particularly in modulating immune responses and inflammation.
  • Researchers screened 23 semi-synthetic derivatives of AA, DHA, and TQs to determine their effects on the production of pro-inflammatory cytokines in dendritic cells, revealing a range of inhibitory activities among them.
  • The most effective compounds significantly inhibited the expression of critical co-stimulatory molecules and pro-inflammatory cytokines, suggesting the potential for developing these derivatives as anti-inflammatory and immunomodulatory agents.

Article Abstract

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1β, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571164PMC
http://dx.doi.org/10.3390/molecules27196684DOI Listing

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