Research Paper onTriptoquinone epimers and semi-synthetic abietic and dehydroabietic acid derivatives inhibit dendritic cell activation caused by LPS.

Description

Title: Triptoquinone epimers and semi-synthetic abietic and dehydroabietic acid derivatives inhibit dendritic cell activation caused by LPS.

Abstract: Abietic acid (AA), dehydroabietic acid (DHA), and triptoquinones (TQs) are bioactive abietane-type diterpenoids that have health-improving properties and are found in a variety of edible vegetables and medicinal herbs. Evidence suggests that diterpenes’ advantageous effects work, at least in part, by influencing immune system cells. A key class of leukocyte known as dendritic cells (DCs) is involved in the induction and control of the immune/inflammatory response. Natural or synthetic substances that alter DC function may have anti-inflammatory or immune-modulating properties. Here, we present the results of an assay using a multi-analyte DC platform to screen 23 known semi-synthetic AA, DHA, and TQ derivatives for their ability to inhibit the production of pro-inflammatory cytokines. A range of activities among compounds, from inactive/weak to very potent inhibitors, were seen, depending on the strength of the inhibitory effect seen and the number of cytokines inhibited. Compounds with higher inhibitory properties structurally exhibited alcohol or methyl ester substituents on ring A, aromaticity and oxidation in ring C, as well as alcohol or methyl ester substituents on ring A. Further research was done on two DHA derivatives and two TQs that showed a significant inhibition of all pro-inflammatory cytokines tested. The outcomes demonstrated their capacity to inhibit the production of the pro-inflammatory cytokines IL-1, IL-6, IL-12, and TNF and the dose-dependent expression of the co-stimulatory molecules CD40 and/or CD86 in response to LPS. Our findings show that semi-synthetic DHA derivatives and TQ epimers can target the DC maturation process, suggesting the potential of these substances as tailorable anti-inflammatory/immunomodulatory drugs.

Keywords: abietane diterpenes; dehydroabietic acid; triptoquinone; cytokines; dendritic cells; surface co-stimulatory molecules

Paper Quality: SCOPUS / Web of Science Level Research Paper

Subject: Chemistry

Writer Experience: 20+ Years

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