Anti-inflammatory, immuno-modulatory, and anti-proliferative effects of 5-mer Oligogalacturonides (OG DP5) from citrus pectin on different types of human cells. Perspectives for treatment of dermal diseases such as atopic dermatitis and psoriasis

Oligogalacturonides (OG) are natural plant cell wall pectin-derived products with different degrees of polymerisation (DP) and methylation (M) (see Yu et al. 2022 ). Their effects as stimulators of plant defence are well documented and they are also known for their potent effects on human health. Here, we investigated the anti-inflammatory effects of OG extracted from Citrus on different types of human cells and cell systems representative of several pathologies. Different concentrations of 5-mer OG (DP5) with different methylation degrees (M: 0, 5, 30 and 70) were tested on cultured human peripheral blood mononuclear cells (PBMC) to see if there were able to decrease LPS-induced IL-1β release. Then, different human cell combination stimulated by specific agonists representative of several pathologies were used to test the effect of the most active OG DP5M0 (0 methylation). IL-1β was monitored in the PBMC culture medium with ELISA and effects on bio-markers typical of pathologies were studied using the BioMAP Diversity PLUS® method (Eurofins, France). DP5M0 dose-dependently reduced LPS-induced IL-1β release by cultured human peripheral blood mononuclear cells (PBMC). This was not observed for DP5M30 or DP5M70. DP5M0 was also more efficient than prednisolone when tested on 12 different human cell systems representative of known pathologies (BioMAP systems). The T BioMAP system, which consists in an equal combination of B cells and PBMC, shows the best response sensitivity to DP5M0. This latter induces a dose-dependent decrease of the biomarkers of inflammation and of those of immune responses (IL-6, IL-8, IL-2, IL-17A, IL-17F and TNF-α). In view that all these cytokines are involved in keratinocytes proliferation and differentiation, this model system fits with a possible beneficial effect of DP5M0 on atopic dermatitis and psoriasis. DP5M0 also showed anti-proliferative properties in 5 different cell systems. The comparison of the BioMAP profiles of DP5M0 and anti-inflammatory products prednisolone and diclofenac indicates that their modes of action are different. These data argue for a possible use of DP5M0 for treatments of psoriasis diseases as alternative strategy to other developed medicines when the patients do not tolerate them.