Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR/NF-κB Signaling at Different Levels

Abstract

Inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, are increasing in populations worldwide. The treatment of patients with AD and other forms of skin inflammation is mainly based on the use of topical corticosteroids or calcineurin inhibitors, which can cause significant side effects with long-term use. Therefore, there is a great need for the development of more effective and less toxic anti-inflammatory agents suitable for the treatment of chronic skin lesions. Here, we screened a number of strains from the ASIB 505 terrestrial algae collection and identified a green algae Chromochloris zofingiensis with pronounced anti-inflammatory properties. We found that a crude nonpolar extract of C. zofingiensis (ID name NAE_2022C), grown upon nitrogen deprivation, acts as a bioactive substance by inhibiting TNFR/NF-κB responses in human skin keratinocyte HaCaT cells. We also found that NAE_2022C suppressed the secretion of pro-inflammatory cytokine tumor necrosis factor α (TNFα) and several Th1- and Th2-related chemokines in a reconstituted human epidermis. The TNFR/NF-κB pathway analysis showed multiple inhibitory effects at different levels and disclosed a direct targeting of IKKβ by the extract. Bioassay-guided fractionation followed by high-resolution mass spectrometry detected diacylglyceryl-trimethylhomoserine (DGTS), Lyso-DGTS (LDGTS), 5-phenylvaleric acid, theophylline and oleamide as leading metabolites in the active fraction of NAE_2022C. Further analysis identified betaine lipid DGTS (32:0) as one of the active compounds responsible for the NAE_2022C-mediated NF-κB suppression. Overall, this study presents an approach for the isolation, screening, and identification of anti-inflammatory secondary metabolites produced by soil algae.

The Clinical Promise of Microalgae in Rheumatoid Arthritis: From Natural Compounds to Recombinant Therapeutics

“…Betaine lipids derive from the turnover of membrane phospholipids under abiotic stresses, mainly temperature and nutrient starvation [147][148][149]. The betaine lipid 1,2diacylglyceryl-3-O-4'-(N,N,N-trimethyl)-homoserine (DGTS, Figure 3E) is the most abundant betaine lipid in microalgae, followed by 1,2-diacylglyceryl-3-O-carboxy-(hydroxymethyl)choline (DGCC, Figure 3F), and 1,2-diacylglyceryl-3-O-2'-(hydroxymethyl)-(N,N,N-trimethyl)β-alanine (DGTA, Figure 3G), with evidence of DGTS-mediated inhibition of the IKK-β kinase causing suppression of the NF-κB pathway and secretion of pro-inflammatory ILs by Th1 and Th2 cells, as recently reported with extracts from the oleaginous chlorophyte Chromochloris zofingiensis (Chlorophyceae) [150].…”

Polar Lipids of Marine Microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis Mitigate the LPS-Induced Pro-Inflammatory Response in Macrophages

“…They are strongly implicated in the pathogenesis of inflammatory diseases like rheumatoid arthritis, atherosclerosis [45], and diabetes [46]. Interestingly, previous work with DGTS-enriched extracts from the soil alga Chromochloris zofingiensis and DGDG species isolated from Iscochrysis galbana and from the cyanobacterium Nodularia harveyana showed strong inhibitory activity against TNF-α secretion [47][48][49]. Thus, this corroborates the strong inhibitory power of these lipids against these cytokines.…”

Prevention of UVB Induced Metabolic Changes in Epidermal Cells by Lipid Extract from Microalgae Nannochloropsis oceanica

“…Furthermore, considering that the activity of the BCRP transporter is enhanced after the irradiation with UVB and the supplementation with the microalga extract, this could improve the transport of these components across keratinocyte membranes. It is known that lipid extracts from algae contain numerous compounds with antioxidant properties, such as PUFAs and low-molecular weight lipophilic compounds [24,[48][49][50][51][52][53], which may have a protective effect after entering cells.…”