MMP-9 and IL-1β as Targets for Diatoxanthin and Related Microalgal Pigments: Potential Chemopreventive and Photoprotective Agents

Abstract

Photochemoprevention can be a valuable approach to counteract the damaging effects of environmental stressors (e.g., UV radiations) on the skin. Pigments are bioactive molecules, greatly attractive for biotechnological purposes, and with promising applications for human health. In this context, marine microalgae are a valuable alternative and eco-sustainable source of pigments that still need to be taken advantage of. In this study, a comparative in vitro photochemopreventive effects of twenty marine pigments on carcinogenic melanoma model cell B16F0 from UV-induced injury was setup. Pigment modulation of the intracellular reactive oxygen species (ROS) concentration and extracellular release of nitric oxide (NO) was investigated. At the cell signaling level, interleukin 1-β (IL-1β) and matrix metallopeptidase 9 protein (MMP-9) protein expression was examined. These processes are known to be involved in the signaling pathway, from UV stress to cancer induction. Diatoxanthin resulted the best performing pigment in lowering MMP-9 levels and was able to strongly lower IL-1β. This study highlights the pronounced bioactivity of the exclusively aquatic carotenoid diatoxanthin, among the others. It is suggested increasing research efforts on this molecule, emphasizing that a deeper integration of plant ecophysiological studies into a biotechnological context could improve the exploration and exploitation of bioactive natural products.

The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells

“…Diatoxanthin is an exclusively aquatic microalgal xanthophyll with a (photo-)protective role [ 27 , 28 , 53 ]. Recent findings highlighted its outstanding bioactivity, with marked antioxidant, anti-inflammatory, and chemopreventive properties ([ 27 , 33 ] unpublished data). Interestingly, Dt can induce ferroptosis in cancer cell lines [ 33 ].…”

“…Dt is eligible as a preventive/therapeutic agent against SARS-CoV-2 infection, cytokine storm consequences at the multiorgan level, and the long-term effects of infection due to the high levels of inflammatory markers in the blood [ 56 ]. A recent in vitro study highlighted that Dt displays antioxidant activity, and exerts an anti-inflammatory role [ 27 ]. Here, it is shown that Dt inhibits IL-6 release in lung cells exposed to the spike glycoprotein, and increases the IL-10 expression, providing an immunomodulatory signaling role.…”

“…Microalgae, instead, sharing photosynthetic and microbial properties, are a promising eco-sustainable alternative [ 60 , 61 , 62 , 63 , 64 , 65 ]. Moreover, the microalgae content and diversity in bioactive compounds—for example, vitamins, carotenoids, or polyphenols [ 23 , 27 , 66 , 67 , 68 ]—make them highly attractive bio-factories [ 60 , 67 , 68 , 69 ].…”

“…Nevertheless, in silico analysis carried out on nine xanthophylls demonstrated their ability to inhibit the main protease (Mpro) and the papain-like protease (PLpro) of SARS-CoV-2 [ 26 ]. It is noteworthy that microalgae present a high diversity of carotenoids, with some of them understudied [ 27 ]. This is the case of the xanthophyll diatoxanthin (Dt), belonging to diatoms and exerting a (photo-)protective role [ 28 , 29 , 30 , 31 , 32 ].…”

“…This is the case of the xanthophyll diatoxanthin (Dt), belonging to diatoms and exerting a (photo-)protective role [ 28 , 29 , 30 , 31 , 32 ]. Recently, its great antioxidant property and in vitro bioactivity have been demonstrated ([ 27 ], unpublished data), satisfying chemopreventive and anti-inflammatory potential, e.g., inhibiting a cytokine storm [ 27 , 33 ]. These recent studies pave the way for further investigation on the human health-induced bioactivity of Dt.…”