Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells

The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the most abundant intermediate involved in cholesterol biosynthesis and is highly enriched in red/brown algae. It exerts a pivotal role in modulating core genes involved in oxidative stress and inflammatory response processes in the ileum epithelial cells (IPI-2I). We observed that the DES extracted from red algae did not affect IPI-2I cell growth or survival. A transcriptomic measurement revealed that the genes enrolled in the oxidative process and cholesterol homeostasis pathway were significantly down-regulated by DES treatment. Consistent with this notion, cellular reactive oxygen species (ROS) levels were markedly decreased in response to DES treatment. In contrast, key inflammatory genes including IL-6, TNF-alpha, and IFN-gamma were remarkably upregulated in the RNA-seq analysis, as further confirmed by qRT-PCR. Given that DES is a specific agonist of nuclear receptor ROR gamma, we also found that DES caused the elevated expression of ROR gamma at mRNA and protein levels, suggesting it is a potential mediator under DES administration. Together, these results underscore the vital physiological actions of DES in inflammatory and oxidative processes possibly via ROR gamma, and may be helpful in anti-oxidation treatment and immunotherapy in the future.

Automated summary

The serum levels of cholesterol and its intermediates are important indicators of metabolism-related disorders. In this study, it was found that desmosterol (DES), the most abundant intermediate in cholesterol biosynthesis and highly enriched in red/brown algae, plays a crucial role in modulating genes related to oxidative stress and inflammatory response in ileum epithelial cells. DES treatment resulted in down-regulation of genes involved in oxidative and cholesterol homeostasis pathways, decreased cellular ROS levels, and upregulation of key inflammatory genes. DES also elevated the expression of nuclear receptor ROR-gamma, suggesting its potential role as a mediator. These findings highlight the physiological actions of DES in inflammatory and oxidative processes, and its potential applications in anti-oxidation treatment and immunotherapy in the future.