It's Not All About Drugs... Endogenous Molecules Can Be Therapeutics Too

Posted on May 23, 2022


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Until recently, bile acids were primarily known as digestive surfactants to aid the absorption of lipids or as the primary pathway for cholesterol catabolism. But today we now recognize bile acids as hormones. They are not just little helpers in biological systems, they are regulators of various metabolic processes. Some of these processes include regulating their own synthesis and circulation, but also the homeostasis of triglycerides, cholesterol, glucose, and energy.

Interest, and thus insight, related to bile acids and their function has rapidly increased in recent years. To meet the demands of the research community, the Avanti catalog has expanded to include more bile acids and bile salts than ever before. With the expansion of bile acid offerings, we have also created a pre-mixed lipidomics product, Bile Acid SPLASH ®, to aid efforts aimed towards new insights into the mechanism of bile acid signaling and their function in lipid metabolism. METLIN also identified bile acids as important additions to their CCS lipids database where you can now find more than 50 bile acids!

Lithocholic acid (LCA) is a secondary bile acid that acts like many other bile acids and aids the absorption of lipids in digestion. But that’s not all this bile acid does. Research has indicated that LCA can activate vitamin D receptor without raising calcium levels as high as Vitamin D itself. LCA has also been shown to bind with the NAPE-PLD enzyme and catalyze the release of anandamide and other N-acetylethanolamines. But one of the more interesting applications of LCA was discovered just last year.

In 2021, LCA (along with deoxycholic acid and 3-oxoLCA) were found to improve psoriasiform dermatitis. Not only did these bile acids show that they were able to improve the common skin condition, but that they were able to do so without hepatotoxicity. Of the tested bile acids, LCA was the most potent and was tested both orally and intravenously. Intravenous administration of a lower dose of LCA was able to induce a comparable antipsoriatic effect to the orally administered LCA.

How is LCA able to improve Psoriasis? LCA is capable of reducing the production of interleukin 17A (IL-17A) which is a member of the IL-17 family known to be involved in the pathogenesis of inflammatory autoimmune diseases like psoriasis. Specifically, IL-17A and IL-17F are highly expressed in psoriatic skin. IL-17A also works with Th17 cytokines to upregulate the production of several chemokines implicated in psoriatic pathogenesis. Previous reports have indicated that IL-17A-targeting antibodies are impressive agents to combat psoriasis. So, LCA works in a similar manner and inhibits the production of IL-17A which consequently improves psoriasis of the skin.

Not even two decades old, researching bile acids as signaling molecules has already led to some pretty interesting findings and could lead to new, innovative uses for bile acids in therapeutics. Having readily available bile acid standards and analytical data only improves the likelihood that this may happen. Check out METLIN’s CCS lipids database of over 860,000 molecules and Avanti’s bile acid catalog if you’re interested in discovering the next big role that these molecules play!

Reference: https://linkinghub.elsevier.co...