How does TUDCA work?

In vitro and animal studies have demonstrated that TUDCA can maintain cellular health by reducing stress to the endoplasmic reticulum (ER).^[1][2][3] The ER is an organelle inside cells that folds proteins so they can function properly. ER stress occurs under certain physiological conditions and results in poor protein folding, a lack of proper protein function, and the triggering of the unfolded protein response which leads to inflammation, fibrosis, or apoptosis (cell death).^[1] Because ER stress is a key component of several chronic conditions, molecules like TUDCA that can reduce ER stress have potential therapeutic value.^[1] Additionally, TUDCA can inhibit inflammatory pathways by reducing NF-kB activity;^[2][4][3] therefore, the potential therapeutic effects of TUDCA may be caused by its effects on ER stress and/or inflammation. That said, it is not completely understood how TUDCA causes these effects.^[1] However, in liver cells, TUDCA has been shown to bind to integrins — receptors on the cellular surface that enable cell-to-cell communication^[5] — and subsequently activate several downstream pathways that prevent apoptosis and enhance bile acid uptake and secretion to prevent cholestasis.^[6] So, there are several mechanisms by which TUDCA might work. However, they are all “potential” mechanisms of action, because further clinical trials are needed to test whether TUDCA conveys therapeutic benefits in humans (see What are TUDCA’s main benefits?).