Taurolithocholic acid

Taurolithocholic acid is an orally active bile acid and antiviral agent. Taurolithocholic acid upregulates FADS2 by activating the TGR5-PI3K/AKT-SREBP2 signaling axis, inhibits SFTSV-induced ferroptosis (Ferroptosis), viral replication and viral entry of HBV/HDV, while reducing the release of IL-1β, lipid ROS and LDH. While exerting antiviral protective effects, Taurolithocholic acid also stimulates the recycling of hepatocellular membrane transporters, impairs canalicular bile acid secretion function, and induces hepatocyte cholestasis, apoptosis and acute hepatocellular injury. Taurolithocholic acid serves as an experimental model compound for hepatocellular cholestasis. At concentrations ≤200 μM, Taurolithocholic acid shows no cytotoxicity and does not activate the interferon pathway. Taurolithocholic acid not only protects mice from lethal SFTSV infection but also is suitable for studies related to severe fever with thrombocytopenia syndrome and cholestasis^[1][2][3]. In Vitro:Taurolithocholic acid (50-200 μM; 24 h) dose-dependently inhibits SFTSV replication in human THP-1 monocytic cells without inducing cytotoxicity^[1].
Taurolithocholic acid (50-200 μM; 24 h) dose-dependently inhibits HRTV replication in human THP-1 monocytic cells^[1].
Taurolithocholic acid (16 h) inhibits the post-entry replication stage of SFTSV infection in human THP-1 monocytic cells, reducing intracellular viral RNA levels and infection rate by approximately 50% when added post-infection or throughout the 16 h infection period^[1].
Taurolithocholic acid (50-200 μM) dose-dependently inhibits SFTSV mini-genome activity in BSR-T7 cells^[1].
Taurolithocholic acid (50-200 μM; 24 h) dose-dependently suppresses SFTSV-induced IL-1β production and NF-κB activation in human THP-1 monocytic cells^[1].
Taurolithocholic acid (200 μM; 24 h) upregulates FADS2 expression in SFTSV-infected human THP-1 monocytic cells, reversing SFTSV-induced FADS2 downregulation^[1].
Taurolithocholic acid (0-24 h) time-dependently activates the TGR5-PI3K/AKT-SREBP2 pathway and upregulates FADS2 in human THP-1 monocytic cells over 0 to 24 h^[1].
Taurolithocholic acid (100 μM; 24 h) alleviates SFTSV-induced ferroptosis in murine BMDMs, as measured by reduced lipid ROS and LDH release^[1].
Taurolithocholic acid (100 μM; pre-treatment, followed by 24 h incubation with ferroptosis agonists) inhibits Fe²⁺- and RSL-3-induced ferroptosis in murine BMDMs via upregulation of FADS2, as shown by reduced lipid ROS and LDH release which is reversed by FADS2 inhibition^[1].
Taurolithocholic acid (5 μM; 4 h) induces robust apoptosis in Ntcp-transfected HepG2 cells, increasing the percentage of apoptotic cells to 65.5% of total cells^[2].
Taurolithocholic acid (2.5-5 μmol/liter; 20 min total incubation) impairs canalicular bile acid secretion by 54% and 60%, respectively, without affecting substrate uptake in isolated rat hepatocyte couplets^[3].
Taurolithocholic acid (5 μmol/liter; 5-60 min) induces sustained activation of PKB/Akt, increasing activity to 194% of control levels after 60 min in isolated rat hepatocytes^[3].