Tauroursodeoxycholate (TUDCA)

Tauroursodeoxycholate (TUDCA) is a cytoprotective agent in a variety of cells including hepatocytes as well as an inducer of apoptosis in cancer cells[1]. Tauroursodeoxycholate, as an endoplasmic reticulum (ER) stress inhibitor, is effective in protecting the hepatocytes and restoring glucose homeostasis by reducing the endoplasmic reticulum stress[2].

In vitro, 200 µM TUDCA suppressed viability of hVSMCs (vascular smooth muscle cells) by inhibition of ERK (extracellular signal-regulated kinase) phosphorylation, through induction of MKP-1 (MAPK phosphatase-1) via PKCα (protein kinase Cα). And TUDCA inhibited both the proliferation and migration of PDGF-stimulated hVSMCs[1]. In vitro, 25 µM Tauroursodeoxycholate (TUDC) increases plasma membrane multidrug resistance-associated protein 2 (MRP2). And TUDC and cAMP increase Rab11 activity[3].

In vivo, TUDCA prevents the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-dependent decrease of dopaminergic fibers and ATP levels, mitochondrial dysfunction and neuroinflammation. TUDCA administration (50 mg/kg), the mice also displayed reduction in foot dragging and an overall improvement in gait[4]. Mice were treated with TUDCA 0.5 mg/g every 3 days, for a total of 7 injections, which showed an increase in neuromuscular junction innervation in the mutated mice[5]. TUDCA treatment (100 mg, 3 times/day) also reduces neurological impairment in rats with acute cerebral infarction[6].

Kim SY, et al. Tauroursodeoxycholate (TUDCA) inhibits neointimal hyperplasia by suppression of ERK via PKCα-mediated MKP-1 induction. Cardiovasc Res. 2011 Nov 1;92(2):307-16.

Kim SY, et al. Tauroursodeoxycholate (TUDCA) inhibits neointimal hyperplasia by suppression of ERK via PKCα-mediated MKP-1 induction. Cardiovasc Res. 2011 Nov 1;92(2):307-16.

Park SW, et al. Rab11, but not Rab4, facilitates cyclic AMP- and tauroursodeoxycholate-induced MRP2 translocation to the plasma membrane. Am J Physiol Gastrointest Liver Physiol. 2014 Oct 15;307(8):G863-70.

[3] Rosa AI, et al. Tauroursodeoxycholic acid improves motor symptoms in a mouse model of Parkinson's disease. Mol Neurobiol. 2018;55(12):9139-9155.

[4] Thams S, et al. A stem cell-based screening platform identifies compounds that desensitize motor neurons to endoplasmic reticulum stress. Mol Ther. 2019;27(1):87-101.

[5] Bian KY, et al. DCA can improve the ACI-induced neurological impairment through negative regulation of Nrf2 signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(1):343-351.

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牛磺酸脱氧胆酸盐(TUDCA)是包括肝细胞在内的多种细胞的细胞保护剂,也是癌症细胞凋亡的诱导剂[1]。牛磺酸脱氧胆酸盐作为一种内质网应激抑制剂,通过减少内质网应激,有效地保护肝细胞和恢复葡萄糖稳态[2]。

在体外,200µM TUDCA通过抑制ERK(细胞外信号调节激酶)磷酸化,通过PKCα(蛋白激酶Cα)诱导MKP-1(MAPK磷酸酶-1),抑制hVSMCs(血管平滑肌细胞)的活力。TUDCA同时抑制PDGF刺激的hVSMCs的增殖和迁移[1]。在体外,25µM牛磺酸脱氧胆酸盐(TUDC)可增加质膜多药耐药相关蛋白2(MRP2)。TUDC和cAMP可提高Rab11活性[3]。

在体内,TUDCA可防止MPTP(1-甲基-4-苯基-1,2,3,6-四氢吡啶)依赖性多巴胺能纤维和ATP水平的降低、线粒体功能障碍和神经炎症。给予TUDCA(50 mg/kg)后,小鼠的拖脚能力也有所减少,步态也有所改善[4]。每3天用TUDCA 0.5 mg/g治疗小鼠,共注射7次,这表明突变小鼠的神经肌肉接头神经支配增加[5]。TUDCA治疗(100 mg,3次/天)也可减少急性脑梗死大鼠的神经损伤[6]。