• TUDCA/Tauroursodeoxycholic Acid Powder CAS 14605-22-2
  • TUDCA/Tauroursodeoxycholic Acid Powder CAS 14605-22-2
TUDCA/Tauroursodeoxycholic Acid Powder CAS 14605-22-2
  • Wuhan Hengheda Pharm Co.,Ltd
  • China
  • Immediately after payment
  • 1000kg/month

Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a US Food and Drug Administration–approved hydrophilic bile acid for the treatment of certain cholestatic liver diseases. There is a growing body of research on the mechanism(s) of TUDCA and its potential therapeutic effect on a wide variety of non-liver diseases. Both UDCA and TUDCA are potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response (UPR). Several studies have demonstrated that TUDCA serves as an anti-apoptotic agent for a number of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. In addition, TUDCA plays an important role in protecting against cell death in certain retinal disorders, such as retinitis pigmentosa. It has been shown to reduce ER stress associated with elevated glucose levels in diabetes by inhibiting caspase activation, up-regulating the UPR, and inhibiting reactive oxygen species. Obesity, stroke, acute myocardial infarction, spinal cord injury, and a long list of acute and chronic non-liver diseases associated with apoptosis are all potential therapeutic targets for T/UDCA. A growing number of pre-clinical and clinical studies underscore the potential benefit of this simple, naturally occurring bile acid, which has been used in Chinese medicine for more than 3000 years.

TUDCA/Tauroursodeoxycholic Acid Powder CAS 14605-22-2

Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a secondary bile acid produced only by intestinal bacteria. T/UDCA has been studied for its ameliorating effects on inflammatory metabolic diseases, including atherosclerosis, diabetes, and renal disease.1 UDCA was originally US Food and Drug Administration (FDA)–approved for the treatment of certain cholestatic liver diseases based on its choleretic effects and ability to protect hepatocytes from hydrophobic bile acids. Studies examining the mechanisms of TUDCA and UDCA action have shown that these compounds act as potent inhibitors of apoptosis by interfering with the mitochondrial pathway of cell death, inhibiting oxygen-radical production, and reducing endoplasmic reticulum stress and caspase activation (Figure 1).2Normally, the endoplasmic reticulum synthesizes proteins and folds them properly with the help of endoplasmic reticulum (ER) chaperones. Too many unfolded proteins signal an ER stress response associated with reduced protein synthesis and increased expression of chaperones, malfunction of the unfolded protein response (UPR) and ultimately cell death.3

TUDCA



Figure 1

Proposed mechanisms of T/UDCA inhibition of apoptosis. T/UDCA negatively modulates the mitochondrial pathway by inhibiting Bax translocation, ROS formation, cytochrome c release, and caspase-3 activation. T/UDCA protects against mitochondrial membrane permeabilization and decreased ΔΨm, which reduces ROS production and apoptosis. T/UDCA can also interfere with the death receptor pathway, inhibiting caspase-3 activation. Moreover, T/UDCA inhibits apoptosis associated with ER stress by modulating intracellular calcium levels and inhibiting calpain and caspase-12 activation. Importantly, T/UDCA interacts with NSR, leading to NSR/hsp90 dissociation and nuclear translocation of the T/UDCA/NSR complex. Once in the nucleus, T/UDCA reduces apoptosis by modulating the E2F-1/p53/Bax pathway, inhibiting MDM2/p53 association, decreasing BAX, PUMA and NOXA expression, reducing p53 transactivation and DNA binding activity, and increasing p53 degradation. Finally, T/UDCA downregulates cyclin D1 and Apaf-1, further inhibiting the mitochondrial apoptotic cascade.

Abbreviations: Cyt c, cytochrome c; Hsp90, heat shock protein 90; T/UDCA, tauroursodeoxycholic/ursodeoxycholic acid.

Reprinted with permission from Amaral et al, 2009.2

Recent studies have shown that T/UDCA can prevent UPR dysfunction and ameliorate ER stress. It does so in part by improving protein folding capacity via the activation of transcription factor 6 and by assisting in the transfer of mutant proteins.4 TUDCA is a co-transporter of Na+/taurocholate and activates α5β1 protein into its active conformation by transferring the β1 unit.5 It also inhibits the phosphorylation of initiation factor 2α(eIF2α), which is normally activated by protein kinase RNA-like ER kinase (PERK).4

Cisplatin is an effective anti-cancer chemotherapeutic drug that is known to cause sensory neuropathy in patients who receive the drug. N18D3 hybrid neurons exposed to cisplatin treatment showed morphological changes such as cell shrinkage and cytoplasmic blebbing, as well as condensed and fragmented nuclear morphology, which are characteristics of apoptotic cell death. A clear 180- to 200-base pair internucleosomal DNA cleavage was induced by cisplatin treatment. Cisplatin treatment not only induced cytotoxicity in N18D3 hybrid neurons but also induced a substantial accumulation of p53 protein. P53 has been reported to play a major role in cisplatin-induced apoptotic cell death. Pre-incubation with UDCA was found to be effective in reducing cisplatin neurotoxicity and completely blocked cell death in N18D3 neurons, in part by suppressing pro-apoptotic p53 protein.6 P53 is also a known tumor suppressor protein as it promotes growth arrest and apoptosis and is dysfunctional in certain cancers. TUDCA has recently been seen to modulate the control of p53 via Mdm-2. Mdm-2 is the direct repressor of p53 and the modulation of Mdm-2 and p53 appears to be a key target of TUDCA.7 The inhibition of p53 action is also a potential treatment for diseases that are associated with increased activation of p53 activity.8

TUDCA improves apolipoprotein E4 (APOE4) macrophage survival and function. APOE4 and APOE3 have important functions in binding to LDL receptors. APOE is a protein associated with several classes of plasma lipoproteins expressed in the liver and other tissues, including those of the central nervous system, vascular smooth muscle cells, adrenals, macrophages, and adipocytes. It contributes to cholesterol transport and modulates metabolic disease progression via lipid transport-independent mechanisms. APOE3 and APOE4 are isoforms of the polymorphic APOE that bind to LDL receptors and other LDL receptor family proteins with similar affinity. However, APOE3 appears to protect against metabolic disorders while APOE4 is a major genetic risk factor of inflammatory metabolic diseases, including atherosclerosis, diabetes, and Alzheimer's disease (AD). Increased cell death was observed in APOE4 macrophages when stimulated with LPS or oxidized LDL and was due mainly to potentiation of ER stress signaling and JNK phosphorylation.1 TUDCA attenuated LPS- and oxLDL-induced apoptosis of APOE4 macrophages to levels observed in APOE3 macrophages.

TUDCA acts as a mitochondrial stabilizer and anti-apoptotic agent in several models of neurodegenerative diseases, including AD, Parkinson's diseases (PD), and Huntington's diseases (HD). Based on mechanistic studies conducted primarily in rodent models, TUDCA may provide a novel and effective treatment in neurological disorders with its neuroprotective activities. TUDCA shows cytoprotective properties through the inhibition of apoptosis,2,9 and it has been convincingly demonstrated that T/UDCA crosses the blood brain barrier in humans.10 That said, not everyone is convinced, and there is at least one report recommending that the use of T/UDCA beyond PBC is unjustified.11


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Every batch of our product was tested by authorized independent third party, Analysis testing center, Shanghai branch, Chinese Academy of Science. We send goods to customers with test report and COA. Our products were also tested by American Analytical Chemistry Laboratories and Chromadex too....more
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