Tudcabil (tauroursodeoxycholic acid) / Bruschettini - LARVOL DELTA

REPURPOSING MITOCHONDRIA PROTECTIVE TARGETS FOR ADJUVANT THERAPY IN INFLAMMATORY BOWEL DISEASES (UEGW 2025) - "Aims & Cellular toxicity of the drugs Acipimox, AICAR, ALCAR, Bezafibrate, Epi-743, Idebenone, Metformin, SS-31 and TUDCA was assessed in the intestinal epithelial cell line Mode-K and murine wild-type (WT) small intestinal (SI) organoids. Selected drugs targeting mitochondrial functions restored seeding efficiency, differentiation, and stemness of intestinal organoids from inflamed tissue sections of TNFΔARE mice, TNFΔARE pigs, and CD patients. These findings clearly support the potential of metabolic drug repurposing for adjuvant IBD therapy and indicate putative risks for Metformin."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • IL10

THE XBP1 ACTIVATOR IXA4 REGULATES HUMAN BILE ACID AND FATTY ACID SYNTHESIS GENES IN IPSC-HEPATOCYTES (AASLD 2025) - "Treating human iPSC-hepatocytes with the pharmacologic XBP1 activator IXA4 profoundly suppressed the bile acid synthesis genes CYP7A1 and CYP8B1. SHP expression did not increase and therefore cannot account for these changes in gene expression. In contrast, XBP1 activation increased the expression of several lipid synthesis genes."

Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Solid Tumor • CYP27A1 • CYP8B1 • ERN1 • FASN • SCD • XBP1

Sevoflurane Exposure in Juvenile Causes Persistent Learning and Memory Impairment via Inducing Endoplasmic Reticulum Stress in Caenorhabditis elegans and Mice. (PubMed, Neurotoxicology) - "Our findings demonstrate that early developmental exposure to sevoflurane induces endoplasmic reticulum stress, which may result in a decrease in memory and learning capabilities. TUDCA may alleviate these effects."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders

Tauroursodeoxycholic acid ameliorates palmitic acid induced endoplasmic reticulum stress and impaired autophagy via IRE1- XBP1-FoxO1 pathway in KGN cells. (PubMed, Biochem Pharmacol) - "However, tauroursodeoxycholic acid application reduced inositol-requiring enzyme 1 phosphorylation and promoted autophagy in KGN cells via the X-box binding protein 1-forkhead box protein O1 pathway, thereby restoring the mitochondrial function. Overall, these findings enhance our understanding of the molecular basis of GC impairment in patients with PCOS and provide potential therapeutic targets for their treatment."

Journal • Metabolic Disorders • Polycystic Ovary Syndrome • Targeted Protein Degradation • ERN1 • XBP1

Biosynthesis of tauro-ursodeoxycholic acid (TUDCA) in Saccharomyces cerevisiae. (PubMed, Microb Cell Fact) - "Here we report strains capable of converting the more widely available primary bile acid, chenodeoxycholic acid (CDCA) into TUDCA. This was achieved by introducing heterologous genes enabling taurine conjugation and taurine biosynthesis, providing a sustainable and scalable approach for TUDCA production."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders • Parkinson's Disease

Ursodeoxycholic acid acts as an ileal FXR agonist in male mice with hepatic deficiency of FXR. (PubMed, eGastroenterology) - "Supplementation of UDCA showed a trend towards increased UDCA and tauroursodeoxycholic acid (TUDCA) levels in serum, liver and intestine, although the male mice displayed more than twice the amount of these bile acids compared with the female mice. The data strongly suggest that UDCA seems to act as an FXR agonist, especially in the ileum, which contrasts with previous reports that UDCA acts as a gut FXR antagonist. In addition, UDCA seems to be exerting liver protective effects predominantly in the male mice."

Journal • Preclinical • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Deoxycholic Acid Promotes Persistent Low-Level Viremia in Chronic Hepatitis B via Enhancing HBV Particle Formation. (PubMed, J Gastroenterol Hepatol) - "Elevated DCA promotes viral persistence by enhancing Dane particle formation and stabilizing HBs-HBc interactions, contributing to LLV during treatment. Modulating BA metabolism may offer new strategies to improve CHB therapy."

Journal • Hepatitis B • Infectious Disease • Inflammation

Exercise-Induced Changes in Enterohepatic Communication Are Linked to Liver Steatosis Resolution. (PubMed, Nutrients) - "Exercise also suppressed hepatic endoplasmic reticulum (ER) stress and downregulated lipogenic genes via the inositol-requiring enzyme 1 alpha (IRE1α)- spliced X-box binding protein 1 (Xbp1s) pathway, while concurrently activating farnesoid X receptor (FXR) signaling to enhance fatty acid oxidation through the FXR-short heterodimer partner (SHP) related to hepatic secondary bile acid abundance change. The beneficial effect of long-term aerobic exercise on high-fat diet-induced hepatic steatosis in mice is potentially mediated through structural changes in the gut microbiota, which influence the abundance of hepatic secondary bile acids (TUDCA, DCA) and subsequently regulate the expression of genes involved in lipid metabolism."

Journal • Hepatology • Liver Failure • Metabolic Disorders • ERN1 • XBP1

Tauroursodeoxycholic Acid Mitigates Inflammation, ER Stress, and Apoptosis in Experimental Endotoxin-Induced Uveitis: In Vivo and In Vitro Evidence. (PubMed, Cell Biol Int) - "Its dual anti-inflammatory and cytoprotective actions support its therapeutic potential in acute ocular inflammatory conditions. TUDCA attenuates clinical, histological, and molecular manifestations of LPS-induced uveitis, highlighting its promise as a candidate for adjunctive therapy in inflammatory retinal diseases."

Journal • Preclinical • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • CASP12 • CASP3 • HSPA5

High-level production of Tauroursodeoxycholic acid from Taurochenodeoxycholic acid in engineered Bacillus subtilis via whole-cell biotransformation. (PubMed, World J Microbiol Biotechnol) - "T-7-KLCA intermediate was undetectable. This study provided a cost-effective and scalable approach for the industrial production of potential bear bile substitutes from readily available chicken bile powder using an engineered probiotic B. subtilis microbial cell factory."

Journal

Accumulation of succinate in the blood is a potential early indicator of metabolic dysfunction-associated steatotic liver disease (MASLD). (PubMed, Free Radic Biol Med) - "Treatment of the Huh-7 and HepG2 cells exposed to fructose with ursodeoxycholic acid (UDCA) or its taurine-conjugated form, TUDCA, which are known to elicit protective hepatocellular effects by inducing antioxidant defenses, strongly inhibited succinate build up by preserving mitochondrial function and preventing H2O2 hyper-production. Collectively, our findings show succinate accumulates rapidly in the extracellular milieu in our mouse model for MASLD and cell culture models for hepatic lipotoxicity. These findings suggest the applicability of succinate as a biomarker of early MASLD particularly among males and especially in pediatric populations."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Pediatrics • Solid Tumor • GLRX

From traditional Chinese medicine to molecular oncology - pleiotropic effects of tauroursodeoxycholic acid. (PubMed, Klin Onkol) - "New findings show that TUDCA finds use not only in the treatment of hepatic disorders, but also in the treatment of cancer, neurodegenerative and cardiovascular diseases, gastrointestinal dysfunctions and glucose metabolism disorders. Due to its multifunctional effects, TUDCA appears to be a promising substance with the potential to become an important part of modern medicine in the treatment of diverse pathological conditions."

Journal • Review • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Oncology • Primary Biliary Cholangitis

LEAF-02: Tauroursodeoxycholic Acid (TUDCA) Plus Camrelizumab and Regorafenib in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab (clinicaltrials.gov) - P2 | N=141 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor

LEAF-02: Tauroursodeoxycholic Acid (TUDCA) Plus Camrelizumab and Regorafenib in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab (clinicaltrials.gov) - P2 | N=141 | Not yet recruiting | Sponsor: Fudan University

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Structure-guided single-point mutagenesis and carboxyl-terminal truncation improved the substrate selectivity of 7α-hydroxysteroid dehydrogenase. (PubMed, Int J Biol Macromol) - "Coupled with 7β-HSDH and applied in biotransformation using CBP as substrate, T94FΔC1-Rg7β-HSDH (β2) eliminated by-products tauroursocholic acid (TUCA) and 3,12-dihydroxy-7-oxocholanoyltaurine (3,12-HOCT) and produced the desired ratio of tauroursodeoxycholic acid (TUDCA):TCDCA in M9-GY medium. This study highlights the crucial role of T94 in determining the substrate specificity and activity of 7α-HSDH, and provides strategies for rational designing and engineering enzymes to enhance their substrate specificity and catalytic activity in practical applications."

Journal

Oral nanoformulation of a host-directed antiviral niclosamide effectively treats severe fever with thrombocytopenia syndrome. (PubMed, Biomed Pharmacother) - "Through target-focused screening, we identified five anti-SFTS candidates: niclosamide (NIC), cepharanthine, nifedipine, zanamivir, and ivacaftor...To address this, we developed NCNP-NIC, an oral nanoparticle formulation encapsulating NIC with tauroursodeoxycholic acid (TUDCA) via non-covalent interactions...Oral administration of NCNP-NIC at both low (20 mg/kg) and high (40 mg/kg) doses completely cured SFTS in IFNAR-/- mouse model. This work establishes NCNP-NIC as a promising oral therapy for SFTS, while its innovative nanoformulation provides a versatile platform for improving the bioavailability of other poorly soluble antiviral drugs."

Journal • Hematological Disorders • Thrombocytopenia • IFNAR1

Tauroursodeoxycholic acid modulates neuroinflammation via STING/NF-κB inhibition after traumatic brain injury. (PubMed, Int Immunopharmacol) - "Mechanistically, TUDCA as a potential STING inhibitor targets the pocket of STING protein. Overall, our results give evidence suggesting that TUDCA serves as a promising therapeutic candidate for TBI, specifically targeting the inflammation mediated damage of neurons."

Journal • CNS Disorders • Inflammation • Vascular Neurology • NLRP3 • STING

Relationship between inner hair cell synaptopathy and outer hair cell loss in two mouse models of accelerated age-related hearing loss. (PubMed, Neurobiol Aging) - "TUDCA provided partial protection against IHC synaptopathy but did not prevent OHC loss. These results in two mouse models of accelerated cochlear pathology provide novel insights into the mechanisms behind age-related hearing loss."

Journal • Preclinical • Otorhinolaryngology • CDH2 • CDH23

Comprehensive Analysis of Bile-derived Medicinal Materials Based on Ultra-High-Performance Liquid Chromatography Coupled With Charged Aerosol Detection and Chemometrics. (PubMed, Anal Sci Adv) - "Hierarchical cluster analysis and principal component analysis successfully achieved accurate classification of the 10 types of bile-derived medicinal materials, while orthogonal partial least squares-discriminant analysis identified nine characteristic differential components with variable importance in projection >1: taurocholic acid, taurochenodeoxycholic acid, glycodeoxycholic acid, tauroursodeoxycholic acid, glycocholic acid, taurodeoxycholic acid, glycohyodeoxycholic acid, glycochenodeoxycholic acid, and chenodeoxycholic acid. This study established a UHPLC-CAD method capable of simultaneously separating 17 bile acids, combined with multidimensional chemometric approaches, to conduct a comprehensive analysis of 10 bile-derived medicinal materials. The research successfully identified characteristic compounds for each bile powder type, providing a reliable methodology for both the identification and quality control of bile-derived medicinal materials."

Journal

Cholecystectomy-related gut microbiota dysbiosis exacerbates colorectal tumorigenesis. (PubMed, Nat Commun) - "gnavus), along with increased levels of glycoursodeoxycholic acid (GUDCA) in human and tauroursodeoxycholic acid (TUDCA) in mice. Significantly, FXR agonist obeticholic acid (OCA) averts cholecystectomy-related colorectal tumorigenesis. The gut microbiota holds a crucial position in cholecystectomy-induced colorectal tumorigenesis, and modulation of the gut microbiota-bile acid-FXR axis represents a promising preventive strategy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Transplantation • CTNNB1

Inhibition of glucagon secretion from pancreatic α-cells by the bile acid TUDCA involves a S1PR2-PI3K pathway. (PubMed, J Nutr Biochem) - "Glucose-induced suppression of glucagon secretion was found to be compromised under hyperglycemic conditions, yet TUDCA was able to inhibit α-cell function, highlighting its glucagonstatic effect in a pathological context. Collectively, these findings suggest that TUDCA-induced inhibition of glucagon secretion involves the opening of α-cell KATP channels and activation of the S1PR2/PI3K pathway, expanding the repertoire of potential therapeutic benefits of TUDCA in diabetes treatment."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • S1PR2

2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces early hearing loss in guinea pigs via activating AhR to trigger mitochondrial and endoplasmic reticulum stress-regulated autophagy. (PubMed, Arch Toxicol) - "The ER stress inhibitor TUDCA further alleviated ROS, Keap1-Nrf2 dysregulation, and autophagy disruption. Our findings demonstrate that early BDE-47 exposure induces hearing impairment via AhR-mediated mitochondrial oxidative stress and ER stress, suppressing autophagy. These findings enhance our understanding of environmental chemical-induced ototoxicity and provide valuable insights for both auditory disorder risk assessment and therapeutic strategies for hearing preservation."

Journal • CNS Disorders • Otorhinolaryngology • ERN1 • SQSTM1

Tauroursodeoxycholic acid (TUDCA) improves cryo-resilience and lowers energy turnover via affecting the mitochondrial bioenergetic profile in bovine embryos. (PubMed, Theriogenology) - "Extracellular flux analysis revealed significantly lower basal respiration, ATP-linked respiration, and maximum respiratory capacity in TUDCA-treated embryos, suggesting a metabolically quieter phenotype. These findings support the "quiet embryo" hypothesis and suggest that TUDCA promotes a more balanced mitochondrial bioenergetic profile, ultimately enhancing embryo quality and resilience under in vitro conditions."

Journal • ATF4 • BAX • HSPA5 • PRDX1 • SOD2

Obesity-Induced Loss of Function of Bone Marrow Mesenchymal Stromal Cells Is Linked to Cellular Stress and Irreversible at Advanced Stages. (PubMed, J Cell Mol Med) - "We assessed base levels of OS and ERS, activation of cellular response mechanisms, and the effects of Melatonin (MT), which is known to decrease OS, and TUDCA, which is known to decrease ERS...Therefore, it is imperative to treat and prevent obesity before the negative effects on stem cells become permanent and irreversible. Early treatment of obesity may not only prevent metabolic diseases; it may also protect tissue resident stem cells."

Journal • Genetic Disorders • Metabolic Disorders • Obesity

TUDCA combined with Syndopa protects the midbrain and gut from MPTP toxicity in a Parkinson's disease mouse model: Immunohistochemical evidence. (PubMed, Biomol Biomed) - "The standard treatment for PD is Syndopa (a combination of levodopa and carbidopa). Additionally, the MPTP-induced changes in α-synuclein expression in the gut were notably reversed by these treatments. Collectively, these results suggest that incorporating TUDCA with Syndopa may represent a promising therapeutic strategy to address the pathophysiological challenges associated with PD."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease