Tudcabil (tauroursodeoxycholic acid) / Bruschettini - LARVOL DELTA

Tauroursodeoxycholic Acid Combined With PD-1/PD-L1 Immunotherapy in Advanced Hepatocellular Carcinoma: A Prospective Study (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Tongji Hospital

IO biomarker • New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Long-term benefits of TUDCA supplement in ARSACS zebrafish model. (PubMed, Sci Rep) - "Long-term treatment with TUDCA, a neuroprotective molecule, was associated with partial improvements in social and cognitive behaviors and modifications in omics profiles in the zebrafish model. These results support the potential of further exploring TUDCA in future preclinical and clinical studies, while also emphasizing the need for additional investigations to better understand its mechanisms of action."

Journal • Ataxia • CNS Disorders • Cognitive Disorders • Inflammation • Movement Disorders • Pain

Cadmium activated oxidative stress and endoplasmic reticulum stress pathway promote apoptosis in the common carp (Cyprinus carpio L.) brain. (PubMed, Fish Shellfish Immunol) - "To further explore the relationship between Cd-induced apoptosis and ER-stress, ER-stress inhibitors (TUDCA) and agonists (TM) were added under Cd exposure to detect ER-stress (ATF4, ATF6 and grp78) and apoptosis related indicators (Bax, Bcl-2, Caspase3 and Caspase9). ER-stress inhibition alleviated Cd-induced apoptosis, while ER-stress activation promoted Cd-induced apoptosis. Basically, Cd induced oxidative stress, and activated ER-stress promoted brain tissue apoptosis, which provides valuable information and a fresh perspective for further research into Cd-induced brain injury in fish."

IO biomarker • Journal • CNS Disorders • Vascular Neurology • ATF4 • ATF6 • BAX • BCL2 • CASP3 • HSPA5 • KEAP1

Renoprotective Effects of Phloretin and TUDCA via Simultaneous Inhibition of TLR4/MyD88/NF-κB and BiP/PERK/CHOP Pathways in AKI Under Diabetic Condition. (PubMed, Appl Biochem Biotechnol) - "In this study, we investigated the renoprotective effect of Phloretin-TLR4 inhibitor and Tauro ursodeoxycholic acid (TUDCA)-ERS inhibitor in AKI under diabetic condition. Notably, combination therapy exhibited a synergistic effect (p < 0.05), offering superior renoprotection compared to monotherapy. Our findings suggest that targeting both TLR4-induced inflammation and ER stress simultaneously offers a promising therapeutic strategy for mitigating AKI in diabetic settings and may pave the way for novel combination treatments in diabetic kidney disease."

IO biomarker • Journal • Acute Kidney Injury • Cardiovascular • Diabetes • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Reperfusion Injury • MYD88 • TLR4

Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome. (PubMed, Chin Med) - "PTH alleviates cholestasis by synergistically regulating certain BA species, enzymes and gut microbiota, leading to holistic BA-submetabolome shaping."

Journal • Preclinical • Cholestasis • Hepatology • Metabolic Disorders

Protocol for measuring force in skinned diaphragm muscle fibers of myopathic SEPN1 knockout mice following chronic tauroursodeoxycholic acid treatment. (PubMed, STAR Protoc) - "We then detail procedures for single muscle fiber isolation and tension measurement. For complete details on the use and execution of this protocol, please refer to Germani et al.1."

Journal • Preclinical • Myositis

HFD Exacerbates Hepatic Lipid Metabolism Disorders After Cholecystectomy by Regulating the Bile Acid and Neutrophil Recruitment. (PubMed, Liver Int) - "Cholecystectomy alongside a high-fat diet aggravates hepatic lipid metabolism disorders and inflammation by modulating hepatic bile acid profiles and promoting neutrophil recruitment."

Journal • Dyslipidemia • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CXCL1

Impact of tauroursodeoxycholic acid and 4-phenylbutyric acid on mitochondrial functions and morphology of SH-SY5Y cells. (PubMed, Gen Physiol Biophys) - "The impact of PBA and combination of TUDCA with PBA on mitochondrial functions might be associated with their possible neuroprotective effects. Although TUDCA exhibits positive effect on inner mitochondrial membrane, the possible neuroprotective effect of TUDCA might involve mechanism distinct from modification of mitochondrial functions."

Journal • HSPA5

Stepwise Administration of Bone-Targeted Lipid Nanoparticles Encapsulating Valproic Acid and TUDCA Facilitates In Vivo Direct Reprogramming for Osteoporosis Treatment. (PubMed, Tissue Eng Regen Med) - "This stepwise bone-targeted drug delivery system presents a promising strategy for osteoporosis treatment via In vivo direct reprogramming."

Journal • Preclinical • Osteoporosis • Rheumatology • NANOG • POU5F1 • SOX2

Commentary: Tauroursodeoxycholic acid regulates macrophage/monocyte distribution and improves spinal microenvironment to promote nerve regeneration through inhibiting NF-κB signaling pathway in spinal cord injury. (PubMed, Front Pharmacol) - No abstract available

Journal • CNS Disorders • Orthopedics

Synergistic effects of commonly used ICU drugs and high temperature on skeletal muscle at the cellular and tissue levels. (PubMed, Anesthesiology) - "These results demonstrate that propofol had harmful effects on skeletal muscle cells and tissues at high temperatures in vitro. As these synergistic effects were closely associated with ER stress, TUDCA could mitigate propofol-induced apoptosis at high temperatures. These findings could help improve drug treatment for patients, including their functional prognosis in the clinical setting."

Journal • Critical care • CASP3 • CASP7 • HSPA5

Unfolded protein response in endoplasmic reticulum stress associated with retinal degenerative diseases: A promising therapeutic target. (PubMed, Neural Regen Res) - "Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies, including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid, which enhance protein folding and reduce endoplasmic reticulum stress...Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies. In conclusion, while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases, additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes."

Journal • Age-related Macular Degeneration • Diabetic Retinopathy • Gene Therapies • Genetic Disorders • Inflammation • Inherited Retinal Dystrophy • Macular Degeneration • Metabolic Disorders • Ocular Inflammation • Oncology • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • Targeted Protein Degradation • XBP1

IFN-Γ DAMAGES SALIVARY GLAND EPITHELIAL CELLS BY ACTIVATING THE IRE1–JNK–AP-1 SIGNALING AXIS IN SJÖGREN'S SYNDROME (EULAR 2025) - "Various inhibitors—TUDCA (an ERS inhibitor), SP600125 (a JNK inhibitor), and SR11302 (an AP-1 inhibitor)—were added to evaluate whether ERS-related proteins (GRP78, CHOP) and p-JNK, p-cFos, p-cJun phosphorylation levels decrease, and to measure changes in MMP9 secretion in the cell culture supernatants. Our study provides a systematic elucidation of the potential mechanism by which IFN-γ activates the IRE1–JNK–AP-1 signaling axis to induce salivary gland epithelial cell damage. Clinical samples and single-cell sequencing data collectively reveal significant upregulation of ERS and the IFN-γ pathway in SS patients. In vitro experiments further confirm that IFN-γ stimulation increases ERS levels and activates the IRE1–JNK–AP-1 signaling axis, thereby elevating MMP9 secretion and exacerbating cellular injury."

Immunology • Inflammation • Sjogren's Syndrome • ATF6 • ERN1 • FOS • HSPA5 • IFNG • MMP9

Integrin-Specific Signaling Drives ER Stress-Dependent Atherogenic Endothelial Activation. (PubMed, bioRxiv) - "Inhibiting ER stress with TUDCA reduces proinflammatory and metabolic gene expression (bulk RNAseq) but does not prevent NF-κB activation, a classic proinflammatory transcription factor...Together, these findings offer new insight into how the arterial microenvironment contributes to atherogenesis, with fibronectin-binding integrin signaling promotes ER stress in response to mechanical and metabolic stressors, thereby amplying proinflammatory endothelial activation through JNK-c-Jun signaling. Fibronectin promotes endothelial ER stress in response to oxLDL and disturbed flow via integrin α5β1 and αvβ3 signaling.Matrix-specific ER stress occurs independently of oxidative stress or misfolded protein accumulation, indicating a non-canonical UPR activation.ER stress amplifies proinflammatory gene expression through JNK-c-Jun signaling, without activating NF-κB.Targeting the integrin-ER stress-JNK axis may offer new therapeutic strategies for early atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • FN1 • MAPK8 • TLN1

Association and mechanism of TUDCA on IgA nephropathy: network pharmacology, molecular docking and experimental validation (ERA 2025) - "Our study clarified the protective effect of bile acid metabolite TUDCA in IgAN therapy, and further clarified the potential renal protection mechanism of TUDCA through network pharmacology, molecular docking and in vitro and in vivo experiments, providing a new reference for future exploration of new therapeutic directions of IgAN based on metabolomics."

Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease • AKT1 • BCL2

Hyperuricemia induces hypertension and kidney injury via endoplasmic reticulum stress (ERA 2025) - " In animal experiment 1, Sprague-Dawley rats were randomly divided into four groups for four weeks: normal controls (NC), hyperuricemic controls (HC, induced by adding 2% oxonic acid and 3% uric acid to food), allopurinol-treated rats (HA), and benzbromarone-treated rats (HB). Animal experiment 2 included four groups for two weeks: NC, HC, 4-phenylbutyric acid-treated rats (HP), and tauroursodeoxycholic acid-treated rats (HT)... In summary, hyperuricemia-induced hypertension and kidney injury were associated with the upregulation of ER stress markers and reversed by ER stress inhibition. We conclude that hyperuricemia induces hypertension and tubulointerstitial injury via ER stress in the kidney."

Cardiovascular • Hypertension • Renal Disease • HSPA5 • NLRP3

Tauroursodeoxycholic acid reduces brain lesion volume and cortical edema in a rat model of Traumatic brain injury. (PubMed, Brain Res) - "Our study showed that TBI rats treated with TUDCA at a hyperacute stage had a statistically significant reduction in lesion volume and improved levels of anxiety. However, a dose-response relationship and ideal therapeutic window still need to be determined. Future studies should consider a multiday therapy paradigm to identify the optimum intervention frequency in a mixed-gender."

Journal • Preclinical • CNS Disorders • Psychiatry • Vascular Neurology

Loss of ARNTL Enhances ER Stress and Apoptosis in CKD Through Disruption of NRF2 Signaling. (PubMed, FASEB J) - "In vitro studies demonstrate that the ER stress inducer tunicamycin (Tm) strongly suppresses ARNTL expression, whereas the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) restores ARNTL levels and alleviates ER stress-induced apoptosis, as indicated by reduced cleaved caspase-3 and caspase-9 levels...Moreover, ARNTL directly binds to the NRF2 promoter region and interacts with NRF2 through protein-protein binding. This study reveals the ARNTL-NRF2 axis as a key protective pathway against stress-induced injury in renal tubular cells, suggesting it as a promising therapeutic target for reducing tubular damage and inflammation in CKD."

Journal • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • ARNT • ARNTL • CASP3 • CASP9

Chemical chaperone 4-phenylbutyrate treatment alleviates the kidney phenotype in a mouse model of Alport syndrome with a pathogenic variant in Col4a3. (PubMed, Kidney Int) - "Our results suggest a therapeutic potential for 4-PBA in combating kidney dysfunction in Alport syndrome."

Journal • Preclinical • Chronic Kidney Disease • Fibrosis • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • Immunology • Nephrology • Renal Disease

Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Robin Goland, MD | Unknown status ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

NFKB1-targeted metabolites as novel therapeutic approaches for erectile dysfunction: evidence from gut microbiota network pharmacology and machine learning. (PubMed, Sex Med) - "Machine learning predictions indicated strong binding affinities between target genes (NFKB1, TLR4, CYP3A4) and bile acid derivatives (Tauroursodeoxycholic acid and Taurochenodeoxycholic acid)...Specific gut microbiota, through metabolites and associated target genes, may influence the onset of ED. These findings highlight potential therapeutic targets and provide a basis for future interventions in ED treatment."

Journal • Erectile Dysfunction • Gastrointestinal Disorder • CYP3A4 • TLR4

Continuous exposure to low concentrations of antimony(III) induces inflammation, apoptosis, oxidative and endoplasmic reticulum stress in Caco-2 intestinal epithelial cells. (PubMed, Environ Res) - "Treatment with ER-stress specific inhibitor tauroursodeoxycholic acid (TUDCA) demonstrated the central role of ER stress in Sb-induced injury. These findings provide new insights in the intestinal epithelial toxicity of low concentrations of Sb(III), suggesting that it would be recommendable to limit Sb use in industrial processes to minimise human health hazards."

IO biomarker • Journal • Inflammation • ATF4 • BCL2 • CASP3 • HSPA5

Tauroursodeoxycholic acid (TUDCA) treatment mitigates hypothalamic inflammation and regulates food intake in a protein-restricted mice model (ECO 2025) - "These findings suggest that TUDCA treatment, likely through the TGR5 receptor, mitigates hypothalamic inflammation. This leads to decreased Agrp expression and leptin levels, subsequently altering feeding behavior in a protein-restricted mice model."

Preclinical • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • GFAP • IL1B • LEP • S1PR2 • S1PR2 • TNFA

ER Stress Causes Reduction of PlGF Production by Trophoblasts Cells (ASRI 2025) - "To inhibit ER stress, cells were pretreated with tauroursodeoxycholic acid (TUDCA)... Our study shows a significant effect of ER stress on decreasing RNA and protein production of PlGF by trophoblasts. Furthermore, limiting ER stress can restore PlGF expression. Moderation of ER stress may represent an alternate approach for lessening the altered expression of angiogenic genes in preeclampsia."

Gynecology • Oncology • ATF6 • FLT1

Endoplasmic reticulum stress induces trophoblast pyroptosis via regulating CYLD during labor initiation. (PubMed, Placenta) - "Our findings indicate that ERS-mediated trophoblast pyroptosis via CYLD under inflammatory conditions sheds light on PTB mechanisms, providing a potential target for modulating labor onset."

Journal • Inflammation • IL18 • IL1B