Tudcabil (tauroursodeoxycholic acid) / Bruschettini - LARVOL DELTA

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

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

Dietary tauroursodeoxycholic acid supports growth and gut health in spotted seabass (Lateolabrax maculatus) under thermal stress conditions. (PubMed, Fish Shellfish Immunol) - "Concurrently, TUDCA treatment enhanced the PI3K-Akt signaling pathway, contributing to the inhibition of apoptosis. The data generated in this study demonstrated that dietary supplementation with 40 mg/kg TUDCA promotes growth, activates the Nrf2-Keap1 and PI3K-AKT signaling pathways, enhances intestinal antioxidant defenses, suppresses inflammation and apoptosis, alleviates endoplasmic reticulum stress, and mitigates the physiological impacts of heat stress in L. maculatus reared at elevated temperatures."

Journal • Inflammation • ATF6 • CASP3 • CASP8 • CXCL8 • ERN1 • HSPA5 • IL10 • IL1B • IL4 • TGFB1 • TNFA

Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy. (PubMed, J Biomol Struct Dyn) - "EGFR, a key player in cellular functions and elevated in various cancers, particularly brain cancer, is targeted using small molecule inhibitors like erlotinib and gefitinib...Utilizing molecular docking and dynamic simulation, our study identified five natural compounds-citicoline, silodosin, picroside I, canertinib, and tauroursodeoxycholic acid-as potential EGFR kinase inhibitors...Additionally, it is noteworthy that all the five proposed compounds predicted to penetrate the blood-brain barrier, meeting the essential criteria for reaching brain. We anticipate that this study will provide valuable leads for experimental testing in the laboratory, advancing the prospects of brain cancer management."

Journal • Brain Cancer • Oncology • Solid Tumor • EGFR

SLFN4 MEDIATES PROTEIN TRANSLATION AND UNFOLDED PROTEIN RESPONSE IN IFNα-ACTIVATED GR-MDSCS (DDW 2025) - "Western blots were used to quantify UPR pathway protein levels modulated by tunicamycin or TUDCA, which induce or suppress ER stress, respectively... Slfn4 is an ER-based tRNA binding protein strongly induced by IFNα and mediates protein translation and UPR adaptation when neutrophils polarize into Gr-MDSCs, supporting their survival during ER stress."

Infectious Disease • ATF4 • CASP3 • IFNA1 • NOS2 • NR3C1

THE EFFECTS OF TAURINE ON ALCOHOL-ASSOCIATED LIVER DISEASE ARE DOSE-DEPENDENT (DDW 2025) - "Moreover, liver levels of taurine-conjugated bile acids, including TUDCA and THDCA, were decreased in AF+3T mice, while increased in AF+0.2T mice... Our results demonstrate that the effects of taurine supplementation on ALD are dose dependent. Low dose of taurine suppresses, while high dose of taurine exacerbates, alcohol-induce steatosis and liver injury. The mechanisms underlying the beneficial vs detrimental effects of low dose vs high dose taurine on ALD pathology warrant further investigation."

Addiction (Opioid and Alcohol) • Hepatology • Inflammation • Liver Failure

Endoplasmic Reticulum Stress as a Regulator of High Glucose-Induced Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells. (PubMed, J Ocul Pharmacol Ther) - "All of these alterations were inhibited by PBA or TUDCA treatment. ER stress regulates HG-induced EMT in lens epithelial cells."

Journal • Cataract • Diabetes • Metabolic Disorders • Ophthalmology • ATF6 • CDH1 • CDH2 • ER • ERN1 • FN1 • HSPA5 • VIM

Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors. (PubMed, Cell Commun Signal) - "Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment."

Journal • Chronic Lymphocytic Leukemia • CNS Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • FGFR1 • FGFR3 • FZD5 • HSPA5 • ROR1

Evaluation of Additive Neuroprotective Effect of Combination Therapy for Parkinson's Disease Using In Vitro Models. (PubMed, Antioxidants (Basel)) - "We demonstrated that some of the medications, used in combination, can exert an additive neuroprotective effect in preclinical models of PD that is superior to that of each of the compounds individually. This project can lead to the development of the first treatment for PD that can slow or prevent its progression."

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

Tauroursodeoxycholic Acid Induces Liver Regeneration and Alleviates Fibrosis Through GATA3 Activation. (PubMed, Biomedicines) - "Additionally, the knockdown of GATA3 eliminated the proliferative effect of TUDCA on BRL-3A cells. TUDCA promotes liver regeneration and alleviates liver fibrosis by activating GATA3."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor • GATA3

Tauroursodeoxycholic Acid Protects Retinal Ganglion Cells and Reduces Inflammation in Mice Following Optic Nerve Crush. (PubMed, Pharmaceuticals (Basel)) - "TUDCA treatment prevented RGC apoptosis, Müller glial cell activation, and retinal expression of several inflammatory cytokines. These data suggest that TUDCA is a promising therapeutic candidate for preserving RGC numbers and function."

Journal • Preclinical • Inflammation • Oncology • GFAP • IL10 • IL6 • TNFA

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) - "TUDCA treatment promoted wound healing, down-regulated genes related to inflammatory response, and up-regulated genes related to spinal cord development in SCI mice. Our study provided evidence that TUDCA treatment regulated monocyte/macrophage distribution and improved the microenvironment to promote nerve regeneration in SCI mice."

Journal • CNS Disorders • Inflammation • Orthopedics

Tauroursodeoxycholic Acid Enhances the Quality of Postovulatory Aged Oocytes by Alleviating Oxidative Stress, Apoptosis, and Endoplasmic Reticulum Stress in Pigs. (PubMed, Vet Sci) - "Interestingly, TUDCA could effectively alleviate the phenomenon of endoplasmic reticulum stress triggered during the oocyte aging process. Taking these findings together, our study demonstrates that TUDCA supplementation beneficially affects the quality of aged porcine oocytes by suppressing oxidative stress, apoptosis, and endoplasmic reticulum stress."

IO biomarker • Journal • BCL2 • CASP3

Fibroblast activation assessed by PRO-C3 and PRO-C6 is associated to accumulation of key bile acids - A hallmark of fibrosis initiation and mortality in alcohol-related liver disease (EASL 2025) - " Serum levels of nordicPRO-C3 (N-terminal pro-peptide of type III collagen) and nordicPRO- C6 (endotrophin; type VI collagen formation) obtained by ELISA; and plasma concentrations of bile acids (CA, TCA, GCA, LCA, DCA, TUDCA, GUDCA) obtained by mass-spectrometry were assessed in a cross-sectional cohort of 450 patients with biopsy-proven ALD... Increased circulating levels of toxic hydrophobic bile acids relate to activation of fibroblasts and to poor prognosis in ALD patients, suggesting that bile acids are linked to activation of fibrogenesis, and therefore are key to the induction and development of liver fibrosis in ALD."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis

Endoplasmic reticulum stress aggravates ferroptosis via PERK/ATF4/HSPA5 pathway in UUO-induced renal fibrosis. (PubMed, Front Pharmacol) - "More importantly, Inhibiting ERS by Tauroursodeoxycholate (TUDCA) reversed the alterations of ferroptosis, including GPX4 expression, reactive oxygen species (ROS) accumulation, iron overload, increased lipid peroxidation production, as well as EMT progression in vivo and in vitro...Mechanistically, Co-immunoprecipitation (Co-IP) tests showed that ATF4 engaged with and SUMOylated HSPA5 to trigger the HSPA5 signaling pathway in response to TGF-β. These findings illuminate that focusing on HSPA5 may present a promising therapeutic approach to enhance tubular epithelial cells' survival and alleviate the progression of CKD."

Journal • Chronic Kidney Disease • Fibrosis • Hematological Disorders • Immunology • Nephrology • Renal Disease • ATF4 • COL1A1 • GPX4 • HSPA5 • HSPA8 • TGFB1

Tauroursodeoxycholic acid (TUDCA) treatment mitigates hypothalamic inflammation and regulates food intake in a protein-restricted mice model (ECO 2025) - No abstract available

Preclinical • Inflammation

A Common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice. (PubMed, Gut) - "This mouse strain provides evidence that the exon 6 deletion causes ER stress and inflammation and is an excellent model to understand its contribution to pancreatic cancer and identify preventive strategies."

Journal • Preclinical • Hepatology • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • AGR2

Supplementation with ursodeoxycholic acid and bile salt benefits lactation performance, health, and rumen and fecal microbiota of transition dairy cows. (PubMed, J Dairy Sci) - "Compared with the control, 8 key BA, including UDCA, tauroursodeoxycholic acid, glycoursodeoxycholic acid, and 5 key BA, including tauro-β-muricholic acid and hyocholic acid, were identified in the UDCA and BAS groups, respectively. Key rumen VFA-production bacteria, including Prevotella_7, Succinivibrionaceae_UCG-001, and Selenomonas, were enriched in the UDCA and BAS groups, along with an increase in beneficial gut microbiota, such as Butyrivibrio, Ruminococcus, and Caproiciproducen, and a reduction in harmful bacteria, such as Stenotrophomonas and Chryseobacterium. These findings suggest that the observed improvements in production performance and health may be mediated by alterations in peripheral BA and rumen and gut microbiota, offering insights for optimizing the nutrition and health of transitional dairy cows."

Journal • HP

Tauroursodeoxycholic Acid (TUDCA) Reduces ER Stress and Lessens Disease Activity in Ulcerative Colitis. (PubMed, medRxiv) - P1 | "Six weeks of oral TUDCA treatment was well-tolerated in patients with active ulcerative colitis and promoted mucosal healing, lessened ER stress, and reduced clinical disease activity. A randomized controlled trial of adjunctive TUDCA therapy in patients with UC is warranted."

Journal • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Constitutive hepatic mTORC1 activation aggravates alcohol-induced liver injury via endoplasmic reticulum stress-mediated ferroptosis. (PubMed, Am J Pathol) - "Torin-1, an ATP-competitive mTOR inhibitor, suppressed the mTORC1 activity and reversed the effects of Depdc5 deletion on ER stress and ferroptosis in ethanol-fed mouse livers. Furthermore, pharmacological relief of ER stress using TUDCA or inhibition of ferroptosis with liproxstatin-1 both alleviated the liver abnormalities induced by Depdc5 ablation in ethanol-fed mice. Additionally, the research uncovered that ER stress functions as an upstream signal of ferroptosis in the progression of ALD. These findings provide novel in vivo evidence that sustained mTORC1 activation leads to alcoholic liver injury by inducing ER stress and ferroptosis, suggesting that targeting these pathways may represent a potential therapeutic strategy for ALD."

Journal • Fibrosis • Hepatology • Immunology • Liver Failure • DEPDC5

Fecal Microbial Profiles and Short-Chain Fatty Acid/Bile Acid Metabolomics in Patients With Age-Related Macular Degeneration: A Pilot Study. (PubMed, Invest Ophthalmol Vis Sci) - "Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04)...This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Bile acid therapy for primary biliary cholangitis: Pathogenetic validation. (PubMed, World J Exp Med) - "In addition to UDCA, the use of obeticholic acid, tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed. The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review. Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug, based on the understanding of the pathogenesis of the initial stages of PBC."

Journal • Review • Cholestasis • Developmental Disorders • Hepatology • Immunology • Primary Biliary Cholangitis

Pharmacological landscape of endoplasmic reticulum stress: uncovering therapeutic avenues for metabolic diseases. (PubMed, Eur J Pharmacol) - "It examines small molecules such as tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (4-PBA), repurposed drugs like 17-AAG (17-N-allylamino-17demethoxygeldanamycin (tanespimycin)) and berberine, and phytochemicals such as resveratrol and hesperidin. The review emphasizes challenges in translating these therapies to clinical applications, such as toxicity, off-target effects, limited bioavailability, and the lack of large-scale randomized controlled trials (RCTs). It also highlights the potential of personalized medicine approaches and pharmacogenomics in optimizing ER stress-targeting therapies."

Journal • Review • Alzheimer's Disease • CNS Disorders • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Parkinson's Disease

Identification of endoplasmic reticulum stress-associated lncRNAs influencing inflammation and VSMC function in abdominal aortic aneurysm. (PubMed, Clin Sci (Lond)) - "In human aortic VSMC and Jurkat T-cells, tunicamycin-induced ER stress triggered the expression of IL21-AS1, LINC00626, LINC00494, LINC00892, PCED1B-AS1, ITPKB-IT and TCL-6, while TUDCA counteracted these effects. Finally, an integrated analysis of mRNA-lncRNA co-expression revealed the correlation between the selected lncRNAs and the DE-mRNAs involved in immune response and muscle contraction. Therefore, these DE-lncRNAs potentially implicated in the ER stress response, a pathological process in AAA, could be considered as potential therapeutic target to handle AAA."

Journal • Cardiovascular • Inflammation • IL21 • PCED1B-AS1