Tudcabil (tauroursodeoxycholic acid) / Bruschettini - LARVOL DELTA

Dietary Intervention with Resistant Starch-Rich Unripe Plantain Flour Restores Gut Microbiome-Metabolome Axis and Ameliorates Type 2 Diabetes in Rats. (PubMed, Foods) - "Consequently, UPF altered bile-acid composition by lowering hydrophobic species (e.g., cholic acid and deoxycholic acid) while elevating hydrophilic species (e.g., ursodeoxycholic acid and tauroursodeoxycholic acid)...Spearman correlation analysis further reinforced the close relationships between the altered microbiota and metabolites. Our results elucidate that UPF exerts its anti-diabetic effects by remodeling the gut microbiota and modulating its associated metabolites, highlighting a novel dietary intervention strategy for diabetes management."

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

Endoplasmic Reticulum Stress: A Novel Target for the Prevention and Treatment of Hypertension and Its Related Diseases. (PubMed, J Cell Mol Med) - "Pharmacological targeting of ERS demonstrates therapeutic promise: chemical chaperones 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA) stabilise proteostasis, reduce oxidative stress, and inhibit apoptosis; antioxidants N-acetylcysteine (NAC) and melatonin attenuate ERS-oxidative stress crosstalk. Future research must prioritise isoform-selective ERS modulator development, validation in human trials, biomarker discovery, and elucidating ERS roles in therapy-induced hypertension. Targeting ERS represents a transformative mechanotherapeutic paradigm for precision hypertension management."

Journal • Review • Cardiovascular • Hypertension • ATF6 • XBP1

Gut microbiota-derived metabolites in immunomodulation and gastrointestinal cancer immunotherapy. (PubMed, Front Immunol) - "Bile acids display dual roles, with ursodeoxycholic acid and tauroursodeoxycholic acid counteracting the tumor-promoting effects of deoxycholic acid and lithocholic acid. These platforms enable quantitative assessment of exposure-response thresholds, dissection of context-dependent effects, and in vitro pre-evaluation of the feasibility and safety of metabolite-based immunologic adjuvants combined with PD-1/PD-L1 blockade. Collectively, microbiota-derived metabolites represent promising targets for precision diagnosis and treatment in GI cancer immunotherapy."

Journal • Review • Gastrointestinal Cancer • Immunology • Oncology • Solid Tumor • CD8

Low-cholesterol egg yolk lipids alleviated the development of atherosclerosis in ApoE -/- mice by regulating bile acid metabolism and gut microbiota. (PubMed, Food Res Int) - "LC intervention inhibited hepatic cholesterol synthesis by upregulating LDLR and CYP7A1, enhanced LDL-C clearance and conversion to bile acids, with a significantly increase in UDCA and TUDCA while decrease in LCA and DCA. These bioactivities of LC were related to the enrichment of Lactobacillus and Akkermansia and decrease of Rikenella and Faecalimonas. Our studies first give direct evidence for evaluating the health effects of eggs, especially eggs with reduced contents of cholesterol, which laid a theoretical foundation for defining the target populations of low-cholesterol eggs."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOE • ICAM1 • IL1B • TNFA • VCAM1

Integrated transcriptomic and metabolomic analyses reveal the pathogenesis of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced liver injury in mice. (PubMed, Toxicol Lett) - "Serum analysis showed significant increases in the concentrations of CA, TCA, GCA, TCDCA, α-MCA, β-MCA, Tβ-MCA, TUDCA, CDCA, UDCA, ω-MCA, and HDCA, along with decreased LCA levels. These findings indicate that DDC-induced liver injury involves multiple pathways and mechanisms, with disruption of bile acid homeostasis representing a central pathological feature."

Journal • Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • ABCC3 • CYP27A1 • CYP8B1

Fibre composition in sow diets influences bile acid profile in colostrum and in intestinal digesta of their new-born suckling piglets. (PubMed, J Nutr Sci) - "In the piglet colon digesta, lithocholic acid and ursodeoxycholic acid were higher in SBP vs. LNC (p = 0.001 and p = 0.007, respectively). Addition of specific dietary fibres to sow diets differentially influences the BA in colostrum. Dietary fibres in sow diets can impact on the intestinal BA composition in piglets with a possible consequence on the digestive physiology and health in the offspring."

Journal

Pre-Administration of Akkermansia Muciniphila Prevents the Development of Severe Acute Graft-Versus-Host Disease in Systemic Organs. (PubMed, Adv Sci (Weinh)) - "Pre-administration of A. muciniphila significantly reduces aGvHD severity, particularly in the gastrointestinal tract, alleviates gut dysbiosis, and increases the levels of metabolites such as tauroursodeoxycholic acid and short-chain fatty acids. These findings provide the basis for new therapeutic strategies for aGvHD and contribute to improving treatment outcomes for patients with intractable diseases."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

Pharmacochaperoning and HDAC Effect of 4-Phenylbutyrate in Cell and Mouse Models: Evidence from SLC6A1 Mutation-Mediated Disorders (AES 2025) - "PBA and tauroursodeoxycholic acid (TUDCA) were tested as pharmacochaperones, while butyrate and suberoylanilide hydroxamic acid (SAHA) were tested as HDAC inhibitors. PBA acts as a pharmacochaperone that restores GAT-1 function and trafficking by stabilizing the mature protein and reducing ER stress. Its therapeutic effect is not attributable to HDAC inhibition, as HDAC inhibitors alone failed to rescue GABA uptake and, in some cases, exacerbated seizure burden. This work provides the first integrated mechanistic and in vivo evidence that pharmacochaperoning can overcome variant-induced trafficking defects and restore GABAergic inhibition."

Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Mental Retardation • Mood Disorders • Psychiatry

Gut microbiota and metabolic signatures of anxiety in ulcerative colitis: a cross-sectional study. (PubMed, Therap Adv Gastroenterol) - "Moreover, the levels of most metabolites (such as L-kynurenine) were increased in the feces, while the levels of a few metabolites decreased, including indole-2-carboxylic acid, N-demethylmirtazapine, and tauroursodeoxycholic acid. Our research further revealed that these gut microbiota and metabolites are highly correlated. This study provides a new perspective for understanding the occurrence and development of anxiety in UC patients, suggesting that RI and BL may serve as potential candidate biomarkers to diagnose UC patients with anxiety."

Journal • Observational data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Mood Disorders • Pain • Psychiatry • Ulcerative Colitis

Integrin-specific signaling drives ER stress-dependent atherogenic endothelial activation. (PubMed, Redox Biol) - "However, pharmacological inhibition of ER stress using TUDCA suppresses proinflammatory and metabolic gene expression (bulk RNA-seq), without affecting NF-κB activation. Blocking this pathway using a JNK inhibitor (SP600125) or dominant-negative c-Jun (TAM67) abrogates inflammatory gene expression following oxLDL or disturbed flow. Together, these findings identify a novel mechanism by which fibronectin-integrin signaling promotes ER stress in response to mechanical and metabolic stressors, amplifying endothelial inflammation through JNK-c-Jun signaling."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • TLN1

Dietary glycyrrhizin enhances reproductive performance by improving intestinal microbiota, liver lipid metabolism and ovarian senescence in aged breeder hens. (PubMed, J Anim Sci Biotechnol) - "These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota, enhancing hepatic vitellogenin synthesis, and ameliorating ovarian function in aged breeder hens. This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period."

Journal • Dyslipidemia • Gastrointestinal Disorder • Metabolic Disorders • PPARA

Chaperon Protein GRP78 Released from MPN Cells Increase Expression of Lysyl Oxidase in Human Stroma Cell Line (ASH 2023) - "To address the mechanism responsible for the induction of GRP78, we treated the HEL and SET-2 cells with 4-phenyl butyric acid and tauroursodeoxycholic acid both of which are well known inhibitors of ER stress, however, these inhibitors did not affect the expression levels of GRP78...In contrast, ruxolitinib, an inhibitor of JAK2V617F, blocked GRP78 expression in these cells...In conclusion, we demonstrated that GRP78 was overexpressed both in MPN derived cell lines and also in primary megakaryocytes from MF patients. Our observations proposed that overexpressed GRP78 in MPN cells contribute development of myelofibrosis through secreted in microenvironment and induced expression of extracellular matrix modulating enzyme LOX in bone marrow stromal cells."

Preclinical • Stroma • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • ATF4 • CALR • HSPA5 • LOX • TCF4

Integrin–ER Stress Crosstalk Links Mechanical and Metabolic Stress to Vascular Inflammation (AHA 2025) - "However, pharmacological inhibition of ER stress using TUDCA suppresses proinflammatory and metabolic gene expression (bulk RNA-seq), without affecting NF-κB activation. Blocking this pathway using a JNK inhibitor (SP600125) or dominant-negative c-Jun (TAM67) abrogates inflammatory gene expression following oxLDL or disturbed flow. Together, these findings identify a novel mechanism by which fibronectin–integrin signaling promotes ER stress in response to mechanical and metabolic stressors, amplifying endothelial inflammation through JNK–c-Jun signaling and contributing to atherogenesis."

Late-breaking abstract • Atherosclerosis • Dyslipidemia • Inflammation • TLN1

Targeting LncRNA MEG3 to Modulate ER Stress and Autophagy: A CRISPR/Cas9-based Strategy in AKI-to-CKD Transition. (PubMed, Exp Cell Res) - "These findings demonstrate that MEG3 promotes maladaptive ER stress and autophagy impairment in tubular epithelial cells, driving AKI-to-CKD transition. Targeting MEG3 through CRISPR-based strategies or in combination with TUDCA may represent a promising therapeutic strategy to mitigate fibrosis and slow disease progression."

IO biomarker • Journal • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • ATF4 • ATF6 • BAX • BCL2 • BECN1 • HSPA5 • MEG3

An oral drug against decline in the autophagy lysosomal pathway (ALP) and systemic inflammation, two "hallmarks" of ALS/FTD (ALS-MND 2025) - "Background: The two drugs against symptoms of syndromic ALS, riluzole and edavarone were approved in 1995 and 2017...After accelerated approval in 2022, the fixed-dose combination PB-TUDCA (Relyvrio) was withdrawn in Apr 2024 based on negative phase 3 results (2)... HP-beta-CD (HPbCD) has been shown to be effective in models of several NDDs and is in phase 3 against NPC, but the presumed MoA of "depleting cholesterol" (CHO) can cause permanent hearing loss. A reanalysis of GWAS data using a patented discovery platform showed that bCDs act by reducing PLs and SLs (4) and, thus, also ceramides (5), which explains how aCDs (too small to fit CHO), were more effective ex vivo in fibroblasts of patients with seven lysosomal storage diseases (LSDs) and in vivo in a SOD1 ALS model (n = 24, ρ<.0001). Improving lysosomal function via HPaCDs, which reduces endocytosis and, thus, lysosomal load, was hypothesized to improve autophagy by preventing lysosomes from both..."

Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Otorhinolaryngology • Rare Diseases • EIF2B4 • RIPK1

How pre-diagnosis comorbidities shape amyotrophic lateral sclerosis prognosis in a large Chinese cohort (ALS-MND 2025) - "Potentially, bile acid (such as TUDCA) metabolism dysfunction may also play a role...Thyroid disease emerged as a protective factor for disease progression, associated with 0.306-points/month slower functional decline (p¼ 0.025), with 21.3% of this effect mediated by the monthly ALSFRS-R progression rate before the baseline (p¼ 0.005). Conversely, gallbladder diseases conferred a 2.69-fold increased mortality risk (95%CI:1.44–5.01,p¼ 0.002). Lower respiratory tract infections showed protective trends (hazard ratio (HR)¼ 0.43, 95%CI:0.19–1.00,p¼ 0.050)."

Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hepatology • Infectious Disease • Metabolic Disorders • Mood Disorders • Otorhinolaryngology • Psychiatry • Respiratory Diseases

Dysregulated Proteostasis Restrains the Developmental HSC Expansion in Fanconi Anemia (ASH 2023) - "Because chaperone supplementation has been shown to enhance HSC protein folding capacity, we serially injected the bile acid TUDCA (a chemical chaperone) into the pregnant dam...Protection of the HSPC proteome appears to be a new, non-canonical function of FANCD2, without immediate connection to the FA pathway and DNA crosslink repair. Importantly, we demonstrate the successful pharmacological rescue of the fetal Fancd2-/- HSPC pool."

Anemia • Aplastic Anemia • Hematological Disorders • CD48 • FANCD2 • KIT • MYC

Particulate Matter Induces Epithelial-to-Mesenchymal Transition via Oxidative and Endoplasmic Reticulum Stress in Normal Rat Kidney Epithelial Cells (KIDNEY WEEK 2025) - "Antioxidants [N-acetylcysteine (NAC), 20 mM; apocynin, 100 uM] and ER stress inhibitors [tauroursodeoxycholic acid (TUDCA), 1 mM, 4-phenylbutyric acid (4-PBA), 5 mM] were used to examine their effects on EMT, NOX1/4 expression, and NLRP3 inflammasome activation in APM-exposed NRK cells at 24 or 48 hours. Treatment with antioxidants (NAC and apocynin) and ER stress inhibitors (TUDCA and 4-PBA) mitigated APM-induced EMT, which was accompanied with reductions in NOX1/4 expression and NLRP3 inflammasome activation (NLRP3, ASC, and cleaved caspase-1) at 24 and 48 hours. Conclusion These findings suggest that APM induces EMT via oxidative and ER stress in NRK cells, highlighting a potential mechanism for air pollution-induced kidney disease."

Preclinical • Cardiovascular • Nephrology • Renal Disease • CASP1 • CDH1 • FN1 • NLRP3

Tauroursodeoxycholic Acid (TUDCA) Restores Intestinal Barrier Function in Sepsis: Mechanistic Insights and a Clinical Intervention Study (ChiCTR) - P=N/A | N=45 | Not yet recruiting | Sponsor: Shanghai Fifth People's Hospital Affiliated to Fudan University; Shanghai Fifth Peoople's Hospital

New trial • Infectious Disease • Septic Shock

Effect and Mechanism of Tauroursodeoxycholic Acid in Blue Fox Bile on Acute Alcohol-Associated Liver Injury in Mice. (PubMed, J Vis Exp) - "Blue fox bile was found to contain tauroursodeoxycholic acid (TUDCA), ursodeoxycholic acid, bilirubin, and taurochenodeoxycholic acid. Network pharmacology and molecular docking suggest that the hepatoprotective effects of blue fox bile may be related to the advanced glycation end product-receptor for advanced glycation end product signaling pathway. Overall, blue fox bile, with its TUDCA content similar to that of bear bile, targets proteins such as AKT1 and PPARG, demonstrating potential anti-inflammatory and antioxidant effects in the management of alcohol-associated liver injury."

Journal • Preclinical • Hepatology • Liver Failure • IGF1 • MMP9 • PPARG

Noise-Induced Stress Amplifies Inflammation through NLRP3 Inflammasome Activated by Endoplasmic Reticulum Stress in the Mouse Hearts (AHA 2025) - "In vitro, hiPSC-cardiomyocytes treated with 4-PBA and TUDCA (ER stress inhibitors) displayed reduced levels of NLRP3, ASC, caspase-1, and IL-1β, establishing a causal link between ER stress and inflammasome activation. Our findings reveal a novel mechanistic pathway linking environmental stressors to cardiac dysfunction. Targeting endoplasmic reticulum stress may provide new therapeutic strategies to reduce inflammation-driven heart disease in noise-exposed populations."

Preclinical • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Inflammation • Psychiatry • Sleep Disorder • IL1B • NLRP3 • XBP1

Bifidobacterium infantis modulates intestinal microecology to inhibit the spread of antimicrobial resistance. (PubMed, mSystems) - "We found that supplementing with B. infantis 15697 significantly enhanced the synthesis of bile acids in mouse feces, particularly tauroursodeoxycholic acid (TUDCA) and taurocholic acid (TCA)...By modulating the gut microbiota and bile acid metabolism, B. infantis has the potential to become an effective means of reducing the spread of AMR. This is of great significance for protecting the gut health of children and adults, reducing the risk of resistant infections, and also provides scientific evidence for the formulation of global public health policies."

Journal • Gene Therapies • Infectious Disease

Modulation of the JNK/c-Jun/HSP27 Pathway in Cardiomyocytes under Chronic Stress-Induced Cardiac Dysfunction: Therapeutic Implications of Tauroursodeoxycholic Acid. (PubMed, Free Radic Biol Med) - "Elevated corticosterone levels in depression contribute to cardiac dysfunction through oxidative damage. TUDCA mitigates these effects via the JNK/c-Jun/HSP27 pathway, which offers potential therapeutic implications for depression-associated cardiac dysfunction."

IO biomarker • Journal • Cardiovascular • CNS Disorders • Depression • Fibrosis • Immunology • Psychiatry • BCL2 • HSPB1

Targeting ER stress-mediated apoptosis by MSC-derived exosomes: A novel therapeutic strategy against pulmonary fibrosis. (PubMed, Regen Ther) - "In this study, bleomycin (BLM) induced apoptosis in A549 cells, and MSC-Ex treatment reduced apoptotic cells and the Bax/Bcl-2 ratio...Moreover, blockade of ER stress with ER stress inhibitor TUDCA contributed to the amelioration of apoptosis in A549 cells, indicating that MSC-Ex reduced BLM-induced apoptosis at least partly by modulating ER stress...In conclusion, ER stress induced apoptosis in BLM-treated A549 cells, and MSC-Ex treatment mitigated apoptosis via inhibiting ER stress. This study provides a novel mechanism for MSC-Ex-mediated protection on apoptosis in an IPF model and suggests that MSC-Ex could be a promising therapeutic strategy for IPF."

IO biomarker • Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • BAX • BCL2 • HSPA5

Tauroursodeoxycholic acid-induced increase in ectopic muscle mineralization occurs exclusively in dystrophic muscles and is independent of endoplasmic reticulum stress. (PubMed, Sci Rep) - "The increase in ectopic calcification in dystrophic muscles induced by TUDCA is specific to muscles lacking dystrophin. This effect is not linked to the alleviation of ER stress or the overexpression of proteins directly involved in calcium mineral accumulation."

Journal • Inflammation • BMP2 • RUNX2