P3, N=150, Recruiting, Xijing Hospital of Digestive Diseases | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2/3, N=104, Recruiting, Xijing Hospital of Digestive Diseases | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

To explore the effect of the combination of Bupleuri Radix and Paeoniae Radix Alba on the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-κB(NF-κB) signaling pathway in rats with cholestatic hepatitis induced by rifampicin(RFP). Forty-two male SD rats were randomly divided into the normal group, the Bupleuri Radix-Paeoniae Radix Alba group(C-B group), the RFP group, the ursodeoxycholic acid(UDCA)+RFP group(UDCA+RFP group), the Bupleuri Radix+RFP group(C+RFP group), the Paeoniae Radix Alba+RFP group(B+RFP group), and the Bupleuri Radix-Paeoniae Radix Alba+RFP group(C-B+RFP group)...Compared with the C-B+RFP group, the ALT activity and the protein expression levels of HMGB1, RAGE, IL-6, and GRP78 were significantly higher in the C+RFP and the B+RFP groups. In conclusion, the combination of Bupleuri Radix and Paeoniae Radix Alba alleviates endoplasmic reticulum stress through the HMGB1/RAGE/NF-κB signaling pathway and reduces inflammatory responses, thereby exerting hepatoprotective effects.

P=N/A, N=90, Completed, Institute of Liver and Biliary Sciences, India | Not yet recruiting --> Completed

Concurrently, UDCA significantly suppressed the secretion of pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP), mitigated oxidative stress, and inhibited β-cell apoptosis by modulating the expression of Bcl-2 and Bax genes. Collectively, these results indicate that UDCA exerts substantial therapeutic potential in ameliorating metabolic disturbances, repairing organ damage, and regulating critical signaling pathways via multi-target synergistic actions, thereby providing novel experimental evidence supporting its pharmacological application in the treatment of T2DM and its associated complications.

In the present study, we demonstrate that ssRNA within fecal extracellular vesicles (FEVs) derived from bacteria, particularly those susceptible to lysis by ursodeoxycholic acid (UDCA), can suppress CRC progression via Piezo1 activation...Notably, oral UDCA administration enhanced FEV rupture, increasing luminal "naked" ssRNA and mitigating high-fat diet-induced CRC in vivo. These findings identify the bacterial ssRNA-Piezo1 axis as a potential therapeutic target in CRC.

P=N/A, N=270, Not yet recruiting, West China Hospital

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) was examined in this study as a novel biomarker to predict the efficiency of ursodeoxycholic acid (UDCA) and thereby improved primary biliary cholangitis (PBC) treatment...In conclusion, TNFAIP3 and fatigue have significant impact on UDCA in PBC. These findings provide a new view on PBC pathophysiology and suggest that TNFAIP3 may be a suitable biomarker or therapeutic target for the disease.

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.

Together, these data identify FXR as an immune checkpoint and support repurposing UDCA for ICC immunotherapy.

P=N/A, N=45, Not yet recruiting, Shanghai Fifth People's Hospital Affiliated to Fudan University; Shanghai Fifth Peoople's Hospital

P=N/A, N=19, Not yet recruiting, Deyang People's Hospital; Deyang People's Hospital