WB403 activated TGR5 and promoted active GLP-1 secretion.

<p>(A) WB403 stimulated hTGR5 in CRE-luciferase report system at the concentration range of 1–20 μmol/l. (B) WB403 stimulated hTGR5 specific cAMP accumulation at the concentration range of 1–50 μmol/l. n = 3. **p<0.01, ***p<0.001 vs. DMSO (+TGR5) group. (C) The hTGR5 targeted CRE-luciferase activity of WB403 and ZY403. EC₅₀ was 5.5 μmol/l and 1.3 μmol/l for WB403 and ZY403 respectively. (D) Effect of WB403 and ZY403 on gallbladders of mice. Normal mice were fasted overnight and treated with compounds (200 mg/kg) or vehicle (DMSO) by ip injection. Gallbladders (GB) were removed 30 min later and volumes measured then normalized to body weight (B.W.). n = 10. **p<0.01 vs. vehicle group. (E) Structure of WB403 and ZY403. WB403 promoted GLP-1 secretion in NCI-H716 cells (F), primary enterocytes (G), and MIN6 cells (H). n = 3. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle group. (I) WB403 promoted GLP-1 in ICR mice. n = 5. **p<0.01 vs. vehicle group. Values represent mean ± SEM.