Ursodiol (UDCA) is a secondary bile acid derived from the 7α/β isomerization of the primary bile acid chenodeoxycholic acid (CDCA) by microorganisms. Ursodiol can be used in the study of various liver diseases and gastrointestinal diseases. Ursodiol has cytoprotective, anti-apoptotic, membrane-stabilizing, antioxidant and immunomodulatory effects[1-3].
Ursodiol can inhibit the viability of HepG2 and BEL7402 cells with IC50 of 0.92 mmol/L and 0.86 mmol/L, respectively, but Ursodiol has no effect on the viability of normal hepatocytes L-02. After Ursodiol (1.0 mmol/L) treatment, the apoptosis rate of HepG2 and BEL7402 cells was significantly increased in a concentration-dependent manner, whereas the apoptosis rate of L-02 cells did not change significantly.Ursodiol inhibits Bcl-2 expression and promotes Bax expression [2].
Mice treated with low and high doses (50 and 450 mg/kg/day) of Ursodiol showed significant weight loss, whereas 150 mg/kg/day had no significant effect on mouse body weight. After 21 days of ursodiol treatment, the microbial community structure and bile acid pool in the ileum and cecum contents and feces of mice were significantly changed compared with those before treatment. Ursodeoxycholic acid (UDCA), Tauroursodeoxycholic acid (TUDCA), Glycoursodeoxycholic acid (GUDCA) and Lithocholic acid (LCA) levels were significantly elevated in the ileum of mice treated with Ursodiol 450 mg/kg[1]. Ursodiol treatment at 416 mg/kg reduces SARS-CoV-2 transmission in a Syrian golden hamster SARS-CoV-2 infection model[4].
References:
[1]Winston JA, Rivera A, Cai J, Patterson AD, Theriot CM. Secondary bile acid ursodeoxycholic acid alters weight, the gut microbiota, and the bile acid pool in conventional mice. PLoS One. 2021 Feb 18;16(2):e0246161.
[2] Liu H, Qin CY, Han GQ, Xu HW, Meng M, Yang Z. Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines. World J Gastroenterol. 2007 Mar 21;13(11):1652-8.
[3] Kumar D, Tandon RK. Use of ursodeoxycholic acid in liver diseases. J Gastroenterol Hepatol. 2001 Jan;16(1):3-14.
[4] Brevini T, Maes M, Webb G J, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2[J]. Nature, 2023, 615(7950): 134-142.
Ursodiol（UDCA）是一种微生物通过初级胆汁酸鹅去氧胆酸（CDCA）的7α/β异构化转化而来的次级胆汁酸。Ursodiol可用于多种肝脏疾病和胃肠道疾病的研究。Ursodiol具有细胞保护、抗凋亡、膜稳定、抗氧化和免疫调节作用[1-3]。
Ursodiol可抑制HepG2和BEL7402细胞的活力，IC50分别为0.92 mmol/L和0.86 mmol/L，但Ursodiol对正常肝细胞L-02的活力没有影响。Ursodiol（1.0 mmol/L）处理后，HepG2和BEL7402细胞的凋亡率显著增加，且呈浓度依赖性，而L-02细胞凋亡率没有明显变化。Ursodiol可抑制Bcl-2表达，促进Bax表达[2]。
使用低剂量和高剂量（50和450 mg/kg/天）的Ursodiol治疗的小鼠体重明显减轻，而150 mg/kg对小鼠体重没有显著影响。与治疗前相比，Ursodiol治疗21天后，小鼠回肠和盲肠内容物以及粪便中微生物群落结构和胆汁酸库发生了明显变化。Ursodiol 450mg/kg处理时，小鼠回肠内熊去氧胆酸（UDCA）、牛黄熊去氧胆酸（TUDCA）、甘氨熊脱氧胆酸（GUDCA）和石胆酸（LCA）含量显著升高[1]。在叙利亚金仓鼠SARS-CoV-2感染模型中，416 mg/kg的Ursodiol治疗可减少SARS-CoV-2传播[4]。