Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fanny M.; Feng, Yibin

doi:10.1155/2016/4305074

Cited by 36 publications

(50 citation statements)

References 57 publications

(79 reference statements)

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“…UDCA is a hydrophilic bile acid first isolated from Ursus maritimus (polar bear). (21) It is a minor bile acid in humans, and oral dosing enriches the bile acid pool up to 40%-60%, depending on the dose used. (22) It is currently U.S. Food and Drug Administration approved for use in primary biliary cholangitis and for cholesterol gallstone dissolution in adults.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

et al. 2019

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Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma‐glutamyl transpeptidase (GGT) <2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5 IU/L (P = 0.105) and GGT, +60.4 IU/L (P = 0.003). In 7 participants, ALT and GGT ≤29 IU/L did not rise above 29 IU/L (null response group). Eight participants had increases of ALT or GGT >100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin‐8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. Conclusion: The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.

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Section: Discussionmentioning

confidence: 99%

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

et al. 2019

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“…It is produced by hepatocytes to take part in fat digestion. Abnormalities in bile secretion can result in digestion problems and serious hepatobiliary diseases [43]. It is believed that exogenous administration of bile components can be a reasonable therapeutic approach improving outcomes of cholestatic liver diseases [43].…”

Section: Tudca As Bile Acid In Hepatobiliary Disordersmentioning

confidence: 99%

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

129

125

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Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.

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“…Many studies have focused on alternatives to bear bile, including pure chemical substitutes, bile from other animals, artificial bear bile (Feng et al, 2009) and cultured bear bile (Zheng et al, 2019). These bear bile alternatives have a chemical composition resembling that of natural bear bile (Li et al, 2016) and exert similar antibacterial, anti‐inflammatory, antispasmodic and hepatoprotective effects (Li et al, 2016; Zheng et al, 2019). Thus, there is optimism that the alternatives could become promising candidates to replace natural bear bile (Feng et al, 2009; Li et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…These bear bile alternatives have a chemical composition resembling that of natural bear bile (Li et al, 2016) and exert similar antibacterial, anti‐inflammatory, antispasmodic and hepatoprotective effects (Li et al, 2016; Zheng et al, 2019). Thus, there is optimism that the alternatives could become promising candidates to replace natural bear bile (Feng et al, 2009; Li et al, 2016). To date, there are no reports of pharmacokinetic studies on bear bile alternatives or natural bear bile.…”

Section: Introductionmentioning

confidence: 99%

A validated surrogate analyte UPLC–MS/MS assay for quantitation of TUDCA, TCDCA, UDCA and CDCA in rat plasma: Application in a pharmacokinetic study of cultured bear bile powder

Zan

Xin-hua

Zhao

et al. 2020

Biomedical Chromatography

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Bear bile is a valuable medicinal material used in traditional Chinese medicine for over 2000 years. However, developing a substitute has become necessary because of protection measures for this endangered species. The ingredients of in vitro cultured bear bile powder (CBBP) include tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA, and it has pharmacological properties that are similar to those of natural bear bile powder (NBBP). In this study, the pharmacokinetic parameters of both CBBP and NBBP were measured in rats with a new surrogate analyte LC–MS method using stable isotopes as surrogate analytes (D4‐TUDCA, D4‐TCDCA, D4‐UDCA and D4‐CDCA) with response factors validated in authentic matrix (plasma) for simultaneously monitoring the authentic analytes (TUDCA, TCDCA, UDCA and CDCA). The method validation was satisfactory for the linear regression (r, 0.9975–0.9994), precision (RSD intra‐day, 0.72–9.35%; inter‐day, 3.82–9.02%), accuracy (RE, −12.42–5.67%) and matrix effect (95.53–99.80%), along with analyte recovery (95.90–98.82%) and stability (89.48–101.81%) of surrogate analytes, and precision (RSD intra‐day, 1.06– 11.51%; inter‐day, 2.23– 11.38%), accuracy (RE, −7.40–10.76%) and stability (87.37–111.70%) of authentic analytes. We successfully applied this method to evaluate the pharmacokinetics of CBBP and NBBP in rats, which revealed the critical in vivo properties of both bear bile preparations.

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Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

Cited by 36 publications

References 57 publications

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

A validated surrogate analyte UPLC–MS/MS assay for quantitation of TUDCA, TCDCA, UDCA and CDCA in rat plasma: Application in a pharmacokinetic study of cultured bear bile powder

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