Combination treatment with n-3 polyunsaturated fatty acids and ursodeoxycholic acid dissolves cholesterol gallstones in mice

Abstract

The increasing prevalence of cholesterol gallstone disease places an economic burden on the healthcare system. To identify novel therapeutics, we assessed the effects of n-3 polyunsaturated fatty acids (PUFA) in combination with UDCA in a mouse model of cholesterol gallstones. Gallstone dissolution, gallbladder wall thickness, mucin gene expression in the gallbladder, and levels of phospholipids, cholesterol, and bile acids in bile and serum were analysed. RNA was extracted from the liver for mRNA sequencing and gene expression profiling. Combination treatment resulted in greater gallstone dissolution compared with the control group, and PUFA and combination treatments reduced the thickness of the gallbladder wall. Expression levels of mucin genes were significantly lower in the UDCA, PUFA, and combination groups. Transcriptome analyses revealed that combination treatment modulated hepatic lipid metabolism. The PUFA and combination groups showed elevated bile phospholipid and bile acid levels and a lower cholesterol saturation index. Combination treatment with PUFA and UDCA dissolves cholesterol gallstones in mice by decreasing mucin production, increasing levels of phospholipids and bile acids in bile, and decreasing cholesterol saturation. Further studies of the therapeutic effects of combination PUFA and UDCA treatment in patients with cholesterol gallstones are warranted.

Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid

“…It is therefore tempting to speculate that the combination of EPA/DHA and UDCA may provide therapeutic benefits in PBC and PSC treatment. While additional in vivo or clinical studies are required to validate this hypothesis, recent investigations revealed that UDCA and n-3 PUFAs synergize to provide superior outcomes than individual treatments in gallstone dissolution and in NASH resolution in mice [ 48 , 49 ]. These last observations support the idea that these in vitro improvements of UDCA-induced responses by n-3 PUFAs reported here will remain in future in vivo studies with PBC and PSC animal models.…”

Chemical Characterization of Chinese Perilla Seed Oil

“…The ALA content of the perilla seed oil was higher than that other ALA rich oils, such as linseed oil (52.1 g/100 g) , sacha inchi oil (50.7 g/100 g) , and chia oil (63.5 g/100 g) 26,27) . The second one was linoleic acid (C18:2) with concentration of 15.3 g/100 g, while the third one was oleic acid (C18:1) at 11.3 g/100 g. The unsaturated fatty acids content was 93.0 g/100 g, among which polyunsaturated fatty acids amounted up to 81.7 g/100 g. The polyunsaturated/saturated fatty acids (PUFA/SFA) ratio reached up to 11.6 g/100 g. High PUFA/SFA ratio has been reported to be relative with reduction of cholesterol, therefore decreasing cardiovascular and atherosclerosis disease 28) .…”

Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer

“…Different animal models have been used to study gallstone formation and its effect on the development of preneoplastic lesions [114][115][116][117]. Our research group established an animal model of gallbladder preneoplasia through a lithogenic diet.…”