Enhancement of anti-inflammatory effect of cattle bile by fermentation and its inhibition of neuroinflammation on microglia by inhibiting NLRP3 inflammasome

As a kind of animal medicine, cattle bile has anti-inflammatory, antipyretic and cholagogic effects. The fermentation process of cattle bile is included in the application of many traditional Chinese medicines. In this study, we fermented cattle bile singly and investigated the impact of fermentation on the anti-inflammatory effect of cattle bile, as well as the mechanism of fermented cattle bile on microglia cells. After high temperature sterilization, cattle bile was fermented with Massa Medicata Fermentata (medicated leaven, Shen Qu). We used ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) to analyze the bile acids of cattle bile and fermented cattle bile. The results showed that 3-dehydrocholic acid, 7-ketolithocholic acid, 12-dehydrocholic acid, 12-Ketolithocholic acid, ursodeoxycholic acid and dehydrolithocholic acid increased more significantly than others; glycocholic acid and glycochenodeoxycholic acid decreased more significantly than others. After fermentation, cattle bile significantly reduced the release of NO and inflammatory factors (TNF-α and IL-1β). Furthermore, the protein expression of TNF-α, IL-1β and iNOS were decreased. In addition, we found that fermented cattle bile could have an anti-inflammatory effect through attenuating the activation of NLRP3 inflammasome. Thus, fermentation can enhance the anti-inflammatory effect of cattle bile. Fermented cattle bile has an anti-inflammatory effect by inhibiting the NLRP3 inflammasome pathway, which can expand the clinical application of cattle bile and provide new thoughts and methods for the application of cattle bile.