AUTHOR=Chen Caiyun , Liu Keyu , Wang Yishu , Song Xinru , Gao Wenjing , Wang Yanlin , Chen Yuxin , An Ziqi , Yin Changting , Wang Haiyan , Wang Shaoping 

TITLE=In vitro colonic fermentation of fermented Radix Astragali by Poria cocos and anti-hyperuricemia mechanism based on network pharmacology and experiment verification

JOURNAL=Frontiers in Nutrition

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1466702

DOI=10.3389/fnut.2024.1466702

ISSN=2296-861X

ABSTRACT=<sec id="sec1001"><title>Aim</title><p>This research aimed to probe the effects of fecal microbiota and <italic>Lactobacillus acidophilus</italic> on the metabolism of Radix Astragali (RA) and <italic>Poria cocos</italic> solid fermenting Radix Astragali (FRA). It further explores pharmacological effects of RA, <italic>Poria cocos</italic>, and FRA on HUA mouse model and the mechanisms in HUA treatment.</p></sec><sec id="sec2001"><title>Methods</title><p>Fecal microbiota and <italic>Lactobacillus acidophilus</italic> were used to ferment FRA and RA in vitro to probe the impacts of microbiota on the metabolism of active compound. A HUA mouse model was used to carry out pharmacodynamic experiment of anti-hyperuricemia. Network pharmacology and molecular docking was utilized to elucidate the underlying mechanisms of RA and <italic>Poria cocos</italic> in the treatment of HUA.</p></sec><sec id="sec3001"><title>Results</title><p>The results indicated that astragaloside IV (AG IV), total saponins, and flavonoids continuously decreased in FRA and RA during 48 h fecal microbiota colonic fermentation. During <italic>Lactobacillus acidophilus</italic> fermentation, in FRA, the content of AG IV peaked at 12 h with a value of 1.14 ± 0.20 mg/g; total saponins and flavonoids reached the highest values of 136.34 ± 6.15 mg/g at 12 h and 6.35 ± 0.06 mg/g at 6 h; AG IV and total saponins reached the highest values 0.63 ± 0.05 mg/g and 115.12 ± 4.12 mg/g at 12 h and 24 h in RA, respectively; and total flavonoids consecutively decreased. The counts of <italic>Lactobacillus acidophilus</italic> increased significantly in FRA compared with RA. Pharmacodynamic outcomes revealed that FRA effectively reduced blood levels of uric acid (UA), triglycerides (TG), xanthine oxidase (XOD), alanine aminotransferase (ALT), and aspartate transaminase (AST) in HUA mice, exerting protective effects on the liver and kidney. Network pharmacology showed that there were 93 common targets for RA, <italic>Poria cocos</italic>, and HUA with the top five core targets tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), cysteinyl aspartate specific proteinase 3 (CASP3), jun proto-oncogene (JUN), and estrogen receptor 1 (ESR1). Molecular docking analysis revealed that AG IV, calycosin and formononetin bond well to the core targets.</p></sec><sec id="sec4001"><title>Conclusion</title><p>This research revealed the interaction of RA and FRA with fecal microbiota and Lactobacillus acidophilus, RA and <italic>Poria cocos</italic> were featured with multiple components, target points, and signaling pathways in HUA treatment, which provided fresh insights for further HUA therapeutics.</p></sec>