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Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation |
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| Affiliation: | 1. The Faculty of Pharmacy, Binzhou Medical University, China;2. The Faculty of Pharmacy, Shandong University of Traditional Chinese Medicine, China;3. The Faculty of Pharmacy, Beijing University of Traditional Chinese Medicine, China |
| Abstract: | Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion. |
| Keywords: | Hyperuricemia Drug metabolism Gut microbiome Feces metabolomic HUA"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"hyperuricemia TCM"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"traditional Chinese medicine AMUP"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "$$":[{"#name":"italic" "_":"astragalus membranaceus"} {"#name":"__text__" "_":" ultrafine powder AM"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "$$":[{"#name":"italic" "_":"astragalus membranaceus rRNA"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"ribosomal RNA UA"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"uric acid HE"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"hematoxylin-eosin ALT"} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"alanine aminotransferase AST"} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"aspartate aminotransferase IBIL"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"indirect bilirubin TG"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "_":"triglyceride Glu"} {"#name":"keyword" "$":{"id":"k0145"} "$$":[{"#name":"text" "_":"glucose LC-MS"} {"#name":"keyword" "$":{"id":"k0155"} "$$":[{"#name":"text" "_":"liquid chromatography-mass spectrometry PCoA"} {"#name":"keyword" "$":{"id":"k0165"} "$$":[{"#name":"text" "_":"principal co-ordinates analysis IL"} {"#name":"keyword" "$":{"id":"k0175"} "$$":[{"#name":"text" "_":"interleukin OPLS-DA"} {"#name":"keyword" "$":{"id":"k0185"} "$$":[{"#name":"text" "_":"orthogonal partial-least-squares discriminant analysis 19 20-diHDPA"} {"#name":"keyword" "$":{"id":"k0195"} "$$":[{"#name":"text" "_":"19 20-dihydroxydocosapentaenoic acid NAFLD"} {"#name":"keyword" "$":{"id":"k0205"} "$$":[{"#name":"text" "_":"non-alcoholic fatty liver disease CA"} {"#name":"keyword" "$":{"id":"k0215"} "$$":[{"#name":"text" "_":"cholic acid EL"} {"#name":"keyword" "$":{"id":"k0225"} "$$":[{"#name":"text" "_":"Enterolactone PCR"} {"#name":"keyword" "$":{"id":"k0235"} "$$":[{"#name":"text" "_":"polymerase chain reaction OUT"} {"#name":"keyword" "$":{"id":"k0245"} "$$":[{"#name":"text" "_":"operational taxonomic unit UPLC–MS"} {"#name":"keyword" "$":{"id":"k0255"} "$$":[{"#name":"text" "_":"ultra-performance liquid chromatography-mass spectrometer |
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