ELIZA

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308129 occurrences (No.71 in the rank) during 5 years in the PubMed. [cache]

8) Moreover, molecular docking and gene expression analysis in vivo and in vitro suggest that BBR and M1 are FXR agonists.

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PMID:33376148 DOI:10.1124/dmd.120.000215

2021 Drug metabolism and disposition: the biological fate of chemicals

* The Hypoglycemic Effect of Berberine and Berberrubine Involves Modulation of Intestinal Farnesoid X Receptor Signaling Pathway and Inhibition of Hepatic Gluconeogenesis.

- Our previous study suggests that berberine (BBR) lowers lipids by modulating bile acids and activating intestinal farnesoid X receptor (FXR). However, to what extent this pathway contributes to the hypoglycemic effect of BBR has not been determined. In this study, the glucose-lowering effects of BBR and its primary metabolites, berberrubine (M1) and demethyleneberberine, in a high-fat diet-induced obese mouse model were studied, and their modulation of the global metabolic profile of mouse livers and systemic bile acids was determined. The results revealed that BBR (150 mg/kg) and M1 (50 mg/kg) decreased mouse serum glucose levels by 23.15% and 48.14%, respectively. Both BBR and M1 markedly modulated the hepatic expression of genes involved in gluconeogenesis and metabolism of amino acids, fatty acids, and purine. BBR showed a stronger modulatory effect on systemic bile acids than its metabolites. Moreover, molecular docking and gene expression analysis in vivo and in vitro suggest that BBR and M1 are FXR agonists. The mRNA levels of gluconeogenesis genes in the liver, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, were significantly decreased by BBR and M1. In summary, BBR and M1 modulate systemic bile acids and activate the intestinal FXR signaling pathway, which reduces hepatic gluconeogenesis by inhibiting the gene expression of gluconeogenesis genes, achieving a hypoglycemic effect. BBR and M1 may function as new, natural, and intestinal-specific FXR agonists with a potential clinical application to treat hyperglycemia and obesity. SIGNIFICANCE STATEMENT: This investigation revealed that BBR and its metabolite, berberrubine, significantly lowered blood glucose, mainly through activating intestinal farnesoid X receptor signaling pathway, either directly by themselves or indirectly by modulating the composition of systemic bile acids, thus inhibiting the expression of gluconeogenic genes in the liver and, finally, reducing hepatic gluconeogenesis and lowering blood glucose. The results will help elucidate the mechanism of BBR and provide a reference for mechanism interpretation of other natural products with low bioavailability.

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(1)346 that	(4)6 an	(7)2 best	(10)2 integrating
(2)46 a	(5)6 that,	(8)2 either
(3)17 the	(6)3 ways	(9)2 further

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--- WordNet output for suggest --- =>〜しようと提案する, を提案する, 示唆する, 暗示する, 提案する Overview of verb suggest The verb suggest has 5 senses (first 5 from tagged texts) 1. (57) propose, suggest, advise -- (make a proposal, declare a plan for something; "the senator proposed to abolish the sales tax") 2. (21) hint, suggest -- (drop a hint; intimate by a hint) 3. (19) suggest, intimate -- (imply as a possibility; "The evidence suggests a need for more clarification") 4. (14) indicate, suggest -- (suggest the necessity of an intervention; in medicine; "Tetracycline is indicated in such cases") 5. (12) suggest, evoke, paint a picture -- (call to mind; "this remark evoked sadness") --- WordNet end ---