At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut m...At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.展开更多
3,4,5-Trimethoxybenzaldehyde was synthesized from p-cresol in an overall yield of 64 5%. p-Cresol was at first brominated and hydrolyzed to give 3,5-dibromo-4-hydroxybenzal-dehyde, which was methoxylated by methanolic...3,4,5-Trimethoxybenzaldehyde was synthesized from p-cresol in an overall yield of 64 5%. p-Cresol was at first brominated and hydrolyzed to give 3,5-dibromo-4-hydroxybenzal-dehyde, which was methoxylated by methanolic sodium methoxide in the presence of cuprous chloride and dimethylformamide(DMF) at 125 ℃(ca. 0 5 MPa) to provide sodium phenolate of 3,5-dimethoxy-4-hydroxybenzaldehyde, from which 3,4,5-trimethoxybenzaldehyde was obtained by methylation directly with dimethyl sulfate in aqueous sodium hydroxide. "One-pot" method was used in the synthesis starting from economical, convenient and environmental awareness.展开更多
基金supported by the National Key R&D Program of China(No.2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(CIFMS+2 种基金Nos.2022-I2M-JB-011,2022-I2M-2-002,and 2021-I2M-1-007,China)National Natural Science Foundation of China(Nos.82173888 and 81973290)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062,China)。
文摘At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.
文摘3,4,5-Trimethoxybenzaldehyde was synthesized from p-cresol in an overall yield of 64 5%. p-Cresol was at first brominated and hydrolyzed to give 3,5-dibromo-4-hydroxybenzal-dehyde, which was methoxylated by methanolic sodium methoxide in the presence of cuprous chloride and dimethylformamide(DMF) at 125 ℃(ca. 0 5 MPa) to provide sodium phenolate of 3,5-dimethoxy-4-hydroxybenzaldehyde, from which 3,4,5-trimethoxybenzaldehyde was obtained by methylation directly with dimethyl sulfate in aqueous sodium hydroxide. "One-pot" method was used in the synthesis starting from economical, convenient and environmental awareness.
