关键词: hypoglycemic molecular docking network pharmacology rice resistant starch α-amylase α-glucosidase

来  源:   DOI:10.3390/metabo14040224   PDF(Pubmed)

Abstract:
Rice (Oryza sativa L.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand-receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.
摘要:
水稻(OryzasativaL.)是人体所需的能量和营养素的主要来源之一,已经发现水稻抗性淀粉(RRS)具有降血糖作用。然而,其生物学活性和具体机制仍需进一步阐明。在本研究中,从小鼠肝脏获得52个RRS差异代谢物,大鼠血清,犬类粪便,和人类尿液,通过文献综述和数据库分析确定了246个潜在目标.通过与2型糖尿病(T2DM)的目标相交,总共确定了151个常见目标。经过网络药理学分析,鉴定出11种核心代谢物,包括亚麻酸,鹅去氧胆酸,熊去氧胆酸,脱氧胆酸,石胆酸,石胆酰甘氨酸,甘草脱氧胆酸,苯丙氨酸,去甲肾上腺素,胆酸,和L-谷氨酸,确定了16个核心目标,包括MAPK3,MAPK1,EGFR,ESR1,PRKCA,FYN,LCK,DLG4,ITGB1,IL6,PTPN11,RARA,NR3C1,PTPN6,PPARA,还有ITGAV.核心途径包括神经活性配体-受体相互作用,癌症,和花生四烯酸代谢途径。分子对接结果表明,胆汁酸如甘草脱氧胆酸,鹅去氧胆酸,熊去氧胆酸,石胆酸,脱氧胆酸,和胆酸表现出与EGFR的强对接作用,ITGAV,ITGB1,MAPK3,NR3C1,α-葡萄糖苷酶,和α-淀粉酶。体外降糖实验进一步提示胆汁酸对α-葡萄糖苷酶和α-淀粉酶有明显的抑制作用,其中CDCA和UDCA具有最突出的抑制作用。总之,本研究揭示了RRS代谢产物可能的降糖途径,为进一步探讨胆汁酸治疗T2DM的作用机制提供了新的研究视角。
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