目的 分离鉴定雅连C. deltoidea醋酸乙酯部位化学成分，并通过体外模型初筛其降糖活性，为雅连资源利用及新型降糖药物的研发提供依据。方法 采用溶剂提取法、硅胶柱色谱等方法进行分离纯化，运用现代波谱技术对化合物进行结构鉴定；通过PTP1B酶活性抑制实验及高糖诱导的胰岛素抵抗HepG2细胞模型（insulin-resistant HepG2 cell model，IR-HepG2），评估单体化合物的降糖活性。结果 从醋酸乙酯部位共分离得到26个化合物，分别鉴定为降氧化北美黄连次碱（1）、6,7-methylenedioxy-1(2H)-isoquinolinone（2）、thalifoline（3）、紫堇定（4）、3,4-dihydro-(4′,5′-dimethoxy-6′-methoxycarbonylbenzoyl)-6,7-(methylenedioxy) isoquinoline（5）、4′,5′-dimethoxy-3′-methoxycarbonylbenzoyl)-6,7-(methyl- enedioxy)isoquinoline（6）、8-氧化小檗碱（7）、黄连碱（8）、3-hydroxy-2-methoxy-9,10-methylenedioxy-8-oxoprotoberberine（9）、8-氧代黄连碱（10）、8,13-dioxo-14-hyroxycanadine（11）、chilenine （12）、tricycoptisine（13）、氧化小檗碱二聚体（14）、N-反式阿魏酰酪胺（15）、(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside（16）、dehydroconiferyl alcohol（17）、woorenosideⅡ（18）、woorenoside Ⅰ（19）、松脂醇（20）、(＋)-丁香脂素（21）、salicifoliol（22）、香草醛（23）、香草酸（24）、5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol（25）、5-O-二甲氧基肉桂酰基奎宁酸（26）。活性筛选实验结果显示，化合物8、19对PTP1B酶活性抑制作用的半数抑制浓度（median inhibition concentration，IC₅₀）分别为104.5、143.1 μmol/L；IR-HepG2细胞模型实验表明，化合物1、3、6、11、14、22、25在15～120 μmol/L浓度下，可剂量相关性改善细胞葡萄糖消耗量。结论 化合物5和14为黄连属植物中首次分离得到。除化合物8以外，其余化合物首次从该植物中分离得到。筛选出2个具PTP1B抑制活性的化合物及7个改善IR-HepG2细胞葡萄糖消耗的化合物，提示其具有潜在降糖作用。

Objective This study aimed to isolate and identify the chemical constituents from the ethyl acetate fraction (EA) of Coptis deltoidea, and preliminarily screen their hypoglycemic activity using in vitro models, so as to provide a basis for the resource utilization of C. deltoidea and the development of new hypoglycemic drugs. Methods Solvent extraction, silica gel column chromatography, and other methods were employed for the separation and purification of chemical constituents. Modern spectroscopic techniques were used to identify the structures of the isolated compounds. The hypoglycemic activity of the monomeric compounds was evaluated through two in vitro models: the protein tyrosine phosphatase 1B (PTP1B) enzyme activity inhibition assay and the high glucose-induced insulin-resistant HepG2 cell model (IR-HepG2). Results A total of 26 compounds were isolated and identified from the ethyl acetate fraction, which are as follows: noroxyhyhydrastinine (1), 6,7-methylenedioxy-1(2H)-isoquinolinone (2), thalifoline (3), corydine (4), 3,4-dihydro-(4′,5′-dimethoxy-6′-methoxycarbonylbenzoyl)-6,7(methylenedioxy)isoquinoline (5), 4′,5′-dimethoxy-3′-methoxycarbonylbenzoyl)-6,7-(methylenedioxy)isoquinoline (6), 8-oxyberberine (7), coptisine (8), 3-hydroxy-2-methoxy-9,10-methylenedioxy-8-oxoprotoberberine (9), 8-oxycoptisine (10), 8,13-dioxo-14-hyroxycanadine (11), chilenine (12), tricycoptisine (13), bis[oxyberberine] (14), N-trans-feruloyl tyramine (15), (7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside (16), dehydroconiferyl alcohol (17), woorenoside Ⅱ (18), woorenoside Ⅰ (19), pinoresinol (20), (＋)-syringaresinol (21), salicifoliol (22), vanillin (23), vanillic acid (24), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (25), 5-O-(dimethoxycinnamoyl) quinic acid (26). The results of the activity screening showed that: Compounds 8 and 19 exhibited inhibitory effects on PTP1B enzyme activity, with median inhibition concentrations (IC₅₀) of 104.5 and 143.1 μmol/L, respectively. The IR-HepG2 cell model experiment demonstrated that compounds 1, 3, 6, 11, 14, 22, and 25 could dose-dependently improve glucose consumption in cells at concentrations ranging from 15 to 120 μmol/L. Conclusion Compounds 5 and 14 were isolated from plants of the Coptis genus for the first time. Except for compound 8, all other compounds were isolated from C. deltoidea for the first time. Two compounds with PTP1B inhibitory activity and seven compounds that could improve glucose consumption in IR-HepG2 cells were screened out, indicating their potential hypoglycemic effects.

R284.1

国家自然科学基金项目（U19A200061）；成都中医药大学“杏林人才提升计划”（MPRC2022026）