目的 研究桔梗总皂苷肠道菌转化产物的化学成分及其抗肝损伤活性。方法 采用AB-8大孔吸附树脂、正相硅胶、Sephadex LH-20凝胶柱色谱和半制备高效液相色谱等柱色谱技术进行分离纯化，根据所分化合物理化性质及质谱、核磁共振波谱数据鉴定化合物结构。采用对乙酰氨基酚诱导AML12细胞肝损伤模型评价所分离化合物的抗肝损伤活性。结果 从桔梗总皂苷肠道菌转化产物中分离得到16个化合物，分别鉴定为3-O-β-D-吡喃葡萄糖氧基-2β,3β,16α,23-四羟基齐墩果烷-12-烯-28-酸-28-O-α-L-吡喃鼠李糖基-(1→2)-α-L-吡喃阿拉伯糖苷（1）、远志皂苷D（2）、3-O-β-D-吡喃葡萄糖基桔梗皂苷元（3）、桔梗皂苷D₃（4）、桔梗皂苷F（5）、桔梗皂苷D（6）、去芹糖桔梗皂苷D（7）、桔梗皂苷元B（8）、3-O-β-D-吡喃葡萄糖基远志酸（9）、雷叶木皂苷A（10）、亚油酸（11）、(6Z,9Z)-6,9-十六碳二烯酸（12）、亚油酸甘油酯（13）、(2S)-1-O-(9Z,12Z-十八烷二烯基)-3-O-β-半乳糖基甘油（14）、邻苯二甲酸二丁酯（15）、三烯丙基异氰脲酸酯（16）。抗药物性肝损伤活性研究表明，化合物1～3、5～7、9、14能显著抑制对乙酰氨基酚诱导的AML12细胞上清液中丙氨酸氨基转移酶、天门冬氨酸氨基转移酶水平（P＜0.05、0.01）。结论 从桔梗总皂苷肠道菌转化产物中成功分离并鉴定了16个化合物，其中化合物1为新化合物，命名为去芹糖木糖基远志皂苷D；化合物1～3、5～7、9、14表现出显著的抗药物性肝损伤活性，具有抗肝损伤潜力。

Objective To investigate the chemical constituents of the intestinal bacteria transformation products of total saponins from Platycodon grandiflorus and their anti-drug-induced liver injury activity. Methods The compounds were isolated and purified by column chromatography techniques including AB-8 macroporous resin, normal phase silica gel, Sephadex LH-20 gel chromatography, and semi-preparative high-performance liquid chromatography. Their structures were identified based on physicochemical properties, mass spectrometry and nuclear magnetic resonance spectral data. The anti-drug-induced liver injury activities of the isolated compounds were evaluated using an acetaminophen-induced AML12 cell hepatic injury model. Results A total of 16 compounds were isolated from the intestinal bacteria transformation products of total saponins from P. grandifloras and identified as 3-O-β-D-glucopyranosyloxy-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid-28-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside (1), polygalacin D (2), 3-O-β-D-glucopyranosyl platycodigenin (3), platycodin D₃ (4), platycoside F (5), platycodin D (6), deapio-platycodin D (7), platycodonoid B (8), 3-O-β-D-glucopyranosyl polygalacic acid (9), leiyemudanoside A (10), linoleic acid (11), (6Z,9Z)-6,9-hexadecadienoic acid (12), glyceryl linoleate (13), (2S)-1-O-(9Z,12Z-octadecandienyl)-3-O-β-galactosyl glycerol (14), dibutyl phthalate (15), and triallyl isocyanurate (16). Anti-drug-induced liver injury activity study showed that compounds 1—3, 5—7, 9, and 14 significantly inhibited the levels of alanine aminotransferase and aspartate aminotransferase in acetaminophen-induced AML12 cell supernatants (P < 0.05,0.01). Conclusion A total of 16 compounds were successfully isolated and identified from the intestinal bacterial transformation products from total saponins of P. grandiflorus. Compound 1 is a new compound named des-apio-xylosyl polygalacin D. Compounds 1—3, 5—7, 9, and 14 exhibit significant anti-drug-induced liver injury activities, showing potential hepatoprotective effects.

R284.1

国家自然科学基金项目(82160736); 江西中医药大学科技创新团队项目(CXTD22002)