Research Center of Natural Drugs, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Food Funct. 2021 Mar 15;12(5):2292-2311. doi: 10.1039/d0fo02814b.
Acanthopanax senticosus leaves (SCL) and Acanthopanax sessiliflorus leaves (SFL), which are usually made into functional teas, possess similar pharmacological activities. With the aim of revealing their chemical compositions and evaluating their sedative-hypnotic effects, comprehensive metabolite profiling analysis based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) as well as bioassay studies in mice were performed for the first time. Firstly, a total of 75 compounds (including 69 shared components) were identified or briefly characterized. Results indicated that the leaves of the two species were both rich in phytochemicals and contained similar structural types. Secondly, 20 and 7 chemical markers were identified from SCL and SFL, respectively. Five oleanane-type triterpene saponins (ciwujianoside C1, C3, D2, E and saniculoside N) and two lupine-type triterpene saponins (1-deoxychiisanoside and 24-hydroxychiisanoside) may be used for rapid identification of SCL and SFL. Thirdly, the contents of rutin, hederacoside D, ciwujianoside B, -C3, -E and ursolic acid in SCL (0.308%, 0.024%, 0.042%, 0.131%, 0.038%, and 0.255%, respectively) were higher than in SFL (0.067%, 0.005%, 0.012%, 0.015%, 0.002%, and 0.087%, respectively). Fourthly, an in vivo bioassay verified that both SCL and SFL could inhibit autonomous activity, shorten sleep latency and prolong sleep duration in a dose-dependent manner. To a certain degree, SCL showed a higher and more stable effect. The hypnotic effect could be inhibited by flumazenil (FLU). The two leaves not only had an obvious antagonism action of p-chlorophenoxyacetic acid (pCPA) but also showed a synergistic hypnotic effect with 5-hydroxytryptophan (5-HTP). The beneficial bioactivity may be mediated by 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA). Finally, network pharmacology analysis showed that the undifferentiated and differentiated compounds were the material basis for the similar and the different activities of two leaves. Some typical chemical markers (such as saniculoside N, hederacoside D, ciwujianoside C3, -E and ursolic acid, 24-hydroxychiisanoside and 1-deoxyisochiisanoside) were the potential active compounds and could be used as quality markers in the future. The present study furnished a basis for the further development and utilization of the leaves of these two Acanthopanax species.
刺五加叶（SCL）和无梗五加叶（SFL）通常被制成功能性茶，具有相似的药理活性。为了揭示它们的化学成分并评估它们的镇静催眠作用，首次采用基于超高效液相色谱与四极杆飞行时间串联质谱联用（UPLC-Q/TOF-MS）和高效液相色谱与蒸发光散射检测联用（HPLC-ELSD）的综合代谢组学分析以及小鼠的生物测定研究。首先，共鉴定或简要描述了 75 种化合物（包括 69 种共有成分）。结果表明，两种植物的叶子都富含植物化学物质，并且含有相似的结构类型。其次，从 SCL 和 SFL 中分别鉴定出 20 种和 7 种化学标志物。五环三萜皂苷（齐墩果酸 C1、C3、D2、E 和桑皮苷 N）和两种羽扇豆烷三萜皂苷（1-去氧奇卡烷苷和 24-羟基奇卡烷苷）可能被用于快速鉴定 SCL 和 SFL。第三，SCL 中芦丁、栀子苷 D、齐墩果酸 B、C3、E 和熊果酸的含量（分别为 0.308%、0.024%、0.042%、0.131%、0.038%和 0.255%）高于 SFL（分别为 0.067%、0.005%、0.012%、0.015%、0.002%和 0.087%）。第四，体内生物测定验证了 SCL 和 SFL 均可剂量依赖性地抑制自主活动，缩短睡眠潜伏期并延长睡眠时间。在一定程度上，SCL 表现出更高且更稳定的效果。氟马西尼（FLU）可抑制催眠作用。两片叶子不仅对对氯苯氧乙酸（pCPA）具有明显的拮抗作用，而且与 5-羟色氨酸（5-HTP）具有协同催眠作用。有益的生物活性可能是通过 5-羟色胺（5-HT）和γ-氨基丁酸（GABA）介导的。最后，网络药理学分析表明，未分化和分化的化合物是两种叶子相似和不同活性的物质基础。一些典型的化学标志物（如桑皮苷 N、栀子苷 D、齐墩果酸 C3、E 和熊果酸、24-羟基奇卡烷苷和 1-去氧奇卡烷苷）是潜在的活性化合物，未来可作为质量标志物。本研究为进一步开发和利用这两种五加属植物的叶子提供了依据。
