Ji Yuanyuan, Zhang Ruifei, Bensalel Johanna, Morcol Taylan, Gu Ronghui, Gallego-Delgado Julio, Kennelly Edward J, Long Chunlin
Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China; Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, 10468, United States.
Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, 10468, United States; Ph.D. Program in Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY, 10016, United States.
J Ethnopharmacol. 2024 Jul 15;329:118163. doi: 10.1016/j.jep.2024.118163. Epub 2024 Apr 6.
Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises.
The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds.
Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds.
In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity.
This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.
金丝桃属（金丝桃科）植物在全球有500多种，许多因其药用特性而受到重视，并被用作传统草药。然而，只有贯叶连翘在几部药典中被正式认可为草药，并在临床上用作抗抑郁药。贯叶连翘在中国自汉代（公元前206年 - 公元220年）起就被用作草药。它在分类学上属于金丝桃属中的金丝桃组。金丝桃组约有42个物种，其中6种在中国有分布。所有这6种都被记载为治疗多种疾病的传统草药，包括肝炎、疟疾、创伤性出血、月经不调、伤口和瘀伤。
本研究旨在表征五种系统发育相关的金丝桃属物种的化学特征，并将它们的代谢产物与三种贯叶连翘产品进行比较。基于民族植物学用途，对这五个物种制备的提取物进一步研究其抗癌、抗炎和抗疟活性。本研究检验了这样一个假设，即对金丝桃组物种进行系统的代谢组学和生物活性表征将有助于验证它们的植物治疗用途并揭示潜在的药物先导化合物。
对金丝桃属中原产于中国的贯叶连翘以及四种药用物种——细叶金丝桃、恩施金丝桃、直立金丝桃和短柱金丝桃进行了靶向和非靶向代谢分析，并结合化学计量学方法。超高效液相色谱 - 四极杆飞行时间串联质谱（UPLC - QTOF - MS/MS）和超高效液相色谱 - 三重四极杆质谱（UPLC - TQD - MS/MS）分别用于非靶向和靶向代谢分析。基于传统药用用途，对金丝桃属物种的提取物进行了针对四种癌细胞系的细胞毒性生物测定、抗炎测试以及对恶性疟原虫3D7的抗疟活性评估。使用Progenesis QI和EZinfo进行化学计量学分析，以将化学特征与生物测定活性联系起来，辅助鉴定生物活性化合物。
从这五个物种中总共鉴定出58种化合物，包括具有明确生物活性的化合物。细叶金丝桃、直立金丝桃和贯叶连翘表现出最高的细胞毒性，分别含有细胞毒性化合物叶柄林A、多育菌素A和金丝桃苷G。短柱金丝桃和贯叶连翘表现出最高的抗炎活性，其中假金丝桃素、槲皮素和绿原酸的含量较高。贯叶连翘和直立金丝桃表现出抗疟活性，这些物种中较高含量的金丝桃素和呫吨酮可能是其抗疟活性的原因。
本研究利用代谢组学表征了五个金丝桃属物种之间的化学差异。这些具有重要民族医学意义的物种在三种不同的体外试验中测试了它们的生物活性。民族植物学数据有助于鉴定具有生物活性的金丝桃属物种。细叶金丝桃、直立金丝桃和短柱金丝桃是很有前景的植物治疗物种，尽管它们的研究比贯叶连翘（圣约翰草）少得多。将民族植物学调查与化学计量学分析和生物活性筛选相结合，可以大大提高有前景的活性成分的发现。
