School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, 60637, USA.
J Ethnopharmacol. 2021 Mar 25;268:113683. doi: 10.1016/j.jep.2020.113683. Epub 2020 Dec 8.
Genkwa flos, as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema.
The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions.
The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation.
Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-β-D-glucoside), H2 (apigenin-7-O-β-D-glucoside), H3 (kaempferol-3-O-β-D-glucoside), H4 (hydroxygenkwanin-5-O-β-D-primeveroside), H5 (apigenin-5-O-β-D-primeveroside), H6 (apigenin-7-O-β-D-glucuronide), H7 (luteolin-5-O-β-D-glucopyranoside), H8 (genkwain-5-O-β-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3'- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14.
Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation.
款冬花，作为一种传统草药，是紫堇属植物的干燥花蕾。它在传统医学中用于治疗咳嗽、喉咙痛、水肿。
本研究旨在探索一种新的多变量评价数学方法，研究紫堇属植物中类黄酮在离体条件下的抗炎和抗血管生成活性。
采用制备液相色谱法分离紫堇属植物中的黄酮类单体，并通过高效液相色谱-电喷雾-串联质谱法（HPLC-ESI-ITMS）进行鉴定。建立了脂多糖诱导的巨噬细胞 RAW264.7 体外炎症模型和 TNF-α诱导的人脐静脉内皮细胞血管生成模型。提取黄酮类化合物进行干预，检测药物干预后分泌量，反映各成分的抗炎和抗血管生成活性。此外，采用主成分分析和功效系数法相结合的新数学方法进行药效学评价。
采用制备液相色谱法分离出 14 种黄酮类单体，并通过高效液相色谱-电喷雾-串联质谱法（HPLC-ESI-ITMS）进行鉴定，包括 H1（羟基芫花素-5-O-β-D-葡萄糖苷）、H2（芹菜素-7-O-β-D-葡萄糖苷）、H3（山奈酚-3-O-β-D-葡萄糖苷）、H4（羟基芫花素-5-O-β-D-新橙皮糖苷）、H5（芹菜素-5-O-β-D-新橙皮糖苷）、H6（芹菜素-7-O-β-D-葡萄糖醛酸苷）、H7（木犀草素-5-O-β-D-吡喃葡萄糖苷）、H8（芫花素-5-O-β-D-葡萄糖苷）、H9（木犀草素）、H10（Daphnodorin G）、H11（桃叶珊瑚苷）、H12（芹菜素）、H13（3'-羟基芫花素）和 H14（芫花素）。我们发现，大多数黄酮类化合物下调 VCAM 和 MMP-3，而 H1、H8、H9、H14 降低了 VEGF，只有 H14 降低了 ICAM。
芫花素可能是紫堇属植物中治疗类风湿关节炎最活跃的类黄酮。同时，本研究中使用的新数学方法为解决多指标药效学评价问题提供了新的方向。
