School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China; Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
Bioorg Chem. 2024 Oct;151:107657. doi: 10.1016/j.bioorg.2024.107657. Epub 2024 Jul 16.
Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo(OCOCH)] complexes, the nuclear magnetic resonance calculation with DP4 probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 μM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.
从贯叶连翘中分离得到 6 个新的多环多聚异戊烯基酰基间苯三酚（PPAPs），分别命名为 hyperidiones A-F（1-6）。通过广泛的光谱分析、原位形成的 [Mo(OCOCH)] 配合物的圆二色谱数据、核磁共振计算与 DP4 概率分析以及计算的电子圆二色谱（ECD）光谱，确定了它们的结构。化合物 1-6 为具有主要双环[3.3.1]壬烷-2,4,9-三酮骨架的双环多聚异戊烯基酰基间苯三酚。值得注意的是，化合物 1 是一种含有过氧基的罕见 PPAP，提出了一种可能的生物合成途径。化合物 4 和 6 在 10 μM 浓度下对皮质酮（CORT）损伤的 SH-SY5Y 细胞表现出显著的神经保护作用。此外，化合物 4 在小鼠悬尾试验（TST）中在 5mg/kg 剂量下表现出显著的抗抑郁作用，与 5mg/kg 的氟西汀相当。并且它可能通过下丘脑-垂体-肾上腺（HPA）轴发挥抗抑郁作用。
