New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-07-16 DOI:10.1016/j.bioorg.2024.107657
Xue-Ge Pan , Xin-Xin Li , Cong-Yuan Xia , Wei-Feng Yin , Kang Ding , Guo-Yan Zuo , Man-Ni Wang , Wei-Ku Zhang , Jun He , Jie-Kun Xu
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Abstract

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (16), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo2(OCOCH3)4] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 16 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.

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从贯叶连翘中提取的具有抗抑郁活性的新的多环多烯酰化酰基氯葡萄糖醇
通过广泛的光谱分析、原位形成的[Mo2(OCOCH3)4]复合物的圆二色性数据、使用 DP4 + 概率分析进行的核磁共振计算以及电子圆二色性(ECD)光谱计算,确定了它们的结构特征。化合物 1-6 是以双环[3.3.1]壬烷-2,4,9-三酮为主要骨架的双环多烯化酰基氯葡萄糖醇。值得注意的是,化合物 1 是一种罕见的带有氢过氧基团的 PPAP,并提出了 1 的合理生物合成途径。化合物 4 和 6 在 10 μM 下对皮质酮(CORT)损伤的 SH-SY5Y 细胞有明显的神经保护作用。此外,化合物 4 在 5 毫克/千克剂量的小鼠尾悬液试验(TST)中表现出显著的抗抑郁效果,相当于 5 毫克/千克氟西汀。它可能通过下丘脑-垂体-肾上腺(HPA)轴发挥抗抑郁作用。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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