2. Academic Validation
  3. New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L

New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L

  • Bioorg Chem. 2024 Jul 16:151:107657. doi: 10.1016/j.bioorg.2024.107657.
Xue-Ge Pan 1,  Xin-Xin Li 2,  Cong-Yuan Xia 3,  Wei-Feng Yin 2,  Kang Ding 3,  Guo-Yan Zuo 2,  Man-Ni Wang 2,  Wei-Ku Zhang 4,  Jun He 5,  Jie-Kun Xu 6
Affiliations

Affiliations

  • 1 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.
  • 2 School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
  • 3 Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
  • 4 Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China. Electronic address: cpuzwk@163.com.
  • 5 Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China. Electronic address: 15010297582@126.com.
  • 6 School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China. Electronic address: xjkbucm@163.com.
PMID: 39053099 DOI: 10.1016/j.bioorg.2024.107657
Abstract

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 [Mo2(OCOCH3)4] 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.

Keywords

Antidepressant; Biosynthetic pathway; Corticosterone; Docking study; Hypericum perforatum; Polycyclic polyprenylated acylphloroglucinols.

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