Citation: Bingchuan Geng, Jiangchun Wei, Dan Hu, Xingpiao Jin, Pingping Fan, Yahui Huang, Xiaoxuan Duan, Yipin Zhao, Yonghui Zhang, Zhengxi Hu. Bioassay- and molecular network-guided discovery of PPAP derivatives from Hypericum monogynum with inhibitory activity against cardiac valve calcification[J]. Chinese Chemical Letters, ;2026, 37(9): 112069. doi: 10.1016/j.cclet.2025.112069 shu

Bioassay- and molecular network-guided discovery of PPAP derivatives from Hypericum monogynum with inhibitory activity against cardiac valve calcification

Bingchuan Geng ^{a, 1} ,
Jiangchun Wei ^{c, d, 1} ,
Dan Hu ^{a, 1} ,
Xingpiao Jin ^d ,
Pingping Fan ^b ,
Yahui Huang ^b ,
Xiaoxuan Duan ^c ,
Yipin Zhao ^{a, *,} ,
Yonghui Zhang ^{b, *,} ,
Zhengxi Hu ^{b, e, *,}

a.
Department of Cardiology, Heart Center of Henan Provincial People’s Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450003, China
b.
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
c.
Laboratory of Clinical Research Center, Department of Pathology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, China
d.
Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shang Dang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
e.
Hubei Shizhen Laboratory, Wuhan 430061, China

zhao1pin@gmail.com

zhangyh@mails.tjmu.edu.cn

hzx616@126.com

Received Date: 14 August 2025
Revised Date: 3 November 2025
Accepted Date: 5 November 2025
Available Online: 6 November 2025

Figures(5)

Bioassay- and molecular network-guided isolation of the extract from Hypericum monogynum led to the identification of five polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, including a previously unreported bis-seco compound, hypermonane A (HMA, 1). HMA possesses a unique 3/6-5/6/5 pentacyclic scaffold, characterized by C-1/C-2 and C-2/C-3 bond cleavage. In addition to HMA, four structurally related biosynthetic analogs (2–5) were also obtained. Its structure was elucidated using computer-assisted structure elucidation (CASE) software and gauge-independent atomic orbital (GIAO)-based nuclear magnetic resonance (NMR) calculations. The absolute configuration of 1 was determined through comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Biological investigations revealed that HMA potently inhibited aortic valve calcification by simultaneously suppressing osteogenic differentiation (runt-related transcription factor 2/alkaline phosphatase, RUNX2/ALP) and extracellular matrix remodeling (collagen type Ⅰ alpha 1 chain/a disintegrin and metalloproteinase with thrombospondin motif 4, COL1A1/ADAMTS4). Moreover, in a murine model of calcific aortic valve disease (CAVD), HMA significantly attenuated pathological aortic valve calcification. These findings highlight HMA as a promising lead compound for the development of anti-CAVD therapeutics.
- Hypericum monogynum,
- PPAPs,
- Quantum chemical calculations,
- RNA sequencing,
- CAVD
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