Meroterpenoids with bicyclic polyprenylated acylphloroglucinol scaffold and anti-inflammatory activity from Hypericum lancasteri

Jin-Qiu You; Yun-Qi Jin; Yu-Meng Miao; Xin-Yu Sun; Jia-Yu Yang; Jin-Chang Huang; Jing-Ya Li; Ai-Jun Hou

doi:10.1016/j.phytochem.2025.114484

Meroterpenoids with bicyclic polyprenylated acylphloroglucinol scaffold and anti-inflammatory activity from Hypericum lancasteri

Phytochemistry. 2025 Jul:235:114484. doi: 10.1016/j.phytochem.2025.114484. Epub 2025 Mar 17.

Authors

Jin-Qiu You¹, Yun-Qi Jin², Yu-Meng Miao³, Xin-Yu Sun³, Jia-Yu Yang⁴, Jin-Chang Huang², Jing-Ya Li⁵, Ai-Jun Hou⁶

Affiliations

¹ Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China; Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215123, People's Republic of China.
² Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
³ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China.
⁴ School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, People's Republic of China.
⁵ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China. Electronic address: jyli@simm.ac.cn.
⁶ Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. Electronic address: ajhou@sjtu.edu.cn.

PMID: 40107642
DOI: 10.1016/j.phytochem.2025.114484

Abstract

Twelve undescribed meroterpenoids possessing bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, (±)-lancasternoids A-D and lancasternoids E-H, together with fourteen known analogues, were isolated from Hypericum lancasteri (Hypericaceae) and structurally characterized. (±)-Lancasternoids A-D are the first examples of bicyclo[3.2.1]octane-type BPAP meroterpenoids present as enantiomeric pairs, while (±)-lancasternoids A-C incorporate an unprecedented 5-oxatetracyclo[7.5.1.0^4,9.0^1,11]pentadecane system. Lancasternoids E-H are two pairs of epimers with [3.3.1]-type BPAP scaffold. Some of the isolates showed inhibition in hypoxia-inducible factor-1α (HIF-1α) responsive element (HRE) luciferase assay, and uraloidin A further decreased the lipopolysaccharide (LPS)-induced pro-inflammatory factor IL-1β expression level in RAW 264.7 cells.

Keywords: Anti-inflammation; Hypericaceae; Hypericum lancasteri; Hypoxia-inducible factor-1α; Meroterpenoids; Structural characterization.

MeSH terms

Animals
Anti-Inflammatory Agents* / chemistry
Anti-Inflammatory Agents* / isolation & purification
Anti-Inflammatory Agents* / pharmacology
Hypericum* / chemistry
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Interleukin-1beta / antagonists & inhibitors
Interleukin-1beta / metabolism
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Macrophages / drug effects
Mice
Molecular Structure
Phloroglucinol* / analogs & derivatives
Phloroglucinol* / chemistry
Phloroglucinol* / isolation & purification
Phloroglucinol* / pharmacology
RAW 264.7 Cells
Stereoisomerism
Structure-Activity Relationship
Terpenes* / chemistry
Terpenes* / isolation & purification
Terpenes* / pharmacology

Substances

Phloroglucinol
Lipopolysaccharides
Terpenes
Anti-Inflammatory Agents
Hypoxia-Inducible Factor 1, alpha Subunit
Interleukin-1beta