1. Academic Validation
  2. Identification of fukinolic acid from Cimicifuga heracleifolia and its derivatives as novel antiviral compounds against enterovirus A71 infection

Identification of fukinolic acid from Cimicifuga heracleifolia and its derivatives as novel antiviral compounds against enterovirus A71 infection

  • Int J Antimicrob Agents. 2019 Feb;53(2):128-136. doi: 10.1016/j.ijantimicag.2018.07.014.
Yipeng Ma 1 Wenjuan Cong 2 Hao Huang 3 Liang Sun 4 Anh Hung Mai 5 Kurt Boonen 6 Wahedi Maryam 7 Wim De Borggraeve 8 Guoan Luo 9 Qingfei Liu 10 Liliane Schoofs 6 Frank Van Kuppeveld 7 Johan Neyts 4 Carmen Mirabelli 4 Walter Luyten 11
Affiliations

Affiliations

  • 1 Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Belgium; Laboratory of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Belgium.
  • 2 Wolfson Wohl Cancer Research Centre, University of Glasgow, Scotland, UK.
  • 3 College of Pharmacy, Gannan Medical University, Ganzhou, China.
  • 4 Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Belgium.
  • 5 R&D Department, PolymerExpert,1 Allée du Doyen Georges Brus, Pessac, France.
  • 6 Laboratory of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Belgium.
  • 7 Departement of infection and immunology, University of Utrecht, the Netherlands.
  • 8 Molecular Design and Synthesis unit, Chemistry department, KU Leuven, Belgium.
  • 9 Department of Chemistry, Tsinghua University, Beijing, China.
  • 10 School of Medicine, Tsinghua University, Beijing, China.
  • 11 Laboratory of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Belgium. Electronic address: walter.luyten@kuleuven.be.
Abstract

Human Enterovirus 71 (EV-A71) infections cause a wide array of diseases ranging from diarrhoea and rashes to hand-foot-and-mouth disease and, in rare cases, severe neurological disorders. No specific Antiviral drug therapy is currently available. Extracts from 75 Chinese medicinal Plants selected for Antiviral activity based on the Chinese pharmacopeia and advice from traditional Chinese medicine clinicians were tested for activity against EV-A71. The aqueous extract of the rhizome of Cimicifuga heracleifolia (Sheng Ma) and Arnebia euchroma (Zi Cao) showed potent Antiviral activity. The active fractions were isolated by bioassay-guided purification, and identified by a combination of high-resolution mass spectrometry and nuclear magnetic resonance. Fukinolic acid and cimicifugic acid A and J, were identified as active anti-EV-A71 compounds for C. heracleifolia, whereas for A. euchroma, two caffeic acid derivatives were tentatively deduced. Commercially available fukinolic acid analogues such as L-chicoric acid and D-chicoric also showed in vitro micromolar activity against EV-A71 lab-strain and clinical isolates.

Keywords

Arnebia euchroma; Cimicifuga heracleifolia; Cimicifugic acid; Enterovirus 71; Fukinolic acid; Traditional Chinese medicine.

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