title: A botulinum neurotoxin-like function of Potentilla chinensis extract that inhibits neuronal SNARE complex formation, membrane fusion, neuroexocytosis, and muscle contraction.
abstract: BACKGROUND
  Botulinum neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis.
  
  
  OBJECTIVE
  In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated.
  
  
  METHODS
  After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined.
  
  
  RESULTS
  The extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 μg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca²⁺-channel blocker verapamil and BoNT type A.
  
  
  CONCLUSIONS
  While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the Potentilla chinensis extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics.
authors.affiliation: School of Life Science and Biotechnology and Center for Human Interface Nano Technology, Sungkyunkwan University, Gyeonggi-do, Korea.
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Jung
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Yang
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Koh
authors.forename: Paul
authors.initials: P
authors.lastname: Heo
authors.forename: Kee-Jung
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Sehyun
authors.initials: S
authors.lastname: Kim
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Park
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Shing
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000009:adverse effects / Q000494:pharmacology; D055808:Drug Discovery; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D035264:Flowers / Q000737:chemistry; D035002:Lower Extremity; D008561:Membrane Fusion / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009465:Neuromuscular Agents / Q000009:adverse effects / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D031987:Potentilla / Q000737:chemistry*; D051381:Rats; D050600:SNARE Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D009419:Nerve Tissue Proteins; D009465:Neuromuscular Agents; D010936:Plant Extracts; D050600:SNARE Proteins; D001905:Botulinum Toxins; D009638:Norepinephrine