title: Synergistic activity and mode of action of flavonoids isolated from smaller galangal and amoxicillin combinations against amoxicillin-resistant Escherichia coli.
abstract: OBJECTIVE
  The smaller galangal is extracted, purified and identified the bioactive compounds. The purpose of this research was to investigate whether these isolated compounds have antibacterial and synergistic activity against amoxicillin-resistant Escherichia coli (AREC) when used singly and in combination with amoxicillin. The primarily mode of action is also studied.
  
  
  RESULTS
  The galangin, kaempferide and kaempferide-3-O-β-d-glucoside were isolated. The minimum inhibitory concentrations(MIC) of amoxicillin and these flavonoids against AREC were between 500 and >1000 μg ml(-1). Synergistic activity was observed on combining amoxicillin with these flavonoids. The combinations of amoxicillin and these flavonoids exhibited a synergistic effect, reducing AREC cell numbers. Electron microscopy showed that these combinations damaged the ultrastructure of AREC cells. The results indicated that these combinations altered outer membrane permeability but not affecting cytoplasmic membrane. Enzyme assays showed that these flavonoids had an inhibitory activity against penicillinase.
  
  
  CONCLUSIONS
  These results indicated that these flavonoids have the potential to reverse bacterial resistance to amoxicillin in AREC and may operate via three mechanisms: inhibition of peptidoglycan and ribosome synthesis, alteration of outer membrane permeability, and interaction with β-lactamases.
  
  
  CONCLUSIONS
  These findings offer the potential to develop a new generation of phytopharmaceuticals to treat AREC.
authors: School of Pharmacology, Institute of Science, Suranaree University of Technology, 111 University Avenue, Suranaree Subdistrict, Muang District, Nakhonratchasima 30000, Thailand. griang@sut.ac.th
authors: G
authors: G
authors: Eumkeb
authors: S
authors: S
authors: Siriwong
authors: S
authors: S
authors: Phitaktim
authors: N
authors: N
authors: Rojtinnakorn
authors: S
authors: S
authors: Sakdarat
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000658:Amoxicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D027343:Rhizome / Q000737:chemistry; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D005419:Flavonoids; D044949:Kaempferols; C037032:galangin; C449720:kaempferide; D000658:Amoxicillin; D001616:beta-Galactosidase