title: Novel anti-infective potential of salvianolic acid B against human serious pathogen Neisseria meningitidis.
abstract: BACKGROUND
  Epidemics of meningococcal meningitis cause significant health problems especially in Sub-Saharan Africa. Novel anti-infective candidates are needed. In modern anti-adhesion therapy initial attachment of bacteria to host cells is prevented. Our unique studies have revealed anti-adhesive candidates from natural products, namely milk and berries, against Neisseria meningitidis adhesion. In the present study against N. meningitidis adhesion, a novel binding inhibitor was found; salvianolic acid B (SA-B), a polyphenol from the radix Salviae miltiorrhizae, an important part of Chinese folk medicine.
  
  
  METHODS
  In order to test inhibition of meningococcal pili binding and anti-adhesion activity of SA-B, bovine thyroglobulin, a reference glycoprotein for meningococcal receptor was used in a microtiter plate assay. Inhibitory activity was tested by using serial dilutions of SA-B extracts of 98 and 70% purity. Results were confirmed in a HEC-1B cell dot assay and antimicrobial activity was measured by using a microbroth dilution assay.
  
  
  RESULTS
  Almost total (93%) inhibition of pili binding, anti-adhesion, was achieved with the 70% extract of SA-B at the concentration of 0.3 mg/mL in the bovine thyroglobulin reference model. 50% binding inhibition activity was achieved with 0.6 µg/mL of the SA-B extract. Total inhibition of the pili binding to HEC-1B cells was found at the tested concentration of 0.5 mg/mL. The 98% pure SA-B resulted in weaker inhibition. At the concentration of 0.3 mg/mL 78% inhibition was achieved in the thyroglobulin model. For 50% inhibition 2.4 μg/mL of pure SA-B was needed. The difference between the binding inhibition activities (70 and 98% pure SA-B) was statistically significant (P = 0.03). Antimicrobial activity of 70% SA-B, when investigated against N. meningitidis, was detected only in relatively high concentrations.
  
  
  CONCLUSIONS
  Our results indicate that plant SA-B may prevent meningococcal infections by inhibiting meningococcal binding and may thus have an impact on the amount of nasopharyngeal carriers of N. meningitidis. This may prevent the spreading of meningococcal infections between humans. One could conclude that SA-B and its source dried radix S. miltiorrhizae, which is an important part of Chinese folk medicine, could be valuable candidates for further research in meningococcal disease prevention.
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. smpyykon@student.uef.fi.|Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. smpyykon@student.uef.fi.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huttunen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. marko.toivanen@fimea.fi.
authors.forename: Marko
authors.initials: M
authors.lastname: Toivanen
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, China. chenghailiu@hotmail.com.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Liu
authors.affiliation: Ruralia Institute, University of Helsinki, Lönnrotinkatu 7, 50170, Mikkeli, Finland. carina.tikkanen-kaukanen@helsinki.fi.
authors.forename: Carina
authors.initials: C
authors.lastname: Tikkanen-Kaukanen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D010861:Fimbriae, Bacterial / Q000187:drug effects*; D006801:Humans; D009345:Neisseria meningitidis / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013954:Thyroglobulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D053630:Depsides
chemical_list: D000900:Anti-Bacterial Agents; D001572:Benzofurans; D010936:Plant Extracts; D013954:Thyroglobulin; C076944:salvianolic acid B; D053630:Depsides