Novel anti-infective potential of salvianolic acid B against human serious pathogen Neisseria meningitidis.

Sanna Huttunen,Carina Tikkanen-Kaukanen,Chenghai Liu,Marko Toivanen

doi:10.1186/s13104-016-1838-4

Abstract

BackgroundEpidemics 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.MethodsIn 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.ResultsAlmost 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.ConclusionsOur 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.

Highlights

Epidemics of meningococcal meningitis cause significant health problems especially in Sub-Saharan Africa
We have shown that in microtiter well binding and cell culture inhibition assays polyphenolic fractions extracted from berries possess anti-adhesive activity against N. meningitidis [6, 9]
In the present study we tested anti-adhesion and antimicrobial activities of salvianolic acid B (SA-B) (Fig. 1), a water soluble polyphenolic acid extracted from dried radix Salvia miltiorrhiza Bunge, which is an important part of Chinese folk medicine

Summary

Introduction

Epidemics of meningococcal meningitis cause significant health problems especially in Sub-Saharan Africa. 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. Epidemics of meningitis are a significant health problem especially in Sub-Saharan Africa [17] and amongst risk groups such as in military forces. The attachment of N. meningitidis to human mucosal epithelial cells, the crucial step of the infection [18], is mediated by type IV pili [19]. HEC-1B epithelial cell line [9, 19] and bovine thyroglobulin [5] have been previously used for adhesion and binding, as well as functioned as binding inhibition models for meningococcal pili

Methods

Results

Discussion

Conclusion