Chemical Compositions of Houttuynia cordata Thunb. Volatile Oil and Its Analogues Attenuate Staphylococcus aureus Virulence by Targeting alpha-Hemolysin

Houttuynia cordata Thunb. is a medicinal and edible plant that has been used to treat phlegm, asthma, cough, carbuncle, swelling, and sore in China for thousands of years. Many previous studies have reported the chemical compositions and pharmacological acivities of hydrodistillation extracted Houttuynia volatile oil. However, no scientific studies on the inhibition activity against virulence factors of Staphylococcus aureus (S. aureus) have been published. So this article analyze the chemical compositions of Houttuynia volatile oil, and evaluate the anti-alpha-hemolysin (Hla) activity of Houttuynia volatile oil, its three compositions (nonanol, alpha-terpineol, 4-terpineol) and eleven analogues. In addition, inhibition activity of three compositions to the A549 cells infection of S. aureus was evaluated in vitro. The results is thirty-four ion chromatographic peaks with matching degree & GE;90% were identified, and main chemical compositions of Houttuynia volatile oil were beta-myrcene (24.48%) and beta-phellandrene (11.28%). The MIC of lauraldehyde against S. aureus ATCC 29213 was found to be 8 mu g/mL, and houttuynin showed the strongest inhibition activity against the six S. aureus strains with the MIC of 64 or 128 mu g/mL. Besides, growth curve analysis revealed the non-bactericidal activity of nonanol, alpha-terpilenol, and 4-terpineol at sub-MIC. The result of anti-virulence study demonstrated that dodecanol, undecanol, and decanol showed the strongest anti-Hla activity by significantly inhibiting hemolysis of rabbit blood. Nonanol, alpha-terpilenol, and 4-terpineol can obviously protect A549 cells from alpha-Hla-mediated injury at 8, 16, and 32 mu g/mL in vitro, respectively.