Amentoflavone Ameliorates Streptococcus suis-Induced Infection and .

, an important zoonotic pathogen, has caused considerable economic losses in the swine industry and severe public health issues worldwide. The development of a novel effective strategy for the prevention and therapy of is urgently needed. Here, amentoflavone, a natural biflavonoid compound isolated from Chinese herbs that has negligible anti- activity, was identified as a potent antagonist of suilysin (SLY)-mediated hemolysis without interfering with the expression of SLY. Amentoflavone effectively inhibited SLY oligomerization, which is critical for its pore-forming activity. The treatment with amentoflavone reduced -induced cytotoxicity in macrophages (J774 cells). Furthermore, -infected mice that received amentoflavone exhibited lower mortality and bacterial burden. Additionally, amentoflavone significantly decreased the production of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in an -infected cell model. Analyses of signaling pathways demonstrated that amentoflavone reduced -induced inflammation in serotype 2 (SS2)-infected cells by regulating the p38, Jun N-terminal protein kinase 1 and 2 (JNK1/2), and NF-κB pathways. The antivirulence and anti-inflammatory properties of amentoflavone against infection provide the possibility for future pharmaceutical application of amentoflavone in the treatment of infection. The widespread use of antibiotics in therapy and in the prevention of infection in the swine industry raises concerns for the emergence of a resistant strain. The use of antivirulence agents has potential benefits, mainly because of the reduced selective pressure for the development of bacterial resistance. In this study, we found that amentoflavone is an effective agent against serotype 2 (SS2) infection both and Our results demonstrated that amentoflavone is a promising anti-infective therapeutic for infections, due to its antivirulence and anti-inflammatory effects without antibacterial activity, with fewer side effects than conventional antibacterial agents.