Proline-Hinged α-Helical Peptides Sensitize Gram-Positive Antibiotics, Expanding Their Physicochemical Properties to Be Used as Gram-Negative Antibiotics.

The outer membrane (OM) of Gram-negative bacteria is the most difficult obstacle for small-molecule antibiotics to reach their targets in the cytosol. The molecular features of Gram-negative antibiotics required for passing through the OM are that they should be positively charged rather than neutral, flat rather than globular, less flexible, or more increased amphiphilic moment. Because of these specific molecular characteristics, developing Gram-negative antibiotics is difficult.

Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2.

We determined the function of phospholipase D2 (PLD2) in host defense in highly lethal mouse models of sepsis using PLD2(-/-) mice and a PLD2-specific inhibitor. PLD2 deficiency not only increases survival but also decreases vital organ damage during experimental sepsis. Production of several inflammatory cytokines (TNF, IL-1β, IL-17, and IL-23) and the chemokine CXCL1, as well as cellular apoptosis in immune tissues, kidney, and liver, are markedly decreased in PLD2(-/-) mice.

Anti-septic activity of α-cubebenoate isolated from Schisandra chinensis.

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model.

The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative colitis.

In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect.

Therapeutic effects of α-iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, against sepsis.

α-Iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, strongly enhances survival rate in cecal ligation and puncture (CLP) challenge-induced sepsis. Mechanistically, α-iso-cubebenol markedly reduces viable bacteria in the peritoneal fluid and peripheral blood, by increasing production of superoxide anion. α-Iso-cubebenol also significantly attenuates widespread immune cell apoptosis in a mouse CLP sepsis model, and inhibits the production of proinflammatory cytokines including interleukin-1β (IL-1β) and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes.