Role of berberine in anti-bacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor

Abstract

BackgroundBerberine is an isoquinoline alkaloid mainly extracted from Rhizoma Coptidis and has been shown to possess a potent inhibitory activity against bacterial. However, the role of berberine in anti-bacterial action has not been extensively studied.MethodsThe animal model was established to investigate the effects of berberine on bacterial and LPS infection. Docking analysis, Molecular dynamics simulations and Real-time RT-PCR analysis was adopted to investigate the molecular mechanism.ResultsTreatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNβ in the RAW264.7 challenged with LPS.ConclusionBerberine can act as a LPS antagonist and block the LPS/TLR4 signaling from the sourse, resulting in the anti-bacterial action.

Inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine

“…It is not known whether berberine modulates p38 MAPK directly. Several studies have shown the suppression of TLR4 signaling by berberine, and a study recently suggested that berberine directly inhibits TLR4-mediated signaling by interacting with MD2, a component of the TLR4 receptor complex [19]. Thus, it may also be possible that berberine suppresses TLR-mediated p38 MAPK kinase activation by inhibiting initial activation of TLR4 upon RSV infection.…”

Berberine inhibits the LPS‑induced proliferation and inflammatory response of stromal cells of adenomyosis tissues mediated by the LPS/TLR4 signaling pathway

“…Previous studies have demonstrated that BBR acts as an LPS antagonist and blocks LPS/TLR4 signaling in an LPS-induced animal model (28)(29)(30). Li et al (30) reported that BBR protects against LPS-induced intestinal injury in mice via reducing enterocyte apoptosis, inhibiting the TLR4 pathway and decreasing neutrophil infiltration.…”

Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage

“…It has been reported that berberine exerts many pharmacological activities such as anti-oxidative, anti-bacterial, and other organ function protective activity. 2,4,32) Considering that intestinal oxidative stress injury plays an important role in the pathogenesis of several gastrointestinal diseases and that reducing intestinal oxidative stress could improve various gastrointestinal injury, [33][34][35] we measured some typical biomarkers, such as MDA and SOD in the intestine, for evaluating the status of oxidative stress in the setting of uremia. 36,37) The results revealed that the intestinal MDA level was significantly increased in the uremic group, compared with that in the control group.…”

“…1) The clinical use of berberine has been increasing worldwide especially in China, Japan, and other Asian countries, thanks to its multiple pharmacological activities, such as anti-oxidative, anti-bacterial, and cholesterol-lowering effects. [2][3][4] More recent studies have demonstrated that berberine ameliorates the intestinal epithelial tight junction damage and decreases intestinal epithelial permeability, preserving intestinal mucosal barrier functions in various in vitro and in vivo models. [5][6][7] We have also recently reported that berberine reduced the intestinal mucosal barrier damage following peritoneal air exposure in open abdominal surgery.…”