Berberine Attenuates Neonatal Sepsis in Mice By Inhibiting FOXA1 and NF-κB Signal Transduction Via the Induction of MiR-132-3p

Inflammation. 2021 Dec;44(6):2395-2406. doi: 10.1007/s10753-021-01510-2. Epub 2021 Sep 14.

Abstract

Neonatal sepsis (NS) is a severe syndrome in newborns that is induced by infections, and the initiation and development of NS are closely associated with the function of miRs. In the current study, the effects of berberine, which is a functional component in traditional Chinese medicine (TCM), against NS were assessed by focusing on the interaction of berberine with miR-132-3p-mediated signaling. An NS model was induced using cecal slurry (CS) in vivo and LPS in vitro, and berberine treatment was applies. The changes in survival rate, intestinal structure, and systemic inflammation in mice and the viability, apoptosis, and inflammatory response in intestinal cells were measured. At the molecular level, miR-132-3p levels and the activities of the FOXA1 and NF-κB pathways were analyzed. The data showed that berberine increased the survival rates of CS-induced mice. The intestinal injuries induced by CS were also attenuated by berberine, which was associated with inhibition of the production of systemic IL-6, IL-1β, and TNF-α. At the molecular level, the expression of miR-132-3p was upregulated, suppressing the expression of FOXA1, p-IκBα, and p65 while inducing the expression of IκBα. The effects of berberine on NS-induced impairments were blocked by the injection of the miR-132-3p antagomir, which exacerbated intestinal injuries, induced systemic inflammation, and reactivated the FOXA1 and NF-κB pathways. The findings in the in vivo model were validated with in vitro assays. Collectively, the findings outlined in the current study indicated that berberine had solid protective effects against NS-induced symptoms in newborn mice, and the effects depended on the upregulation of miR-132-3p.

Keywords: FOXA1; NF-κB.; berberine; inflammation; miR-132-3p; neonatal sepsis.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents / pharmacology*
  • Berberine / pharmacology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Intestines / drug effects*
  • Intestines / immunology
  • Intestines / metabolism
  • Intestines / pathology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Neonatal Sepsis / genetics
  • Neonatal Sepsis / immunology
  • Neonatal Sepsis / metabolism
  • Neonatal Sepsis / prevention & control*
  • Signal Transduction
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Foxa1 protein, mouse
  • Hepatocyte Nuclear Factor 3-alpha
  • MIRN132 microRNA, mouse
  • MicroRNAs
  • NF-kappa B
  • Berberine