Maslinic acid alleviates LPS-induced mice mastitis by inhibiting inflammatory response, maintaining the integrity of the blood-milk barrier and regulating intestinal flora

Int Immunopharmacol. 2023 Sep:122:110551. doi: 10.1016/j.intimp.2023.110551. Epub 2023 Jul 3.

Abstract

Mastitis occurs frequently in breastfeeding women and not only affects the women's health but also hinders breastfeeding. Maslinic acid is a type of pentacyclic triterpenoid widely found in olives that has good anti-inflammatory activity. This study aims to discuss the protective function of maslinic acid against mastitis and its underlying mechanism. For this, mice models of mastitis were established using lipopolysaccharide (LPS). The results revealed that maslinic acid reduced the pathological lesions in the mammary gland. In addition, it reduced the generation of pro-inflammatory factors and enzymes (IL-6, IL-1β, TNF-α, iNOS, and COX2) in both mice mammary tissue and mammary epithelial cells. The high-throughput 16S rDNA sequencing of intestinal flora showed that in mice with mastitis, maslinic acid treatment altered β-diversity and regulated microbial structure by increasing the abundance of probiotics such as Enterobacteriaceae and downregulating harmful bacteria such as Streptococcaceae. In addition, maslinic acid protected the blood-milk barrier by maintaining tight-junction protein expression. Furthermore, maslinic acid downregulated mammary inflammation by inhibiting the activation of NLRP3 inflammasome, AKT/NF-κB, and MAPK signaling pathways. Thus, in a mice model of LPS-induced mastitis, maslinic acid can inhibit the inflammatory response, protect the blood-milk barrier, and regulate the constitution of intestinal flora.

Keywords: Blood-milk barrier; Intestinal flora; MAPK; Maslinic acid; Mastitis; NF-κB; NLRP3.

MeSH terms

  • Animals
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mammary Glands, Animal / pathology
  • Mastitis* / chemically induced
  • Mastitis* / drug therapy
  • Mastitis* / metabolism
  • Mice
  • Milk / metabolism
  • NF-kappa B / metabolism

Substances

  • Lipopolysaccharides
  • maslinic acid
  • NF-kappa B