Involvement of p38 mitogen-activated protein kinase in the induction of interleukin-12 p40 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid

Biochem Pharmacol. 2002 May 15;63(10):1901-10. doi: 10.1016/s0006-2952(02)00982-6.


Interleukin (IL)-12 plays a pivotal role in the development of T helper type 1 (Th1)-immune response, which may have therapeutic effects on diseases associated with pathologic Th2 responses such as allergic disorders and asthma. In this study, we investigated the effects of berberine, a benzodioxoloquinolizine alkaloid with anti-microbial and anti-tumor activities, on the production of IL-12 p40, an inducible subunit of IL-12, in mouse macrophages. Berberine-induced IL-12 p40 production and activation of p38 mitogen-activated protein kinase (MAPK) in dose-dependent manners, which were significantly inhibited by p38 MAPK inhibitors and yohimbine, indicating that p38 MAPK and alpha(2)-adrenergic receptor were involved in the induction of IL-12 p40 production in mouse macrophages by berberine. Furthermore, berberine significantly enhanced IL-12 p40 production in mouse macrophages when combined with lipopolysaccharide, a well-known inducer of IL-12 production. These findings may explain some of the known biological effects of berberine and suggests berberine as an immunotherapeutic compound for induction of IL-12, which is potentially applicable for tumors, infectious disease, and airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Berberine / pharmacology*
  • Drug Interactions
  • Female
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 Subunit p40
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred DBA
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism
  • Protein Subunits
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Spleen / cytology
  • p38 Mitogen-Activated Protein Kinases


  • Alkaloids
  • Interleukin-12 Subunit p40
  • Lipopolysaccharides
  • NF-kappa B
  • Protein Subunits
  • Receptors, Adrenergic, alpha-2
  • Berberine
  • Interleukin-12
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases