Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

Phytomedicine. 2019 Sep;62:152956. doi: 10.1016/j.phymed.2019.152956. Epub 2019 May 10.

Abstract

Background: Cepharanthine (CEP) is a drug used in Japan since the 1950s to treat a number of acute and chronic diseases, including treatment of leukopenia, snake bites, xerostomia and alopecia. It is the only approved drug for Human use in the large class of bisbenzylisoquinoline alkaloids. This natural product, mainly isolated from the plant Stephania cephalantha Hayata, exhibits multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic properties.

Purpose: The mechanism of action of CEP is multifactorial. The drug exerts membrane effects (modulation of efflux pumps, membrane rigidification) as well as different intracellular and nuclear effects. CEP interferes with several metabolic axes, primarily with the AMP-activated protein kinase (AMPK) and NFκB signaling pathways. In particular, the anti-inflammatory effects of CEP rely on AMPK activation and NFκB inhibition.

Conclusion: In this review, the historical discovery and development of CEP are retraced, and the key mediators involved in its mode of action are presented. The past, present, and future of CEP are recapitulated. This review also suggests new opportunities to extend the clinical applications of this well-tolerated old Japanese drug.

Keywords: Alkaloids; Cancer; Cepharanthine; Inflammation; Natural products; Stephania.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / drug effects
  • AMP-Activated Protein Kinases / metabolism
  • Anti-Infective Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Benzylisoquinolines / pharmacology*
  • Biological Products / pharmacology
  • Humans
  • Immunologic Factors / pharmacology*
  • Japan
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Stephania / chemistry*

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Benzylisoquinolines
  • Biological Products
  • Immunologic Factors
  • NF-kappa B
  • cepharanthine
  • AMP-Activated Protein Kinases