Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes

J Cell Biochem. 2015 Nov;116(11):2577-88. doi: 10.1002/jcb.25202.


Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice. Here, we investigated the effect of piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, piperine inhibited CD25 expression, synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of κBα, but not ZAP-70. The ability of piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Benzodioxoles / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects
  • Lymphocyte Activation / drug effects*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Phosphorylation / drug effects
  • Piper nigrum / chemistry*
  • Piperidines / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Polyunsaturated Alkamides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / metabolism


  • Alkaloids
  • Benzodioxoles
  • Piperidines
  • Plant Extracts
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-akt
  • piperine