Oridonin inhibits SASP by blocking p38 and NF-κB pathways in senescent cells

Biochem Biophys Res Commun. 2022 Jan 29;590:55-62. doi: 10.1016/j.bbrc.2021.12.098. Epub 2021 Dec 28.


Cellular senescence is a state of irreversible cell growth arrest that functions as a biological defense mechanism against severe DNA damage. Senescent cells with DNA damage produce pro-inflammatory cytokines, such as IL-6 and IL-8, and this phenomenon is called the senescence-associated secretory phenotype (SASP). SASP factors have been implicated in various disorders, including cancer. We performed a screening assay and identified oridonin as a candidate SASP inhibitor. Oridonin is an active diterpenoid that is isolated from Isodon plants and has been reported to exhibit anti-inflammatory, antibacterial, antioxidant, and antitumor activities. It reduced the secretion of IL-6 and IL-8 in senescent cells at the protein and mRNA levels. Oridonin also inhibited p65 subunit of NF-κB activity. However, oridonin did not affect SA β-gal activity and enhanced the expression of p21. The expression and phosphorylation of p38 were down-regulated by oridonin. The p38 inhibitor SB203580 inhibited the secretion of IL-8, slightly inhibited the secretion of IL-6, and did not affect NF-κB activity. Therefore, the NF-κB and p38 pathways may contribute to the inhibition of SASP by oridonin. Oridonin has potential as a therapeutic agent for SASP-related diseases.

Keywords: NF-κB; Oridonin; SASP; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bleomycin
  • Cell Line
  • Cellular Senescence* / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Humans
  • NF-kappa B / metabolism*
  • Senescence-Associated Secretory Phenotype* / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Diterpenes, Kaurane
  • NF-kappa B
  • oridonin
  • Bleomycin
  • p38 Mitogen-Activated Protein Kinases