Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol

PLoS One. 2018 May 17;13(5):e0197563. doi: 10.1371/journal.pone.0197563. eCollection 2018.


Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells. A kae-induced increase in DPPH and ABTS radical scavenging activity, inhibition of concanavalin A (Con A)-induced activation of T cell proliferation and NO or ROS production in LPS-induced RAW 264.7 macrophage cells were also seen. Kae glycosides were used to produce kae via environment-friendly enzymatic hydrolysis. Kae-7-O-glu and kae-3-O-rut were hydrolyzed to kae by β-glucosidase and/or α-L-rhamnosidase. This paper demonstrates the application of enzymatic catalysis to obtain highly biologically active kae. This work provides a novel and efficient preparation of high-value flavone-related products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical
  • Free Radicals
  • Glucosides / pharmacology*
  • Glycoside Hydrolases / metabolism
  • Glycosides / pharmacology*
  • Humans
  • Hydrolysis
  • Kaempferols / isolation & purification
  • Kaempferols / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / metabolism
  • beta-Glucosidase / metabolism


  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Free Radicals
  • Glucosides
  • Glycosides
  • Kaempferols
  • Reactive Oxygen Species
  • Recombinant Proteins
  • kaempferol 3-O-rhamnoside
  • Nitric Oxide
  • kaempferol-3-O-rutinoside
  • kaempferol
  • Glycoside Hydrolases
  • beta-Glucosidase
  • alpha-L-rhamnosidase
  • kaempferol 7-O-glucoside

Grants and funding

This work was supported by The National Key Research Development Program of China, (Grant # 2017YFD0600805 to LZ); The National Natural Science Foundation of China (Grant No. 31600465 to XF); The National Natural Science Foundation of China (Grant # 31570565 to LZ); The Forestry Achievements of Science and Technology to Promote Projects ([2017] 10 to LZ); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); and The Study on biocatalysis and transformation of natural drugs (Grant No. 028340002). Authors ZW and WX received support in the form of salary from Jiangsu Kanion Pharmaceutical Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.