Tea seed saponin‑reduced extract ameliorates palmitic acid‑induced insulin resistance in HepG2 cells

Mol Med Rep. 2024 Feb;29(2):26. doi: 10.3892/mmr.2023.13149. Epub 2023 Dec 15.


Tea (Camellia sinensis) seed cake is a potential resource that contains a wealth of bioactive compounds. However, the high toxicity of tea saponins in tea seed cake restricts its applications. The present study aimed to i) develop a method of extracting bioactive compounds and reducing tea saponins during the process of tea seed cake extraction and ii) investigate the anti‑insulin resistance effect of tea seed saponin‑reduced extract (TSSRE) in a palmitic acid (PA)‑induced insulin resistance HepG2‑cell model. The concentration of tea saponins in TSSRE was ~10‑fold lower than that in tea seed crude extract (TSCE) after the saponin‑reduction process. In addition, TSSRE cytotoxicity was significantly lower than that of TSCE in HepG2 cells. TSSRE treatment improved glucose consumption as well as glucose transporter (GLUT) 2 and GLUT4 expression levels in PA‑stimulated HepG2 cells. Moreover, TSSRE enhanced the phosphorylation of the insulin receptor substrate 1/protein kinase B/forkhead box protein O1/glycogen synthase kinase 3β and inhibited the elevated expression of phosphoenolpyruvate carboxykinase in PA‑exposed HepG2 cells. The effect of TSSRE on the mediation of the insulin signaling pathway was attributed to the inhibition of PA‑induced mitogen‑activated protein kinase activation. The findings of the present study indicated that TSSRE ameliorates hepatic insulin resistance by ameliorating insulin signaling and inhibiting inflammation-related pathways.

Keywords: MAPK; TSCE; TSSRE; insulin resistance; tea saponins.

MeSH terms

  • Glucose / metabolism
  • Hep G2 Cells
  • Humans
  • Insulin / metabolism
  • Insulin Resistance* / physiology
  • Palmitic Acid / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Saponins* / pharmacology
  • Seeds
  • Tea


  • Palmitic Acid
  • Saponins
  • Proto-Oncogene Proteins c-akt
  • Insulin
  • Glucose
  • Tea

Grants and funding

The present study was supported by Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University under Interdisciplinary Research Center on Material and Medicinal Chemistry (D112-G2202).