Carnosol suppresses microglia cell inflammation and apoptosis through PI3K/AKT/mTOR signaling pathway

Immunopharmacol Immunotoxicol. 2022 Oct;44(5):656-662. doi: 10.1080/08923973.2022.2074448. Epub 2022 Jun 6.

Abstract

Context: Ischemic stroke is the most common type of acute cerebrovascular disease. Carnosol is a polyphenol compound extracted from rosemary.Objective: This study aimed to explore the effects of carnosol on the oxygen-glucose deprivation (OGD) treated BV2 microglia cells.Materials and methods: MTT and EdU assays were used to detect the cell viability and proliferation. Flow cytometry was conducted to measure the apoptosis rates. Additionally, the protein expression was determined by western blot. The inflammatory factors and antioxidant indexes were detected by corresponding kits.Results and discussion: Carnosol promoted the proliferation and inhibited the apoptosis of the OGD treated BV2 cells. What's more, the protein expressions of PCNA and Bcl-2 were up-regulated, the Bax expression was down-regulated after carnosol treatment. In addition, carnosol decreased the levels of MDA, LPO, TNF-α, IL-1β and IL-6, and increased the levels of GSH, SOD, IL-4 and IL-10 in the OGD treated BV2 cells. Furthermore, the PI3K/AKT/mTOR signaling pathway was activated after carnosol treatment and inhibition of the PI3K/AKT/mTOR signaling pathway reversed the carnosol effects.Conclusions: Carnosol promotes the proliferation, inhibits the apoptosis, relieves the oxidative damage and inflammation of OGD treated cells through regulating the PI3K/AKT/mTOR signaling pathway.

Keywords: Carnosol; PI3K signaling; apoptosis; ischemic stroke; microglia.

MeSH terms

  • Abietanes
  • Antioxidants / pharmacology
  • Apoptosis
  • Glucose / metabolism
  • Glucose / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Microglia / metabolism
  • Oxygen / metabolism
  • Oxygen / pharmacology
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Polyphenols / metabolism
  • Polyphenols / pharmacology
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • TOR Serine-Threonine Kinases
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Abietanes
  • Antioxidants
  • Interleukin-6
  • Polyphenols
  • Proliferating Cell Nuclear Antigen
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Interleukin-10
  • Interleukin-4
  • carnosol
  • Superoxide Dismutase
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Glucose
  • Oxygen