Atractylenolide III alleviates isoflurane-induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

J Food Biochem. 2021 Sep;45(9):e13892. doi: 10.1111/jfbc.13892. Epub 2021 Aug 6.

Abstract

The use of anesthetics relieves discomfort in patients during operation, but extensive application of anesthetics can cause damage to the nervous system. Atractylenolide III (ATL-III) is an active ingredient derived from Baizhu, which is a kind of traditional Chinese medicines. Recent studies have shown that ATL-III alleviates inflammation and oxidative stress in various tissues by regulating the PI3K/Akt/mTOR signaling pathway. However, whether or not the application of ATL-III could relieve isoflurane-induced damage in rat hippocampal neurons remains unclear. In this study, rats were stimulated with isoflurane and treated with ATL-III (intragastric administration) simultaneously. After rats were sacrificed, apoptosis and autophagy in the hippocampal neurons were assessed using TUNEL assays and western blotting, respectively. Then, the expression of inflammatory factors was determined by q-PCR and ELISA. The levels of p-PI3K, p-Akt, and p-mTOR were quantified by western blotting. We found that ATL-III relieved isoflurane-induced apoptosis, autophagy and inflammation in hippocampal neurons in rats. ATL-III treatment also inhibited the expression of TNF-α, IL-1β, and IL-6 in these cells. Furthermore, ATL-III promoted the expression of p-PI3K, p-Akt, and p-mTOR in the hippocampal neurons. All these results indicated that ATL-III alleviated isoflurane-induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR signaling pathway. PRACTICAL APPLICATIONS: Whether or not Atractylenolide III (ATL-III) could alleviate neurotoxicity induced by anesthetics is unclear. In this study, we investigated the effect of ATL-III on anesthetic-induced nervous system damage. The findings from this study could also provide a novel therapy for the treatment of patients with anesthetic-induced nerve injury.

Keywords: ATL-III; apoptosis; central nerve injury; inflammation; isoflurane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / metabolism
  • Humans
  • Isoflurane* / toxicity
  • Lactones
  • Neurons / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Lactones
  • Sesquiterpenes
  • atractylenolide III
  • Isoflurane
  • MTOR protein, human
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases