Cryptotanshinone regulates gut microbiota and PI3K-AKT pathway in rats to alleviate CUMS induced depressive symptoms

Biomed Pharmacother. 2023 Dec 31:169:115921. doi: 10.1016/j.biopha.2023.115921. Epub 2023 Nov 26.

Abstract

Cryptotanshinone (CPT), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza, exhibits promising antidepressant properties. Employing a rat model subjected to Chronic Unpredictable Mild Stress (CUMS), behavioral analyses (open field experiment, elevated cross maze experiment, sugar water preference experiment, forced swimming experiment) and inflammatory factor assessments were conducted to assess the efficacy of CPT in alleviating depressive symptoms and inflammatory responses induced by CUMS. Moreover, 16 S rDNA analysis revealed alterations in the gut microbiota of rats exposed to both CUMS and CPT administration. Notably, CPT administration was found to mitigate harmful bacterial shifts associated with depression. Preliminary exploration of the molecular mechanism underlying CPT's antidepressant effects via transcriptomics analysis and molecular docking indicated that CPT might exert its influence by regulating the PI3K-AKT pathway. This study sheds light on the potential therapeutic role of CPT in managing depressive disorders, offering a comprehensive understanding of its impact on behavior, inflammation, gut microbiota, and molecular pathways.

Keywords: 16 S rDNA; Cryptotanshinone; Depression; PI3K-AKT pathway; Transcriptomics.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depression* / drug therapy
  • Depression* / metabolism
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Hippocampus
  • Molecular Docking Simulation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • cryptotanshinone
  • Antidepressive Agents