Nao-Fu-Cong ameliorates diabetic cognitive dysfunction by inhibition of JNK/CHOP/Bcl2-mediated apoptosis in vivo and in vitro

Chin J Nat Med. 2020 Sep;18(9):704-713. doi: 10.1016/S1875-5364(20)60009-7.

Abstract

Chinese herbal compound Nao-Fu-Cong (NFC) has been mainly used to treat cognitive disorders in Traditional Chinese Medicine (TCM). The present study aimed to investigate whether its neuroprotective effects might be related to the inhibition of JNK/CHOP/Bcl2-mediated apoptosis pathway or not. We randomly assigned STZ (60 mg·kg-1)-induced diabetic rats into control group, diabetic model group and NFC groups (low-dose, medium-dose and high-dose). The primary culture of hippocampal neurons were transferred into different culture media on the third day. The cells were then divided into control group, high-glucose group, NFC (low-dose, medium-dose and high-dose) groups, CHOP si-RNA intervention group, JNK pathway inhibitor SP600125 group and oxidative stress inhibitor N-acetylcysteine (NAC) group. NFC significantly improved the cognitive function of diabetic rats, and had neuroprotective effect on hippocampal neurons cultured in high glucose. Further research results showed that NFC could reduce the apoptosis of hippocampal neurons in rats with diabetic cognitive dysfunction. NFC had inhibitory effects on CHOP/JNK apoptosis pathway induced by high glucose, and also decreased the levels of ROS and increased the mitochondrial membrane potential. These suggested that the neuroprotective effect of NFC might be related to the inhibition of CHOP and JNK apoptotic signaling pathways, and the cross pathway between oxidative stress and mitochondrial damage pathway.

Keywords: Apoptosis; High glucose; Hippocampal neurons; Nao-Fu-Cong.

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Anthracenes / pharmacology
  • Apoptosis / drug effects*
  • Cognitive Dysfunction / drug therapy*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Hippocampus / drug effects
  • MAP Kinase Signaling System / drug effects
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Random Allocation
  • Rats
  • Transcription Factor CHOP / antagonists & inhibitors

Substances

  • Anthracenes
  • Bcl2 protein, rat
  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • naofucong
  • Transcription Factor CHOP
  • pyrazolanthrone
  • Acetylcysteine