Forsythiaside prevents β-amyloid-induced hippocampal slice injury by upregulating 2-arachidonoylglycerol via cannabinoid receptor 1-dependent NF-κB pathway

  • Neurochem Int. 2019 May:125:57-66. doi: 10.1016/j.neuint.2019.02.008.
Liqing Chen  1 ,  Yan Yan  1 ,  Tinggui Chen  1 ,  Liwei Zhang  1 ,  Xiaoxia Gao  1 ,  Chenhui Du  2 ,  Huizhi Du  3
Affiliations
  • 1. Institute of Molecular Science, Shanxi University, Taiyuan, 030006, China.
  • 2. School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, 030619, China. Electronic address: [email protected].
  • 3. Institute of Molecular Science, Shanxi University, Taiyuan, 030006, China. Electronic address: [email protected].
PMID: 30769029 DOI: 10.1016/j.neuint.2019.02.008
Abstract

In the study, the neuroprotectivities of forsythiaside, a main constituent of Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese), were investigated in the hippocampal slices. Forsythiaside suppressed the overexpression of cyclooxygenase-2 (COX-2) and monoacylglycerol Lipase (MAGL) proteins induced by β-amyloid (Aβ25-35) to upregulate the levels of 2-arachidonoylglycerol (2-AG), an endogenous endocannabinoids. Then the inhibition of forsythiaside on COX-2 was deeply studied by the molecular docking. Forsythiaside prevented neuroinflammation and Apoptosis from Aβ25-35 insults, and this action appeared to be mediated via Cannabinoid Receptor 1 (CB1R)-dependent nuclear factor-κB (NF-κB) signaling pathways. More importantly, forsythiaside functionally improved Aβ25-35-induced learning and memory deficits, which was indicated by long term potentiation (LTP). Taken together, forsythiaside may have therapeutic potential for Alzheimer's diseases (AD) by increasing the levels of 2-AG.

Keywords
2-Arachidonoylglycerol; Cyclooxygenase-2; Forsythiaside; Long term potentiation; Neuroinflammation; β-Amyloid.
Products