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

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.

• Authors: Liqing Chen, Yan Yan, Tinggui Chen, Liwei Zhang, Xiaoxia Gao, Chenhui Du, Huizhi Du
• Journal: Neurochemistry international (Neurochem Int) Vol. 125 Pg. 57-66 (05 2019) ISSN: 1872-9754 [Electronic] England
• PMID: 30769029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• Amyloid beta-Peptides
• Arachidonic Acids
• Cannabinoid Receptor Agonists
• Drugs, Chinese Herbal
• Endocannabinoids
• Glycerides
• Glycosides
• NF-kappa B
• Peptide Fragments
• Receptor, Cannabinoid, CB1
• amyloid beta-protein (25-35)
• glyceryl 2-arachidonate
• forsythiaside

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Arachidonic Acids (biosynthesis, chemistry)
• Cannabinoid Receptor Agonists (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Endocannabinoids (biosynthesis, chemistry)
• Glycerides (biosynthesis, chemistry)
• Glycosides (pharmacology)
• Hippocampus (drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Organ Culture Techniques
• Peptide Fragments (toxicity)
• Protein Structure, Secondary
• Receptor, Cannabinoid, CB1 (metabolism)
• Signal Transduction (drug effects, physiology)
• Up-Regulation (drug effects, physiology)