A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

Abstract

Aim: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown antiapoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. Methods: SD rats were administered IMM-H004 (8 mg·kg -1 ·d -1 , ig) or donepezil (positive control, 1 mg·kg -1 ·d -1 , ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and β-amyloid (Aβ) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. Results: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aβ protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. Conclusion: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aβ pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.

Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats

“…However, pretreatment with CHRE at all doses reduced these effects. This result is supported by a previous study, which found that 7-hydroxy-5-methoxy-4-methyl-3-(4-methyl piperazin-1-yl)-coumarin (IMM-H004) inhibited Aβ accumulation in the hippocampus [ 44 ]. Another study also found that coumarins may interfere with the process of Aβ accumulation by interacting with aromatic residues within the hydrophobic core of Aβ [ 45 ].…”

Pharmacological Basis for Use of Armillaria mellea Polysaccharides in Alzheimer’s Disease: Antiapoptosis and Antioxidation

“…AMPS also enhanced the serum levels of A β while reducing the hippocampal expression of A β . The overproduction of A β protein and resulting formation of intracellular neurofibrillary tangles lead to the generation of extracellular senile plaques, which serve as the pathological index in the brain of a rodent with AD [ 30 ]. A β aggregation induces oxidative stress and mitochondrial dysfunction and leads to the production of ROS, which are involved in the pathogenesis of AD [ 31 ].…”