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Ambrosin, a potent NF-?? inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

ABSTRACT: Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-??. NF-?? is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-?? inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-??p65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-?, IL-1?, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (A?) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics.

SUBMITTER: Khalil MNA

PROVIDER: S-EPMC6611615 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Khalil Mohammed N A MNA Choucry Mouchira A MA El Senousy Amira S AS Hassan Azza A El-Marasy Salma A SA El Awdan Sally A SA Omar Farghaly A FA

PloS one 20190705 7

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NF-κβ is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κβ inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorab ...[more]

PMID: 31276550

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Dataset Information

Ambrosin, a potent NF-?? inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Publications

Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

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