Mohammed N.A. Khalil * 1,2
Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NFκβ is a target for new therapeutics because it plays a pivotal role in the
pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin which is a potent NF-κβnhibitor, 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.
Ambrosin was isolated and purified from extract of the traditional herb Ambrosia maritima. 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-κβ65 transcript and protein levels.
Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNFα IL-1βCOX-2 and iNOS. BACE1 was inhibited, thereby reducing
amyloid plaques (Aβ) 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.
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