AbstractBackgroundAluminum, a potent neurotoxicant is a major risk factor involved in the perturbation of neurochemicals leading to the development and progression of Alzheimer’s disease. Byrophyllum pinnatum is widely distributed in Southern Nigeria and used locally for the treatment of various ailments including neurological disorders. This study was aimed to access the neuro restorative potential of B. pinnatum flavonoids (BPF) in aluminum chloride (AlCl3)‐induced AD‐like condition in Wistar ratsMethods B. pinnatum flavonoids were characterized using FTIR and ultra‐high‐performance Liquid chromatography coupled with a mass spectrometry UPLC‐MS/MS. Thirty (30) male adult Wistar rats were used in this study and divided into five groups (n=6). Symptoms mimicking AD were induced in rats by administering 150mg/kg b.w of AlCl3 orally for 21 days. After the induction, animals were divided into five groups (n=6) and treated with BPF (50 and 100 mg/kg body weight) and 3 mg/kg of Rivastigmine for another 21 days. Neuro behavioral activities were assessed using Morris water maze tasks. Acetyl‐cholinesterase (AChE), BACE‐1 and oxidative stress markers were assessed following standard protocols. Semi‐quantitative reverse transcriptase‐PCR (RT‐PCR) was used to access the expression patterns of AChE and BACE‐1 mRNA in the cortex of rats.ResultsCharacterization of BPF revealed the presence of flavonols and flavone as the major constituents. Furthermore, AlCl3 overload caused behavioral alterations and showed impaired cognitive function similar to AD alongside increased brain cortical AChE activity, MDA level and decrease in antioxidant enzymes. In addition, AlCl3 induction caused the up‐regulation of AChE and BACE‐1 mRNA expressions in the cortex of rats. Conversely, oral administration of BPF (50 and 100 mg/kg body weight) significantly ameliorated cognitive deficits, restored oxidant‐antioxidant balance and modulated neurochemical markers, as evidenced by the improvement in brain function. Besides, BPF contributed towards the down‐regulation of AlCl3‐increased AChE and BACE‐1 mRNA expressions in the cortex.ConclusionThe current work demonstrates the therapeutic potential of B. pinnatum and suggests that it can ameliorate cognitive impairment caused by AlCl3 through reverting oxidative stress, restoring neurochemical function.