The current investigation aimed to scrutinize the neuro-protective effect of hyperforin on β‑amyloid peptide (Aβ)_1-42 and H₂O₂ induced injury in PC12 cells and colchicine induced Alzheimer’s disease (AD). PC12 cells were treated with H₂O₂ and (Aβ)_1-42 in the presence of hyperforin. The cell viability was determined via suing the MTT assay; malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels were also scrutinized. Colchicine induced the destruction of memory and learning which was exhibited in neurobehavioral theory (passive avoidance and Morris water maze) connected with reduced activity of acetylcholinesterase (AChE). Anti‑oxidant and inflammatory parameters also estimated. Hyperforin dose dependently increased the cell viability and reduced the MDA and LDH release via PC12 cell injured with H₂O₂ and (Aβ)_1-42. Hyperforin treatment lead to a considerable enhance in TLT in the retention trials as comparisian to acquisition trial suggesting as boosting memory and learning in rats. Hyperforin treatments significantly increase the AChE and reduced the superoxide dismutase, glutathione, MDA, protein carbonyl, glutathione peroxdiase, catalase, NF‑kB and IL‑1β at dose dependent manner. In summary, the model of H₂O₂ and (Aβ)_1-42 induced PC12 cell injury was successfully developed and dose dependently treatment of hypoforin showed the neuroprotective effect against the H₂O₂ and (Aβ)_1-42 induced cell damage. These finding clearly exhibited that hyperforin reverted the colchicine induced neuro‑chemical and behavioural alteration via potent anti‑inflammatory and anti‑oxidant activity.