Cryptotanshinone ameliorates cladribine-induced cognitive impairment in rats

Objective: To evaluate the neuroprotective effect of cryptotanshinone against cladribine-induced cognitive impairment in rats. Methods: Rats were administered with cladribine (1 mg/kg, p.o.) and cryptotanshinone (10 and 20 mg/kg, i.p.) for four weeks. Behavioral tests such as Morris water maze and elevated plus maze were conducted to check memory impairment caused by cladribine. On day 29, all rats were sacrificed, and the brains were separated for estimation of neuroinflammatory factors, biochemical parameters, neurotransmitters, Aβ(1-42), blood-brain barrier permeability, nuclear factor erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). Results: Treatment with cryptotanshinone dose-dependently enhanced spatial memory, improved the levels of neurotransmitter and antioxidant enzymes, and suppressed proinflammatory cytokine release. Cryptotanshinone also decreased Aβ(1-42) accumulation and increased the levels of Nrf2 and BDNF in the hippocampus. Additionally, the histopathological results showed that cryptotanshinone reduced cladribine-induced neuronal death in the hippocampus. Conclusions: Cryptotanshinone exhibits a promising neuroprotective effect against cladribine-induced cognitive impairment in preclinical studies, and may be a potential phytochemical for the treatment and management of cognitive impairment.