title: Protective effect of Z-ligustilide against amyloid beta-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains.
abstract: Neuroinflammatory responses induced by accumulation and aggregation of beta-amyloid (Abeta) peptide are mainly involved in Alzheimer's disease (AD) pathogenesis. Z-ligustilide (LIG), a novel neuroprotectant against ischemic stroke, was reported to have significant anti-inflammatory effects via inhibition of TNF-alpha production and bioactivity. The present study investigated the effect of LIG on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of Abeta(25-35) at a dose of 50 nmol/rat. Rats received oral administration of 40 mg/kg LIG or volume-matched vehicle 1 h before Abeta(25-35) treatment then once daily for 15 days. Morris water maze was used to detect the cognitive dysfunction induced by Abeta(25-35). Compared to the sham-operated rats, Abeta(25-35) injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test (p < 0.01) and increased both AD-related neuropathological signs (i.e., Abeta, amyloid precursor protein, and phosphorylated Tau immunoreactivity) and pro-inflammatory mediators (i.e., TNF-alpha and activated NF-kappaB) in the prefrontal cortex and CA1 subregion of the hippocampus. And these neurotoxic effects of Abeta(25-35) were significantly ameliorated with LIG treatment (p < 0.01 vs. vehicle-treated group). The present data suggest that LIG modulates TNF-alpha-activated NF-kappaB signaling pathway with respect to its protective effect against Abeta(25-35)-induced neurotoxicity. LIG would be a potential candidate for further preclinical study aimed at the prevention and treatment of cognitive deficits in AD.
authors.affiliation: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Kuang
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Du
authors.forename: Ya-Shu
authors.initials: YS
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yan-Nan
authors.initials: YN
authors.lastname: Wang