Linzia gerberiformis (Asteraceae) pretreatment prevents cognitive deficits induced by the combined effects of ovariectomy and chronic unpredictable mild stress in rats.

The leaves of Linzia gerberiformis are used in traditional Cameroonian medicine for the treatment of respiratory infections and hepatitis. The present study was conducted to evaluate the anti-amnesic effects of the aqueous extract of L. gerberiformis leaves in ovariectomized rats exposed to chronic unpredictable mild stress (CUMS). A total of 42 female rats were used for this study. Thirty five ovariectomized rats were subjected to chronic unpredictable mild stress, distributed across five treatment groups, while 7 non-ovariectomized rats served as a control group receiving distilled water and were labeled as the vehicle. Ovariectomized (OVX) female rats exposed to CUMS for 1 week were treated with distilled water, estradiol valerate (1 mg/kg), and the aqueous extract of L. gerberiformis leaves (75, 150, and 300 mg/kg) for 14 days starting from the 8th day after OVX. Memory integrity was assessed using the novel object recognition test (NORT) and the Morris water maze test (MWM). Hippocampus was collected to assess the cholinergic system [acetylcholinesterase (AChE) and acetylcholine], pro-oxidants (nitric oxide (NO) and malondialdehyde (MDA)), anti-oxidants (superoxide dismutase (SOD), catalase, and, GSH (reduced glutathione)) as well as 17-β-estradiol. Plasma was also collected to measure the concentration of 17-β-estradiol. The aqueous extract of L. gerberiformis leaves at 75 mg/kg and 150 mg/kg improved short-term recognition memory and long-term spatial learning memory compared to OVX animals exposed to CUMS treated with distilled water. The aqueous extract of L. gerberiformis leaves increased plasma and hippocampal 17-β-estradiol compared to OVX + CUMS animals. In addition, L. gerberiformis significantly prevented the effect induced by the combined action of ovariectomy and CUMS in rats by preventing the decrease of estrogen, acetylcholine, SOD, CAT and GSH; and the increase in AChE, NO and MDA. Pretreatment with L. gerberiformis aqueous extract leaves protects against the combined effects of ovariectomy and CUMS-induced memory deficits, suggesting its anti-amnesic properties. These properties could be mediated through the prevention of estrogen decline, modulation of the cholinergic system and oxidative stress.