Early life stress caused glucose homeostasis impairment and anxiety-like behavior along with oxidative stress in adolescent male rat offspring: Protective effect of saffron extract

Early life stress (ELS) significantly contributes to metabolic and psychological disorders by triggering oxidative stress and disrupting the hypothalamic–pituitary–adrenal (HPA) axis. This research examined ELS effects on redox status, along with anxiety-like behavior, in adolescent male Wistar rats, also assessing saffron (Crocus sativus L.) extract’s potential benefits. Rats were exposed to foot shock stress from postnatal days 15–19, with treatment groups receiving saline or saffron extract (10 mg/kg) via intraperitoneal injection. Control groups were maintained without stress exposure. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. Corticosterone, glucose, and insulin levels, oxidative stress markers [malondialdehyde (MDA), glutathione (GSH), and catalase activity] in the plasma, pancreas, and amygdala were determined, and the HOMA-β index was estimated. Saffron extract markedly restored ELS effects by reducing fasting plasma glucose and corticosterone levels, while increasing insulin levels and the HOMA-β index in adolescent offspring. Additionally, saffron extract inhibited oxidative stress, evidenced by reduced MDA, normalized catalase activity, and augmented GSH levels in the plasma, pancreas, and amygdala. Behaviorally, saffron extract-treated rats exhibited diminished anxiety-like behaviors, characterized by increased time spent in the open arms of the EPM and the center zone in the OFT. This study suggests that ELS induces disturbances in glucose metabolism and anxiety-like behavior, accompanied by oxidative stress and increased HPA axis activity. The protective role of saffron extract underscores its capability to serve as a medicinal compound for preventing and treating stress-induced metabolic and anxiety disorders.