Abstract Background: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition. Although crocin has shown potential in reducing stress-related symptoms, its low bioavailability limits its effectiveness. Caffeine may enhance the bioavailability of various compounds by modulating liver enzymes. This study examined whether caffeine could improve crocin’s efficacy in a rat model of PTSD. Materials and Methods: Male Wistar rats (8–10 weeks old) were divided into five groups: control, PTSD, crocin-treated, caffeine-treated, and crocin + caffeine-treated. PTSD was induced using repeated foot shocks, followed by 7 days of treatment. Behavioral assessments were performed using the elevated plus maze and shuttle box tests. Serum corticosterone levels were measured as a biochemical marker of anxiety, and histological evaluation of the hippocampus was conducted using Cresyl Violet and Golgi–Cox staining. Results: The combination treatment significantly reduced serum corticosterone levels compared to either compound alone ( P < 0.01). Behavioral improvements—including increased grooming, time spent in open arms, and reduced freezing latency—were most pronounced in the crocin + caffeine group. Histological analysis also revealed reduced neuronal damage in this group. Conclusions: We concluded that a combination of crocin and caffeine could improve the efficacy of crocin given alone. These findings indicate that caffeine can help further enhance the neuroprotective efficacy of crocin in this model.
Alfideh et al. (Sun,) studied this question.