Effects of Aqueous Saffron Extract on Glucoregulation as Well as Hepatic Agt and TNF-α Gene Expression in Rats Subjected to Sub-Chronic Stress.

Background: Stress and saffron seem to affect glucoregulation mechanisms and insulin resistance in different ways. Impacts of the aqueous saffron extract were investigated on serum glucose levels, serum insulin levels, the homeostatic model assessment of ß-cell function (HOMA-B), the homeostatic model assessment of insulin resistance (HOMA-IR), adrenal weight, and hepatic gene expression of angiotensinogen (Agt) and tumor necrosis factor-α (TNF-α) in rats under sub-chronic stress. Materials and Methods: Forty-two male rats were divided into six groups: control, restraint stress (6h/day for seven days), saffron (30 and 60 mg/kg) treatments for seven days, and post-stress saffron (30 and 60 mg/kg) treatments for seven days. The serum glucose and insulin levels, hepatic gene expressions of Agt and TNF-α, HOMA-IR, HOMA-B, and adrenal gland weight were measured. Results: One-week recovery following sub-chronic stress led to non-significant hyperglycemia, hyperinsulinemia, and insulin resistance. The hepatic Agt and TNF-α mRNA levels increased significantly in this group. Saffron administration led to enhanced hepatic Agt mRNA in the non-stressed subjects. In addition, serum glucose levels, insulin resistance, and hepatic Agt gene expression significantly increased in stress-saffron groups. The hepatic TNF-α gene expression was reduced only in the stress-saffron 60 group. Conclusion: Saffron treatment after sub-chronic stress not only did not improve glucose tolerance but also enhanced insulin resistance. It indicated the interaction of saffron and sub-chronic stress to promote renin-angiotensin system activity. In addition, the saffron treatment decreased TNF-α gene expression after sub-chronic stress. The synergistic stimulating effect of saffron and sub-chronic stress on gene expression of hepatic Agt led to insulin resistance and hyperglycemia.

Therapeutic effects of saffron extract on different memory types, anxiety, and hippocampal BDNF and TNF-α gene expressions in sub-chronically stressed rats.

Objective: While stress reportedly impairs memory, saffron enhances it. This study investigated the therapeutic effects of saffron extract on different memory types, anxiety-like behavior, and expressions of BDNF and TNF-α genes in sub-chronically stressed rats.Methods: Rats were randomly assigned to control, restraint stress (6 h/day/7 days), two 7-days saffron treatments with 30 and 60 mg/kg, and two stress-saffron groups (30 and 60 mg/kg/7 post-stress days). Serum cortisol level and hippocampal BDNF and TNF-α gene expressions were measured. Open field, passive avoidance, novel object recognition, and object location tests were performed to assess anxiety-like behavior and avoidance as well as cognitive and spatial memories, respectively.Results: The low saffron dose in the sub-chronic stressed group led to a significant increase in passive avoidance latency from day 3 onward whereas this effect was observed after 7 days under the high-dose treatment that simultaneously led to a significant decline in serum cortisol level. While the low saffron dose led to a sharp drop in hippocampal TNF-α gene expression, the high dose significantly increased the hippocampal BDNF gene expression in the sub-chronic stress group. Finally, both saffron doses reduced anxiety in the stressed groups.Conclusion: Compared to the low saffron dose, the high dose had a latent but long-lasting impact. Cognitive and spatial memories remained unaffected by either stress or saffron treatment. In addition, only the high saffron dose reversed anxiety in the sub-chronically stressed group. These findings suggest that various doses of saffron act differently on different brain functions under sub-chronic stress conditions.Abbreviations: Brain derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), hypothalamic-pituitary-adrenal axis (HPA), novel object recognition task (NORT), novel object location task (NOLT), open field test (OFT), passive avoidance (PA).