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

Abstract

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 beta-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-alpha (TNF-alpha) 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-alpha, 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-alpha 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-alpha 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-alpha 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.