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

ABSTRACT

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).

KEYWORDS:

• anxiety
• avoidance memory‌
• brain-derived neurotrophic factor
• cognitive memory‌
• spatial memory‌
• stress
• saffron
• tumor necrosis factor-alpha

Acknowledgments

The authors would like to thank Dr. Mohammad Kazemi and Mrs. Arezou Dabiri for their valuable assistance. The study would not have become possible without the financial support provided by Isfahan University of Medical Sciences, Isfahan, Iran.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical statement

All the experiments were approved by the Research and Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1394.1.214) and the approved date of research proposal was 2017.

Additional information

Funding

This work was supported by Isfahan University of Medical Sciences.