Cinnamic Acid Improved Lipopolysaccharide-Induced Depressive-Like Behaviors by Inhibiting Neuroinflammation and Oxidative Stress in Mice.

Abstract

AIM:

Recent evidence indicates that neuroinflammation and oxidative stress play vital roles in the pathological process of major depressive disorder (MDD). Cinnamic acid (CA), a naturally occurring organic acid, has been reported to ameliorate neuroinflammation and oxidative stress for treatment of diabetes-related memory deficits. Here, we explored whether CA pretreatment ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice by suppressing neuroinflammation and by improving oxidative stress status.

METHODS:

The mice were treated with CA, vehicle, or fluoxetine as a positive control. After 14 days, LPS (1 mg/kg, i.p.) or saline was administered. The depression-like behaviors were examined by the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). Furthermore, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex of mice were assayed.

RESULTS:

Our results demonstrated that CA pretreatment at the doses of 100 and 200 mg/kg significantly attenuated depressive-like behaviors in the TST, FST, and SPT. In addition, not only the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) but also oxidative stress parameters including SOD, GSH, and MDA in the hippocampus and cortex of mice treated with LPS were dramatically improved by CA pretreatment. Finally, CA pretreatment strikingly ameliorated the downregulation of BDNF induced by LPS in the hippocampus and cortex of mice.

CONCLUSION:

Our results indicated that CA may have therapeutic potential for MDD treatment through attenuating the LPS-induced inflammation and oxidative stress along with significant improvement of BDNF impairment.

• Authors: Rengong Zhuo, Xiaoling Cheng, Lili Luo, Luying Yang, Yun Zhao, Yu Zhou, Lu Peng, Xin Jin, Lishan Cui, Feng Liu, Lichao Yang
• Journal: Pharmacology (Pharmacology) Vol. 107 Issue 5-6 Pg. 281-289 ( 2022) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 35325888 (Publication Type: Journal Article)
• Copyright: © 2022 S. Karger AG, Basel.

Chemical References

• Brain-Derived Neurotrophic Factor
• Cinnamates
• Interleukin-6
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• cinnamic acid
• Superoxide Dismutase
• Glutathione

Topics

• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Cinnamates
• Depression (chemically induced, drug therapy)
• Depressive Disorder, Major
• Glutathione (metabolism)
• Hippocampus (metabolism)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (toxicity)
• Mice
• Neuroinflammatory Diseases
• Oxidative Stress
• Superoxide Dismutase
• Tumor Necrosis Factor-alpha (metabolism)