Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway
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ORIGINAL ARTICLE
Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway Min Li,1 Huanzhang Shao,1 Xia Zhang,1 and Bingyu Qin1,2
Abstract—Previous studies have demonstrated that hesperidin, a flavanone glycoside from citrus fruits, produces antidepressant-like effects in both mice and rats. However, whether these effects are mediated by pro-inflammatory cytokines remains unknown. In the present study, we attempted to investigate the effects of hesperidin on the depressive-like behavior; the serum corticosterone concentrations; and the interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels in lipopolysaccharide (LPS)induced depression-like mice. In particular, we evaluated the miRNA-132 expression after LPS and hesperidin treatment. We found that LPS injection not only decreased the sucrose preference and increased the serum corticosterone levels but also elevated IL-1β, IL-6, and TNF-α in the prefrontal cortex. More importantly, LPS down-regulated the expression of miRNA-132. Pre-treatment with hesperidin (25, 50, 100 mg/kg) for 7 days prevented these abnormalities induced by LPS injection. In contrast, this effect of hesperidin was abolished by a miRNA-132 antagomir. Taken together, these results suggest that the antidepressant-like mechanisms of hesperidin are at least partially related to decreased pro-inflammatory cytokine levels via the miRNA-132 pathway in the brain. KEY WORDS: Hesperidin; Antidepressant; Lipopolysaccharide (LPS); Pro-inflammatory cytokines; miRNA-132.
INTRODUCTION Depression is a state of low mood and interest in activities that can affect thoughts, behaviors, feelings, and sense of well-being. Recently, a growing body of evidence suggests that pro-inflammatory cytokines play an important role in the pathogenesis of depression. In clinical studies, researchers found that depressed patients had higher levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) [1, 2]. In contrast, antidepressant medication can decrease the concentration of pro-inflammatory cytokines [3, 4]. This phenomenon is also observed in depressive-like animals in pre-clinical 1
Central ICU, Henan Province People’s Hospital, Zhengzhou, 450003, Henan Province, PR China 2 To whom correspondence should be addressed at Central ICU, Henan Province People’s Hospital, Zhengzhou, 450003, Henan Province, PR China. E-mail: [email protected]
studies [5, 6]. Thus, these observations imply that we can search for antidepressants by focusing on agents that possess anti-inflammatory properties. miRNA-132, a short non-coding RNA molecule, regulates protein expression in animals. It has been shown to be involved in inflammation. A previous study found that miRNA-132 strengthens cholinergic anti-inflammatory signaling [7]. Furthermore, another previous study demonstrated that miRNA-132 was decreased in a chronic depression-like model and suggested miRNA-132 as a target for antidepressant restoration [8]. Over
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