Quercetin Mitigates Methamphetamine-Induced Anxiety-Like Behavior Through Ameliorating Mitochondrial Dysfunction and Neuroinflammation

Abstract

Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression. Studies have reported an association between MA exposure and anxiety, nonetheless, the underlying mechanism remains elusive. In the present study, we developed a mouse model of anxiety-like behavior induced by MA administration. RNA-seq was then performed to profile the gene expression patterns of hippocampus (HIPP), and the differentially expressed genes (DEGs) were significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Based on these, mitochondria was hypothesized to be involved in MA-induced anxiety. Quercetin, as a mitochondrial protector, was used to investigate whether to be a potential treatment for MA-induced anxiety; accordingly, it alleviated anxiety-like behavior and improved mitochondrial impairment in vivo. Further experiments in vitro suggested that quercetin alleviated the dysfunction and morphological abnormalities of mitochondria induced by MA, via decreasing the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and increasing the oxygen consumption rate (OCR) and ATP production. Moreover, the study examined the effect of quercetin on astrocytes activation and neuroinflammation, and the results indicated that it significantly attenuated the activation of astrocytes and reduced the levels of IL-1β, TNFα but not IL-6. In light of these findings, quantitative evidence is presented in the study supporting the view that MA can evoke anxiety-like behavior via the induction of mitochondrial dysfunction. Quercetin exerted antipsychotic activity through modulation of mitochondrial function and neuroinflammation, suggesting its potential for further therapeutic development in MA-induced anxiety.

Natural Polyphenols—Resveratrol, Quercetin, Magnolol, and β-Catechin—Block Certain Aspects of Heroin Addiction and Modulate Striatal IL-6 and TNF-α

“…Our results are in accordance with those of Singh et al, who reported that repeated administration of quercetin (25 and 50 mg/kg) for 9 days suppressed naloxone-precipitated morphine (10 mg/kg) withdrawal [31]. On the other hand, quercetin inhibited nicotinetriggered CPP reinstatement [42], alleviated METH-induced anxiety-like behavior in mice, attenuated the activation of astrocytes, and reduced the levels of IL-1beta and TNF-α, but not IL-6 [43]. In addition, quercetin (10, 30 and 100 mg/kg i.p.)…”

Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms

“…High levels of ROS have been linked to cell death and degeneration, notably in disorders that include type 2 diabetes, Alzheimer's disease, autism, mood disorders and attention-deficit/hyperactivity disorder (ADHD), among others (Michel et al, 2012). These observations have been expanded in recent studies that demonstrate correlations between mitochondrial dysfunction and various psychiatric disorders (Burtscher et al, 2022;Chen et al, 2022;Umare et al, 2022). In these cases, viruses and bacteria were identified as tightly involved in promoting alterations of mitochondrial and host cellular function via hypoxia and immune-mediated upregulation of inflammatory factors and conditions associated with oxidative stress.…”

Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder

“…Among them, the anxiolytic effects of quercetin, luteolin and narigenin are closely related to the inhibition of inflammatory response, suggesting that inhibition of inflammatory response may be the potential mechanism of Wendan Decoction in treating GAD. 57,61 The PPI results reveal that IL-6, TNF, SRC and AKT1 are the key targets of WDD in the treatment of GAD. KEGG enrichment analysis suggests that mechanism of WDD for GAD treatment is closely correlated with neuroactive ligand receptor interaction, calcium signaling pathway, cAMP signaling pathway, PI3K/AKT signaling pathway and MAPK signaling pathway.…”

“…LC-MS found that all these molecules were present in the aqueous extract of WDD we prepared. After a systematic literature search, naringenin, 56 quercetin, 57 , 58 glabridin, 59 beta-sitosterol, 60 luteolin 61 , 62 of them was the candidate molecule for anxiety. Among them, the anxiolytic effects of quercetin, luteolin and narigenin are closely related to the inhibition of inflammatory response, suggesting that inhibition of inflammatory response may be the potential mechanism of Wendan Decoction in treating GAD.…”

“…Among them, the anxiolytic effects of quercetin, luteolin and narigenin are closely related to the inhibition of inflammatory response, suggesting that inhibition of inflammatory response may be the potential mechanism of Wendan Decoction in treating GAD. 57 , 61 …”