Roman chamomile inhalation combined with clomipramine treatment improves treatment-resistant depression-like behavior in mice

Hashikawa-Hobara, Narumi; Otsuka, Ami; Ishikawa, Risa; Hashikawa, Naoya

doi:10.1016/j.biopha.2019.109263

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…Consistent with a previous study [53], pathological changes such as decreased cortical neuronal cells, and disordered arrangement, nuclear loss, nucleus light staining, swelling, fragmentation, and even vacuolization and nuclear pyknosis. All of the above changes in CUMS mice could be reversed by XYS and Flu treatments.…”

Section: Discussionsupporting

confidence: 93%

Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Liu

Ding

Wang

et al. 2019

BMC Complement Altern Med

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Background Mounting evidence indicates that the cerebral cortex is an important physiological system of emotional activity, and its dysfunction may be the main cause of stress. Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS), which initiates rapid signal transmission in the synapse before its reuptake into the surrounding glia, specifically astrocytes (ASTs). The astrocytic excitatory amino acid transporters 1 (EAAT1) and 2 (EAAT2) are the major transporters that take up synaptic glutamate to maintain optimal extracellular glutamic levels, thus preventing accumulation in the synaptic cleft and ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with depression. Therefore, we hypothesized that the underlying antidepressant-like mechanism of Xiaoyaosan (XYS), a Chinese herbal formula, may be related to the regulation of astrocytic EAATs. Therefore, we studied the antidepressant mechanism of XYS on the basis of EAAT dysfunction in ASTs. Methods Eighty adult C57BL/6 J mice were randomly divided into 4 groups: a control group, a chronic unpredictable mild stress (CUMS) group, a Xiaoyaosan (XYS) treatment group and a fluoxetine hydrochloride (Flu) treatment group. Except for the control group, mice in the other groups all received chronic unpredictable mild stress for 21 days. Mice in the control and CUMS groups received gavage administration with 0.5 mL of normal saline (NS) for 21 days, and mice in the XYS and Flu treatment groups were administered dosages of 0.25 g/kg/d and 2.6 mg/kg/d by gavage. The effects of XYS on the depressive-like behavioral tests, including the open field test (OFT), forced swimming test (FST) and sucrose preference test (SPT), were examined. The glutamate (Glu) concentrations of the prefrontal cortex (PFC) were detected with colorimetry. The morphology of neurons in the PFC was observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), NeuN, EAAT1 and EAAT2 proteins in the PFC of mice was detected by using Western blotting and immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of the GFAP, NeuN, EAAT1 and EAAT2 genes in the PFC of mice. Results The results of behavioral tests showed that CUMS-induced mice exhibited depressive-like behavior, which could be improved in some tests with XYS and Flu treatment. Immunohistochemistry and Western blot analysis showed that the protein levels of GFAP, NeuN, EAAT1 and EAAT2 in the PFC of CUMS mice were significantly lower than those in the control group, and these changes could be reversed by XYS and Flu. The results of qPCR analysis showed that the expression of GFAP, NeuN, EAAT1 and EAAT2 mRNAs in the PFC of CUMS mice was not significantly changed, with the exception of EAAT2, compared with that of the control group, while the expression of the above mRNAs was significantly higher in the XYS and Flu groups than that in the CUMS group. ...

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Section: Discussionsupporting

confidence: 93%

Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Liu

Ding

Wang

et al. 2019

BMC Complement Altern Med

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“…Our study shows that chronic clomipramine treatment significantly increased the hippocampal volume for the first time, which may have something to do with the reverse of depressive-like behavior and neuroinflammation induced by CMS. Besides, it has been demonstrated that hippocampal cell proliferation, as well as neurogenesis, could be promoted by chronic clomipramine treatment [ 14 , 57 ], which may account for the changes in hippocampal volume [ 58 , 59 ]. On the other hand, clomipramine likely increased the rat’s hippocampal volume by promoting gliosis, which could have something to do with the increase of hippocampal volume under pathological conditions [ 60 , 61 ] since our previous work indicated that chronic clomipramine treatment increased GFAP level in the hippocampus of rats exposed to chronic unpredictable stress [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress

Zhang

Liu³

et al. 2022

Transl Psychiatry

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It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic antidepressant, clomipramine. We designed a series of experiments to find its role in depressive-like behavior, hippocampal neuroinflammation as well as hippocampal volume changes induced by chronic unpredictable mild stress (CMS). Rats exhibited defective behavior and hippocampal neuroinflammation after 12 weeks of CMS, which included elevated expression of cleaved interleukin-1β (IL-1β) and NLRP3 inflammasome together with the activation of microglia. Rats exposed to CMS showed weakened behavioral defects, reduced expression of IL-18, IL-6, and IL-1β along with reversed activation of microglia after clomipramine treatment. This indicates that the antidepressant effect of clomipramine may be related to the reduced expression of NLRP3 inflammasome and cleaved IL-1β. Moreover, we found an increased hippocampal volume in rats exposed to CMS after clomipramine treatment while CMS failed to affect hippocampal volume. All these results indicate that the NLRP3 inflammasome of microglia in the hippocampus is related to the antidepressant effects of clomipramine and CMS-induced depressive-like behavior in rats.

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“…They found that inhalation of Roman chamomile essential oil combined with chlorpromazine reduced drug-resistant depression-like behavior in mice, and had a crucial role in drug-resistant depression-like behavior. Their results may help people suffering from drug-resistant depression and provide a target for innovative antidepressant therapies ( Hashikawa-Hobara et al, 2019 ). Future emphasis should be placed on animal studies with chamomile involving animal models of various psychiatric disorders, which will help develop chamomile as a promising therapeutic agent ( Srivastava et al, 2010 ).…”

Section: Aromatic Plants and Extracts For Mood Disordersmentioning

confidence: 99%

Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders

Cui

Wei

et al. 2022

Front. Pharmacol.

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Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants’ volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.

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Roman chamomile inhalation combined with clomipramine treatment improves treatment-resistant depression-like behavior in mice

Cited by 16 publications

References 34 publications

Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress

Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders

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