Novel Therapeutic Approach for the Management of Mood Disorders: In Vivo and In Vitro Effect of a Combination of L-Theanine, Melissa officinalis L. and Magnolia officinalis Rehder &amp; E.H. Wilson

Borgonetti, Vittoria; Governa, Paolo; Biagi, Marco; Galeotti, Nicoletta

doi:10.3390/nu12061803

Cited by 17 publications

(8 citation statements)

References 75 publications

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“…The marble burying behavioral test was performed as previously described [ 45 ]. Briefly, mice were individually placed in clear cages (27 × 16 × 14 cm), each containing 20 glass marbles (1 cm diameter) equidistantly located in a 5 × 4 arrangement.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons

et al. 2020

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The long-term use of anxiolytic and antidepressant drugs can cause a plethora of side effects and the use of complementary and alternative medicine, which is generally considered safer than conventional medicine, is consistently increasing. Helichrysum stoechas (L.) Moench methanolic extract (HSE) has shown MAO-A inhibitory properties in previous studies. With the aim of obtaining innovative and safer therapies for mood disorders, this study investigated the potential activity of HSE in the management of anxiety- and depression-related symptoms. HSE showed dose-dependent (30–100 mg/kg p.o.) anxiolytic-like activity in the light dark box and marble burying tests, without any antidepressant-like activity, as shown by the results of the tail suspension test. Additionally, HSE did not have any effect on the modulation of pain, which highlights its selectivity in the control of anxiety-related behavior. At active doses, HSE did not produce any sedative effect or result in impaired motor coordination and memory functions. Western blotting experiments showed the ability of HSE to counteract the reduction in the phosphorylation of ERK44/42, to restore brain-derived neurotrophic factor (BDNF) expression and to return cyclic AMP response element binding (CREB) levels to basal levels in noradrenergic hippocampal neurons of mice exposed to an anxiety-related environment, which indicates a protective role against anxiety behavior. These results suggest that oral administration of HSE might represent an interesting opportunity for the management of anxiety disorders.

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Section: Methodsmentioning

confidence: 99%

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons

et al. 2020

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“…Light dark box (LDB) test : The LDB test was performed as previously reported (Borgonetti, Governa, et al, 2020). Briefly, each mouse was allowed to move freely for 5 min in a box with two different compartments, the dark, and the light chamber, separated by a small door (10 cm × 3.2 cm).…”

Section: Methodsmentioning

confidence: 99%

Helichrysum stoechas (L.) Moench reduces body weight gain and modulates mood disorders via inhibition of silent information regulator 1 (SIRT1) by arzanol

Borgonetti

Caroli

Governa

et al. 2023

Phytotherapy Research

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The prevalence of obesity is steadily rising, making safe and more efficient anti‐obesity treatments an urgent medical need. Growing evidence correlates obesity and comorbidities, including anxiety and depression, with the development of a low‐grade inflammation in peripheral and central tissues. We hypothesized that attenuating neuroinflammation might reduce weight gain and improve mood. We investigated the efficacy of a methanolic extract from Helichrysum stoechas (L.) Moench (HSE), well‐known for its anti‐inflammatory properties, and its main constituent arzanol (AZL). HPLC‐ESI‐MS2 and HPLC‐UV were used to characterize the extract. HSE effects on mood and feeding behavior was assessed in mice. The mechanism of action of HSE and AZL was investigated in hippocampus samples and SH‐SY5Y cells by western blotting and immunofluorescence. Oral administration of HSE for 3 weeks limited weight gain with no significant decrease in food intake. HSE produced an anxiolytic‐like and antidepressant‐like phenotype comparable to diazepam and amitriptyline, respectively, in the absence of locomotor and cognitive impairments and induced neuroprotective effects in glutamate‐exposed SH‐SY5Y cells. A dose‐dependent reduction of SIRT1 expression was detected in SH‐SY5Y cells and in hippocampal samples from HSE‐treated mice. The inhibition of the SIRT1‐FoxO1 pathway was induced in the hypothalamus. Molecular docking studies proposed a mechanism of SIRT1 inhibition by AZL, confirmed by the evaluation of inhibitory effects on SIRT1 enzymatic activity. HSE limited weight gain and comorbidities through an AZL‐mediated SIRT1 inhibition. These activities indicate HSE an innovative therapeutic perspective for obesity and associated mood disorders.

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“…A response was considered positive when the animals licked themselves, shacked their heads or jumped. In SNI mice, this test was performed in the baseline (BL) condition and at day 7-21-28 after surgery [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Rosmarinic Acid Reduces Microglia Senescence: A Novel Therapeutic Approach for the Management of Neuropathic Pain Symptoms

Borgonetti

Galeotti

2022

Biomedicines

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The worldwide incidence of neuropathic pain is around 7–8% and is associated with significant and disabling comorbidities (sleep disturbances, depression, anxiety). It is now known that cellular ageing of microglia contributes to neurodegenerative diseases, mood disorders, and, even if with less evidence, chronic pain. The aim of this work was to investigate in vitro and in vivo the senolytic activity of rosmarinic acid (RA) to be exploited for the management of NP symptoms. BV2 cells were stimulated with LPS 500 ng/mL for 24 h. Treatment with RA 1 µM improved cell viability and reduced IL-1ß release leading to an attenuation of neuroinflammation. We then moved on to test the efficacy of RA in reducing microglial senescence. In our model, BV2 cells were stimulated with LPS 500 ng/mL every 72 h for 4 h/day, over a period of 10 days. RA 1 µM reduced the expression of the β-galactosidase enzyme, reduced the release of senescence-associated secretory phenotype (SASP) factors, increased cell viability, and reduced the presence of nuclear foci of senescence (SAHF), well-known cellular senescence markers. In the Spared Nerve Injury (SNI) model, 28 days from surgery, repeated oral administration of RA 5 mg/kg reduced hyperalgesia and NP-associated symptoms, such as anxiety and depression. A reduction of senescence markers was detected on both hippocampal and spinal samples of SNI-treated mice. This study represents a starting point for investigating the role of microglial senescence as a possible pharmacological target in controlling symptoms related to the more advanced stages of peripheral neuropathy.

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Novel Therapeutic Approach for the Management of Mood Disorders: In Vivo and In Vitro Effect of a Combination of L-Theanine, Melissa officinalis L. and Magnolia officinalis Rehder & E.H. Wilson

Cited by 17 publications

References 75 publications

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons

Helichrysum stoechas (L.) Moench reduces body weight gain and modulates mood disorders via inhibition of silent information regulator 1 (SIRT1) by arzanol

Rosmarinic Acid Reduces Microglia Senescence: A Novel Therapeutic Approach for the Management of Neuropathic Pain Symptoms

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