Possible directions for the discovery of new antidepressant

Young, Simon N.

doi:10.1503/jpn.100169

Cited by 8 publications

(8 citation statements)

References 28 publications

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“…Clinical and preclinical studies suggested that plasma levels and excretion rates of catecholamines like epinephrine were significantly lower in pesticide exposed individuals than controls. [15,40,48] The reduction in the levels of neurotransmitters, including dopamine, serotonin, and their metabolites, as observed in the present study, suggested that chronic exposure to pesticides among farmworkers persisted for a long period of time and the depressive symptoms could be due to the increased activities of MAO associated with the low level of serotonin and its metabolite HIAA.…”

Section: Discussionsupporting

confidence: 68%

“…[38,39] Serotonin has been found to be involved in modulating cognition, reward, learning, memory, and numerous physiological processes. [40,41] A few studies have demonstrated the decreased expression of 5-HT 1A receptors in the brain of pesticide exposed rats. [22,23] However, various questionnaire-based studies have been carried out to report the association of pesticide exposure with depression and suicidal ideation but neurochemical measurements were not carried out earlier in pesticide exposed individuals.…”

Section: Discussionmentioning

confidence: 99%

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Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers

Kori

Mandrah

Hasan

et al. 2020

J Biochem & Molecular Tox

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Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide‐induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory‐II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4‐dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO‐A and MAO‐B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidence of depression in agricultural workers.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers

Kori

Mandrah

Hasan

et al. 2020

J Biochem & Molecular Tox

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“…5 The use of nutraceuticals is one of the main approaches to that effect. [5][6][7][8] The Aronia shrub, a member of the Rosaceae family, has become a very popular cultivar in Eastern and Northern Europe, where it is grown as an ornamental plant and industrial source of natural coloring agents. 9 The berry of Aronia melanocarpa Elliott (Black chokeberry; the genus name Aronia has been replacing this common name) is rich source of polyphenols, especially anthocyanins, which are correlated with high antioxidant activity.…”

Section: Introductionmentioning

confidence: 99%

Reduction of anxiety-like and depression-like behaviors in rats after one month of drinking Aronia melanocarpa berry juice

et al. 2016

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The treatment of mood and anxiety disorders by nutraceuticals is gaining growing awareness. Berries of Aronia melanocarpa (Black chokeberry) and their extracts, exceptionally abundant in diverse phenolic compounds, have become famous for the highest in vitro antioxidant activity among fruits and notable health benefits (e.g. anti-diabetic, anti-inflammatory, cardioprotective). This study was designed to investigate the behavioral effects of month-long unlimited consumption of Aronia master juice (AJ) and/or juice reconstruct without polyphenols (RJ), in young male rats. AJ was initially evaluated for its content of phenolic compounds by spectrophotometric assays and HPLC-DAD. Rats that were supplied with three various water concentrations of AJ and RJ, respectively: 20% + 0% (ARO group), 5% + 15% (RAJ) and 0 + 20% (PLC), were compared with those which consumed only water (CTL). Daily drinking of AJ solution was significantly elevated from the second or third week onward, which was most expressed in the ARO group. Only this group displayed behavioral variations, manifested by certain hyperactivity in open field tests and prominent reductions of anxiety-like behaviors in the elevated plus maze. The ARO rats also expressed an alleviation of depression-like behavior in forced swimming tests. These findings demonstrate the beneficial behavioral effects of the one-month-long free drinking of phenolic-rich AJ in rats (>20 ml per kg b. mass daily) that may be recognized as stimulating, anxiolytic-like and antidepressant-like. The in vitro assays suggested that MAO-A/MAO-B inhibitions by the phenolic compounds of AJ might be the possible in vivo mechanisms for such behavioral actions.

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“…Clinically, l ‐methionine and its metabolite S ‐adenosyl methionine (SAM) have demonstrated its efficacy as antidepressant, with a recommended daily dosage of 0.5–1 g/day. [ 13 ] Recent reports have also confirmed that supplementation of l ‐methionine has contributed significantly in controlling various cancers while having a protective role in the liver from numerous chronic diseases such as jaundice, liver necrosis, fibrosis, and so forth. [ 14,15 ] These effects of l ‐methionine are being mediated on account of its ability to donate methyl groups to various biological entities as well as its capability in modulating metabolic homeostasis.…”

Section: Introductionmentioning

confidence: 98%

l‐Methionine potentiates anticancer activity of Sorafenib by epigenetically altering DUSP3/ERK pathway in hepatocellular carcinoma

Pal,

Kabeer,

Sharma

et al. 2024

J Biochem & Molecular Tox

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Hepatocellular carcinoma (HCC) is the third most common cancer‐related cause of death worldwide. Although Sorafenib is the standard systemic therapy for treating HCC, but it develops resistance very quickly, leading to poor prognosis. The current study was planned to explore the effect of l‐methionine on the anticancer activity of Sorafenib in HCC. Ten millimolar of l‐methionine treatment significantly reduced the IC50 of Sorafenib from 5.513 ± 0.171 to 0.8095 ± 0.0465 µM in HepG2 cell line. It also resulted in concomitant increase in oxidative stress and deactivation of ERK/AMPK/AKT pathway. Additionally, it also resulted in the increased expression of dual specificity phosphatase 3 (DUSP3). In a rat model of sorafenib‐resistant HCC induced by diethylnitrosamine (DEN) (100 mg/L/day) and Sorafenib (10 mg/kg), l‐methionine (300 and 500 mg/kg/day) supplementation overcame the drug resistance, as indicated by the reduced formation of surface tumor nodules, prevention of cellular hypertrophy, hyperplasia and inflammation, and improved animal survival. Furthermore, l‐methionine in combination with Sorafenib also inhibited AMPK/AKT and ERK pathway. At chromatin level, l‐methionine supplementation prevented global methylation of H3K27me3, an inactivation mark, and demethylation of H3K36me2, an activation mark. Interestingly, our findings suggest that inhibition of the ERK pathway via increased activity of DUSP3 is epigenetically regulated. Besides, chromatin immunoprecipitation data exhibited augmented H3K36me2 (an activation mark) levels on the DUSP3 promoter region. To the best of our knowledge, we are the first to report that l‐methionine supplementation improves the chemosensitivity in Sorafenib‐resistant HCC via modulating the epigenetic landscape and can be a potential therapeutic strategy.

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Possible directions for the discovery of new antidepressant

Cited by 8 publications

References 28 publications

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers

Reduction of anxiety-like and depression-like behaviors in rats after one month of drinking Aronia melanocarpa berry juice

l‐Methionine potentiates anticancer activity of Sorafenib by epigenetically altering DUSP3/ERK pathway in hepatocellular carcinoma

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