Stimulation of Dopamine Production by Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive1

Rangasamy, Suresh B.; Dasarathi, Sridevi; Nutakki, Aparna; Mukherjee, Shreya; Nellivalasa, Rohith; Pahan, Kalipada

doi:10.3233/adr-210001

Cited by 7 publications

(2 citation statements)

References 33 publications

(41 reference statements)

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“…TH catalyzes the rate-limiting step in catecholamine biosynthesis, i.e., the conversion of tyrosine to L-DOPA (L-3′,4′-dihydroxyphenyalalanine) [ 54 ]. The mechanism probably involves activation of the transcription factor CREB (cAMP response element-binding protein) [ 59 , 60 ]. GRK2-mediated TH upregulation results in increased catecholamine (norepinephrine and epinephrine) biosynthesis in the adrenal medulla [ 53 ].…”

Section: Research Hypothesis: Dapagliflozin Attenuates Adrenal Catecholamine Productionmentioning

confidence: 99%

Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland

Lymperopoulos

Borges

Cora

et al. 2021

IJMS

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Heart failure (HF) remains the leading cause of morbidity and death in the western world, and new therapeutic modalities are urgently needed to improve the lifespan and quality of life of HF patients. The sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed and mainly indicated for diabetes mellitus treatment, have been increasingly shown to ameliorate heart disease, and specifically HF, in humans, regardless of diabetes co-existence. Indeed, dapagliflozin has been reported to reduce cardiovascular mortality and hospitalizations in patients with HF and reduced ejection fraction (HFrEF). This SGLT2 inhibitor demonstrates these benefits also in non-diabetic subjects, indicating that dapagliflozin’s efficacy in HF is independent of blood glucose control. Evidence for the effectiveness of various SGLT2 inhibitors in providing cardiovascular benefits irrespective of their effects on blood glucose regulation have spurred the use of these agents in HFrEF treatment and resulted in FDA approvals for cardiovascular indications. The obvious question arising from all these studies is, of course, which molecular/pharmacological mechanisms underlie these cardiovascular benefits of the drugs in diabetics and non-diabetics alike. The fact that SGLT2 is not significantly expressed in cardiac myocytes (SGLT1 appears to be the dominant isoform) adds even greater perplexity to this answer. A variety of mechanisms have been proposed over the past few years and tested in cell and animal models and prominent among those is the potential for sympatholysis, i.e., reduction in sympathetic nervous system activity. The latter is known to be high in HF patients, contributing significantly to the morbidity and mortality of the disease. The present minireview first summarizes the current evidence in the literature supporting the notion that SGLT2 inhibitors, such as dapagliflozin and empagliflozin, exert sympatholysis, and also outlines the main putative underlying mechanisms for these sympatholytic effects. Then, we propose a novel hypothesis, centered on the adrenal medulla, for the sympatholytic effects specifically of dapagliflozin. Adrenal medulla is responsible for the production and secretion of almost the entire amount of circulating epinephrine and of a significant percentage of circulating norepinephrine in the human body. If proven true experimentally, this hypothesis, along with other emerging experimental evidence for sympatholytic effects in neurons, will shed new light on the pharmacological effects that mediate the cardiovascular benefits of SGLT2 inhibitor drugs, independently of their blood glucose-lowering effects.

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Section: Research Hypothesis: Dapagliflozin Attenuates Adrenal Catecholamine Productionmentioning

confidence: 99%

Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland

Lymperopoulos

Borges

Cora

et al. 2021

IJMS

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“…However, it is a good model for screening and also for studying the mechanism of action of the substance. In another study, sodium benzoate was shown to stimulate dopamine production by dopaminergic neurons by affecting the expression and protein levels of tyrosine hydroxylase [ 176 ]. As previously mentioned, locomotor improvement occurred in the animals.…”

Section: Beneficial Properties Of Sodium Benzoatementioning

confidence: 99%

Sodium Benzoate—Harmfulness and Potential Use in Therapies for Disorders Related to the Nervous System: A Review

Walczak-Nowicka

Herbet

2022

Nutrients

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Currently, due to the large number of reports regarding the harmfulness of food additives, more and more consumers follow the so-called “clean label” trend, i.e., prefer and choose the least-processed food products. One of the compounds known as a preservative with a high safety profile is sodium benzoate. While some studies show that it can be used to treat conditions such as depression, pain, schizophrenia, autism spectrum disorders, and neurodegenerative diseases, others report its harmfulness. For example, it was found to cause mutagenic effects, generate oxidative stress, disrupt hormones, and reduce fertility. Due to such disparate results, the purpose of this study is to comprehensively discuss the safety profile of sodium benzoate and its potential use in neurodegenerative diseases, especially in autism spectrum disorder (ASD), schizophrenia, major depressive disorder (MDD), and pain relief.

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Caffeine affects the neurobehavioral impact of sodium benzoate in adolescent rats

Sabry,

Masoud,

Georgy

2024

Neuroscience Letters

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Stimulation of Dopamine Production by Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive1

Cited by 7 publications

References 33 publications

Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland

Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland

Sodium Benzoate—Harmfulness and Potential Use in Therapies for Disorders Related to the Nervous System: A Review

Caffeine affects the neurobehavioral impact of sodium benzoate in adolescent rats

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