A beating heart cell model to predict cardiotoxicity: Effects of the dietary supplement ingredients higenamine, phenylethylamine, ephedrine and caffeine

Calvert, Richard J.; Vohra, Sanah; Ferguson, Martine; Wiesenfeld, Paddy L.

doi:10.1016/j.fct.2015.01.022

Cited by 22 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with these findings, our laboratory demonstrated that higenamine stimulates CHO cells expressing the human β 2 ‐adrenoceptor (described below). Complimentary studies on β 2 ‐adrenoceptor expressed in a different cell line (SK‐N‐MC) result in similar conclusions: higenamine stimulated β 2 ‐adrenoceptors, and its effects were abolished in the presence of the β 2 ‐selective antagonist, ICI‐118,551 8 . Finally, Kato et al 12,39 showed that higenamine and a number of synthetic analogues enhanced glucose uptake in a rat muscle cell line and did so with a potency and efficacy similar to that of epinephrine and norepinephrine.…”

Section: Higenamine As a β2‐adrenoceptor Agonistmentioning

confidence: 76%

“…These higenamine‐containing plant species have been utilized in traditional Chinese medicine to treat a range of medical conditions including asthma and heart failure 2 . First isolated in the 1970s, 3 higenamine was shown to have ionotropic and chronotropic effects in isolated heart preparations 3–8 stimulating interest in the substance as a potential ‘cardiotonic’. Additionally, higenamine was shown to have relaxant effects upon smooth muscle of the isolated trachea 9–11 and colon 10 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

β₂‐Adrenoceptor agonist activity of higenamine

Hudzik

Patel

Brown

2021

Drug Testing and Analysis

View full text Add to dashboard Cite

Higenamine was included in the World Anti‐Doping Agency (WADA) Prohibited Substances and Methods List as a β2‐adrenoceptor agonist in 2017, thereby resulting in its prohibition both in and out of competition. The present mini review describes the physiology and pharmacology of adrenoceptors, summarizes the literature addressing the mechanism of action of higenamine and extends these findings with previously unpublished in silico and in vitro work. Studies conducted in isolated in vitro systems, whole‐animal preparations and a small number of clinical studies suggest that higenamine acts in part as a β2‐adrenoceptor agonist. In silico predictive tools indicated that higenamine and possibly a metabolite have a high probability of interacting with the β2‐receptor as an agonist. Stable expression of human β2‐receptors in Chinese hamster ovary (CHO) cells to measure agonist activity not only confirmed the activity of higenamine at β2 but also closely agreed with the in silico prediction of potency for this compound. These data confirm and extend literature findings supporting the inclusion of higenamine in the Prohibited List.

show abstract

Section: Higenamine As a β2‐adrenoceptor Agonistmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

β₂‐Adrenoceptor agonist activity of higenamine

Hudzik

Patel

Brown

2021

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…the ed dose used in the experiment provides a dose of 250 µM of caffeine/L, which is cardiotoxic for humans [17]. according to many researchers, consumption of caffeine-containing beverages increases the risk of cardiovascular diseases because it increases blood pressure and contributes to the increase in homocysteine blood levels [18,19].…”

Section: Discussionmentioning

confidence: 99%

Prolonged consumption of energy drinks does not affect the processes of memory, and increases the activity of transaminases, and cholesterol concentration – animal model study results

Nieradko-Iwanicka¹,

Pietraszek²,

Pośnik³

2016

fmpcr

View full text Add to dashboard Cite

A -Study Design, B -Data Collection, C -Statistical analysis, D -Data interpretation, E -Manuscript Preparation, F -Literature Search, G -Funds CollectionBackground. the consumption of energy drinks (ed) is popular among young people. there are concerns that it could be harmful for their health. Objectives. the aim of the study was to analyze the influence of ed consumption on animals for 30 subsequent days on memory, weight gain and biochemical parameters (alanine transaminase-aLt, asparagine transaminase-ast, creatinine, cholesterol and glycated hemoglobin-Hba 1c ). Material and methods. the study was conducted on 32 mice (16 females and 16 males). the mice received standard feed for rodents ad libitum. the animals were randomly assigned to four groups (8 animals each): i -female controls provided with water ad libitum, ii -females provided with ED ad libitum, iii -male controls provided with water, and iV -males provided with ed. every 7 days memory retention in a passive avoidance task, and fresh spatial memory in a Y-maze were checked. the results were analyzed with statistica 10.0. p < 0.05 was considered statistically significant. Results. the consumption of ed did not affect fresh spatial memory or memory retention in the experiment. Males drinking ed gained weight at a faster rate than control males. ed significantly increased the activity of ast in the blood sera of females and, to a lesser degree, of aLt in both males and females drinking ed. ed did not significantly affect the concentration of creatinine or Hba 1c , but significantly increased the concentration of cholesterol in the blood of males from group iV. Conclusions. the prolonged consumption of ed does not affect memory processes, but increases the activity of transaminases and cholesterol concentration in blood sera in the mice model. Key words: memory, cholesterol, energy drink, transaminases.

show abstract

“…While a short-term exposure to such agents can have protective properties in cardiac injury (Lee et al, 2006; Wang et al, 2013), prolonged exposure can lead to increased blood pressure and cardiac rhythm disturbances (Temple et al, 2017) as well as cardiac toxicities in subjects with poor cardiovascular health (Venhuis et al, 2014). Moreover, when combined, these alkaloids may exacerbate each other’s pharmacodynamic effects (Calvert et al, 2015; Kimura et al, 1989). Such additive or synergistic effects may produce unexpected cardiovascular toxicities, as was demonstrated for caffeine and ephedrine (Brown et al, 2012; Dunnick et al, 2007), and caffeine and 1,3-dimethylamylamine (DMAA) (Farney et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments

Skinner

Miousse

Ewing

et al. 2018

Food and Chemical Toxicology

View full text Add to dashboard Cite

Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITEPRO™ New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.

show abstract

A beating heart cell model to predict cardiotoxicity: Effects of the dietary supplement ingredients higenamine, phenylethylamine, ephedrine and caffeine

Cited by 22 publications

References 33 publications

β₂‐Adrenoceptor agonist activity of higenamine

β₂‐Adrenoceptor agonist activity of higenamine

Prolonged consumption of energy drinks does not affect the processes of memory, and increases the activity of transaminases, and cholesterol concentration – animal model study results

Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments

Contact Info

Product

Resources

About

A beating heart cell model to predict cardiotoxicity: Effects of the dietary supplement ingredients higenamine, phenylethylamine, ephedrine and caffeine

Cited by 22 publications

References 33 publications

β2‐Adrenoceptor agonist activity of higenamine

β2‐Adrenoceptor agonist activity of higenamine

Prolonged consumption of energy drinks does not affect the processes of memory, and increases the activity of transaminases, and cholesterol concentration – animal model study results

Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments

Contact Info

Product

Resources

About

β₂‐Adrenoceptor agonist activity of higenamine

β₂‐Adrenoceptor agonist activity of higenamine