Evodiamine Reduces Caffeine-Induced Sleep Disturbances and Excitation in Mice

Abstract

Worldwide, caffeine is among the most commonly used stimulatory substances. Unfortunately, significant caffeine consumption is associated with several adverse effects, ranging from sleep disturbances (including insomnia) to cardiovascular problems. This study investigates whether treatment with the Evodia rutaecarpa aqueous extract (ERAE) from berries and its major molecular component, evodiamine, can reduce the adverse caffeine-induced sleep-related and excitation effects. We combined measurements from the pentobarbital-induced sleep test, the open field test, and the locomotor activity test in mice that had been dosed with caffeine. We found that ERAE and evodiamine administration reduced the degree of caffeine-induced sleep disruption during the sleep test. Additionally, we found that evodiamine significantly inhibits caffeine-induced excitation during the open field test, as well as decreasing hyperlocomotion in the locomotor activity test. Additional in vitro experiments showed that caffeine administration decreased the expression of γ-aminobutyric acid (GABA)A receptor subunits in the mouse hypothalamus. However, evodiamine treatment significantly reversed this expression reduction. Taken together, our results demonstrate that ERAE and its major compound, evodiamine, provide an excellent candidate for the treatment or prevention of caffeine-induced sleep disturbances and excitatory states, and that the mechanism of these beneficial effects acts, at least in part, through the GABAA-ergic system.

Hypnotic Effects of Lactobacillus fermentum PS150TM on Pentobarbital-Induced Sleep in Mice

“…The orally administrated diphenhydramine hydrochloride (DIPH, 20 mg/mL, Sigma), an antihistamine with sleep aid effects, was used in the drug control group. Caffeine (15 mg/mL, Sigma) was intraperitoneally injected 30 min before the pentobarbital-induced sleep test to induce sleep disturbance in mice [21,22].…”

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

“…Unphosphorylated NF-κB fails to regulate the expression of inflammatory mediators above [96]. Additionally, Ko and his team compared Evo with L-NAME (an NOS inhibitor) and found that Evo can significantly Isoquinoline alkaloid BBR Water decoction Inhibits AChE, BChE activity and β-secretase [75] Indole alkaloids Evo Hot water reflux extraction Inhibits AChE [76] Terpenoids alkaloids Voacangine 90% ethanol reflux extraction Inhibits AChE [77] Steroidal alkaloids Conessine 90% ethanol extraction Inhibits AChE and the activation of NF-κB [78] Corynoxine 70% ethanol reflux extraction Reduce Ca2+ overload and tau protein hyperphosphorylation [79] Other alkaloids Caffeine Ethanol extraction Reduce caspase-3 and β-secretase [80] Isorhynchophylline 70% ethanol reflux extraction Down-regulate GSK-3β activity and activation of PI3K/Akt signaling pathway [79,81,82] reduce NO production and iNOS protein expression in mouse microglia, likely due to its regulation of interferon IFN-γ-related events [83]. To sum up, Evo can alleviate the pathological symptoms of AD in several ways.…”

Caffeine versus antioxidant combination (Antox) and their role in modifying cadmium‐induced testicular injury in adult male albino rats

“…However, only exceedingly high caffeine blood concentrations, up to 150 mg/kg (equivalent to 50 caffeine pills or 1 tablespoon of powdered caffeine), are fatal and could lead to electrolyte imbalance, cardiac and circulatory deficits and death (Beauchamp et al, 2017). Caffeine is a central nervous system excitant (Ko et al, 2018) that is used in treatment of respiratory diseases and apnoea-related symptoms in newborns (Dobson & Hunt, 2013).…”