Romaine Lettuce/Skullcap Mixture Improves Sleep Behavior in Vertebrate Models

Abstract

The aim of this study is to investigate the effects of romaine lettuce leaves extract (RE), skullcap root extract (SE) and their mixture on sleep behaviors in vertebrate models. HPLC analysis showed that RE contains lactucopicrin (0.02±0.01 mg/g extract), chlorogenic acid (4.05±0.03 mg/g extract), caffeic acid (2.38±0.03 mg/g extract), and chicoric acid (7.02±0.32 mg/g extract) as main phenolic compounds, while SE includes baicalin (99.4±0.5 mg/g extract), baicalein (8.28±0.21 mg/g extract), and wogonin (3.09±0.32 mg/g extract). The mixture of RE (100 mg/g extract) and SE (40 mg/g extract) increased total sleep time by 50.9% compared with the control in pentobarbital-induced sleep model. In electroencephalography (EEG) analysis, RE/SE mixture significantly increased Non-Rapid Eye Movement (NREM), in which delta wave was enhanced by around 40% compared with normal control, leading to the increase of sleep time. In caffeine-induced wake model, RE/SE mixture greatly decreased (53%) caffeine-induced wake time, showing a similar level to normal control. In addition, caffeine-induced decreased of NREM and delta wave effectively increased with RE/SE mixture; NREM and delta wave increased by 85% and 108%, respectively. Furthermore, RE/SE mixture was shown to bind to a gamma-aminobutyric acid type A (GABA)-benzodiazepine (BZD) receptor stronger than RE or SE single extract. Taken together, RE/SE mixture effectively improved sleep behavior with the increase of NREM via GABA-BZD receptor binding. RE/SE mixture can be used as an herbal agent for sleep disorders.

Effectiveness of the Sleep Enhancement by Green Romaine Lettuce (<i>Lactuca sativa</i>) in a Rodent Model

“…Research has indicated that many herbal extracts are ligands of the GABA A receptors in the central nervous system (CNS) and bind to the benzodiazepine binding site, resulting in sleep modulating actions. 15,29) Flumazenil, known as an antagonist of benzodiazepine, is a water-soluble imidazobenzodiazephine that acts antagonistically with benzodiazepine in the gamma-amino-butyric acid type A (GABA A ) receptors in the CNS. 30) Therefore, by treating with the 3 H-labeled flumazenil, we investigated whether GABA A -BDZ receptor response is involved in a GRE-mediated sleep promoting effects, and as a result demonstrate that GRE effectively binds to GABA A receptors to promote sleep time (Fig.…”

“…Cerebral cortical membranes of male SD rats were prepared in cold Tris-HCl buffer (30 mM, pH 7.4) following a previous report. 15) For membrane-binding experiments, 33. with ice-cold buffer. Radioligands bound to the membrane were counted by a Hidex 300SL counter (Hidex, Finland).…”

“…Several herbs have been reported to have a sedative or sleep-promoting capacity: valerian (Valeriana officinalis), hops (Humulus lupulus), German chamomile (Matricaria recutita), passionflower (Passiflora incarnata), and Polygonatum sibiricum. [12][13][14][15] Our previous study revealed that the mixture of Lactuca sativa and skullcap extracts played an active role in sleep promotion. 16) In this study, we focus on the sleep-promoting effect of romaine lettuce and its mechanisms by investigating antagonistic behaviors on sleep-related receptors.…”

Bioactive compounds in lettuce: Highlighting the benefits to human health and impacts of preharvest and postharvest practices

“…Recently, lettuce seed extracts were reported to exert anti‐inflammatory effects in an animal model, the carrageenan‐induced hind paw edema assay (Ismail & Mirza, 2015; Sayyah et al., 2004). Moreover, a mixture of lettuce seeds and skullcap root improved sleep behavior in vertebrate models and could potentially be used to treat sleep disorders (Hong et al., 2018).…”

Wogonin preventive impact on hippocampal neurodegeneration, inflammation and cognitive defects in temporal lobe epilepsy

“…Wogonin, the primary chemical constituents of this herb, is flavone derivatives containing a phenylbenzopyrone nucleus. As part of the screening of conventional herbal extracts for benzodiazepine-like activity, it was reported that several flavonoids isolated from this herb exhibited moderate affinities for the GABA (γ-aminobutyric acid) A receptor ( Afzal et al, 2012 , Gupta et al, 2017 , Hong et al, 2018 ). There is increasing evidence that wogonin could afford neuroprotection against oxidative stress-induced brain insult.…”