Department of Food Science and Technology, Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea; Research & Development Center, Nutra-it Inc., Busan 48513, Republic of Korea.
Department of Food Science and Technology, Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
Biomed Pharmacother. 2024 Oct;179:117410. doi: 10.1016/j.biopha.2024.117410. Epub 2024 Sep 12.
Polyphenols have been well-established to exert sedative-hypnotic effects in psychopharmacology. Lime (Citrus aurantifolia) peel is rich in biologically active polyphenols; however, the effects of lime peel extract on sleep have not yet been demonstrated. A comparison was conducted in mice, between the sleep-promoting effects of a standardized lime peel supplement (SLPS) and a well-known hypnotic drug, zolpidem, and its hypnotic mechanism was investigated using in vivo and in vitro assays. The effects of SLPS on sleep were assessed using a pentobarbital-induced sleep test and sleep architecture analysis based on recording electroencephalograms and electromyograms. Additionally, a GABA receptor binding assay, electrophysiological measurements, and in vivo animal models were used to elucidate the hypnotic mechanism. SLPS (200 and 400 mg/kg) was found to significantly decrease sleep latency and increase the amount of non-rapid eye movement sleep without altering delta activity. The hypnotic effects of SLPS were attributed to its flavonoid-rich ethyl acetate fraction. SLPS had a binding affinity to the GABA-binding site of the GABA receptor and directly activated the GABA receptors. The hypnotic effects and GABA receptor activity of SLPS were completely blocked by bicuculline, a competitive antagonist of the GABA receptor, in both in vitro and in vivo assays. To the best of our knowledge, this study is the first to demonstrate the hypnotic effects of SLPS, which acts via the GABA-binding site of the GABA receptor. Our results suggest that lime peel, a by-product abundantly generated during juice processing, can potentially be used as a novel sedative-hypnotic.
多酚在精神药理学中已被证实具有镇静催眠作用。酸橙（Citrus aurantifolia）果皮富含具有生物活性的多酚；然而，酸橙皮提取物对睡眠的影响尚未得到证实。在小鼠中进行了一项比较研究，比较了标准化酸橙皮补充剂（SLPS）和一种著名的催眠药物唑吡坦的促睡眠作用，并通过体内和体外测定研究了其催眠机制。使用戊巴比妥诱导的睡眠试验和基于记录脑电图和肌电图的睡眠结构分析来评估 SLPS 对睡眠的影响。此外，还使用 GABA 受体结合测定、电生理测量和体内动物模型来阐明催眠机制。结果发现，SLPS（200 和 400mg/kg）可显著缩短睡眠潜伏期并增加非快速眼动睡眠量，而不改变 delta 活动。SLPS 的催眠作用归因于其富含黄酮的乙酸乙酯部分。SLPS 对 GABA 受体的 GABA 结合位点具有结合亲和力，并直接激活 GABA 受体。在体外和体内试验中，GABA 受体的竞争性拮抗剂印防己毒素完全阻断了 SLPS 的催眠作用和 GABA 受体活性。据我们所知，这项研究首次证明了 SLPS 的催眠作用，它通过 GABA 受体的 GABA 结合位点发挥作用。我们的结果表明，酸橙皮是果汁加工过程中产生的大量副产物，可能可用作新型镇静催眠药。
