Department of Biotechnology, Chonnam National University, Gwangju 61186, Korea.
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 61886, Korea.
Int J Mol Sci. 2022 Jan 4;23(1):544. doi: 10.3390/ijms23010544.
Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT through electrophysiological studies at the molecular level using KAE extracted from . This study confirmed the interaction between 5-HT and KAE at the molecular level. KAE inhibited 5-HT receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT receptors of KAE.
单胺类物质 5-羟色胺是一种主要的神经递质，作用于广泛的中枢神经系统和外周神经系统功能，已知在各种过程中发挥作用。最近发现，5-HT 通过与胆碱能途径相互作用参与认知和记忆功能。从 中提取的天然类黄酮山奈酚（KAE）是植物的次生代谢物。最近的研究证实，由于其强大的抗氧化活性，KAE 具有神经保护作用。已经通过体内试验证实 KAE 参与了 5-羟色胺能途径。然而，这些结果需要在分子水平上得到证实，因为尚未阐明 KAE 产生这种作用的确切机制。因此，本研究的目的是通过使用从 中提取的 KAE 在分子水平上进行电生理学研究来证实 KAE 与 5-HT 的相互作用。这项研究在分子水平上证实了 5-HT 和 KAE 之间的相互作用。KAE 以浓度依赖性和电压非依赖性方式抑制 5-HT 受体。定点突变和分子对接研究证实，D177 和 F199 是 KAE 与人 5-HT 受体结合的主要结合位点。
