Fukuda Takafumi, Ohya Rena, Kobayashi Keiko, Ano Yasuhisa
Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd., Yokohama, Japan.
Front Neurosci. 2019 Jan 28;13:41. doi: 10.3389/fnins.2019.00041. eCollection 2019.
Recent studies have demonstrated a close association between neural inflammation and development of mental illnesses, such as depression. Clinical trials have reported that treatment with non-steroidal anti-inflammatory drugs is associated with reduced risk of depression. Moreover, nutritional approaches for the prevention and management of depression have garnered significant attention in recent years. We have previously demonstrated that iso-α-acids (IAAs)-the bitter components in beer-suppress hippocampal microglial inflammation, thereby improving cognitive decline. However, effects of hop-derived components other than IAAs on inflammation have not been elucidated. In the present study, we demonstrated that consumption of matured hop bitter acids (MHBAs) generated from α- and β-acids, which show a high similarity with the chemical structure of IAAs, suppress lipopolysaccharide (LPS)-induced cytokine productions in the brain. MHBAs administration increased norepinephrine (NE) secretion and reduced immobility time which represents depression-like behavior in the tail suspension test. Moreover, MHBAs components, including hydroxyallohumulinones and hydroxyalloisohumulones, reduced LPS-induced immobility time. Although further researches are needed to clarify the underlying mechanisms, these findings suggest that MHBAs reduce inflammatory cytokine productions and increase NE secretion, thereby improving depression-like behavior. Similarly, inoculation with LPS induced loss of dendritic spines, which was improved upon MHBAs administration. Additionally, vagotomized mice showed attenuated improvement of immobility time, increase in NE level, and improvement of dendrite spine density following MHBAs administration. Therefore, MHBAs activate the vagus nerve and suppress neuronal damage and depression-like behavior induced by inflammation.
最近的研究表明，神经炎症与抑郁症等精神疾病的发展密切相关。临床试验报告称，使用非甾体抗炎药进行治疗与降低抑郁症风险有关。此外，近年来，用于预防和治疗抑郁症的营养方法受到了广泛关注。我们之前已经证明，啤酒中的苦味成分异α-酸（IAAs）可抑制海马小胶质细胞炎症，从而改善认知能力下降。然而，除IAAs之外，啤酒花衍生成分对炎症的影响尚未阐明。在本研究中，我们证明，由α-酸和β-酸生成的成熟啤酒花苦味酸（MHBAs），其化学结构与IAAs高度相似，可抑制脂多糖（LPS）诱导的大脑细胞因子生成。给予MHBAs可增加去甲肾上腺素（NE）分泌，并减少不动时间，不动时间代表尾悬测试中的抑郁样行为。此外，包括羟基别葎草酮和羟基异别葎草酮在内的MHBAs成分可减少LPS诱导的不动时间。尽管需要进一步研究以阐明潜在机制，但这些发现表明，MHBAs可减少炎性细胞因子生成并增加NE分泌，从而改善抑郁样行为。同样，接种LPS会导致树突棘丢失，给予MHBAs后这种情况会得到改善。此外，迷走神经切断的小鼠在给予MHBAs后，不动时间的改善减弱，NE水平升高，树突棘密度增加。因此，MHBAs可激活迷走神经，并抑制炎症诱导的神经元损伤和抑郁样行为。
