Lee Kihwan, Choi Young In, Im Sang-Taek, Hwang Sung-Min, Lee Han-Kyu, Im Jay-Zoon, Kim Yong Ho, Jung Sung Jun, Park Chul-Kyu
Tooth-Periodontium Complex Medical Research Center (MRC), Department of Physiology, School of Dentistry, Seoul National University, Seoul, South Korea.
Department of Physiology, College of Medicine, Hanyang University, Seoul, South Korea.
Front Mol Neurosci. 2021 Jun 18;14:643483. doi: 10.3389/fnmol.2021.643483. eCollection 2021.
Riboflavin, also known as vitamin B, isfound in foods and is used as a dietary supplement. Its deficiency (also called ariboflavinosis) results in some skin lesions and inflammations, such as stomatitis, cheilosis, oily scaly skin rashes, and itchy, watery eyes. Various therapeutic effects of riboflavin, such as anticancer, antioxidant, anti-inflammatory, and anti-nociceptive effects, are well known. Although some studies have identified the clinical effect of riboflavin on skin problems, including itch and inflammation, its underlying mechanism of action remains unknown. In this study, we investigated the molecular mechanism of the effects of riboflavin on histamine-dependent itch based on behavioral tests and electrophysiological experiments. Riboflavin significantly reduced histamine-induced scratching behaviors in mice and histamine-induced discharges in single-nerve fiber recordings, while it did not alter motor function in the rotarod test. In cultured dorsal root ganglion (DRG) neurons, riboflavin showed a dose-dependent inhibitory effect on the histamine- and capsaicin-induced inward current. Further tests wereconducted to determine whether two endogenous metabolites of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have similar effects to those of riboflavin. Here, FMN, but not FAD, significantly inhibited capsaicin-induced currents and itching responses caused by histamine. In addition, in transient receptor potential vanilloid 1 (TRPV1)-transfected HEK293 cells, both riboflavin and FMN blocked capsaicin-induced currents, whereas FAD did not. These results revealed that riboflavin inhibits histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how riboflavin exerts antipruritic effects and suggests that it might be a useful drug for the treatment of histamine-dependent itch.
核黄素，也被称为维生素B，存在于食物中并用作膳食补充剂。其缺乏症（也称为核黄素缺乏病）会导致一些皮肤病变和炎症，如口腔炎、唇炎、油性鳞屑性皮炎以及眼睛瘙痒、流泪。核黄素的各种治疗作用，如抗癌、抗氧化、抗炎和抗伤害感受作用，是众所周知的。尽管一些研究已经确定了核黄素对包括瘙痒和炎症在内的皮肤问题的临床效果，但其潜在的作用机制仍然未知。在本研究中，我们基于行为测试和电生理实验，研究了核黄素对组胺依赖性瘙痒作用的分子机制。核黄素显著减少了小鼠中组胺诱导的抓挠行为以及单神经纤维记录中组胺诱导的放电，而在转棒试验中它并未改变运动功能。在培养的背根神经节（DRG）神经元中，核黄素对组胺和辣椒素诱导的内向电流表现出剂量依赖性抑制作用。进一步的试验是为了确定核黄素的两种内源性代谢产物，黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD），是否具有与核黄素类似的作用。在此，FMN而非FAD显著抑制了辣椒素诱导的电流以及组胺引起的瘙痒反应。此外，在瞬时受体电位香草酸亚型1（TRPV1）转染的HEK293细胞中，核黄素和FMN均阻断了辣椒素诱导的电流，而FAD则没有。这些结果表明，核黄素通过调节TRPV1活性来抑制组胺依赖性瘙痒。本研究将有助于理解核黄素如何发挥止痒作用，并表明它可能是治疗组胺依赖性瘙痒的一种有用药物。
