Ohshima Kaori, Miyano Kanako, Nonaka Miki, Aiso Sayaka, Fukuda Mao, Furuya Saho, Fujii Hideaki, Uezono Yasuhito
Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
Department of Pathology, Immunology, and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Biomolecules. 2025 Apr 5;15(4):533. doi: 10.3390/biom15040533.
Cancer cachexia, often observed in patients with advanced-stage cancer, is characterized by the loss of body weight and appetite. The Japanese herbal medicine Ninjinyoeito (NYT), which is composed of 12 crude herbal components, has been used as a therapeutic in Japan to improve anorexia and fatigue, which are commonly observed in cancer patients with cachexia. We have previously reported that peel (CUP) contained in NYT can enhance food intake by activating the orexin 1 receptor (OX1R). Using the CellKey™ system, which offers detection of OXR activity in intracellular impedance changes, NYT and CUP were found to activate OX1R, which in turn was inhibited by SB-674042, a selective OX1R antagonist. Among the flavonoids contained in CUP, nobiletin and hesperidin, but not naringin, activated OX1R. Furthermore, some monoterpenes contained in CUP, including limonene and linalool, but not terpineol, activated OX1R. In addition, nobiletin and limonene synergistically activated OX1R when added simultaneously. However, neither NYT nor CUP induced OX2R activity. The results collectively suggested that the CUP contained in NYT activates OX1R, but not OX2R, and that flavonoids and monoterpenes in CUP can synergistically activate OX1R. These findings could provide evidence supporting the therapeutic potential of NYT in cancer patients with cachexia.
癌症恶病质常见于晚期癌症患者，其特征为体重减轻和食欲减退。日本草药人参养荣汤（NYT）由12种生药成分组成，在日本已被用作一种治疗方法，以改善恶病质癌症患者中常见的厌食和疲劳症状。我们之前报道过，NYT中含有的陈皮（CUP）可通过激活食欲素1受体（OX1R）来增加食物摄入量。使用能够检测细胞内阻抗变化中OXR活性的CellKey™系统，发现NYT和CUP可激活OX1R，而OX1R又会被选择性OX1R拮抗剂SB - 674042抑制。在CUP所含的黄酮类化合物中，橙皮素和橙皮苷可激活OX1R，而柚皮苷则不能。此外，CUP中含有的一些单萜类化合物，包括柠檬烯和芳樟醇，可激活OX1R，而萜品醇则不能。另外，橙皮素和柠檬烯同时添加时可协同激活OX1R。然而，NYT和CUP均未诱导OX2R活性。这些结果共同表明，NYT中含有的CUP可激活OX1R，但不能激活OX2R，且CUP中的黄酮类化合物和单萜类化合物可协同激活OX1R。这些发现可为NYT在恶病质癌症患者中的治疗潜力提供证据支持。
