Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors
Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors
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DOI：
10.3389/fnut.2020.00005
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发表时间：
2020-02-27
影响因子：
5
通讯作者：
Uezono, Yasuhito
中科院分区：
文献类型：
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作者：
Miyano, Kanako;Ohshima, Kaori;Uezono, Yasuhito
癌症恶病质在进展性癌症患者中非常普遍，其特征是食物消耗和体重减少。日本草药 Ninjinyoeito (NYT) 由 12 种草药生药组成，在亚洲国家用于改善癌症恶病质患者常见的厌食和疲劳等多种症状。然而，NYT改善癌症患者厌食或疲劳的作用机制尚不清楚。因此，在本研究中，我们使用 CellKey (TM) 系统进行体外测定，检测 NYT 对几种 G 蛋白偶联受体 (GPCR) 活性的影响，GPCR 激活中枢神经系统中的过度进食信号传导，该系统通过细胞内阻抗 (Delta Z) 的变化来检测 GPCR 的激活。 NYT 以剂量依赖性方式增加表达食欲素 1 受体 (OX1R) 的人胚胎肾 293 (HEK293) 细胞和表达神经肽 Y1 受体 (NPY1R) 的细胞的 Delta Z。相反，NYT 没有显着增加表达生长激素促分泌素受体（GHSR）的 HEK293A 细胞和表达 NPY5R 的细胞的 Delta Z。选择性 OX1R 拮抗剂 SB674042 显着降低 NYT 诱导的 OX1R 表达细胞中 Delta Z 的增加。相反，选择性 NPY1R 拮抗剂 BIBO3340 未能抑制 NPY1R 表达细胞中 NPY 诱导的 Delta Z 增加。此外，我们还制备了不含 NYT 中 12 种草药的改良 NYT，并研究了其对 OX1R 活性的影响。在 12 种改良的 NYT 配方中，不含柑橘温州皮的配方未能激活 OX1R。对12种草药的筛选结果显示，温州柑皮显着激活OX1R，而SB674042显着抑制OX1R。这些发现表明，NYT 和温州柑橘皮可以通过激活下丘脑中表达食欲的 OX1R 神经元来增加食物摄入量。这项研究提供了科学证据来支持 NYT 对患有厌食症的癌症患者的潜力。
Cancer cachexia is highly prevalent in patients with progressive cancer and is characterized by decreased food consumption, and body weight. Japanese herbal medicine Ninjinyoeito (NYT), composed of 12 herbal crude drugs, is prescribed in Asian countries to improve several symptoms such as anorexia and fatigue, which are commonly observed in patients with cancer cachexia. However, the action mechanisms of NYT in improving anorexia or fatigue in patients with cancer are not clear. Therefore, in the present study, we examined the effects of NYT on the activities of several G-protein-coupled receptors (GPCRs), which activate hyperphagia signaling in the central nervous system, using an in vitro assay with the CellKey (TM) system, which detects the activation of GPCRs as a change in intracellular impedance (Delta Z). NYT increased the Delta Z of human embryonic kidney 293 (HEK293) cells expressing orexin 1 receptor (OX1R) and those expressing neuropeptide Y1 receptor (NPY1R) in a dose-dependent manner. On the contrary, NYT did not significantly increase the Delta Z of HEK293A cells expressing growth hormone secretagogue receptor (GHSR) and those expressing NPY5R. The selective OX1R antagonist SB674042 significantly decreased the NYT-induced increase in Delta Z in OX1R-expressing cells. Contrarily, the selective NPY1R antagonist BIBO3340 failed to inhibit the NPY-induced increase in Delta Z in NPY1R-expressing cells. Additionally, we prepared modified NYT excluding each one of the 12 herbal crude drugs in NYT and investigated the effects on the activity of OX1R. Among the 12 modified NYT formulations, the one without citrus unshiu peel failed to activate OX1R. A screening of each of the 12 herbal crude drugs showed that citrus unshiu peel significantly activated OX1R, which was significantly suppressed by SB674042. These finding suggest that NYT and citrus unshiu peel could increase food intake via activation of orexigenic OX1R-expressing neurons in the hypothalamus. This study provides scientific evidence to support the potential of NYT for cancer patients with anorexia.