Key Lab of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, China.
Food Funct. 2021 Jul 5;12(13):5755-5769. doi: 10.1039/d1fo00505g.
l-Theanine is a characteristic amino acid in tea with various effects including antioxidant and anti-inflammatory effects. Previously, most studies had reported that l-theanine regulates the immune function in vivo by inhibiting the expression of the inflammatory factors, but how l-theanine regulates the inflammatory factors' pathway is not known. In this study, we innovatively found the binding target of l-theanine in vivo-cannabinoid receptor 1, and demonstrated that l-theanine regulated the immune function and glutamine metabolism by competitively binding cannabinoid receptor 1. Mechanistically, l-theanine competitively binds cannabinoid receptor 1, leading to inhibition of cannabinoid receptor 1 activity, and regulates glutamine metabolism and immune function in normal and E44813-stressed rats. In normal rats, l-theanine inhibits ERK1/2 phosphorylation through Gβy by antagonizing cannabinoid receptor 1, thus affecting GS expression. From the point of view of immune signaling, after LTA antagonizes the activity of cannabinoid receptor 1, it relieves the inhibition of cannabinoid receptor 1 on COX-2 expression, downregulates Pdcd4 expression and NFκB, and ultimately enhances the expression of the anti-inflammatory factor IL-10. In E44813-stressed rats, l-theanine promotes the nuclear translocation of p-ERK1/2 by inhibiting the activity of cannabinoid receptor 1, and finally acts on GS. At the same time, it decreases the expression of the pro-inflammatory factor TNF-α and increases the expression of the anti-inflammatory factor IL-10 in stressed rats through the COX2-Pdcd4-NFκB-IL10 and TNFα pathways. In summary, these results demonstrate that l-theanine regulates glutamine metabolism and immune function by competitively binding to cannabinoid receptor 1.
茶氨酸是茶叶中的一种特征性氨基酸，具有抗氧化和抗炎等多种作用。先前的大多数研究报告称，茶氨酸通过抑制炎症因子的表达来调节体内的免疫功能，但茶氨酸如何调节炎症因子的途径尚不清楚。在这项研究中，我们创新性地发现了茶氨酸在体内的结合靶标——大麻素受体 1，并证实茶氨酸通过竞争性结合大麻素受体 1来调节免疫功能和谷氨酰胺代谢。从机制上讲，茶氨酸竞争性地结合大麻素受体 1，导致大麻素受体 1 活性的抑制，调节正常和 E44813 应激大鼠的谷氨酰胺代谢和免疫功能。在正常大鼠中，茶氨酸通过 Gβy 拮抗大麻素受体 1 抑制 ERK1/2 磷酸化，从而影响 GS 的表达。从免疫信号的角度来看，LTA 拮抗大麻素受体 1 的活性后，缓解了大麻素受体 1 对 COX-2 表达的抑制作用，下调了 Pdcd4 表达和 NFκB，最终增强了抗炎因子 IL-10 的表达。在 E44813 应激大鼠中，茶氨酸通过抑制大麻素受体 1 的活性促进 p-ERK1/2 的核转位，最终作用于 GS。同时，它通过 COX2-Pdcd4-NFκB-IL10 和 TNFα 途径降低应激大鼠中促炎因子 TNF-α 的表达，增加抗炎因子 IL-10 的表达。综上所述，这些结果表明茶氨酸通过竞争性结合大麻素受体 1 调节谷氨酰胺代谢和免疫功能。
