Seo Yoonhee, Tak Hyunji, Park Dohee, Song Hyejin, Choe Sooyoung, Park Chaehyeong, Park Byeongdeog
Efficacy Evaluation Center, Dt & CRO, Yongin 17042, Korea.
Pomona College, 333 N College Way, Claremont, CA 91711, USA.
Life (Basel). 2022 Sep 30;12(10):1529. doi: 10.3390/life12101529.
GPR119 is a novel cannabinoid receptor that is primarily expressed in the pancreas and gastrointestinal tract and has beneficial effects on glucose homeostasis exerted through the stimulation of GLP-1 secretion, as demonstrated in the rodent brain. GLP-1 also has important anti-inflammatory effects in chronic inflammatory diseases, including type 1 and 2 diabetes, asthma, psoriasis, and neurodegenerative disorders. Recently, there has been increasing interest in the effect of the gut microbiota on both the gut and the brain. However, few studies have examined how gut microbes affect brain health through the endocannabinoid system. NEUROMIDE is a compound that shares a bioidentical structure with certain commensal bacterial metabolites, acting as a CB1 and GPR119 agonist. In an in vitro system exposed to reactive oxygen species (ROS), pretreatment with NEUROMIDE resulted in a significant increase in cell viability. The ROS-exposed system also showed decreased acetylcholine and an increase in inflammatory cytokines such as IL-1β, changes that were counteracted in a dose-dependent manner in the NEUROMIDE treatment groups. To measure the effectiveness of NEUROMIDE in an in vivo system, we used scopolamine-treated mice as a neurodegenerative disease model and performed a series of passive avoidance tests to observe and quantify the cognitive impairment of the mice. Mice in the NEUROMIDE treatment group had increased latency time, thus indicating an improvement in their cognitive function. Furthermore, the NEUROMIDE treatment groups showed dose-dependent increases in acetylcholine along with decreases in TNF-α and IL-1β. These experiments demonstrate that NEUROMIDE can potentially be used for neuroprotection and the improvement of cognitive ability.
GPR119是一种新型大麻素受体，主要在胰腺和胃肠道表达，对葡萄糖稳态具有有益作用，通过刺激胰高血糖素样肽-1（GLP-1）分泌发挥作用，如在啮齿动物脑中所证实的那样。GLP-1在慢性炎症性疾病中也具有重要的抗炎作用，包括1型和2型糖尿病、哮喘、银屑病和神经退行性疾病。最近，人们对肠道微生物群对肠道和大脑的影响越来越感兴趣。然而，很少有研究探讨肠道微生物如何通过内源性大麻素系统影响大脑健康。NEUROMIDE是一种与某些共生细菌代谢产物具有相同生物结构的化合物，作为CB1和GPR119激动剂。在暴露于活性氧（ROS）的体外系统中，用NEUROMIDE预处理导致细胞活力显著增加。暴露于ROS的系统还显示乙酰胆碱减少，炎症细胞因子如IL-1β增加，这些变化在NEUROMIDE治疗组中以剂量依赖的方式得到抵消。为了测量NEUROMIDE在体内系统中的有效性，我们使用东莨菪碱处理的小鼠作为神经退行性疾病模型，并进行了一系列被动回避试验，以观察和量化小鼠的认知障碍。NEUROMIDE治疗组的小鼠潜伏期延长，从而表明其认知功能有所改善。此外，NEUROMIDE治疗组显示乙酰胆碱剂量依赖性增加，同时TNF-α和IL-1β减少。这些实验表明，NEUROMIDE可能具有神经保护作用并能改善认知能力。
