Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia.
Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova Street, 1, 117997 Moscow, Russia.
Molecules. 2023 Apr 26;28(9):3734. doi: 10.3390/molecules28093734.
Tetrahydrocurcumin (THC) is a metabolite of curcumin (CUR). It shares many of CUR's beneficial biological activities in addition to being more water-soluble, chemically stable, and bioavailable compared to CUR. However, its mechanisms of action have not been fully elucidated. This paper addresses the preventive role of THC on various brain dysfunctions as well as its effects on brain redox processes, traumatic brain injury, ischemia-reperfusion injury, Alzheimer's disease, and Parkinson's disease in various animal or cell culture models. In addition to its strong antioxidant properties, the effects of THC on the reduction of amyloid β aggregates are also well documented. The therapeutic potential of THC to treat patterns of mitochondrial brain dysmorphic dysfunction is also addressed and thoroughly reviewed, as is evidence from experimental studies about the mechanism of mitochondrial failure during cerebral ischemia/reperfusion injury. THC treatment also results in a dose-dependent decrease in ERK-mediated phosphorylation of GRASP65, which prevents further compartmentalization of the Golgi apparatus. The PI3K/AKT signaling pathway is possibly the most involved mechanism in the anti-apoptotic effect of THC. Overall, studies in various animal models of different brain disorders suggest that THC can be used as a dietary supplement to protect against traumatic brain injury and even improve brain function in Alzheimer's and Parkinson's diseases. We suggest further preclinical studies be conducted to demonstrate the brain-protective, anti-amyloid, and anti-Parkinson effects of THC. Application of the methods used in the currently reviewed studies would be useful and should help define doses and methods of THC administration in different disease conditions.
四氢姜黄素（THC）是姜黄素（CUR）的代谢产物。与 CUR 相比，它除了具有更高的水溶性、化学稳定性和生物利用度外，还具有 CUR 的许多有益的生物学活性。然而，其作用机制尚未完全阐明。本文探讨了 THC 在各种脑功能障碍中的预防作用，以及其对脑氧化还原过程、创伤性脑损伤、缺血再灌注损伤、阿尔茨海默病和帕金森病的影响，这些作用是在各种动物或细胞培养模型中观察到的。除了其强大的抗氧化特性外，THC 对减少淀粉样β聚集的作用也有很好的记录。THC 治疗线粒体脑畸形功能障碍模式的治疗潜力也得到了探讨和彻底审查，以及关于脑缺血/再灌注损伤期间线粒体衰竭机制的实验研究证据。THC 治疗还导致 ERK 介导的 GRASP65 磷酸化的剂量依赖性降低，从而防止高尔基体进一步分隔。PI3K/AKT 信号通路可能是 THC 抗细胞凋亡作用中最相关的机制。总的来说，各种不同脑疾病动物模型的研究表明，THC 可用作膳食补充剂，以预防创伤性脑损伤，甚至改善阿尔茨海默病和帕金森病的大脑功能。我们建议进行进一步的临床前研究，以证明 THC 的脑保护、抗淀粉样蛋白和抗帕金森作用。应用目前综述研究中使用的方法将是有用的，并有助于确定不同疾病状况下 THC 的剂量和给药方法。
