Curcumae Radix Decreases Neurodegenerative Markers through Glycolysis Decrease and TCA Cycle Activation

Abstract

Neurodegenerative diseases (ND) are being increasingly studied owing to the increasing proportion of the aging population. Several potential compounds are examined to prevent neurodegenerative diseases, including Curcumae radix, which is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied, and its influence on energy metabolism in ND is unclear. We focused on the relationship between ND and energy metabolism using Curcumae radix extract (CRE) in cells and animal models. We monitored neurodegenerative markers and metabolic indicators using Western blotting and qRT-PCR and then assessed cellular glycolysis and metabolic flux assays. The levels of Alzheimer’s disease-related markers in mouse brains were reduced after treatment with the CRE. We confirmed that neurodegenerative markers decreased in the cerebrum and brain tumor cells following low endoplasmic reticulum (ER) stress markers. Furthermore, glycolysis related genes and the extracellular acidification rate decreased after treatment with the CRE. Interestingly, we found that the CRE exposed mouse brain and cells had increased mitochondrial Tricarboxylic acid (TCA) cycle and Oxidative phosphorylation (OXPHOS) related genes in the CRE group. Curcumae radix may act as a metabolic modulator of brain health and help treat and prevent ND involving mitochondrial dysfunction.

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

“…In this study, TCA cycle‐related metabolites, including citrate, isocitrate, and succinate, were significantly altered in children with poor outcomes, suggesting that dysregulation of aerobic energy metabolism is associated with the prognosis of SE. Dysregulation of the TCA cycle has been associated with several diseases related to oxidative stress, such as atrial fibrillation, heart failure, 32 diabetic kidney disease, 33 and neurodegenerative disease 34 . In an in vitro model of amyotrophic lateral sclerosis, oxidative stress disrupted the concentrations of succinate and malate in motor neurons, indicating an impaired TCA cycle in disease physiology 35 .…”

“…Dysregulation of the TCA cycle has been associated with several diseases related to oxidative stress, such as atrial fibrillation, heart failure, 32 diabetic kidney disease, 33 and neurodegenerative disease. 34 In an in vitro model of amyotrophic lateral sclerosis, oxidative stress disrupted the concentrations of succinate and malate in motor neurons, indicating an impaired TCA cycle in disease physiology. 35 TCA cycle intermediates, including citrate and α-ketoglutarate, show significantly higher concentrations in Alzheimer's disease.…”

Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism

“…We previously reported that curcumin induced a redox imbalance by increasing ROS production and activation of the mitochondrial pathway of apoptosis thus sensitising ACHN cells to TRAIL induced death [16]. Similarly, other studies found that curcumin activated the TCA cycle [91,92] while reducing glucose consumption and lactate production. Curcumin can also induce reprogramming of tumour metabolism via targeting the ATP machinery of mitochondria, leading to the activation of apoptosis due to energy shutdown [93].…”

Futoquinol improves Aβ25–35‐induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota

“…Wang et al, 2023). There is increasing evidence that the changes in aerobic glycolysis are closely related to AD pathogenesis (Goyal et al, 2023;Jo et al, 2022). In the process of inflammatory activation, cell metabolism is reprogrammed from oxidative phosphorylation to aerobic glycolysis, thus aggravating the occurrence of AD (Baik et al, 2019).…”

“…Impaired glucose metabolism in the brain is an important physiological feature of AD, closely related to its development and cognitive dysfunction (Preziuso et al, 2023; Z. J. Wang et al, 2023). There is increasing evidence that the changes in aerobic glycolysis are closely related to AD pathogenesis (Goyal et al, 2023; Jo et al, 2022). In the process of inflammatory activation, cell metabolism is reprogrammed from oxidative phosphorylation to aerobic glycolysis, thus aggravating the occurrence of AD (Baik et al, 2019).…”