Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI

Abstract

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

“…Accumulating evidence has demonstrated that small molecule metabolites and alterations in their metabolic pathways play an important role in ischemic stroke development [ 62 ]. Intraperitoneal injections of NBP (20 mg·kg −1 body mass, daily) for 7 d significantly improved ATP metabolism, antioxidant levels, and the sodium-potassium ion balance in a rat model of permanent MCAO (pMCAO) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) imaging [ 63 ].…”

Predictive Value of Gray-Matter–White-Matter Ratio on Brain Computed Tomography for Delayed Encephalopathy after Acute Carbon Monoxide Poisoning: A Retrospective Cohort Study

“…The reduction in oxygen-carrying capacity due to elevated COHB levels is exacerbated by impaired perfusion, which results from hypoxic cardiac dysfunctions, and triggers ischemia [ 25 ]. The brain, as the main energy-consuming organ [ 26 ], is highly sensitive to hypoxia and ischemia. Neuronal death and demyelination are common abnormalities found in patients with CO poisoning [ 27 ].…”

Naringin attenuates cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress

“…Approximately 1 million CI/R injury-caused deaths and 5 million CI/R injury patients who become appear disability or paralysis has worldwide distribution [ 1 ]. With high incidence, disability, and mortality, CI/R injury seriously threatens health and life of patients and also leads to a marked reduction in their quality of life [ 2 ]. It has been shown that oxidative stress damage indirectly induced by CI/R injury leads to physiological dysfunction of the endoplasmic reticulum, known as endoplasmic reticulum stress (ERS).…”