Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice.

BACKGROUND: A blockage in a blood vessel can cause reduced blood flow to the brain, which eventually leads to the death of surrounding tissue. Several studies have attempted to develop an effective intervention to reverse this process and improve the health status of affected individuals. Due to its indirect effect on cellular functions and metabolism, the hypoxia-inducible factor (HIF-1α) protein has been proposed as a promising transcription factor in the treatment of stroke. PURPOSE: The current study aims to explore the relation between HIF-1 α and thymoquinone (TQ) in the attenuation of ischemic brain damage and the possible mechanism of this relation to reduce cell death. METHODS: For this purpose, dimethyloxallyl glycine (DMOG), 8 mg/kg, Acriflavine (ACF), 1.5 mg/kg, and both combined with TQ (5 mg/kg) were assessed. Male C57 mice were used to establish an ischemic stroke model by using endothelin-1 (ET-1) (400 pmole/µl) intra- cranial injection. The ultrastructure alterations of neuronal soma, axons, and mitochondria after stroke and treatment were well addressed. Besides, the expression levels of VEGF, HIF-1α, Nrf2, and HO-1 were evaluated. Meanwhile, apoptosis and autophagy-related proteins were also investigated. RESULTS: Treatment of ischemic stroke by TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis. Our study revealed that TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke. Further, we demonstrated that both TQ and DMOG effectively attenuate the organelle's damage following ischemic stroke, which was confirmed by the cryogenic transmission electron microscope. The synergistic effect of TQ and DMOG may lead to a chemo-modulation action in the autophagy process after stroke onset and this result is validated by the western blot and rt-qPCR techniques. CONCLUSION: Our finding revealed the potential role of TQ as a HIF-1 α activator to reduce cell death, modulate autophagy and decrease the infarct volume after ischemic stroke onset. The neuroprotective effect of TQ is achieved by decreasing the inflammation and increasing angiogenesis as well as neurogenesis via induction of the HIF-1α-VEGF/Nrf2-HO-1-TrkB-PI3K pathway.

Therapeutic Effect of Curcumin and Methylprednisolone in the Rat Spinal Cord Injury.

In addition to imperiling an individual's daily life, spinal cord injury (SCI), a catastrophic medical damage, can permanently impair an individual's body function. Methylprednisolone (MP), a medically accepted therapeutic drug for SCI, is highly controversial for the lack of consensus on its true therapeutic effect. In recent years, curcumin has served as a potential and novel therapeutic drug in SCI. Our study was intended to investigate the precise effect of MP and curcumin in SCI. We examined the function of MP and curcumin in a SCI model rat, both in vivo and in vitro, and found that there was a momentous improvement in Basso-Beattie-Bresnahan scores in the MP-treated group when compared with Cur-treated group within 14 days. Results obtained from the histological, immunohistochemistry and ultrastructural examinations evidenced the curative effect of MP was better than curcumin before Day 14. Nonetheless, there was a significant variation in the treatment effect between the MP-treated and Cur-treated groups after 14 days. The curcumin's effectiveness was more obvious than MP after 14 days following SCI. As such, we surmise that curcumin has a better therapeutic potential than MP with a prolong treatment time in the wake of SCI. Anat Rec, 301:686-696, 2018. © 2017 Wiley Periodicals, Inc.

Nutrition: Review on the Possible Treatment for Alzheimer's Disease.

Since its discovery some hundred years ago, Alzheimer's disease (AD), a neurodegenerative disease and an eminent cause of most dementia, continues to pose problems for affected families and society, especially in developed countries. With the approved medications by the Food and Drugs Administration in the United States, effectual treatment of AD apropos to the complete eradication of the disease continues to be elusive due to complexities relating to the pathophysiology of the disease. Nutrition has and continues to play a salient role in the survival of living organisms with no exception for human beings. Herein, we report the connection between nutrition and AD with particular attention to vitamins, curcumin, and the Mediterranean diet.

Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells.

As an active compound extracted from the Chinese herb Tripterygium wilfordii, triptolide (TP) was demonstrated to have potent antiinflammatory and immunosuppressive properties in previous studies. Recently, it has been shown that TP prevented the loss of dopaminergic neurons in the substantia nigra of rats in a model of Parkinson's disease, but little is known about the precise neuroprotective mechanism of TP. This study was designed to elucidate whether the neuroprotective effect of TP is partially based on its direct inhibition of inflammatory molecules by investigating the effects of TP on the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) related to the nuclear factor (NF)-κB pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. The activation of related upstream molecules such as NF-κB, P38, extracellular signal-regulated kinase (ERK)1/2, and beta-alanyl-alpha-ketoglutarate transaminase (AKT), in PC12 cells were investigated by real time polymerase chain reaction (PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). Our results showed that TP directly inhibited the expression of both mRNA and protein of COX-2 (p < 0.01), decreased PGE2 production (p < 0.01) in a dose-dependent manner, down-regulated NF-κB activity (p < 0.01), and significantly inhibited the phosphorylation of p38, ERK1/2 (p42/p44) and AKT in PC12 cells after LPS challenge. This suggests that the neuroprotective effects of TP may be partially mediated by direct inhibition of the expression of COX-2, activation of NF-κB, and phosphorylation of p38, ERK1/2 (p42/p44) and AKT proteins of neuronal cells.

N-methyl-D-aspartate receptor and apoptosis in Alzheimer's disease and multiinfarct dementia.

This study investigates the role of excitotoxicity in Alzheimer's disease and in multiinfarct dementia by examining, via immunohistochemical methods, the number of cells that are positive for N-methyl-D-aspartate (NMDA) receptor and the degree of colocalization between NMDA receptor and apoptosis markers such as TUNEL or activated caspase-3 in the frontal cortex of individuals with these two conditions, comparing the results with those from subjects who died of normal aging. We showed an increased number of NMDA receptor-positive cells and an increased number of TUNEL-labeled cells in the frontal cortex of subjects with Alzheimer's disease, especially in the deeper layers of the cortex. However, only about 10% of cells showed colocalization of NMDA receptor with the apoptosis markers studied, suggesting that NMDA-mediated excitotoxicity does not play a major role in neuronal apoptosis in Alzheimer's disease or in multiinfarct dementia.