Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart.
Ontology highlight
ABSTRACT:
SUBMITTER: El-Far AH
PROVIDER: S-EPMC8268720 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Aging represents the accumulation of progressive changes in a human being over time and can cover physical, psychological, and social changes. It is an oxidative stress-associated process that progresses with age. The antioxidant activity of either eugenol (EU) or carvacrol (CAR) for aging in rats induced by D-gal for 42 days was investigated in the current study using 10 and 20 mg of EU/kg/day/orally, while CAR was supplemented by 40 and 80 mg /kg/day/orally. Biochemical, mRNA expression, and histopathological assessments of brain samples evaluated the oxidative alterations induced by D-gal and the protective role of EU and CAR. Results showed that D-gal was causing oxidative alternation of the brain that was recognized via upregulation of p53 and p21 mRNA expression levels, as aging markers and Bax mRNA expression level, as an apoptotic marker. Also, the results observed alterations in the levels of biochemical markers as creatine phosphokinase (CPK) and triacylglycerol (TAG), besides, enhancement of brain antioxidant capacity. Finally, these results compared with the groups treated with EU and CAR to observe that the EU and CAR potentially attenuate these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that EU and CAR supplementations are considered promising natural protective compounds that could delay aging and maintain health.
| S-EPMC9232455 | biostudies-literature
Project description:Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-?B, IL-1?, and TNF-?), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.
| S-EPMC7352460 | biostudies-literature
Project description:Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age.
| S-EPMC9914014 | biostudies-literature
Project description:Mood disorders such as anxiety and depression are heterogeneous disorders with many sufferers unresponsive to current pharmacological treatments. Individual differences in temperament represent one factor that may underlie symptom heterogeneity, so understanding its biological underpinnings can help pave the way to personalized therapies and improved patient outcomes. The present study uses a rodent model of temperamental differences to examine whether individual differences in emotional behavior phenotypes correspond to altered limbic brain cellular metabolism, an indicator of neuronal activity. The model uses two selectively bred rat lines - high novelty responder rats (HRs) that show highly exploratory behavior in a novel environment, active coping style and resilience to chronic mild stress compared to low novelty responder rats (LRs), which are inhibited in novel environments, display passive coping style, and are susceptible to chronic stress. Utilizing transcriptome data from a prior study in adult HR/LR rats, we first show that a preponderance of genes differing in the HR vs. LR hippocampus and amygdala are involved in cellular metabolism. This led us to then ask if oxygen consumption was altered in isolated mitochondria of the hippocampus and amygdala of HR/LR rats; here we found increased oxygen consumption reserve capacity in LR amygdala. Our last experiment examined activity of cytochrome c oxidase (COX), an enzyme responsible for ATP production and correlate of metabolic activity, in several brain regions of HR/LR rats. We found that LRs displayed higher COX activity in the dentate gyrus, prefrontal cortex, and dorsal raphe compared to HRs, with no significant HR/LR difference in nuclei of the amygdala. Correlational analyses of COX activity across brain regions suggested divergent connectivity between the prefrontal cortex, amygdala, hippocampus, and dorsal raphe of HR vs. LR rats. Together these studies point to altered cellular metabolism in the limbic brain of LR/HR animals, which may reflect altered neural circuitry that drives their divergent behavioral profiles.
| S-EPMC6708503 | biostudies-literature
Project description:Aging, a critical risk factor of several diseases, including neurodegenerative disorders, affects an ever-growing number of people. Cacao supplementation has been suggested to improve age-related neuronal deficits. Therefore, this study investigated the protective effects of raw cacao powder on oxidative stress-induced aging. Male Sprague-Dawley rats were divided into 4 groups: Control (C), D-galactose-induced aging (G), D-galactose injection with 10% (LC), and 16% (HC) cacao powder mixed diet. D-galactose (300 mg/3 mL/kg) was intraperitoneally injected into all but the control group for 12 weeks. Cacao supplemented diets were provided for 8 weeks. The levels of serum Malondialdehyde (MDA), Advanced Glycation End-products (AGEs), brain and liver MDA, the indicators of the D-galactose induced oxidative stress were significantly decreased in LC and HC but increased in G. The Acetylcholinesterase (AChE) activity of brain showed that the cholinergic impairment was significantly lower in LC, and HC than G. Furthermore, the expression levels of catalase (CAT), phospho-Akt/Akt, and procaspase-3 were significantly increased in LC and HC. In conclusion, cacao consumption attenuated the effects of oxidative stress, cholinergic impairment and apoptosis, indicating its potential in future clinical studies.
| S-EPMC8429651 | biostudies-literature
Project description:Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine- and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal diet, and mice injected with D-galactose and fed an SGD diet. The results showed that D-galactose resulted in oxidative and inflammatory responses, while serine deficiency alone showed no such effects. However, serine deficiency significantly exacerbated oxidative stress and inflammation in D-galactose-treated mice. The composition of fecal microbiota was affected by D-galactose injection, which was characterized by decreased microbiota diversity and downregulated ratio of Firmicutes/Bacteroidetes, as well as decreased proportion of Clostridium XIVa. Furthermore, serine deficiency exacerbated these changes. Additionally, serine deficiency in combination with D-galactose injection significantly decreased fecal butyric acid content and gene expression of short-chain fatty acid transporters (Slc16a3 and Slc16a7) and receptor (Gpr109a) in the brain. Finally, serine deficiency exacerbated the decrease of expression of phosphorylated AMPK and the increase of expression of phosphorylated NF?B p65, which were caused by D-galactose injection. In conclusion, our results suggested that serine deficiency exacerbated inflammation and oxidative stress in D-galactose-induced aging mice. The involved mechanisms might be partially attributed to the changes in the microbiota-gut-brain axis affected by serine deficiency.
| S-EPMC7071807 | biostudies-literature
Project description:The aim of the present study was to determine the effects of curcumin on antioxidants using a rat model of type 1 diabetes. Seven‑week‑old male Sprague‑Dawley rats were injected with Streptozotocin (STZ) intraperitoneally to induce this model, and then treated with 1.0% curcumin (weight ratio) mixed in their diet for 21 days. The present study included three groups: Control group (NC), diabetic rat model group (DC) and a curcumin treated group (Diab‑Cur). The results demonstrated that curcumin treatment markedly decreased the blood glucose levels, plasma malondialdehyde concentration and plasma activity of glutathione peroxidase (GSH‑Px) and catalase (CAT); however, it increased the plasma superoxide dismutase (SOD) and insulin levels. Curcumin treatment increased the expression of the CAT, GSH‑Px, HO‑1 and norvegicus NAD(P)H quinone dehydrogenase 1, and decreased the SOD1 expression, which, led to a diminished oxidative stress status. In addition, curcumin treatment significantly increased the protein expression of Keap1 in the Diab‑Cur group when compared with the DC group, decreased cytosolic concentrations of Nrf2 while increasing nuclear accumulation of Nrf2. The results provide evidence that oxidative stress in the STZ‑induced diabetic rat model may be attenuated by curcumin via the activation of the Keap1‑Nrf2‑ARE signaling pathway, as evidenced by a decrease in the blood glucose concentration and an increase in the transcription of several antioxidant genes.
| S-EPMC5780069 | biostudies-literature
Project description:Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 ?M concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence potential. Thus, both thymoquinone and curcumin appeared to be promising anthelmintic compounds for further investigations.
| S-EPMC5289557 | biostudies-literature
Project description:Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p?<?0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic ?-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p?<?0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.
| S-EPMC7561705 | biostudies-literature
Project description:Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA.
| S-EPMC9242463 | biostudies-literature