Effect of spermidine on long non-coding RNAs MALAT1 in a rotenone induced-rat model of Parkinson's disease.

BACKGROUND: Spermidine is a natural biologically active substance that has widespread influences on the body. OBJECTIVE: This study aims to enhance our understanding of the potential effect of spermidine on long non-coding RNA MALAT1 and explore the underlying mechanism in the rotenone-induced rat model of Parkinson's disease. METHODS: Rats were sacrificed after locomotor behavioral testing. Striatal tissues were used to assess the expression of MALAT1, oxidative stress markers, and autophagy markers. RESULTS: Our study found that treatment with spermidine for 2 weeks during the induction of the model significantly improved behavioral assessment, dopamine levels, and attenuated the histopathological changes that occurred in PD in comparison to the non-treated group. CONCLUSION: Our preliminary study supports the protective effect of spermidine on the activation of autophagy and its antioxidant properties. Part of the antioxidant activity is due to the inhibition of MALAT1. However, MALAT1 does not correlate with the spermidine-induced autophagy pathway.

Reversal Effects of Royal Jelly and Propolis Against Cadmium-Induced Hepatorenal Toxicity in Rats.

Heavy metal toxicity is an exponentially growing health problem. In this study, we aimed to assess the protective properties of propolis and royal jelly against cadmium adverse effects. Thirty-two adult male rats were included in our study; kidney and liver functions, histopathological changes, and the level of oxidative stress were evaluated in rats exposed to a daily dose of 4.5 mg cadmium per kilogram of body weight for 1 month and those cotreated simultaneously with either propolis (50 mg/kg/day) or royal jelly (200 mg/kg/day) with cadmium compared to control animals. Cadmium-mediated hepatorenal toxicity was manifested as per the increased oxidative stress, function deterioration, and characteristic histopathological aberrations. The supplementation of royal jelly or propolis restores most of the affected parameters to a level similar to the control group. However, the parameters describing the grade of DNA damage and the interleukin-1ß expression in the liver, as well as the levels of malondialdehyde and metallothionein, were slightly elevated compared to controls, despite the regular use of royal jelly or propolis. It is worth noting that better results were found in the case of royal jelly compared to propolis administration. Most likely, the ability of both products to chelate cadmium and contribute in reducing oxidative stress is of great importance. However, further investigations are needed to complement the knowledge about the expected nutritional and medicinal values.

Sericin and melatonin mitigate diethylnitrosamine-instigated testicular impairment in mice: Implications of oxidative stress, spermatogenesis, steroidogenesis, and modulation of Nrf2/WT1/SF-1 signaling pathways.

AIMS: This study aimed to investigate the therapeutic influence of combination therapy with sericin and melatonin on attenuating diethylnitrosamine (DEN)-instigated testicular dysfunction in mice and defining the molecular mechanisms involved in orchestrating redox signaling pathways and restoring spermatogenesis and steroidogenesis. MATERIALS AND METHODS: Different groups of male Swiss albino mice were established and injected with respective drugs intraperitoneally. Semen analysis, hormonal assays, and oxidative stress biomarkers were evaluated. Additionally, melatonin and its receptors, WT1, SF-1, vimentin, Nrf2, and ANXA1 expressions were assessed. Histopathological and ultrastructural features of the testes were investigated by semithin, SEM, and TEM analyses. KEY FINDINGS: Exposure to DEN exhibited pathophysiological consequences, including a remarkable increase in lipid peroxidation associated with substantial diminutions in SOD, CAT, GPx, GSH, GSH:GSSG, and GST. Furthermore, it disrupted spermatozoa integrity, testosterone, FSH, LH, melatonin, and its receptors (MT1 and MT2) levels, implying spermatogenesis dysfunction. By contrast, treatment with sericin and melatonin significantly restored these disturbances. Interestingly, the combination therapy of sericin and melatonin noticeably augmented the Nrf2, WT1, and SF-1 expressions compared to DEN-treated mice, deciphering the amelioration perceived in antioxidant defense and spermatogenesis inside cells. Furthermore, immunohistochemical detection of ANXA1 alongside histopathological and ultrastructural analyses revealed evident maintenance of testicular structures without discernible inflammation or anomalies in mice administered with sericin and melatonin compared to the DEN-treated group. SIGNIFICANCE: Our findings highlighted that treatment with sericin and melatonin alleviated the testicular tissues in mice from oxidative stress and dysregulated spermatogenesis and steroidogenesis engendered by DEN.

HR LC-MS/MS metabolomic profiling of Yucca aloifolia fruit and the potential neuroprotective effect on rotenone-induced Parkinson's disease in rats.

Yucca aloifolia L. fruit (Yucca or Spanish bayonet, family Asparagaceae) is recognized for its purplish red color reflecting its anthocyanin content, which has a powerful antioxidant activity. This study aimed to investigate yucca (YA) fruit extract's protective effect on Parkinson's disease (PD). In vitro study, the anti-inflammatory activity of yucca fruit extracts was explored by measuring tumor necrosis factor receptor 2 (TNF-R2) and nuclear factor kappa B (NF-KB) to choose the most effective extract. Afterward, a detailed in vivo investigation of the protective effect of the most active extract on rotenone-induced PD was performed on male albino Wister rats. First, the safety of the extract in two different doses (50 and 100 mg/kg in 0.9% saline orally) was confirmed by a toxicological study. The rats were divided into four groups: 1) normal control (NC); 2) rotenone group; and third and fourth groups received 50 and 100 mg/kg yucca extract, respectively. The neurobehavioral and locomotor activities of the rats were tested by rotarod, open field, and forced swim tests. Striatal dopamine, renal and liver functions, and oxidative stress markers were assessed. Western blot analysis of brain tissue samples was performed for p-AMPK, Wnt3a, and ß-catenin. Histopathological examination of striatal tissue samples was performed by light and electron microscopy (EM). The metabolites of the active extract were characterized using high-resolution LC-MS/MS, and the results showed the prevalence of anthocyanins, saponins, phenolics, and choline. Biochemical and histopathological tests revealed a dose-dependent improvement with oral Yucca extract. The current study suggests a possible neuroprotective effect of the acidified 50% ethanol extract (YA-C) of the edible Yucca fruit, making it a promising therapeutic target for PD.

Effect of icariin in a rat model of colchicine-induced cognitive deficit: role of ß-amyloid proteolytic enzymes.

ABSTRACTThe deposition of ß-amyloid plaques, either due to their over-production or insufficient clearance, is an important pathological process in cognitive impairment and dementia. Icariin (ICA), a flavonoid compound extracted from Epimedium, has recently gained attention for numerous age-related diseases, such as neurodegenerative diseases. We aimed to explore the possible neuro-protective effect of ICA supplementation in colchicine-induced cognitive deficit rat model and exploring its effect on the ß-amyloid proteolytic enzymes. The study included four groups (10 rats each): normal control, untreated colchicine, colchicine + 10 mg/kg ICA, and colchicine + 30 mg/ kg ICA. Results revealed that intra-cerebro-ventricular colchicine injection produced neuronal morphological damage, ß amyloid deposition, and evident cognitive impairment in the behavioral assessment. Icariin supplementation in the two doses for 21 days attenuated neuronal death, reduced the ß amyloid levels, and improved memory consolidation. This was associated with modulation of the proteolytic enzymes (Neprilysin, Matrix Metalloproteinase-2, and insulin-degrading enzyme) concluding that ß-amyloid enzymatic degradation may be the possible therapeutic target for ICA.

Potential mechanisms underlying the association between type II diabetes mellitus and cognitive dysfunction in rats: a link between miRNA-21 and Resveratrol's neuroprotective action.

Cognitive impairment is considered as a typical feature of neurodegenerative diseases in diabetes mellitus (DM). However, the exact link between cognitive dysfunction and diabetes mellitus is still vague. This study aims to investigate some of the mechanisms underlying cognitive impairment that associates diabetes mellitus and insulin resistance. We investigated the role of resveratrol as well on cognitive function in experimentally induced type 2 diabetes highlighting on its influence on the expression of brain miRNA 21. Resveratrol is a naturally occurring, biologically active compound that has numerous significant impacts on the body. Type 2 diabetes mellitus was induced by high fat diet followed a single dose of streptozotocin. Diabetic rats were treated with resveratrol for four weeks. Rats were sacrificed after neurobehavioral testing. Hippocampal tissues were used to assess expression of miRNA 21, GSK and oxidative stress markers. Serum samples were obtained to determine glucose levels, lipid profile and insulin levels. Hippocampal and serum AGEs were measured as well and HOMA IR was calculated. We detected memory impairment and disturbed insulin signaling in diabetic rats. These derangements were reversed by resveratrol treatment partially due to increased expression of miRNA-21. Our study pins the role of miRNA-21 in modulating brain insulin signaling and hence alleviating cognitive dysfunction accompanying diabetes mellitus.