Therapeutic Effects of Selenium on Alpha-Synuclein Accumulation in Substantia Nigra Pars Compacta in a Rat Model of Parkinson's Disease: Behavioral and Biochemical Outcomes.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the accumulation of accumulated alpha-synuclein (α-Syn) in substantia nigra. Research has shown that selenium (Se) can protect neural cells through the actions of selenoproteins, including selenoprotein P (SelP) and selenoprotein S (SelS), which participate in endoplasmic reticulum-associated protein degradation (ERAD). In this study, we investigated the potential protective role of Se in a pre-clinical PD rat model.We aimed to evaluate the therapeutic effects of Se administration in the 6-hydroxydopamine (6-OHDA) induced unilateral rat PD model. Male Wistar rats were utilised for unilateral PD animal model which were subjected to stereotaxic surgery and injected with 20 µg 6-OHDA/5 µl 0.2% ascorbate saline. After confirming the model, the rats were intraperitoneally injected with 0.1, 0.2, and 0.3 mg/kg of sodium selenite for 7 days. We then performed behavioral tests, including apomorphine-induced rotation, hanging, and rotarod tests. Following sacrifice, we analysed the substantia nigra area of the brain and serum for protein quantification, element analysis, and gene expression analysis.Our results indicate that the administration of 0.3 mg/kg of Se improved the motor deficiency in hanging, rotarod, and apomorphine-induced rotational tests. While there was no significant improvement in the expression of α-Syn, Se increased the expression of selenoproteins. Additionally, levels of selenoproteins, Se, and α-Syn both brain and serum were re-established by the treatment, suggesting the role of Se on the α-Syn accumulation. Furthermore, Se improved PD-induced biochemical deficits by increasing the levels of SelS and SelP (p<0.005).In conclusion, our findings suggest that Se may have a protective role in PD. 0.3 mg/kg dosage of Se increased the expression of selenoproteins, reduced the accumulation of α-Syn in the brain, and improved PD-induced motor deficits. These results suggest that Se may be a potential therapeutic option for PD treatment.

Selenium and selenoproteins role in Parkinson's disease: Is there a link between selenoproteins and accumulated alpha-synuclein?

BACKGROUND: While Parkinson's disease (PD) etiology is not clear yet, accumulated alpha-synuclein is proposed to induce neurodegeneration. Selenium (Se) and its functional proteins play a key role in aggregation of misfolded proteins. However, their implications in neurodegenerative process are unclear. AIM: Diagnosing Se and selenoprotein P (SelP), selenoprotein S (SelS) proportions in serum of PD patients to compare with healthy controls, whether the changes in their concentration could be a biomarker for PD. METHODS: Se concentration was investigated in 30 PD patients and 30 controls using atomic absorption spectrometry. Also, alpha-Synuclein, SelP, and SelS levels were evaluated by ELISA. The parameters were compared in PD patients and controls. Also, the variations within the case group according to their age, disorder stage, and drug administration were evaluated. RESULTS: PD subjects had higher Se concentration. The mean SelP in PD patients was lower from controls, whilst SelS levels were higher. Also, the concentration of alpha-synuclein was higher in PD patients. However, age, stage (except UPDRS III), and disorder duration had no influence on the Se and selenoproteins level, whilst there was a direct association between alpha-synuclein levels and disorder stage. Also, alpha-synuclein proportions in subjects using levodopa was significantly higher. CONCLUSION: Our results suggest that serum levels of Se and SelP could be a biomarker or risk factor for PD. Although SelS interferes to reduce aggregated proteins, its pathway in PD is not clearly understood. Future studies could focus on how SelS can reduce on alpha-synuclein aggregation. Thus, other studies should be performed on this issue to induce the selenoproteins in PD.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Bio-synthesized selenium nanoparticles ameliorate Brain oxidative stress in Parkinson disease rat models.

AIM: Parkinson disease (PD) is a prevalent central nervous system degenerative condition that impacts elderly people. Recent clinical and experimental study findings have established oxidative stress as one of the main pathogeneses of PD. Selenium, a trace metals with antioxidant effects, might reverse the neurobehavioral impairments and oxidative stress in rats. Thus, the goal of this study was to ascertain if Selenium Nano Particles (SeNPs) are also effective to protect brain cells from oxidative stress or not. MAIN METHODS: SeNPs were synthesized utilizing Ascorbic acid and chitosan as a reducing and stabilizing agent. Next, eight groups (N: 6) of male Wistar rats were randomly assigned and injected by different dosage (0.1, 0,2, and 0.3 mg/kg) of Se and SeNP. Finally, to ascertain the protective benefits of SeNP on PD rats, behavioral evaluation, clinical symptoms, antioxidant activity, and oxidant levels were examined. KEY FINDINGS: According to the findings, PD rats' motor functions had developed by SeNP injection. Higher MDA levels and inhibited antioxidant activities (SOD, CAT, and GPX) in lesion group are highlighting the significant role of oxidative stress in dopaminergic neuron death and neurobehavioral abnormalities. SeNP also protect against oxidative stress as compared to the lesion group. The levels of MDA had greatly reduced while the activities of enzymes, TAC, and SeNP both had significantly increased. SIGNIFICANCE: By enhancing antioxidant activity, administration of SeNP can reduce the hazardous consequences of oxidative stress.

PEGylated Lecithin-Chitosan-Folic Acid Nanoparticles as Nanocarriers of Allicin for In Vitro Controlled Release and Anticancer Effects.

In this study, chitosan-lecithin nanoparticles modified with polyethylene glycol (PEG) and folic acid (FA) were used to deliver allicin (AC) to colon cancer cells. AC-loaded polyethylene glycol (PEG) and folic acid (FA)-modified chitosan-lecithin nanoparticles (AC-PLCF-NPs) were fabricated via self-assembling procedure. HPLC for AC encapsulation and FA binding, MTT for viability assay, ABTS and DPPH for antioxidant capacity, disc diffusion, MIC and MBC for antibacterial assay, qPCR and AO/PI staining for apoptotic, and CAM assay for angiogenesis effects of AC-PLCF-NPs were used. AC-PLCF-NPs (113.55 nm) were synthesized as single dispersed (PDI: 0.28) and stable (ZP: + 33.18 mV) with 81% AC encapsulation and 48% FA binding. The antioxidant power of AC-PLCF-NPs was confirmed by inhibiting free radicals ABTS (74.25 µg/mL) and DPPH (366.214 µg/mL) and its antibacterial capacity with very high inhibitory effects against gram-negative bacterial strains. MTT results showed higher toxicity of AC-PLCF-NPs (68.06 µg/mL) compared to AC (171.45 µg/mL). Increased expression of caspase 3 and 9 genes showed activation of the intrinsic apoptosis pathway in treated cells, and on the other hand, reduction of vascular and embryonic growth factors in CAM model confirmed the anti-angiogenesis effects of AC-PLCF-NPs. AC-PLCF-NPs can be suggested as a promising therapeutic agent for studies in the field of colon cancer treatment.

Modulatory effect of berberine on plasma lipoprotein (or lipid) profile: a review.

Berberine is a bioactive isoquinoline alkaloid compound extracted from various medicinal plants, such as Barberry. Berberine shows various pharmacological properties that are mainly attributed to its anti-inflammatory and antioxidant effects. A growing body of evidence has shown that berberine influences cholesterol metabolism, and consequently, may ameliorate dyslipidemias and atherosclerosis. Plasma high-density lipoprotein cholesterol (HDL-C) is known to have an independent negative association with incident cardiovascular disease (CVD). However, several outcomes trials and genetic studies have failed to meet expecting the beneficial effects of elevating plasma HDL-C concentrations. Hence, investigations are currently focused on enhancing the functionality of HDL particles, independent of their plasma concentrations. HDL particles show various qualities because of a heterogeneous composition. Consistent with complex metabolism and composition, various biological functions are found for HDL, such as anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic activities. Protective effects of berberine may impact the functionality of HDL; therefore, the present literature review was intended to determine whether berberine can amplify HDL function. It was concluded that berberine may regulate markers of HDL activity, such as apo-AI, cholesterol efflux, LCAT, PON1, and S1P activities and levels. Consequently, berberine may recuperate conditions with dysfunctional HDL and, therefore, have the potential to emerge as a therapeutic agent. However, further human trials of berberine are warranted to evaluate its impact on HDL function and cholesterol metabolism.

Selenium Effects on Oxidative Stress-Induced Calcium Signaling Pathways in Parkinson's Disease.

Parkinson's disease (PD) is a neurological disorder in which oxidative stress and reactive oxygen species productions are proposed to be involved in its pathogenesis. Despite considerable advancement in Selenium's (Se) molecular biology and metabolism, we do not know much about the cell type-specific pattern of Se distribution in the brain of PD humans and experimental animals. Although, there is plenty of evidence around the role of Se deficiency in PD's pathogenesis impacting lipid peroxidation and reducing glutathione (GSH) and glutathione peroxidase (GPX). It has been suggested that Se has an inducible role in selenium-dependent GPX activity in PD animals and humans. However, calcium as a second messenger regulates the neuron cells' essential activities, but its overloading leads to cellular oxidative stress and apoptosis. Therefore, Se's antioxidant role can affect calcium signaling and alleviate its complications. There are signs of Se and Selenoproteins incorporation in protecting stress oxidative in various pathways. In conclusion, there is convincing proof for the crucial role of Se and Calcium in PD pathogenesis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01031-1.

Acetyl-11-Keto-ß-Boswellic Acid (AKBA) Prevents Lipopolysaccharide-Induced Inflammation and Cytotoxicity on H9C2 Cells.

Acetyl-11-keto-beta-boswellic acid (AKBA), the major component of Boswellia serrata, exhibits anti-inflammatory activities. This in vitro study investigated the protective effects of AKBA against lipopolysaccharide (LPS)-induced cardiac dysfunction. In this study, the H9C2 cardiomyocytes were pretreated with AKBA (2.5, 5, and 10 µM for 24 h), and then cotreated with LPS for another 24 h. The MTT assay, ELISA test kits, and quantitative real-time PCR analysis assessed the cell viability, levels of proinflammatory factors (IL-ß, IL-6, TNF- α, and PGE2), and the gene expression of IL-ß, IL-6, TNF- α, iNOS, and COX-2, respectively. The nitric oxide (NO) and thiol levels were also measured using a biochemical assay. The results indicated that LPS exposure markedly reduced cell viability and total thiol content, but increased the inflammatory cytokines, NO metabolites, and gene expression of proinflammatory mediators in H9C2 cells. AKBA pretreatment significantly altered the mentioned factors induced by LPS. Our results demonstrated that AKBA might be a promising therapeutic agent for treating sepsis-related cardiac dysfunction in the future.

Protective effects of propolis on hepatic steatosis and fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) evaluated by real-time two-dimensional shear wave elastography: A randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, while no drugs have been approved for its treatment. The pieces of evidence indicate that propolis as a novel anti-inflammatory agent might be a promising candidate to treat NAFLD. We aimed to evaluate the efficacy of propolis on hepatic steatosis and fibrosis in patients with NAFLD. This randomized clinical trial was conducted on 54 patients with NAFLD. Patients were randomly assigned to receive propolis tablets at a dose of 250 mg twice daily for 4 months or placebo. The improvement in hepatic steatosis and fibrosis was evaluated using two-dimensional shear wave elastography. Improvement in the hepatic steatosis was significantly higher in the propolis group than the placebo group, even after adjustment for baseline value and changes in weight, energy intake, and physical activity (odds ratio [OR]: 5.67; 95% confidence intervals [CI]: 1.41-22.8; p = .014). A significant reduction was observed on the liver stiffness in the propolis group (-0.65 ± 0.56 kPa; p = .001), whereas it increased in the placebo group (0.27 ± 0.59 kPa; p = .037). Also, the intake of propolis significantly decreased high-sensitivity C-reactive protein (hs-CRP) levels compared with the placebo group (-0.371; 95%CI: -0.582 to -0.16 mg/L; p = .01). Changes in serum levels of fasting blood sugar, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, cholesterol, and triglyceride did not differ significantly between the two groups (p > .05). There was no significant improvement in insulin resistance in both groups (p > .05). Propolis seems to have protective effects on hepatic steatosis and fibrosis and to reduce the serum levels of hs-CRP in patients with NAFLD.

Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of Rhus coriaria L. (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.

5'-Adenosine monophosphate-activated protein kinase: A potential target for disease prevention by curcumin.

Curcumin (diferuloylmethane), a yellowish agent extracted from turmeric, is a bioactive compound known for its anti-inflammatory, antiproliferative, antidiabetic, and anticancer activities. Multiple lines of evidence have indicated that curcumin regulates several regulatory proteins in the cellular signal transduction pathway. AMP-activated protein kinase (AMPK) is one of the central regulators of cellular metabolism and energy homeostasis, which is activated in response to increasing cellular adenosine monophosphate/adenosine triphosphate ratio. AMPK plays a critical role in regulating growth and reprogramming metabolism and is linked to several cellular processes including apoptosis and inflammation. Recently, it has been demonstrated that AMPK is a new molecular target affected by curcumin and its derivatives. In this review, we discuss recent findings on the targeting of AMPK signaling by curcumin and the resulting impact on the pathogenesis of proinflammatory diseases. We also highlight the therapeutic value of targeting AMPK by curcumin in the prevention and treatment of proinflammatory diseases, including cancers, atherosclerosis, and diabetes.

Herbal medicine in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory and T cell-mediated autoimmune disease in which the oral mucosa, tongue, and gingiva are involved. Different treatments have been suggested to reduce the symptoms of this disease. Currently, a common treatment for OLP is the use of corticosteroids as the gold standard, although they have considerable side effects. The chronicity of the disease needs the long-term use of these drugs with ensuing side effects. Therefore, various studies have been done to find an alternative and effective treatment. The use of herbal medicine as an alternative therapy with antioxidant and anti-inflammatory properties seems promising. Hence, this review study was done to summarize the efficiency of different herbal medicine in the treatment of OLP.