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The concept of the vitamin D response index was developed based on vitamin D intervention studies conducted with Finnish cohorts. In this study, we challenged the concept by performing a single vitamin D3 bolus (80,000 IU) intervention with a cohort of 100 native Saudis. The change of serum levels of the proinflammatory cytokines interleukin 6, interleukin 8 and tumor necrosis factor measured directly before intervention in comparison to samples taken one and thirty days after vitamin D3 supplementation were used as biomarkers for distinguishing low, mid and high responders. Interestingly, we identified 39 % of the study participants as low responders. In contrast, when we used in a subset of 37 study participants whole blood expression changes of seven well-known vitamin D target genes one and thirty days after supplementation as alternative biomarkers, only 9 persons (24 %) were identified as low responders. In conclusion, in Saudi Arabia the rate of low vitamin D responders is equal or even higher than that in Finland. Therefore, similar to Nordic countries also in Saudi Arabia appropriate vitamin D3 supplementation is essential, in order to fulfill the needs of low responders.
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The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs. The class of natural compounds known as flavonoids is well-known for their therapeutic potential. In this study, we focus on discovering novel inhibitors of MEK2 from flavonoids using virtual screening, molecular docking analyses, pharmacokinetic prediction, and molecular dynamics (MD) simulations. A library of drug-like flavonoids containing 1289 chemical compounds prepared in-house was screened against the MEK2 allosteric site using molecular docking. The ten highest-scoring compounds based on docking binding affinity (highest score: -11.3 kcal/mol) were selected for further analysis. Lipinski's rule of five was used to test their drug-likeness, followed by ADMET predictions to study their pharmacokinetic properties. The stability of the best-docked flavonoid complex with MEK2 was examined for a 150 ns MD simulation. The proposed flavonoids are suggested as potential inhibitors of MEK2 and drug candidates for cancer therapy.
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Antineoplásicos , Neoplasias , Humanos , Flavonoides , Simulação de Acoplamento Molecular , Antineoplásicos/química , Simulação de Dinâmica MolecularRESUMO
BACKGROUND: Previously reported data suggest that hibiscetin, isolated from roselle, contains delphinidin-3-sambubioside and cyanidin-3-sambubioside including anthocyanidins and has a broad range of physiological effects. In this study, we aim to analyze the effect of hibiscetin neuroprotective ability in rats against 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD). METHODS: To investigate possible toxicities in animals, oral acute toxicity studies of hibiscetin were undertaken, and results revealed the safety of hibiscetin in animals with a maximum tolerated dose. Wistar rats were divided into four groups (n = 6); (group-1) treated with normal saline, (group-2) hibiscetin (10 mg/kg) only, (group-3) 3-NPA only, and (group-4) 3-NPA +10 mg/kg hibiscetin. The efficacy of hibiscetin 10 mg/kg was studied with the administration of 3-NPA doses for the induction of experimentally induced HD symptoms in rats. The mean body weight (MBW) was recorded at end of the study on day 22 to evaluate any change in mean body weight. Several biochemical parameters were assessed to support oxidative stress (GSH, SOD, CAT, LPO, GR, and GPx), alteration in neurotransmitters (DOPAC, HVA, 5-HIAA, norepinephrine, serotonin, GABA, and dopamine), alterations in BDNF and cleaved caspase (caspase 3) activity. Additionally, inflammatory markers, i.e., tumor necrosis factor alpha (TNF-α), interleukins beta (IL-1ß), and myeloperoxidase (MPO) were evaluated. RESULTS: The hibiscetin-treated group exhibits a substantial restoration of MBW than the 3-NPA control group. Furthermore, 3-NPA caused a substantial alteration in biochemical, neurotransmitter monoamines, and neuroinflammatory parameters which were restored successfully by hibiscetin. CONCLUSION: The current study linked the possible role of hibiscetin by offering neuroprotection in experimental animal models.
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Doença de Huntington , Fármacos Neuroprotetores , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos Wistar , Doença de Huntington/induzido quimicamente , Doença de Huntington/tratamento farmacológico , Estresse Oxidativo , Nitrocompostos/farmacologia , Propionatos/farmacologia , Neurotransmissores/farmacologia , Peso Corporal , EncéfaloRESUMO
Approximately 1 in 36 children are diagnosed with autism spectrum disorder (ASD). The disorder is four times more common in males than in females. Zinc deficiency and mutations in SHANK2 and SHANK3 (members of a family of excitatory postsynaptic scaffolding proteins) are all risk factors that may contribute to the pathophysiology of the disease. The presence of shankopathies (loss of one copy of the SHANK3 gene) can lead to the development of Phelan-McDermid syndrome (PMDS)-a rare genetic disorder characterized by developmental delay, intellectual disability, poor motor tone, and ASD-like symptoms. We reviewed the relationship between zinc, ASD, and PMDS as well as the effect of zinc supplementation in improving symptoms of ASD and PMDS based on 22 studies published within 6 years (2015-2020). Zinc deficiency (assessed by either dietary intake, blood, hair, or tooth matrix) was shown to be highly prevalent in ASD and PMDS patients as well as in preclinical models of ASD and PMDS. Zinc supplements improved the behavioral deficits in animal models of ASD and PMDS. Clinical trials are still needed to validate the beneficial therapeutic effects of zinc supplements in ASD and PMDS patients.
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Transtorno do Espectro Autista , Transtornos Cromossômicos , Animais , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Deleção Cromossômica , Transtornos Cromossômicos/tratamento farmacológico , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/metabolismo , Cromossomos Humanos Par 22 , Suplementos Nutricionais , Feminino , Humanos , Masculino , Zinco/uso terapêuticoRESUMO
Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.
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Colecalciferol , Deficiência de Vitamina D , Biomarcadores , Cálcio , Suplementos Nutricionais , Humanos , Interleucina-6 , Interleucina-8 , Masculino , Hormônio Paratireóideo , Fosfatos , Arábia Saudita , Triglicerídeos , Fatores de Necrose Tumoral , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , VitaminasRESUMO
Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.
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Antineoplásicos/farmacologia , Butilaminas/farmacologia , Espermidina/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Butilaminas/síntese química , Butilaminas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cricetinae , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Estrutura Molecular , Espermidina/síntese química , Espermidina/química , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacosRESUMO
Objective: The development of coronavirus disease 2019 (COVID-19) vaccines was a crucial preventative measure toward controlling the pandemic. Several side effects have been reported. This study investigated the long-term side effects reported by the Saudi population. post-COVID-19 vaccination. Methods: The cross-sectional study involved Saudi participants of both genders, aged ≥16 years, and had received at least one dose of any of the available vaccines in Saudi Arabia. They were asked to fill out an online questionnaire divided into three sections: Demographics, medical history, and side effects that appeared post-COVID-19 vaccines. Results: The findings indicated that the undesirable effects were reported by 82% of the participants. These side effects involve three categories: The most common, additional or reported, and persistent side effects. The most common side effects were pain at the site of injection (88.16%), bone pain/joint pain (68.7%), and fatigue (68.46%). Menstrual disorders (n = 46), hair loss (n = 34), and memory problems (n = 19) were reported by participants as additional side effects. Among all side effects, fatigue, joint pain, hair loss, and menstrual disorders were the most persistent side effects. Moreover, 190 participants reported that they were diagnosed with diseases soon after receiving the COVID-19 vaccine including COVID-19, thyroid gland disorder, and irritable bowel disease. The quality of life of some of the participants was affected by post-COVID-19 vaccines, as 25.28% had anxiety, 21.22% had depression, and 33.16% had discomfort. Conclusion: These findings may contribute to understanding the effect of COVID-19 vaccines on the Saudi population's health and public opinion about these vaccines.
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Human transcriptome can undergo RNA mis-splicing due to spliceopathies contributing to the increasing number of genetic diseases including muscular dystrophy (MD), Alzheimer disease (AD), Huntington disease (HD), myelodysplastic syndromes (MDS). Intron retention (IR) is a major inducer of spliceopathies where two or more introns remain in the final mature mRNA and account for many intronic expansion diseases. Potential removal of such introns for therapeutic purposes can be feasible when utilizing bioinformatics, catalytic RNAs, and nano-drug delivery systems. Overcoming delivery challenges of catalytic RNAs was discussed in this review as a future perspective highlighting the significance of utilizing synthetic biology in addition to high throughput deep sequencing and computational approaches for the treatment of mis-spliced transcripts.
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It has been demonstrated that noncoding RNAs have significant physiological and pathological roles. Modulation of noncoding RNAs may offer therapeutic approaches as per recent findings. Small RNAs, mostly long noncoding RNAs, siRNA, and microRNAs make up noncoding RNAs. Inhibiting or promoting protein breakdown by binding to 3' untranslated regions of target mRNA, microRNAs post-transcriptionally control the pattern of gene expression. Contrarily, long non-coding RNAs perform a wider range of tasks, including serving as molecular scaffolding, decoys, and epigenetic regulators. This article provides instances of long noncoding RNAs and microRNAs that may be a biomarker of CVD (cardiovascular disease). In this paper we highlight various RNA-based vaccine formulation strategies designed to target these biomarkers-that are either currently in the research pipeline or are in the global pharmaceutical market-along with the physiological hurdles that need to be overcome.
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A participant of the chemical family recognized as anthocyanins, hirsutidin is an O-methylated anthocyanidin. It is a natural substance, i.e., existing in Catharanthus roseus (Madagascar periwinkle), the predominant component in petals, as well as callus cultures. The literature review indicated a lack of scientifically verified findings on hirsutidin's biological activities, particularly its anti-Parkinson's capabilities. Using the information from the previous section as a reference, a present study has been assessed to evaluate the anti-Parkinson properties of hirsutidin against rotenone-activated Parkinson's in experimental animals. For 28 days, rats received hirsutidin at a dose of 10 mg/kg and rotenone at a dose of 0.5 mg/kg s.c. to test the neuroprotective effects. The hirsutidin was given 1 h before the rotenone. Behavioral tests, including the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field analysis, were performed. The levels of neurotransmitters (5-HT, DOPAC, 5-HIAA, dopamine, and HVA), neuroinflammatory markers (TNF-α, IL-6, IL-1ß, caspase-3), an endogenous antioxidant, nitrite content, and acetylcholine were measured in all the rats on the 29th day. Hirsutidin exhibited substantial behavioral improvement in the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field test. Furthermore, hirsutidin restored neuroinflammatory markers, cholinergic function, nitrite content, neurotransmitters, and endogenous antioxidant levels. According to the study, hirsutidin has anti-inflammatory and antioxidant characteristics. As a result, it implies that hirsutidin may have anti-Parkinsonian effects in rats.
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The research was undertaken to assess the antidiabetic activity of rosiridin in the streptozotocin (STZ)-induced diabetic model. Type 2 diabetes mellitus was elicited chemically in experimental animals using STZ (60 mg/kg, i.p.). Experimental rats were arbitrarily allocated to normal control, rosiridin perse, diabetic control, and STZ + rosiridin groups. After the confirmation of diabetes, rosiridin (10 mg/kg) was given orally to the experimental animals for 30 days. Various anti-diabetic (blood glucose, insulin), hypolipidemic, anti-inflammatory (Nuclear factor kappa B, tumour necrosis factor-α, interleukin beta (IL-1ß), and IL-6), antioxidant (and malondialdehyde level, hepatic function and others markers (ALT, AST, adiponectin, and FNDC5) and histopathological indices of injury were evaluated. In addition, the rosinidin was docked into the active site of NF-Kß (1SVC), FNDC5 (4LSD) and adiponectin (5LXG) proteins with AutoDock tools. MD simulations were carried out for the complexes of rosiridin with NF-Kß, myokine and human adiponectin receptor 1. Rosiridin treatment restored the biochemical parameters and preserved the histopathological building of the pancreas as compared to the diabetic rats. Histopathological analysis of the pancreas confirmed that rosiridin antidiabetic efficacy in the STZ-induced diabetes mellitus model. The 5LXG_rosinidin showed favourable affinity with the best binding energies at -7.534 kcal/mol. MD simulations were carried out for the complexes of rosiridin with NF-Kß, myokine and human adiponectin receptor 1, the complex of myokine and rosiridin exhibited the most stable complex. Rosiridin may exhibit considerable anti-diabetic activity in the STZ-induced diabetes mellitus model.Communicated by Ramaswamy H. Sarma.
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Objectives: The examination was sighted to study the preventive effects of rosinidin against rotenone-activated Parkinson's disease in rats. Methods: Animals were randamoized into five groups: I-saline, II-rotenone (0.5 mg/kg/b.wt.), III- IV-10 and 20 mg/kg rosinidin after rotenone and V-20 mg/kg rosinidin per se for 28 days and were assigned for behavioral analysis., Biochemical parameters i.e. lipid peroxidation, endogenous antioxidants, nitrite level, neurotransmitter levels, proinflammatory biomarkers such as interleukin- 6 (IL-6), tumor necrosis factor-α, IL-1ß, nuclear factor kappa B, nuclear factor erythroid 2-related factor 2, and caspase-3 were assessed on the 29th day of the research. Results: Rosinidin augmented the effectiveness of rotenone on akinesia, catalepsy, forced-swim test, rotarod, and open-field test. Biochemical findings indicated that treatment of rosinidin showed restoring neuroinflammatory cytokines, antioxidants, and neurotransmitter levels in rotenone-injected rats. Conclusion: As a result of rosinidin treatment, the brain was protected from oxidative stress-induced neuronal damage and inhibited neuroinflammatory cytokines.
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Streptozotocin (STZ) impairs memory in rats through altering the central nervous systems (CNS) as a result of impaired cholinergic dysfunction, oxidative stress, persistent hyperglycemia, and alterations in the glucagon-like peptide (GLP). In this model cholinergic agonist, antioxidant and antihyperglycemic treatment has been shown to have positive effects. Barbaloin has a variety of pharmacological effects. However, there is no evidence on how barbaloin improves memory dysfunction caused by STZ. Thus, we examined its effectiveness against cognitive damage caused by STZ at a dose of 60 mg/kg i.p. in Wistar rats. Blood glucose levels (BGL) and body weight (BW) were assessed. To assess learning and memory skills, the Y-maze test and Morris water maze (MWM) test were utilized. Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione (GSH) as oxidative stress markers were regulated to reverse the cognitive deterioration, and choline-acetyltransferase (ChAT) and acetyl-cholinesterase (AChE) as indicators of cholinergic dysfunction, nuclear factor kappa-B (NF-κB), IL-1ß (interleukin-1ß), IL-6, and tumor necrosis factor-α (TNF-α) contents were used. Barbaloin treatment thereby significantly decreased the BW and learning and memory capacities, resulting in substantial behavioral improvement in the Y-maze and MWM test. BGL, SOD, CAT, MDA, GSH, AChE, ChAT, NF-κB, IL-6, TNF-α, and IL-1ß levels were also altered. In conclusion, the findings revealed that barbaloin had a protective impact against cognitive dysfunction caused by STZ.
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The current study was designed for the evaluation of barbigerone on memory loss. In this experimental study, 24 Wistar rats (n = 6) were used. Control rats and scopolamine (SCOP)-treated control group rats were orally administered with 3 ml of 0.5% sodium carboxymethyl cellulose (vehicle), whereas barbigerone was (10 and 20 mg kg-1) administered orally to the rats from the test group. During the 14-day treatment, control group rats were given 3 ml kg-1 day-1 saline, and all other groups were administered SCOP (1 mg kg-1 day-1, i.p.) 1 h after barbigerone p.o. treatment. The spontaneous alternation activities, learning capacities of a rat's memory were tested with Morris water maze and Y-maze. Reduced glutathione, malondialdehyde, acetylcholine esterase (AChE) and catalase (CAT) levels were measured in rat brain tissue as oxidative stress/antioxidant markers. Moreover, the levels of tumour necrosis factor, interleukin-6 (IL-6) and IL-1ß were also estimated. Treatment with barbigerone in SCOP-administered rats dramatically reduced SCOP-induced neurobehavioural deficits, oxidative stress and neuroinflammatory markers, improved endogenous antioxidants, and restored AChE activity. By improving cholinergic function and reducing oxidative damage, barbigerone could mitigate the effects of SCOP-induced changes in the brain.
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Rheumatoid arthritis causes irreparable damage to joints. The present research sought to check fustin's anti-arthritic efficacy against the complete Freund's adjuvant-induced arthritis paradigm in animals by altering the inflammatory response. In the rats, complete Freund's adjuvant was used to trigger arthritis and they received fustin at 50 and 100 mg/kg for 21 days. At regular intervals, the hind paw volume and arthritic score were assessed. After the trial period, hematological, antioxidant, pro-inflammatory cytokines, and other biochemical parameters were estimated. Fustin-treated rats showed the down-regulation of hind paw volume, arthritic score, and altered hematological parameters (TLC, DLC (neutrophil, lymphocyte, monocyte, eosinophil, basophil)). Furthermore, fustin significantly mitigates proinflammatory cytokine (reduced interleukin, tumor necrosis factor-a (TNF-α), IL-6, IL-1ß), oxidative stress (attenuated malondialdehyde (MDA), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD)), attenuated production of prostaglandin E2 and myeloperoxidase (MPO) and improved nuclear factor erythroid 2-related factor (Nrf2) action. Fustin led to the benefit in arthritis-prone animals elicited by complete Freund's adjuvant via pro-inflammatory cytokine.
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Artrite Experimental , Ratos , Animais , Adjuvante de Freund/efeitos adversos , Artrite Experimental/tratamento farmacológico , Estresse Oxidativo , Citocinas/efeitos adversos , Fator de Necrose Tumoral alfa/efeitos adversos , Glutationa/efeitos adversosRESUMO
BACKGROUND: The effect of europinidin on alcoholic liver damage in rats was examined in this research. METHODS: A total of 24 Wistar rats were grouped in the same way into four groups: normal control (normal), ethanol control (EtOH), europinidin low dose (10 mg/kg), and europinidin higher dose (20 mg/kg). The test group rats were orally treated with europinidin-10 and europinidin-20 for 4 weeks, whereas 5 mL/kg distilled water was administered to control rats. In addition, 1 h after the last dose of the above-mentioned oral treatment, 5 mL/kg (i.p.) EtOH was injected to induce liver injury. After 5 h of EtOH treatment, samples of blood were withdrawn for biochemical estimations. RESULTS: Administration of europinidin at both doses restored all of the estimated serum, i.e., liver function tests (ALT, AST, ALP), biochemical test (Creatinine, albumin, BUN, direct bilirubin, and LDH), lipid assessment (TC and TG), endogenous antioxidants (GSH-Px, SOD, and CAT), malondialdehyde (MDA), nitric oxide (NO), cytokines (TGF-ß, TNF-α, IL-1ß, IL-6, IFN-γ, and IL-12), caspase-3, and nuclear factor kappa B (NF-κB) associated with the EtOH group. CONCLUSION: The results of the investigation showed that europinidin had favorable effects in rats given EtOH and may have hepatoprotective potential property.
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This comprehensive review aims to provide an overview of the pharmacological properties of erucic acid (EA) and highlight areas that require further research. EA is an omega-9 fatty acid found in certain vegetable oil, such as rapeseed oil has demonstrated favourable effects in rodents, including ameliorating myocardial lipidosis (fat accumulation in the heart muscle), congestive heart disease, hepatic steatosis (fat accumulation in the liver), and memory impairments. These findings have prompted regulatory bodies to establish limits on EA content in food oils. The studies were performed on rodents and led to caution on ingesting the EA at high levels. Moreover, EA is frequently utilized as a nutritional supplement for the treatment of adrenoleukodystrophy, myocardial disease, and memory improvement. The review of the article indicated that EA improves cognitive function, has a part in Huntington's disease, interacts with peroxisome proliferator-activated receptors, inhibits elastase and thrombin, has anti-inflammatory, antioxidant, and anti-tumour properties, and inhibits influenza A virus. This article elucidates the pharmacological effects of EA, an omega-9 fatty acid.
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The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs' protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds' flavonoids are known for their anticancer activity. This study aims to explore flavonoids for their inhibition ability, targeting MEK1 using virtual screening, molecular docking, ADMET prediction, and molecular dynamics (MD) simulations. Flavonoids (n = 1289) were virtually screened using molecular docking and have revealed possible inhibitors of MEK1. The top five scoring flavonoids based on binding affinity (highest score for MEK1 is -10.8 kcal/mol) have been selected for further protein-ligand interaction analysis. Lipinski's rule (drug-likeness) and absorption, distribution, metabolism, excretion, and toxicity predictions were followed to find a good balance of potency. The selected flavonoids of MEK1 have been refined with 30 (ns) molecular dynamics (MD) simulation. The five selected flavonoids are strongly suggested to be promising potent inhibitors for drug development as anticancer therapeutics of the therapeutic target MEK1.
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Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.
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Colecalciferol , Deficiência de Vitamina D , Cálcio , Cálcio da Dieta , Citocinas , Suplementos Nutricionais , Feminino , Humanos , Interleucina-6 , Interleucina-8 , Hormônio Paratireóideo , Fosfatos , Fatores de Necrose Tumoral , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , VitaminasRESUMO
Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione-GSH, superoxide dismutase-SOD, catalase-CAT, and malondialdehyde-MDA), alteration in neurotransmitters (gamma-aminobutyric acid-GABA-and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1ß, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm.