Evaluation of Prunus domestica gum as a novel tablet binder

To evaluate binding potential of Prunus domestica gum in tablets formulations. Six tablet batches (F-1B to F-6B) were prepared by wet granulation method, containing Avicel pH 101 as diluent, sodium diclofenac as model drug using 10, 15 and 20 mg of Prunus domestica gum as binder and PVP K30 was used as standard binder. Magnesium stearate was used as lubricant. Flow properties of granules like bulk density, tapped density, Carr index, Hausner’s ratio, angle of repose as well as physical parameters of the compressed tablets including hardness, friability, thickness and disintegration time were determined and found to be satisfactory. The FTIR spectroscopic analysis showed that the formulation containing plant gum is compatible with the drug and other excipients used in tablets formulation. Hence the plant gum has role as a potential binder in tablets formulations. The dissolution profile showed that tablets formulations containing Prunus domestica gum 15 mg/200 mg of total weight of tablet as binder showed better results as compared to PVP K30.Para avaliar a propriedade aglutinante da goma Prunus domestica em formulações de comprimidos, seis lotes (F-1B para F-6B) foram preparados pelo método de granulação úmida, contendo Avicel pH 101 como diluente e diclofenaco de sódio como fármaco modelo, usando 10, 15 e 20 mg de goma de Prunus domestica como agente aglutinante e PVP K30 como aglutinante padrão. O estearato de magnésio foi utilizado como lubrificante. Propriedades de fluxo dos grânulos, como a densidade, índice de Carr, razão de Hausner, ângulo de repouso, bem como parâmetros físicos dos comprimidos, incluindo o tempo de dureza, friabilidade, espessura e desintegração foram determinados e se mostraram satisfatórios. A análise espectroscópica no FTIR mostrou que a formulação contendo goma vegetal é compatível com o fármaco e outros excipientes utilizados na formulação dos comprimidos. Assim, a goma vegetal tem papel potencial como aglutinante em formulações de comprimidos. O perfil de dissolução das formulações que contêm 15 mg/200 mg do peso total do comprimido em goma de Prunus domestica como aglutinante mostrou melhores resultados comparativamente ao PVP K30

Carveol Promotes Nrf2 Contribution in Depressive Disorders through an Anti-inflammatory Mechanism

Major depressive disorder (MDD) is a progressive deteriorating mental state with a feeling of worthlessness and frequent mood swings. Several studies reported the favorable effects of natural drug substances on MMD associated oxidative stress and neuroinflammation. The present study is attempted to examine whether carveol could affect lipopolysaccharide- (LPS-) induced depression, and if so, how nuclear factor E2-related factor (Nrf2) contributed to the neuroprotective effects of carveol mechanistically. Two experimental cohorts were used using the SD rats: first to evaluate the promising dose of carveol (whether 20 mg/kg or 50 mg/kg) and secondly to determine the effect of carveol on Nrf2-mediated antidepression. Significant neuronal alterations were noticed in the cortex and hippocampus regions in the LPS-treated group, accompanied by elevated inflammatory cytokine levels such as tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), and c-Jun N-terminal kinase (p-JNK). Moreover, amassing of free radicals exacerbated lipid peroxidase (LPO) and oxidative stress with a limited antioxidant capacity. Carveol (20 mg/kg) significantly ameliorated these detrimental effects by promoting the antioxidant Nrf2 gene and protein, which critically regulate the downstream antioxidant and anti-inflammatory pathway. To further elaborate our hypothesis, we employed all-trans retinoic acid (ATRA), an Nrf2 inhibitor, and we found that ATRA exaggerated LPS-induced depressive-like effects associated with elevated neuroinflammatory markers. Our results demonstrated that carveol (20 mg/kg) could activate the endogenous antioxidant Nrf2, which regulates the downstream antioxidant signaling pathway, eventually leading to amelioration of LPS-induced neuroinflammation and neurodegeneration

Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity

Acetaminophen (N-acetyl p-aminophenol or APAP) is used worldwide for its antipyretic and anti-inflammatory potential. However, APAP overdose sometimes causes severe liver damage. In this study, we elucidated the protective effects of carveol in liver injury, using molecular and in silico approaches. Male BALB/c mice were divided into two experimental cohorts, to identify the best dose and to further assess the role of carveol in the nuclear factor E2-related factor; nuclear factor erythroid 2; p45-related factor 2 (Nrf2) pathway. The results demonstrated that carveol significantly modulated the detrimental effects of APAP by boosting endogenous antioxidant mechanisms, such as nuclear translocation of Nrf2 gene, a master regulator of the downstream antioxidant machinery. Furthermore, an inhibitor of Nrf2, called all-trans retinoic acid (ATRA), was used, which exaggerated APAP toxicity, in addition to abrogating the protective effects of carveol; this effect was accompanied by overexpression of inflammatory mediators and liver = 2ltoxicity biomarkers. To further support our notion, we performed virtual docking of carveol with Nrf2-keap1 target, and the resultant drug-protein interactions validated the in vivo findings. Together, our findings suggest that carveol could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating the APAP-induced inflammation and oxidative stress

Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain

Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice

Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen

The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain’s length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles 1a–c with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of 1a–c with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and 1H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives 1a–c were found to have a significant impact on the solubility of NAP and IBP in pure water

MOESM1 of Anthocyanins encapsulated by PLGA@PEG nanoparticles potentially improved its free radical scavenging capabilities via p38/JNK pathway against Aβ1–42-induced oxidative stress

Additional file 1. Additional figures

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain