Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration.

Neuroinflammation affects millions of people around the world as a result of injury or stress. Neuroinflammation represents almost all types of neurological diseases such as multiple sclerosis and Alzheimer's disease. Neurodegenerative diseases comprise demyelination and synaptic loss. The inflammatory response is further propagated by the activation of glial cells and modulation of constitutively expressed extracellular matrix proteins. The aim of the present study was to identify the anti-inflammatory effects of purified compounds gallic acid (GA, 1.0 µM) and vanillic acid (VA, 0.2 µM) on the lysolecithin (LPC, 0.003%)-induced model of inflammation. Hippocampal neurons were co-cultured with glial cells, and LPC was added to induce inflammation. Neurite outgrowth was measured by morphometry software. The level of myelination and demyelination was identified by immunostaining and sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting techniques using different antibodies. Whole-cell patch clamp recordings were used to observe the sustained repetitive firing pattern. The data showed that GA and VA significantly increased the neurite outgrowth after 48 h in culture. Both compounds significantly reduced the expression of cyclooxygenase-2, NFκB, tenascin-C, chondroitin sulfate proteoglycans and glial fibrillary acidic protein in astrocytes in the LPC-induced model of inflammation. The level of myelin protein in neurites and oligodendrocyte cell bodies was significantly upregulated by GA and VA treatment. The reduction in sustained repetitive firing in the LPC-induced model of inflammation was reversed by both GA and VA treatment. This study supports the hypothesis that VA and GA have anti-inflammatory activities and could be regarded as potential treatments for neurodegenerative disease.

Phytotoxicity of pesticides mancozeb and chlorpyrifos: correlation with the antioxidative defence system in Allium cepa.

Pesticides are a group of chemical substances which are widely used to improve agricultural production. However, these substances could be persistent in soil and water, accumulative in sediment or bio-accumulative in biota depending on their solubility, leading to different types of environmental pollution. The present study was done to assess the impact of pesticides-mancozeb and chlorpyrifos, via morphological and physiological parameters using Allium cepa test system. Phytotoxic effects of pesticides were examined via germination percentage, survival percentage, root and shoot length, root shoot length ratio, seedling vigor index, percentage of phytotoxicity and tolerance index. Oxidative stress on Allium seedlings caused by pesticides was also assessed by investigating the activity of antioxidative enzymes viz. catalase, peroxidase and superoxide dismutase. Correlation was worked out between morphological parameters and antioxidative enzymes to bring out the alliance between them. Mancozeb and chlorpyrifos concentrations were significantly and positively correlated with the activity of antioxidative enzymes and negatively correlated with morphological parameters. Significant positive correlation between various morphological parameters showed their interdependency. However, negative correlation was obtained between activity of antioxidative enzymes and morphological parameters. The enzymes however, showed positive correlation with each other. Based on our result we can conclude that all morphological parameters were adversely affected by the two pesticides as reflected by phytotoxicity in Allium. Their negative correlation with activity of antioxidative enzymes indicates that upregulation of antioxidative enzymes is not sufficient to overcome the toxic effect, thereby signifying the threat being caused by the regular use of these pesticides.

Piperine attenuates the cancerous activity response in Neuro-2a cell line.

Interactions of cancer cells with their microenvironment play a significant role in defining the severity of the disease. In search of novel compounds with anti-inflammatory and anticancerous capabilities, the effects of purified compound piperine were investigated in Neuro-2a cell line. The neuronal lineage of Neuro-2a cell line was confirmed by using antibody against ß-III tubulin protein. The cells were treated with different concentrations of piperine (µM: 10, 50 and 100) for 48 hrs at 37ºC. A dose of 100 µM was selected that induces a 50% inhibition in the cell growth calculated by MTT and morphometery assays. The result shows that in the presence of piperine neurite outgrowth was decreased in a dose dependent manner. The gene expression of TN-C, TNfnD and TnfnC were significantly reduced whereas the expression intensities of TnfnA1, TnfnA2, CSPGs and Laminin were significantly elevated when compared to their respective untreated controls. Similarly proinflammatory marker COX-2 expression was significantly inhibited in the presence of piperine when compared to untreated controls. This is the first time we have illustrated that irrespective of increased expressions of CSPGs, a significant reduction in Tenascin-C and its TNfnD and TNfnC domains are necessary to inhibit the tumor progression. Taken together, the capabilities of piperine to induce an apoptosis by decreasing the neurite outgrowth, proliferation rate and expression of TN-C and COX-2 in Neuro-2a cell line confirmed for its anticancerous and anti-inflammatory potential.

Neurite outgrowth properties of Calotropis procera: In search for a neuroprotectant.

In view of the well-documented medicinal properties of Calotropis procera (CP), the present study was designed to evaluate the neuroprotective effect of the extract. We have prepared a methanolic extract of Calotropis procera and screen varying concentration of CP (20, 30, 40, 50 and 70µg/ml) for the stimulatory potency on neurite outgrowth. The stimulatory effect of CP on neurite outgrowth was assessed in primary hippocampal neurons. Neurite lengths were measured using optika provison analysis software. Neuritogenesis was further analyzed by immunostaining by using specific neuronal marker ß III-tubulin. The data show that neurite outgrowth from hippocampal neurons were significantly enhanced in the presence of CP (40µg/ml). The most stimulatory neurite outgrowth effects were appeared after 48hrs incubation of neurons with CP (40µg/ml). These data confirm that CP extract could promote invitro hippocampal neurite outgrowth in a dose-dependent manner. Our results indicate that CP can be used as a healthy dietary supplement for the cognitive functions of the brain.

Neuroprotective capabilities of Vitex negundo in primary hippocampal neurons.

Vitex negundu (Vn) is a well-known aromatic shrub commonly used as a traditional folk medicine famous for its potential pharmacological and biological activities. Several chemical compounds are extracted and identified from the different parts of the Vn such as leaves, root, seeds and flowers. Number of researches reported the herb as antimicrobial, anti-androgenic, anti-osteoporotic, and anti-tumour, anti-cancer, anti-inflammatory, anti-oxidant, anti-hyperglycemic and hepatoprotective. The effects of Vn on neurite outgrowth have not been identified till now. Therefore present study was designed to investigate the neurite outgrowth effects of Vn extract in hippocampal neurons. Neurons from P0 mice were isolated and cultured in defined medium containing the different concentrations of Vn (20, 30, 40, 50, 100, 150 and 200 µg/ml) for 48 hrs. The presence of the neurites was confirmed by using ßIII-tubulin antibody which specifically labels only the neurites. Morphometric analysis was done by using Optika Pro-Vision software. The data show that Vn at 30 and 40 µg/ml significantly increased the mean average length of the longest neurite whereas at 150 and 200 µg/ml it significantly decreased the mean average length of the 10 longest neurite in hippocampal neurons. Nevertheless Vn did not show any significant effects on the sum of all the neurite lengths at any concentrations tested. Taken together the result shows that methanolic extract of Vn has potential to produce long neurites at 30 and 40 µg/ml and therefore can be act as a neuroprotective agent in the future drug development.

Diabetes Driven Oncogenesis and Anticancer Potential of Repurposed Antidiabetic Drug: A Systemic Review.

Diabetes and cancer are two prevalent disorders, pose significant public health challenges and contribute substantially to global mortality rates, with solely 10 million reported cancer-related deaths in 2020. This review explores the pathological association between diabetes and diverse cancer progressions, examining molecular mechanisms and potential therapeutic intersections. From altered metabolic landscapes to dysregulated signaling pathways, the intricate links are delineated, offering a comprehensive understanding of diabetes as a modulator of tumorigenesis. Cancer cells develop drug resistance through mechanisms like enhanced drug efflux, genetic mutations, and altered drug metabolism, allowing them to survive despite chemotherapeutic agent. Glucose emerges as a pivotal player in diabetes progression, and serving as a crucial energy source for cancer cells, supporting their biosynthetic needs and adaptation to diverse microenvironments. Glycation, a non-enzymatic process that produces advanced glycation end products (AGEs), has been linked to the etiology of cancer and has been shown in a number of tumor forms, such as leiomyosarcomas, adenocarcinomas, and squamous cell carcinomas. Furthermore, in aggressive and metastatic breast cancer, the receptor for AGEs (RAGE) is increased, which may increase the malignancy of the tumor. Reprogramming glucose metabolism manifests as hallmark cancer features, including accelerated cell proliferation, angiogenesis, metastasis, and evasion of apoptosis. This manuscript encapsulates the dual narrative of diabetes as a driver of cancer progression and the potential of repurposed antidiabetic drugs as formidable countermeasures. The amalgamation of mechanistic understanding and clinical trial outcomes establishes a robust foundation for further translational research and therapeutic advancements in the dynamic intersection of diabetes and cancer.

Cyanosomes: A pilot study.

Cyanobacteria are the most primitive, oxygen-evolving prokaryotic organism. Several, conspicuous investigations have been done around lipids from cyanobacteria. However, to date and to the best of our knowledge, no study was conducted to formulate and evaluate liposomal vesicles prepared from cyanobacterial lipid. In the present study, cyanosomes were formulated using natural lipids extracted from the cyanobacterium Synechococcus elongatus PCC7942 which were further loaded with thymoquinone. The results showed that the prepared cyanosomes were homogenous with an overall negative charge of particle size ranging between 200 to 210 nm and entrapment efficacy was 70.9 ± 1.86%. The obtained release profiles demonstrated sustained drug release pattern. The study of encapsulated thymoquinone on CCl4 induced liver insult in balb/c mice revealed the better efficacy of encapsulated thymoquinone as compared to thymoquinone alone indicating cyanosome as a promising candidate for drug carrier. However, more studies are required to establish the safety profile, pharmacokinetic pattern and biodistribution parameters of cyanosome for its clinical intricacies in future applications.

Monitoring of morphotoxic, cytotoxic and genotoxic potential of mancozeb using Allium assay.

The present experiment was designed to monitor the morphotoxic, cytotoxic and genotoxic potential of Mancozeb (fungicide) in non-target plants using bulbs of Allium cepa. Mancozeb is classified as a contact fungicide and is registered for use on a variety of crop plants. In the present monitoring, Allium cepa bulbs were exposed to different concentrations of mancozeb viz., 10, 30, 50, 70, 90, 110, 130 and 150 ppm for 24 and 48 h. The potential morphotoxic and cytotoxic effects of mancozeb were examined by determining the average root number, average root length, mitotic index, relative abnormality rate (%) and frequency of abnormalities (%). A progressive significant concentration and time dependent inhibition of the average root number, average root length indicated the morphotoxic nature. The cytotoxic effect was significantly increased for 48 h treatment as compared to 24 h treatment time, by reducing the mitotic index of meristematic cells. The results indicated an indirect genotoxic effect by inducing different types of chromosomal abnormalities, likely sticky, disoriented and fragmented chromosomes. Thus indicating that the investigated fungicide have genotoxic potential due to abnormal DNA condensation and chromosome coiling by spindle inactivation. The observations of cyto and genotoxic effects suggest that the fungicide mancozeb is clastogenic agent. Thus the different concentrations used in the field could be harmful for the end-receptors of food-chain and needs constant monitoring and management for the better development of crop plants.