RESUMO

Parkinson's Disease (PD) is a progressive disorder worldwide and its etiology remains unidentified. Over the last few decades, animal models of PD have been extensively utilized to explore the development and mechanisms of this neurodegenerative condition. Toxic and transgenic animal models for PD possess unique characteristics and constraints, necessitating careful consideration when selecting the appropriate model for research purposes. Animal models have played a significant role in uncovering the causes and development of PD, including its cellular and molecular processes. These models suggest that the disorder arises from intricate interplays between genetic predispositions and environmental influences. Every model possesses its unique set of strengths and weaknesses. This review provides a critical examination of animal models for PD and compares them with the features observed in the human manifestation of the disease.

RESUMO

The prevalence of neurodegenerative diseases has increased with longer life expectancies, necessitating the exploration of novel neuroprotective agents. Tangeretin, a polymethoxylated flavone derived from citrus fruits, has gathered attention for its potential therapeutic effects. This review highlights the neuroprotective properties of tangeretin via its antioxidant and anti-inflammatory mechanisms. Tangeretin demonstrates efficacy in mitigating oxidative stress, neuroinflammation, and neuronal damage across various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, and epilepsy. It shows promise in ameliorating cognitive deficits and memory impairments associated with these diseases. Moreover, tangeretin modulates multiple signalling pathways and protects against neuronal apoptosis, underscoring its potential as a therapeutic agent.

RESUMO

The prolonged exposure of agricultural soils to heavy metals from wastewater, particularly in areas near industrial facilities, poses a significant threat to the well-being of living organisms. The World Health Organization (WHO) has established standard permissible limits for heavy metals in agricultural soils to mitigate potential health hazards. Nevertheless, some agricultural fields continue to be irrigated with wastewater containing industrial effluents. This study aimed to assess the concentration of lead in soil samples collected from agricultural fields near industrial areas. Subsequently, we determined the lethal concentration (LC50) of lead (Pb) and other heavy metals for two Collembola species, namely Folsomia candida, a standard organism for soil ecotoxicity tests, and comparing it with Proisotoma minuta. The research further examined the toxic effects of lead exposure on these two species, revealing depletion in the energy reservoirs and alterations in the tissue histology of both organisms. The study revealed that lead can induce genotoxic damage as it evidently has moderate binding affinity with the ct-DNA and hence can cause DNA fragmentation and the formation of micronuclei. Elevated lipid peroxidation (LPO) levels and protein carbonylation levels were observed, alongside a reduction in antioxidant enzymes (CAT, SOD & GPx). These findings suggest that lead disrupts the balance between oxidants and the antioxidant enzyme system, impairing defense mechanisms and consequential derogatory damage within microarthropods. The investigation elucidates a complex network of various signaling pathways compromised as a result of lead toxicity. Hence, it presents a novel perspective that underscores the pressing necessity for implementing an integrated risk assessment framework at the investigated site.

Assuntos

RESUMO

Rotenone is a naturally occurring plant product used as an insecticide, pesticide and piscicide. It is lipophilic in nature and can cross the blood-brain barrier and induce the degeneration of neurons. It inhibits the mitochondrial respiratory chain complex I and stops the transfer of electrons. It induces ROS generation, which impairs mitochondrial activity. Rotenone is a toxic agent which causes the death of neurons. The present review describes the effect of rotenone on neurodegeneration with an emphasis on behavioral, pathological and neuropathological components carried out on various experimental models such as cell lines, Drosophila melanogaster, mice and rats.

Assuntos

RESUMO

Resveratrol is a biologically active natural phenolic plant product. It has several properties which make them useful to treat the disease. In this review, we have highlighted the neuroprotective effects of resveratrol. Several available animal models have been proven to help understand the disease pathway and mechanism of action by resveratrol. In this review, we have highlighted the neuroprotective activity of resveratrol in AD, which effectively counter the neurodegenerative disease by decreasing the formation of plaques. Resveratrol is a natural plant product that is easily available, cost-effective, and possesses neuroprotective activity, which is useful for treating neurodegenerative diseases. Resveratrol presents a promising avenue for AD treatment due to its diverse neuroprotective mechanisms. Given the ongoing global challenge in treating AD, researchers have increasingly focused on exploring the therapeutic potential of resveratrol.

Assuntos

RESUMO

Introduction: In the present study the cytotoxic and genotoxic effects of Bisphenol-A glycidyl methacrylate (BisGMA) was studied on the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. Materials and methods: The concentration of BisGMA i.e. 0.005, 0.010, 0.015 and 0.020 M were established in diet and the larvae were allowed to feed on it for 24 h. Results: A dose dependent significant increase in the activity of ß-galactosidase was observed compared to control. A significant dose dependent tissue damage was observed in the larvae exposed to 0.010, 0.015 and 0.020 M of BisGMA compared to control. A dose dependent significant increase in the Oxidative stress markers was observed compared to control. BisGMA also exhibit significant DNA damaged in the third instar larvae of transgenic D. melanogaster (hsp70-lacZ)Bg9 at the doses of 0.010, 0.015 and 0.020 M compared to control. Conclusion: BisGMA at 0.010, 0.015 and 0.020 M was found to be cytotoxic for the third instar larvae of transgenic D. melanogaster (hsp70-lacZ) Bg9.

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the depletion of striatal dopamine content and aggregation of alphasynuclein in the substantia nigra (SN). It is possible to treat the symptoms of PD with a variety of medications, but they often result in complications and are not able to cure or stop the progression of the disease. Flavonoids (the phytocomponents present in almost all fruits and vegetables) are the class of secondary metabolites that have generated a peak of interest because of their medicinal properties, including a reduction in the risk of PD. Several flavonoids such as quercetin, kaempferol, hesperitin, anthocyanin and many more have been reported for their anti- Parkinson's effect. This review deals with the neuroprotective benefits of different classes of flavonoids against PD.

Assuntos

RESUMO

Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aß) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.

Assuntos

RESUMO

Neurodegenerative diseases (NDDs), such as Alzheimer's and Parkinson's, are the most frequent age-related illnesses affecting millions worldwide. No effective medication for NDDs is known to date and current disease management approaches include neuroprotection strategies with the hope of maintaining and improving the function of neurons. Such strategies will not provide a cure on their own but are likely to delay disease progression by reducing the production of neurotoxic chemicals such as reactive oxygen species (ROS) and related inflammatory chemicals. Natural compounds such as flavonoids that provide neuroprotection via numerous mechanisms have attracted much attention in recent years. This review discusses evidence from different research models and clinical trials on the therapeutic potential of one promising flavonoid, apigenin, and how it can be helpful for NDDs in the future prospects. We have also discussed its chemistry, mechanism of action, and possible benefits in various examples of NDDs.

Assuntos

RESUMO

Bis(2-ethylhexyl) phthalate, generally known as DEHP is a synthetic compound mainly used as a plasticizer to make polyvinyl chloride products flexible and soft. The present work aimed to study the toxicity of Bis(2-ethylhexyl) phthalate on the third instar larvae of transgenic Drosophila melanogaster(hsp70-lacZ) Bg9. The hsp70 gene is associated with the ß-galactosidase in our present transgenic strain therefore, the more activity of ß-galactosidase will indirectly correspond to hsp70 expression. The third instar larvae were allowed to feed on the diet for 24 h having 0.001, 0.005, 0.01, and 0.02 M of Bis(2-ethylhexyl) phthalate at the final concentration. After the exposure of 24hrs, the larvae were subjected to ONPG assay, X-gal staining, trypan blue exclusion test, oxidative stress markers assays, and comet assay. A dose-dependent increase in hsp70 expression, tissue damage, Glutathione-S-transferase (GST) activity, lipid peroxidation, monoamine oxidase, caspase-9 & 3, protein carbonyl content (PCC), DNA damage and decrease in the glutathione (GSH) content, delta-aminolevulinic acid dehydrogenase (ẟ-ALD-D) and acetylcholinesterase activity were observed in the larvae exposed to 0.005, 0.01, 0.02 M of Bis-(2-ethylhexyl) phthalate. The dose of 0.001 M of Bis(2-ethylhexyl) phthalate did not showed any toxic effects and hence can be considered as No Observed Adverse Effect Level (NOAEL) for Bis(2-ethylhexyl) phthalate. The study supports the use of Drosophila for the evaluation of possible toxic effects associated with synthetic compounds.

Assuntos

RESUMO

CONCLUSION: The results suggest that donepezil hydrochloride is potent enough to reduce the AD symptoms being mimicked in transgenic flies.

RESUMO

BACKGROUND: An annual plant, Fenugreek (Trigonellafoenum-graecum L.) has well-known health care benefits in Ayurvedic and Chinese medicine. Its leaves and seeds have alkaloids, amino acids, caumarins, flavonoids, saponins, and other bioactive components. Various pharmacological properties such as antioxidants, hypoglycemic, and hypolipidemic have been attributed to fenugreek. Trigonelline, diosgenin, and 4- hydroxyisoleucine have shown neuroprotection against Alzheimer's disease, and the extract have also been reported to act as an anti-depressant, anti-anxiety, and also regulate cognitive functions. This review highlights various studies carried out on animals as well as on humans for the protective effect against Alzheimer's disease. METHODS: The data presented in this review is taken from popular search engines, viz, Google Scholar, PubMed, and Scopus. This review highlights the studies and clinical trials performed to show the protective effect of Fenugreek on neurodegenerative diseases with special reference to AD from 2005 to 2023. RESULTS: Fenugreek improves cognitive deficits by Nrf2-mediated antioxidative pathway and provides neuroprotection against amyloid-beta-induced mitochondria dysfunction. It enhances SOD and catalase activities and scavenges reactive oxygen species to protect the cellular organelle from oxidative stress. It normalizes the tubulin protein and improved axonal growth by regulating nerve growth factors. Fenugreek can also influence metabolism. DISCUSSION: Fenugreek significantly improves the pathological symptoms of neurodegenerative disease, especially AD and can be used as a therapeutic agent to control disease conditions as evidenced by the review of the literature.

Assuntos

RESUMO

Agents that suppress the toxic effect of arecoline (a chemical present in the Areca nut fruit) have become a need of the hour owing to its several harmful effects on human beings. Although some drug molecules have been developed for this purpose, yet, simple, easy to prepare, and economical molecules with remarkable potency are still a challenge to design. The present work thus becomes important as it involves the synthesis of a new charge transfer complex (CTC) material, which has, for the first time, been screened to investigate its effect on the toxic effects of arecoline. The newly designed material (CL), which is generated from the reaction between 2,4,6-trinitrophenol (TNP) and pyrazole (PYZ), has been crystallized by a slow evaporation method and characterized by employing spectral studies including single crystal X-ray crystallography. Spectrophotometry studies with the inclusion of the Benesi-Hildebrand equation reveal 1 : 1 stoichiometry and physical parameters of CL. Assays were used for determining the protective effect of CL against arecoline. CL was found to (dose-dependently) decrease ß-galactosidase activity, damage in tissue and DNA damage caused by arecoline (80 µM) in the third-instar larvae of the transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. The possible mechanism of this effect was explored through fluorescence and UV-vis spectroscopy. The possibility of suppression of arecoline action on the muscarinic acetylcholine receptor 1-G11 protein complex (found in the cell membrane) in the presence of CL was studied theoretically by molecular docking. Density functional theory (DFT) also theoretically supported various aspects of the designed material concerning the energy profile of the orbitals (HOMO-LUMO) as well as the energy minimized structure. Furthermore, time dependent (TD) DFT corroborated the electronic properties of the designed material.

Assuntos

RESUMO

Parkinson's disease (PD) is the second most debilitating neurodegenerative movement disorder. It is characterized by the presence of fibrillar alpha-synuclein amassed in the neurons, known as Lewy bodies. Certain cellular and molecular events are involved, leading to the degeneration of dopaminergic neurons. However, the origin and implication of such events are still uncertain. Nevertheless, the role of microRNAs (miRNAs) as important biomarkers and therapeutic molecules is unquestionable. The most challenging task by far in PD treatment has been its late diagnosis followed by therapeutics. miRNAs are an emerging hope to meet the need of early diagnosis, thereby promising an improved movement symptom and prolonged life of the patients. The continuous efforts in discovering the role of miRNAs could be made possible by the utilisation of various animal models of PD. These models help us understand insights into the mechanism of the disease. Moreover, miRNAs have been surfaced as therapeutically important molecules with distinct delivery systems enhancing their success rate. This review aims at providing an outline of different miRNAs implicated in either PD-associated gene regulation or involved in therapeutics.

Assuntos

RESUMO

Unani system of medicine is based on the use of natural plant products. Unani polyherbal formulations (UPFs) are being prescribed for the treatment of various ailments. The preparations of the UPFs also required the animal products such as honey and umber. UPFs have been reported to cure various diseases but still lack scientific credibility. The Unani system is based on the holistic approach; the synergistic role of the compounds has been suggested to play a protective role against the illness. The present review has compiled the studies carried out on UPFs used to treat various diseases with special reference to neurodegenerative ailments. The exorbitant cost of conventional treatment has led the world to think towards alternative therapy with less cost and no or little side effects compared to conventional treatments. More research is required for UPFs on the experimental models along with the case controlled studies in order to establish UPFs in the mainstream of treatment.

Assuntos

RESUMO

Background: Adjunct chlorhexidine mouthrinse is used routinely in orthodontic clinical practice for plaque control. However, chlorhexidine has genotoxic effects on the oral cells. Moreover, orthodontic appliance leach Ni, Cr metals ions into saliva causing toxicity of surrounding mucosa. Hence, the aim of the study was to assess the periodontal status and genotoxicity in orthodontic patients on fixed mechanotherapy with and without adjunct chlorhexidine using micronucleus (MN) test. Materials and Methods: A randomized control clinical trial was conducted in 30 patients who were on fixed mechanotherapy. The patients were randomly assigned into two treatment groups; Group-A (Control Group): Included 15 patients who are on fixed orthodontic therapy with mechanical plaque control measures only., Group-B (Experimental Group:) included 15 patients on fixed orthodontic therapy with mechanical plaque control and adjunct chlorhexidine mouthrinse (0.2%) for 2 weeks. Periodontal status and genotoxicity using MN test were done at following time points; T0: Just before start of the orthodontic treatment., T1: 2 weeks after start of the orthodontic treatment., T2: 6 weeks after start of the orthodontic treatment., T3: 12 weeks after start of the orthodontic treatment. Results: Plaque index (PI) and bleeding on probing (BOP) were significantly decreased in Group B as compared to Group A in the time intervals; T0-T2, T0-T3, T1-T3 (P < 0.05). Probing pocket depth (PPD) and Clinical attachment level (CAL) showed no significant change in both the groups. The genotoxicity assessed by MN test was significantly increased in Group B than Group A at time intervals; T0-T1, T0-T2 and T0-T3. Conclusion: Adjunct chlorhexidine resulted in decreased PI and BOP scores but nonsignificant change in PPD and CAL. However, the genotoxicity increased significantly in both the groups but more with adjunct chlorhexidine.

RESUMO

Alzheimer's Disease (AD) is characterized as a progressive neurodegenerative disease most commonly associated with memory deficits and cognitive decline. The formation of amyloid plaques and neurofibrillary tangles are important pathological markers of AD. The accumulation of amyloid plaques and neurofibrillary tangles leads to the loss of neurons including the cholinergic neurons thus decreasing the levels of acetylcholine (a neurotransmitter). To reduce the AD symptoms cholinesterase inhibitors are widely used to decrease the hydrolysis of acetylcholine released from presynaptic neurons. In the present study we have studied the effect of rivastigmine and galantamine (commonly used cholinesterase inhibitors) on the transgenic Drosophila model of AD expressing human Aß-42 in the neurons. The effect of similar doses of rivastigmine and galantamine (i.e. 0.1,1 and 10 â€‹mM) was studied on the climbing ability, lifespan, oxidative stress markers, caspase 9 and 3, acetylcholinesterase activity and on the formation of Aß-42 aggregates. The results suggest that the rivastigmine is more potent in reducing the oxidative stress and improving climbing ability of AD flies. Both the drugs were found to be effective in increasing the lifespan of AD flies. Galantamine was found to be a more potent inhibitor of acetylcholinesterase compared to rivastigmine. Galantamine prevents the formation of Aß-42 aggregates more effectively compared to rivastigmine.

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The available drugs improve the symptoms but do not play role in modifying disease effects. Currently, the treatment strategies focus on inhibiting the production of Aß-42 aggregates and tau filaments. In this context the natural plant products could act as a potent candidate. Therefore, we decided to study the effect of apigenin on the transgenic Drosophila model of AD i.e., expressing Aß-42 in the neurons. The AD flies were allowed to feed on the diet having 25, 50, 75 and 100 µM of apigenin for 30 days. The exposure of AD flies to apigenin showed a dose dependent significant decrease in the oxidative stress and delay in the loss of climbing ability. Apigenin also inhibits the activity of acetylcholinesterase. The immunostaining and molecular docking studies suggest that apigenin inhibits the formation of Aß-42 aggregates. Apigenin is potent in reducing the AD symptoms being mimicked in the transgenic Drosophila model of AD.

Assuntos

RESUMO

Human Central Nervous System (CNS) is the complex part of the human body, which regulates multiple cellular and molecular events taking place simultaneously. Parkinsons Disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). The pathological hallmarks of PD are loss of dopaminergic neurons in the substantianigra (SN) pars compacta (SNpc) and accumulation of misfolded α-synuclein, in intra-cytoplasmic inclusions called Lewy bodies (LBs). So far, there is no cure for PD, due to the complexities of molecular mechanisms and events taking place during the pathogenesis of PD. Drosophila melanogaster is an appropriate model organism to unravel the pathogenicity not only behind PD but also other NDs. In this context as numerous biological functions are preserved between Drosophila and humans. Apart from sharing 75% of human disease-causing genes homolog in Drosophila, behavioral responses like memory-based tests, negative geotaxis, courtship and mating are also well studied. The genetic, as well as environmental factors, can be studied in Drosophila to understand the geneenvironment interactions behind the disease condition. Through genetic manipulation, mutant flies can be generated harboring human orthologs, which can prove to be an excellent model to understand the effect of the mutant protein on the pathogenicity of NDs.

Assuntos

RESUMO

Alzheimer's Disease (AD) is one of the major neurodegenerative disorders. Deposition of amyloid fibrils and tau protein is associated with various pathological symptoms. Currently, limited medication is available for AD treatment. Most of the drugs are basically cholinesterase inhibitors and associated with various side effects. Natural plant products have shown potential as a therapeutic agent for the treatment of AD symptoms. A variety of secondary metabolites such as flavonoids, tannins, terpenoids, alkaloids, and phenols are used to reduce the progression of the disease. Plant products have fewer or no side effects and are easily available. The present review gives a detailed account of the potential of natural plant products against AD symptoms.

Assuntos