Toxicological Profile of Polyethylene Terephthalate (PET) Microplastic in Ingested Drosophila melanogaster (Oregon R+) and Its Adverse Effect on Behavior and Development.

Microplastics are readily available in the natural environment. Due to the pervasiveness of microplastic pollution, its effects on living organisms necessitate further investigation. The size, time of exposure, and amount of microplastic particles appear to be the most essential factor in determining their toxicological effects, either organismal or sub-organismal. For our research work, we preferred to work on a terrestrial model organism Drosophila melanogaster (Oregon R+). Therefore, in the present study, we characterized 2-100 µm size PET microplastic and confirmed its accumulation in Drosophila, which allowed us to proceed further in our research work. At larger dosages, research on locomotory activities such as climbing, jumping, and crawling indicated a decline in physiological and neuromuscular functions. Our studies also determined retarded development in flies and decreased survival rate in female flies after exposure to the highest concentration of microplastics. These experimental findings provide insight into the possible potential neurotoxic effects of microplastics and their detrimental effects on the development and growth of flies.

Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling.

Hepatotoxicity caused by the overdose of various medications is a leading cause of drug-induced liver injury. Overdose of drugs causes hepatocellular necrosis. Nutraceuticals are reported to prevent drug-induced liver failure. The present article aims to review the protection provided by various medicinal plants against hepatotoxic drugs. Ayurveda is considered a conventional restorative arrangement in India. It is consistently used for ages and is still used today to cure drug-induced hepatotoxicity by focusing on antioxidant stress response pathways such as the nuclear factor erythroid-2 (Nrf-2) antioxidant response element signaling pathway. Nrf-2 is a key transcription factor that entangles Kelch-like ECH-associating protein 1, a protein found in the cell cytoplasm. Some antioxidant enzymes, such as gamma glycine cysteine ligase (γ-GCL) and heme oxygenase-1 (HO-1), are expressed in Nrf-2 targeted genes. Their expression, in turn, decreases the stimulation of hepatic macrophages and induces the messenger RNA (mRNA) articulation of proinflammatory factors including tumor necrosis factor α. This review will cover various medicinal plants from a mechanistic view and how they stimulate and interact with Nrf-2, the master regulator of the antioxidant response to counterbalance oxidative stress. Interestingly, therapeutic plants have become popular in the medical sector due to safer yet effective supplementation for the prevention and treatment of new human diseases. The contemporary study is expected to collect information on a variety of therapeutic traditional herbs that have been studied in the context of drug-induced liver toxicity, as nutraceuticals are the most effective treatments for oxidative stress-induced hepatotoxicity. They are less genotoxic, have a lower cost, and are readily available. Together, nutraceuticals exert protective effects against drug-induced hepatotoxicity through the inhibition of oxidative stress, inflammation, and apoptosis. Its mechanism(s) are considered to be associated with the γ-GCL/HO-1 and Nrf-2 signaling pathways.KEY TEACHING POINTSThe liver is the most significant vital organ that carries out metabolic activities of the body such as the synthesis of glycogen, the formation of triglycerides and cholesterol, as well as the formation of bile.Acute liver failure is caused by the consumption of certain drugs; drug-induced liver injury is the major condition.The chemopreventive activity of nutraceuticals may be related to oxidative stress reduction and attenuation of biosynthetic processes involved in hepatic injury via amelioration of the nuclear factor erythroid-2 (Nrf-2) signaling pathway.Nrf-2 is a key transcription factor that is found in the cell cytoplasm resulting in the expression of various genes such as gamma glycine cysteine ligase and heme oxygenase-1.Nutraceutical-rich phytochemicals possess high antioxidant activity, which helps in the prevention of hepatic injury.

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases.

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

Proteinopathies: Deciphering Physiology and Mechanisms to Develop Effective Therapies for Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are a cluster of diseases marked by progressive neuronal loss, axonal transport blockage, mitochondrial dysfunction, oxidative stress, neuroinflammation, and aggregation of misfolded proteins. NDs are more prevalent beyond the age of 50, and their symptoms often include motor and cognitive impairment. Even though various proteins are involved in different NDs, the mechanisms of protein misfolding and aggregation are very similar. Recently, several studies have discovered that, like prions, these misfolded proteins have the inherent capability of translocation from one neuron to another, thus having far-reaching implications for understanding the processes involved in the onset and progression of NDs, as well as the development of innovative therapy and diagnostic options. These misfolded proteins can also influence the transcription of other proteins and form aggregates, tangles, plaques, and inclusion bodies, which then accumulate in the CNS, leading to neuronal dysfunction and neurodegeneration. This review demonstrates protein misfolding and aggregation in NDs, and similarities and differences between different protein aggregates have been discussed. Furthermore, we have also reviewed the disposal of protein aggregates, the various molecular machinery involved in the process, their regulation, and how these molecular mechanisms are targeted to build innovative therapeutic and diagnostic procedures. In addition, the landscape of various therapeutic interventions for targeting protein aggregation for the effective prevention or treatment of NDs has also been discussed.

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers.

Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and motor sclerosis. This study aimed to compare the ethnopharmacological effects of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) on the amelioration of rotenone-induced toxicity in wild-type Drosophila melanogaster (Oregon R+) at biochemical, cellular, and behavioral levels. Phytoextracts were prepared from all three plants, i.e., UD, MC, and MK (aqueous and ethanolic fractions), and their bioactive compounds were evaluated using in vitro biochemical parameters (DPPH, ABTS, TPC, and TFC), UV-Vis, followed by FT-IR and HPLC. Third instar larvae and freshly eclosed flies were treated with 500 µM rotenone alone or in combination with UD, MC, and MK for 24 to 120 h. Following exposure, cytotoxicity (dye exclusion test), biochemical (protein estimation and acetylcholinesterase inhibition assays), and behavioral assays (climbing and jumping assays) were performed. Among all three plant extracts, MK exhibited the highest antioxidant properties due to the highest TPC, TFC, DPPH, and ABTS, followed by UD, then MC. The overall trend was MK > UD > MC. In this context, ethnopharmacological properties mimic the same effect in Drosophila, exhibiting significantly (p < 0.05) reduced cytotoxicity (trypan blue), improved biochemical parameters (proteotoxicity and AChE activity), and better behavioral parameters in the organisms cotreated with phyto extracts compared with rotenone. Conclusively, UV-Vis, FTIR, and HPLC analyses differentiated the plant extracts. The findings of this research may be beneficial in the use of select herbs as viable sources of phyto-ingredients that could be of interest in nutraceutical development and various clinical applications.

Contributive Role of Hyperglycemia and Hypoglycemia Towards the Development of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the causes of dementia that results from several infections/biological conditions leading to either cell disruption or loss of neuronal communication. Studies have documented the accumulation of two proteins, beta-amyloid (Aß), which accumulates on the exteriors of neurons, and tau (Tau), which assembles at the interiors of brain cells and is chiefly liable for the progression of the disease. Several molecular and cellular pathways account for the accumulation of amyloid-ß and the formation of neurofibrillary tangles, which are phosphorylated variants of Tau protein. Moreover, research has revealed a potential connection between AD and diabetes. It has also been demonstrated that both hypoglycemia and hyperglycemia have a significant role in the development of AD. In addition, SUMO (small ubiquitin-like modifier protein) plays a crucial role in the pathogenesis of AD. SUMOylation is the process by which modification of amyloid precursor protein (APP) and Tau takes place. Furthermore, Drosophila melanogaster has proven to be an efficient model organism in studies to establish the relationship between AD and variations in blood glucose levels. In addition, the review successfully identifies the common pathway that links the effects of fluctuations in glucose levels on AD pathogenesis and advancements.