Antibacterial potential of selected phytomolecules: An experimental study.

Antibiotic resistance is a snowballing international threat. Some of the antibiotics have lost their effectiveness due to overuse and underuse. Thus, there is an urgent need to tackle this global challenge, either by inhibiting the resistance mechanisms or by the development of new chemical entities. Thus, in the current study, the antibacterial activity of selected phytomolecules was investigated against bacterial strains, alone and in combination, with standard drugs. The antibacterial potential of these phytomolecules was explored using in vitro assays (microtiter assay, bacterial growth kinetics, percentage retardation of growth, and antimicrobial synergy study) and in vivo studies (zebrafish infection model). In vitro and in vivo studies have shown promising antibacterial effects against, both, Gram-positive and Gram-negative bacteria. Moreover, a cell viability assay also indicated the cytoprotective effect of these phytomolecules in combination with standard antibiotics (SABX). Thus, these phytomolecules could be a promising broad-spectrum antibacterial agent in combination with standard antibiotics.

Mitochondrial dysfunction and traffic jams in amyotrophic lateral sclerosis.

Neurodegenerative diseases are characterized by progressive neuronal loss anatomically or physiologically and accumulation of protein in the cells. Mitochondria provide energy to these neuronal cells consuming 20% of the body's oxygen. Mitochondria are the dynamic membrane-bound cell organelles that function to generate ATP, regulate calcium homeostasis, and produce reactive oxygen species. Because of alterations in the electron transport chain, mutation, and environmental toxins, there is reduced ATP production, calcium dyshomeostasis, and increased oxidative stress, resulting in mitochondrial dysfunction, leading to the pathogenesis of neurodegenerative diseases such as ALS. ALS is described as the loss of upper and lower motor neurons resulting in progressive muscle denervation and loss of voluntary movements. There are multiple shreds of evidence in the literature regarding the mechanism involved in mitochondrial dysfunction and possible therapeutic targets to treat the condition. Moreover, different studies reported the role of different gene mutations and malfunctions in transport system responsible for the accumulation and aggregation of the proteins inside the brain cells. This accumulation and/or aggregation of proteins in the neuronal cells is known as neuronal traffic jam, which also plays the leading role in the progressive neurodegenerative diseases. In this review, we have elucidated the critical insights into mitochondrial dysfunction and neuronal traffic jam; and its role in the initiation and progression of ALS. Moreover, the pharmacological targets and possible conducts to this scenario are also brought together.

Importance of Zebrafish as an Efficient Research Model for the Screening of Novel Therapeutics in Neurological Disorders.

Over the previous years, the use of an animal model has become very common for the screening of novel drugs. Animal model represents the complex problems of humans into the simplest forms, so these can be extended further to be included in the experimental procedure. The most successful models in neuroscience, rats and mice, are undoubtedly considered as one of the best models to understand the psychology of the mammalian brain and its associated functions involved in behavioral repertoire. Moreover, recently researchers in behavioral neuroscience are focusing more on the use of aquatic animals, especially fish, as model species due to their simplicity and cost-effectiveness. Zebrafish (Danio rerio) is a tropical fish from the minnow family, a genetic structure surprisingly 84% similar to humans. It is gaining popularity as a model to study the mechanism in behavioral neuropharmacology. Moreover, zebrafish has numerous advantages over other rodent models like the ease in maintenance due to their small size, more breeding power, transparency of embryos, overall reduced cost of experimentation, and many more. Nowadays, it is considered an ideal model to study the neurobehavioral aspects with relevance to humans. It is also used in a variety of scientific studies like genetics, neuroscience, pharmacology, and toxicology. In this manuscript, we have described the feasibility and importance of zebrafish as a model for the screening of novel drugs for different neurological disorders.

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson's Disease: A Perspective on Associated Therapeutic Interventions.

Current pharmacotherapy of Parkinson's disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient's life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

Phytomolecules against bacterial biofilm and efflux pump: an in silico and in vitro study.

Antibiotic resistance is a global threat whose incidences are increasing day by day worldwide. Thus, there is a need for new chemical entities (NCEs) or exploration of existing molecules against these types of infections. In the current investigation, we have tested the inhibitory potential of four different phytomolecules (berberine, gallic acid, piperine, and rutin) against bacterial biofilm and efflux pumps by using in-silico and in-vitro techniques. The phytomolecules (berberine, piperine, and rutin) except gallic acid have shown good interaction towards biofilm and efflux pump proteins. Further, In-vitro studies have also shown the good inhibitory effect of tested phytomolecules (berberine, rutin, and piperine) against bacterial biofilm formation and efflux pumps. In conclusion, berberine, piperine, and rutin could be the promising antibacterial candidates, particularly against resistant bacterial strains.Communicated by Ramaswamy H. Sarma.