Essential oils for clinical aromatherapy: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Aromatherapy, a holistic healing practice utilizing the aromatic essences of plant-derived essential oils, has gained significant attention for its therapeutic potential in promoting overall well-being. Use of phytoconstituent based essential oil has played a significant role in the evolving therapeutic avenue of aromatherapy as a complementary system of medicine. AIM OF THE STUDY: This comprehensive review article aims to explore the usage of essential oils for aromatherapy, shedding light on their diverse applications, scientific evidence, and safety considerations. Furthermore, the growing interest in using essential oils as complementary therapies in conjunction with conventional medicine is explored, underscoring the significance of collaborative healthcare approaches. MATERIALS AND METHODS: Literature search was performed from databases like PubMed, ScienceDirect, Scopus, and Bentham using keywords like Aromatherapy, Aromatic Plants, Essential oils, Phytotherapy, and complementary medicine. The keywords were used to identify literature with therapeutic and mechanistic details of herbal agents with desired action. RESULTS: The integration of traditional knowledge with modern scientific research has led to a renewed interest in essential oils as valuable tools in contemporary healthcare. Various extraction methods used to obtain essential oils are presented, emphasizing their impact on the oil's chemical composition and therapeutic properties. Additionally, the article scrutinizes the factors influencing the quality and purity of essential oils, elucidating the significance of standardization and certification for safe usage. A comprehensive assessment of the therapeutic effects of essential oils is provided, encompassing their potential as antimicrobial, analgesic, anxiolytic, and anti-inflammatory agents, among others. Clinical trials and preclinical studies are discussed to consolidate the existing evidence on their efficacy in treating diverse health conditions, both physical and psychological. Safety considerations are of paramount importance when employing essential oils, and this review addresses potential adverse effects, contraindications, and best practices to ensure responsible usage. CONCLUSIONS: This comprehensive review provides valuable insights into the exploration of essential oils for aromatherapy, emphasizing their potential as natural and potent remedies for a wide range of ailments. By amalgamating traditional wisdom and modern research, this article aims to encourage further investigation into the therapeutic benefits of essential oils while advocating for their responsible and evidence-based incorporation into healthcare practices.

Microtubule acetylation dyshomeostasis in Parkinson's disease.

The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule (MT)-mediated axonal transport system. This mechanistically regulated system delivers cargos (proteins, mRNAs and organelles such as mitochondria) back and forth from the soma to the synapse. Motor proteins like kinesins and dynein mechanistically regulate polarized anterograde (from the soma to the synapse) and retrograde (from the synapse to the soma) commute of the cargos, respectively. Proficient axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications (PTMs) of α- and ß-tubulin heterodimers, core components constructing the MTs. Occurring within the lumen of MTs, K40 acetylation of α-tubulin via α-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible, which in turn promotes their lifespan. The movement of various motor proteins, including kinesin-1 (responsible for axonal mitochondrial commute), is enhanced by this PTM, and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions, including Alzheimer's disease and Parkinson's disease (PD). PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation levels. Although the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question, our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in PD. The enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly explored. Moving towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it.

GSK-3ß: An exuberating neuroinflammatory mediator in Parkinson's disease.

Neuroinflammation is a critical degradative condition affecting neurons in the brain. Progressive neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease (PD) have been strongly linked to neuroinflammation. The trigger point for inflammatory conditions in the cells and body is the physiological immune system. The immune response mediated by glial cells and astrocytes can rectify the physiological alterations occurring in the cell for the time being but prolonged activation leads to pathological progression. The proteins mediating such an inflammatory response, as per the available literature, are undoubtedly GSK-3ß, NLRP3, TNF, PPARγ, and NF-κB, along with a few other mediatory proteins. NLRP3 inflammasome is undeniably a principal instigator of the neuroinflammatory response, but the regulatory pathways controlling its activation are still unclear, besides less clarity for the interplay between different inflammatory proteins. Recent reports have suggested the involvement of GSK-3ß in regulating NLRP3 activation, but the exact mechanistic pathway remains vague. In the current review, we attempt to provide an elaborate description of crosstalk between inflammatory markers and GSK-3ß mediated neuroinflammation progression, linking it to regulatory transcription factors and posttranslational modification of proteins. The recent clinical therapeutic advances targeting these proteins are also discussed in parallel to provide a comprehensive view of the progress made in PD management and lacunas still existing in the field.

Understanding the involvement of innate immunity and the Nrf2-NLRP3 axis on mitochondrial health in Parkinson's disease.

Parkinson's disease (PD), a multifactorial movement disorder, is interlinked with numerous molecular pathways, including neuroinflammation, which is a critical factor in the development and progression of PD. Microglia play a central role in driving neuroinflammation through activation and overexpression of the M1 phenotype, which has a significant impact on mitochondria. Multiple regulators converge together, and among these, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes have been implicated in transmitting inflammatory and deleterious components to the mitochondria. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the NLRP3 inflammasome and acts as the saviour of the mitochondria. Together, the NLRP3-Nrf2 axis functions in regulating mitochondrial function in the case of PD. It regulates fundamental processes such as oxidative stress, mitochondrial respiratory function, and mitochondrial dynamics. In this review, we discuss the contributions that a variety of miRNAs make to the regulation of the NLRP3 inflammasome and Nrf2, which can be used to target this important axis and contribute to the preservation of mitochondrial integrity. This axis may prove to be a crucial target for extending the lives of Parkinson's patients by deferring neuroinflammatory damage to mitochondria.

Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's Disease: An Update.

Memory, cognition, dementia, and neurodegeneration are complexly interlinked processes with various mechanistic pathways, leading to a range of clinical outcomes. They are strongly associated with pathological conditions like Alzheimer's disease, Parkinson's disease, schizophrenia, and stroke and are a growing concern for their timely diagnosis and management. Several cognitionenhancing interventions for management include non-pharmacological interventions like diet, exercise, and physical activity, while pharmacological interventions include medicinal agents, herbal agents, and nutritional supplements. This review critically analyzed and discussed the currently available agents under different drug development phases designed to target the molecular targets, including cholinergic receptor, glutamatergic system, GABAergic targets, glycine site, serotonergic targets, histamine receptors, etc. Understanding memory formation and pathways involved therein aids in opening the new gateways to treating cognitive disorders. However, clinical studies suggest that there is still a dearth of knowledge about the pathological mechanism involved in neurological conditions, making the dropouts of agents from the initial phases of the clinical trial. Hence, a better understanding of the disease biology, mode of drug action, and interlinked mechanistic pathways at a molecular level is required.

Pathological and Therapeutic Advances in Parkinson's Disease: Mitochondria in the Interplay.

Parkinson's disease (PD) is the second most common neurodegenerative illness majorly affecting the population between the ages of 55 to 65 years. Progressive dopaminergic neuronal loss and the collective assemblage of misfolded alpha-synuclein in the substantia nigra, remain notable neuro-pathological hallmarks of the disease. Multitudes of mechanistic pathways have been proposed in attempts to unravel the pathogenesis of PD but still, it remains elusive. The convergence of PD pathology is found in organelle dysfunction where mitochondria remain a major contributor. Mitochondrial processes like bioenergetics, mitochondrial dynamics, and mitophagy are under strict regulation by the mitochondrial genome and nuclear genome. These processes aggravate neurodegenerative activities upon alteration through neuroinflammation, oxidative damage, apoptosis, and proteostatic stress. Therefore, the mitochondria have grabbed a central position in the patho-mechanistic exploration of neurodegenerative diseases like PD. The management of PD remains a challenge to physicians to date, due to the variable therapeutic response of patients and the limitation of conventional chemical agents which only offer symptomatic relief with minimal to no disease-modifying effect. This review describes the patho-mechanistic pathways involved in PD not only limited to protein dyshomeostasis and oxidative stress, but explicit attention has been drawn to exploring mechanisms like organelle dysfunction, primarily mitochondria and mitochondrial genome influence, while delineating the newer exploratory targets such as GBA1, GLP, LRRK2, and miRNAs and therapeutic agents targeting them.

Role of gut microbiota in depression: Understanding molecular pathways, recent research, and future direction.

Gut microbiota, also known as the "second brain" in humans because of the regulatory role it has on the central nervous system via neuronal, chemical and immune pathways. It has been proven that there exists a bidirectional communication between the gut and the brain. Increasing evidence supports that this crosstalk is linked to the etiology and treatment of depression. Reports suggest that the gut microbiota control the host epigenetic machinery in depression and gut dysbiosis causes negative epigenetic modifications via mechanisms like histone acetylation, DNA methylation and non-coding RNA mediated gene inhibition. The gut microbiome can be a promising approach for the management of depression. The diet and dietary metabolites like kynurenine, tryptophan, and propionic acid also greatly influence the microbiome composition and thereby, the physiological activities. This review gives a bird-eye view on the pathological updates and currently used treatment approaches targeting the gut microbiota in depression.

Neuroepigenetic Changes in DNA Methylation Affecting Diabetes-Induced Cognitive Impairment.

Chronic diabetic conditions have been associated with certain cerebral complications, that include neurobehavioral dysfunctional patterns and morphological alterations of neurons, especially the hippocampus. Neuroanatomical studies done by the authors have shown decreased total dendritic length, intersections, dendritic length per branch order and nodes in the CA1 hippocampal region of the diabetic brain as compared to its normal control group, indicating reduced dendritic arborization of the hippocampal CA1 neurons. Epigenetic alterations in the brain are well known to affect age-associated disorders, however its association with the evolving diabetes-induced damage in the brain is still not fully understood. DNA hypermethylation within the neurons, tend to silent the gene expression of several regulatory proteins. The findings in the study have shown an increase in global DNA methylation in palmitic acid-induced lipotoxic Neuro-2a cells as well as within the diabetic mice brain. Inhibiting DNA methylation, restored the levels of HSF1 and certain HSPs, suggesting plausible effect of DNMTs in maintaining the proteostasis and synaptic fidelity. Neuroinflammation, as exhibited by the astrocyte activation (GFAP), were further significantly decreased in the 5-azadeoxycytidine group (DNMT inhibitor). This was further evidenced by decrease in proinflammatory cytokines TNF⍺, IL-6, and mediators iNOS and Phospho-NFkB. Our results suggest that changes in DNA methylation advocate epigenetic dysregulation and its involvement in disrupting the synaptic exactitude in the hippocampus of diabetic mice model, providing an insight into the pathophysiology of diabetes-induced neuroepigenetic changes.

NLRP3 inflammasomes: A potential target to improve mitochondrial biogenesis in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative condition for which no approved treatment exists to prevent collective neuronal death. There is ample evidence that mitochondrial dysfunction, reactive oxygen species (ROS), and associated caspase activity underlie the pathology observed. Neurons rely on mitochondrial activity since they have such high energy consumption. Therefore, it is not surprising that mitochondrial alterations favour neuronal degeneration. In particular, mitochondrial dysregulation contributes to PD, based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models. Also, it is known that inflammatory cytokine-mediated neuroinflammation is the key pathogenic mechanism in neuronal loss. In recent years, the research has focussed on mitochondria being the platform for nucleotide-binding oligomerization domain-like receptors 3 (NLRP3) inflammasome activation. Mitochondrial dysfunction and NLRP3 activation are emerging as critical players in inducing and sustaining neuroinflammation. Moreover, mitochondrial-derived ROS and mitochondrial DNA (mtDNA) could serve as the priming signal for forming inflammasome complexes responsible for the activation, maturation, and release of pro-inflammatory cytokines, including interleukin-1(IL-1) and interleukin-18 (IL-18). The current review takes a more comprehensive approach to elucidating the link between mitochondrial dysfunction and aberrant NLRP3 activation in PD. In addition, we focus on some inhibitors of NLRP3 inflammatory pathways to alleviate the progression of PD.

Phytochemicals in the Management of Arsenic Toxicity.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.