A review of the gastrointestinal, olfactory, and skin abnormalities in patients with Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative motor disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. The substantia nigra is neither the first nor the only brain region affected by PD. Recent and old studies have shown that PD does not only affect the CNS; in fact, autonomic innervation in the GIT, skin, and olfactory system was found to be affected by α-synuclein pathology outside the CNS, affecting patients' quality of life. In the gastrointestinal system, dysphagia, constipation, and bacterial overgrowth in the small intestine are common in patients with PD. In addition, several skin conditions were reported in PD, including seborrheic dermatitis, rosacea, melanoma, and others. Finally, olfactory system dysfunction, such as reduced touch sensation and smell, was associated with motor abnormalities. Further high-quality studies are needed to develop reliable tests that could help in the early diagnosis of PD.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Target-based virtual screening and molecular interaction studies for lead identification of natural olive compounds against glioblastoma multiforme.

Glioblastoma multiforme, a rare traumatic brain disorder, is at the research climax for its uncontrolled growth leading to a catastrophic outcome. Throwing light on the target-based virtual screening of drugs using natural phytocompounds is a striking cornerstone in glioblastoma-based drug discovery, accelerating with leaps and bounds. This project aims to develop promising lead compounds against glioblastoma brain cancer using OliveNet™, an open-source database. In this pursuit, our rationale for selecting molecules was based on their capability to pass through the blood-brain barrier. Out of 51 derivative molecules from flavonoids and polyphenols, 17 molecules were screened out bearing the best ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, alongside fulfilling our rationale of lead selection. Two polyphenols, 3,4,5-trimethoxybenzoic acid and 4-ethyl guaiacol, have binding affinity for the antioxidant flavonoid luteolin of -5.1 and -4.3 kcal/mol, respectively. According to docking studies, the residues ASN1960, ASN1966, ASN1960, PHE1984, TYR1896, VAL1911, and LYS1966 make both polar and nonpolar interactions with 3,4,5-trimethoxybenzoic acid and 4-ethylguanidine, respectively. LD50 values of toxicity screening using TOX Pro brought to limelight the excellent safety profile of polyphenols and flavonoids. Furthermore, studies using in silico cytotoxicity prediction and molecular modelling have decisively shown that these polyphenols are likely to be effective brain cancer inhibitors and promising future lead candidates against glioblastoma multiforme.

Ameliorative Effects of Phytomedicines on Alzheimer's Patients.

INTRODUCTION: Alzheimer's disease (AD) is a progressive, neurodegenerative disease that severely affects individuals' cognitive abilities, memory, and quality of life. It affects the elderly population, and there is no permanent prevention or cures available to date, treatments mainly aiming to alleviate the symptoms as and when they appear. Alternate therapeutic approaches are being researched constantly, and there is a growing focus on phytomedicine, herbal medicine, organic compounds, and ayurvedic compounds for the treatment of AD. METHODS: The current study aims to provide an extensive review of these plants against AD from the currently existing literature. Most relevant keywords like Alzheimer's Disease, phytomedicines, ethnic medicines, the role of phytomedicine in neuroprotection, common phytomedicines against AD, etc., were used to select the plants and their metabolites effective in treating AD. The study focuses on six plants: Panax ginseng, Ginkgo biloba, Bacopa monnieri, Withania somnifera, Curcuma longa, and Lavandula angustifolia. Their active components have been studied along with neuroprotective properties, and evidence of in-vitro, pre-clinical, and clinical studies conducted to prove their therapeutic potential against the disease have been presented. RESULTS: All plants envisaged in the study show potential for fighting against AD to varying degrees. Their compounds have shown therapeutic effects by reversing the neurological changes such as clearing Aß plaque and neurofibrillary tangle formation, and ameliorative effects against neurodegeneration through processes including improving concentration, memory, cognition and learning, higher working and cue memory, improved spatial memory, inhibition of NF-κB expression, inhibiting the release of pro-inflammatory cytokines, inhibition of AChE and lipid peroxidase enzymes, and reduction of interleukin levels and tumor necrosis factor-alpha. CONCLUSION: The present review is a comprehensive and up-to-date analysis supported by the evidentiary proofs from pre-clinical studies, meta-analyses, and review papers related to natural phytochemicals' impact on neurodegenerative disorders like AD.

Leucine encoding codon TTG shows an inverse relationship with GC content in genes involved in neurodegeneration with iron accumulation.

We determined various forces involved in shaping codon usage of the genes linked to brain iron accumulation and infantile neuroaxonal dystrophy. The analysis paved the way for determining the forces responsible for composition, expression level, physical properties and codon bias of a gene. An interesting observation related to composition was that, on all the three codon positions, any two of the four nucleotides had similar compositions. CpG, TpA, and GpT dinucleotides were underrepresented with the overrepresentation of TpG dinucleotide. CpG and TpA containing codons ATA, CTA, TCG, and GCG were underrepresented, while TpG dinucleotide containing codon CTG was overrepresented, indicative of compositional constraints importance. GC ending codons were favored when the genome is GC rich, except leucine encoding codon TTG, which exhibits an inverse relationship with GC content. Nucleotide disproportions are found associated with the physical properties of proteins. The values of CAI and ENc are suggestive of low codon bias in genes. Considering the results of neutrality analysis, parity analysis, underrepresentation of TpA and CpG codons, and over-representation of TpG codons, the correlation between the compositional constraints and skew relationships with protein properties suggested the role of all the three selectional, mutational and compositional forces in shaping codon usage with the dominance of selectional pressure.

Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects.

Inflammation is a natural protective mechanism that occurs when the body's tissue homeostatic mechanisms are disrupted by biotic, physical, or chemical agents. The immune response generates pro-inflammatory mediators, but excessive output, such as chronic inflammation, contributes to many persistent diseases. Some phenolic compounds work in tandem with nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit pro-inflammatory mediators' activity or gene expression, including cyclooxygenase (COX). Various phenolic compounds can also act on transcription factors, such as nuclear factor-κB (NF-κB) or nuclear factor-erythroid factor 2-related factor 2 (Nrf-2), to up-or downregulate elements within the antioxidant response pathways. Phenolic compounds can inhibit enzymes associated with the development of human diseases and have been used to treat various common human ailments, including hypertension, metabolic problems, incendiary infections, and neurodegenerative diseases. The inhibition of the angiotensin-converting enzyme (ACE) by phenolic compounds has been used to treat hypertension. The inhibition of carbohydrate hydrolyzing enzyme represents a type 2 diabetes mellitus therapy, and cholinesterase inhibition has been applied to treat Alzheimer's disease (AD). Phenolic compounds have also demonstrated anti-inflammatory properties to treat skin diseases, rheumatoid arthritis, and inflammatory bowel disease. Plant extracts and phenolic compounds exert protective effects against oxidative stress and inflammation caused by airborne particulate matter, in addition to a range of anti-inflammatory, anticancer, anti-aging, antibacterial, and antiviral activities. Dietary polyphenols have been used to prevent and treat allergy-related diseases. The chemical and biological contributions of phenolic compounds to cardiovascular disease have also been described. This review summarizes the recent progress delineating the multifunctional roles of phenolic compounds, including their anti-inflammatory properties and the molecular pathways through which they exert anti-inflammatory effects on metabolic disorders. This study also discusses current issues and potential prospects for the therapeutic application of phenolic compounds to various human diseases.