Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

Diosgenin, a steroidal sapogenin, arrests arthritis through modulation of inflammatory cytokines and oxidative stress biomarkers in Wistar rats.

Diosgenin (DGN) is a well-known steroidal sapogenin that is obtained from the hydrolysis of dioscin. The current research aimed to explore the anti-inflammatory and anti-arthritic potential of DGN alone and in combination with methotrexate (MTX). The in-vitro antioxidant, and anti-arthritic potential was assessed by protein denaturation and Human red blood cell membrane stabilization assays. The in-vivo anti-inflammatory effect was examined by carrageenan-induced paw edema and xylene-induced ear edema methods. The arthritis was induced in Wistar rats by inoculation of 0.1 ml Complete Freund's adjuvant in the left hind paw at day 1. The arthritic animals received MTX 1 mg/kg as standard, DGN at 5, 10, 20 mg/kg, and a combination treatment (DGN 20 mg/kg + MTX) was administered orally from 8 to 28th day while normal and disease control received normal saline. DGN at 1600 µg/ml exhibited the highest in-vitro activities in contrast to other tested concentrations. DGN at 20 mg/kg exhibited the maximum (p < 0.05-0.0001) inhibition of inflammation in carrageenan and xyleneinduced edema models. Treatment with DGN and MTX alone and in combination significantly reduced the paw diameter, body weight, arthritic index, and pain. It restored altered blood parameters and oxidative stress biomarkers in contrast to the diseased control rats. DGN profoundly (P < 0.0001) downregulated mRNA expression of TNF-α, IL-1ß, NF-ĸß, and COX-2 while upregulated IL-4 and -10 in treated rats. The combination of DGN with MTX showed the highest therapeutic efficacy than individual therapy, so it can be used as an adjunct for rheumatoid arthritis treatment.

Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials.

Daphnetin (DAP), a coumarin derivative extracted from Daphne species, is biologically active phytochemical with copious bioactivities including anti-inflammatory, anti-oxidant, neuroprotective, analgesic, anti-pyretic, anti-malarial, anti-bacterial, anti-arthritic, neuroprotective, hepatoprotective, nephroprotective, and anti-cancer activities. A wide range of studies have been conducted exploring the significance and therapeutic potential of DAP. This study reviewed various databases such as NCBI, PubMed, Web of Science, Scopus and Google Scholar for published research articles regarding the sources, synthesis, and various bioactivities of DAP using different key words, including but not limited to "pharmacological activities," "sources," "neuroprotective effect," "synthesis," "cancer," "anti-inflammatory effect" of "daphnetin." Furthermore, this review encompasses both in-vivo and in-vitro studies on DAP for treating various diseases. A comprehensive review of the literature revealed that the DAP had a promising pharmacological and safety profile, and could be employed as a pharmaceutical moiety to treat a variety of illnesses including microbial infections, cancer, arthritis, hepatic damage, inflammation and neurological anomalies. The current review intends to provide an in-depth focus on all pharmacological activities and therapeutic approaches for the pharmaceutical and biomedical researchers.