Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.

Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines. In conventional medicational therapies, several plants have been reported to bestow remedial effects. Phytochemicals from medicinal plants can provide a better and safer alternative to synthetic molecules. Many phytochemicals have been identified that cure the human body from a number of diseases. The present article reviews the potential efficacy of plant-derived alkaloids, which possess potential therapeutic effects against several NDDs including Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD), Epilepsy, Schizophrenia, and stroke. Alkaloids include isoquinoline, indole, pyrroloindole, oxindole, piperidine, pyridine, aporphine, vinca, β-carboline, methylxanthene, lycopodium, and erythrine byproducts. Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of α-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist.

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut–lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman’s correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.