Mitigating Effect of Lindera obtusiloba Blume Extract on Neuroinflammation in Microglial Cells and Scopolamine-Induced Amnesia in Mice.

Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditionally in the treatment of trauma and neuralgia. In this study, we investigated the neuroinflammatory effect of methanol extract of L. obtusiloba stem (LOS-ME) in a scopolamine-induced amnesia model and lipopolysaccharide (LPS)-stimulated BV2 microglia cells. LOS-ME downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, inflammatory cytokines, and inhibited the phosphorylation of nuclear factor kappa-B (NF-ĸB) and extracellular signal-regulated kinase (ERK) in LPS-stimulated BV2 cells. Male C57/BL6 mice were orally administered 20 and 200 mg/kg of LOS-ME for one week, and 2 mg/kg of scopolamine was administered intraperitoneally on the 8th day. In vivo behavioral experiments (Y-maze and Morris water maze test) confirmed that LOS-ME alleviated cognitive impairments induced by scopolamine and the amount of iNOS expression decreased in the hippocampus of the mouse brain. Microglial hyper-activation was also reduced by LOS-ME pretreatment. These findings suggest that LOS-ME might have potential in the treatment for cognitive improvement by regulating neuroinflammation.

Biological evidence of gintonin efficacy in memory disorders.

Gintonin is a novel glycolipoprotein, which has been abundantly found in the root of Korean ginseng. It holds lysophosphatidic acids (LPAs), primarily identified LPA C18:2, and is an exogenous agonist of LPA receptors (LPARs). Gintonin maintains blood-brain barrier integrity, and it has recently been studied in several models of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Gintonin demonstrated neuroprotective activity by providing action against neuroinflammation-, apoptosis- and oxidative stress-mediated neurodegeneration. Gintonin showed an emerging role as a modulator of synaptic transmission and neurogenesis and also potentially regulated autophagy in primary cortical astrocytes. It also ameliorated the toxic agent-induced and genetic models of cognitive deficits in experimental NDDs. As a novel agonist of LPARs, gintonin regulated several G protein-coupled receptors (GPCRs) including GPR40 and GPR55. However, further study needs to be investigated to understand the underlying mechanism of action of gintonin in memory disorders.

Anti-Neuroinflammatory Agent, Restricticin B, from the Marine-Derived Fungus Penicillium janthinellum and Its Inhibitory Activity on the NO Production in BV-2 Microglia Cells.

A new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine-derived fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via the analyses of NOESY spectroscopy data, the comparison of optical rotation values with those of reported restricticin derivatives and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.

G-Protein-Coupled Receptors in CNS: A Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits.

Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals. Here, GPCRs' role in the pathophysiology of different neurodegenerative disease progressions and cognitive deficits has been highlighted, and an emphasis has been placed on the current pharmacological developments with GPCRs to provide an insight into a potential therapeutic target in the treatment of neurodegeneration.

Medicinal Profile, Phytochemistry, and Pharmacological Activities of Murraya koenigii and its Primary Bioactive Compounds.

The discovery of several revitalizing molecules that can stop or reduce the pathology of a wide range of diseases will be considered a major breakthrough of the present time. Available synthetic compounds may provoke side effects and health issues, which heightens the need for molecules from plants and other natural resources under discovery as potential methods of replacing synthetic compounds. In traditional medicinal therapies, several plant extracts and phytochemicals have been reported to impart remedial effects as better alternatives. Murraya koenigii (M. koenigii) belongs to the Rutaceae family, which is commonly used as a medicinally important herb of Indian origin in the Ayurvedic system of medicine. Previous reports have demonstrated that the leaves, roots, and bark of this plant are rich sources of carbazole alkaloids, which produce potent biological activities and pharmacological effects. These include antioxidant, antidiabetic, anti-inflammatory, antitumor, and neuroprotective activities. The present review provides insight into the major components of M. koenigii and their pharmacological activities against different pathological conditions. The review also emphasizes the need for more research on the molecular basis of such activity in various cellular and animal models to validate the efficacy of M. koenigii and its derivatives as potent therapeutic agents.

Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment.

Quercetin (QC) is a flavonoid and crucial bioactive compound found in a variety of vegetables and fruits. In preclinical studies, QC has demonstrated broad activity against several diseases and disorders. According to recent investigations, QC is a potential therapeutic candidate for the treatment of nervous system illnesses because of its protective role against oxidative damage and neuroinflammation. QC acts on several molecular signals, including ion channels, neuroreceptors, and inflammatory receptor signaling, and it also regulates neurotrophic and anti-oxidative signaling molecules. While the study of QC in neurological disorders has focused on numerous target molecules, the role of QC on certain molecular targets such as G-protein coupled and nuclear receptors remains to be investigated. Our analysis presents several molecular targets of QC and its derivatives that demonstrate the pharmacological potential against cognitive impairment. Consequently, this article may guide future studies using QC and its analogs on specific signaling molecules. Finding new molecular targets of QC and its analogs may ultimately assist in the treatment of cognitive impairment.

Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms.

Taurine is a sulfur-containing amino acid and known as semi-essential in mammals and is produced chiefly by the liver and kidney. It presents in different organs, including retina, brain, heart and placenta and demonstrates extensive physiological activities within the body. In the several disease models, it attenuates inflammation- and oxidative stress-mediated injuries. Taurine also modulates ER stress, Ca2+ homeostasis and neuronal activity at the molecular level as part of its broader roles. Different cellular processes such as energy metabolism, gene expression, osmosis and quality control of protein are regulated by taurine. In addition, taurine displays potential ameliorating effects against different neurological disorders such as neurodegenerative diseases, stroke, epilepsy and diabetic neuropathy and protects against injuries and toxicities of the nervous system. Several findings demonstrate its therapeutic role against neurodevelopmental disorders, including Angelman syndrome, Fragile X syndrome, sleep-wake disorders, neural tube defects and attention-deficit hyperactivity disorder. Considering current biopharmaceutical limitations, developing novel delivery approaches and new derivatives and precursors of taurine may be an attractive option for treating neurological disorders. Herein, we present an overview on the therapeutic potential of taurine against neurological disorders and highlight clinical studies and its molecular mechanistic roles. This article also addresses the neuropharmacological potential of taurine analogs.