Targeting GABA receptors with chalcone derivative compounds, what is the evidence?

INTRODUCTION: In medicinal chemistry, privileged structures have been frequently exploited as a successful template for drug discovery. Common simple scaffolds like chalcone are present in a wide range of naturally occurring chemicals. Chalcone exhibits extensive biological activity and has drawn attention in this context due to its function in the GABA receptor. Epilepsy and GABA receptors are related. It is a chronic neurological condition that affects globally. AREAS COVERED: Numerous neurological disorders, including anxiety and epilepsy, have been related to GABA, the brain's most prevalent inhibitory neurotransmitter. We go through the role of GABA receptors in anxiety and epilepsy in this review. The structure-activity relationship of chalcone and its derivatives on the GABA receptor is covered in our final section. EXPERT OPINION: GABA is a potential therapeutic target for issues associated with the nervous system. We talk about the potential effects of chalcone as a treatment for epilepsy and anxiety on the GABA receptor. Therefore, thorough research is necessary in this regard; the value of in silico tools in developing and enhancing GABA agonists is significant.

Signaling mechanisms involved in the regulation of remyelination in multiple sclerosis: a mini review.

Multiple sclerosis is an autoimmune neurodegenerative disease of the CNS that causes progressive disabilities, owing to CNS axon degeneration as a late result of demyelination. In the search for the prevention of axonal loss, mitigating inflammatory attacks in the CNS and myelin restoration are two possible approaches. As a result, therapies that target diverse signaling pathways involved in neuroprotection and remyelination have the potential to overcome the challenges in the development of multiple sclerosis treatments. LINGO1 (Leucine rich repeat and Immunoglobulin domain containing, Nogo receptor- interaction protein), AKT/PIP3/mTOR, Notch, Wnt, RXR (Retinoid X receptor gamma), and Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathways are highlighted in this section. This article reviews the present knowledge regarding numerous signaling pathways and their functions in regulating remyelination in multiple sclerosis pathogenesis. These pathways are potential biomarkers and therapeutic targets in MS.

A pharmacological exploration of targeted drug therapy in non-small cell lung cancer.

Lung cancer is the prime cause of cancer-related deaths globally, with a contribution of 85% from non-small cell lung cancer. Before a few decades back, conventional chemotherapy was the most chosen treatment option for NSCLC but with side effects. Now, the treatment approaches have shifted to a new trend, targeted therapy, and a better treatment strategy with minimal side effects compared to chemotherapy. Advances in technologies and understanding the pathways lead to the discovery of new targets and through which it is possible to improve treatment outcomes and patient compliance. Unlike chemotherapy, targeted therapy focuses on the tumor cells and does not produce toxicity to healthy cells. The last two decades were very crucial in the development of many small molecules with the capability to target-specific proteins or genes in the disease progression pathway. Although the targeted therapy approach was a gemstone with many successful drugs for the treatment of NSCLC, various resistance mechanisms and activation of bypass signaling pathways put many of these drugs in the trash. In this review, we will discuss the major targeted proteins involved in NSCLC as well as the inhibitor drugs developed to target them for now and along with the future directions.

Pathophysiological basis in the management of myasthenia gravis: a mini review.

Myasthenia gravis is an autoimmune disorder characterized by the presence of autoantibodies against the acetylcholine receptor present in the post-synaptic membrane of the neuromuscular junction impairing the muscle contraction and causing the patient suffering from the disorder to develop a myriad of muscular defects ranging from drooping of eyelids, blurred or double vision, shortness of breath, difficulty in swallowing, as well as weakness of limbs and arms. Myasthenia gravis is known as the disease of old men and young women but in contrast to the global scenario, in India, myasthenia gravis was found to be predominant in males with the ratio of 2.70:1. Though the disorder has been studied for centuries, the true reason for disease and its pathophysiology still eludes us. But recent advancement in molecular biology and diagnostic tools has enabled us to identify many targets for pharmacotherapy as well as for early diagnosis. Thus, improving the patient's morbidity and quality of life. In this article, we are discussing the recent advancements made in diagnosis and therapy of the disease.

Bacoside-A inhibits inflammatory cytokines and chemokine in experimental autoimmune encephalomyelitis.

Chronic inflammation of the myelin sheath is the crucial event behind the progression of multiple sclerosis (MS). Bacoside-A is one of the major constituents obtained from Bacopa monerii (L.) Wettst., and possess neuroprotective as well as anti-inflammatory actions. The current study explores the effect of Bacoside-A in acute and chronic models of Experimental Autoimmune Encephalomyelitis (EAE). The results indicate that the Bacoside-A treated mice produced a significant reduction in disease score compared to disease control in both models. The treatment with Bacoside-A downregulated the inflammatory cytokines (IL-6, IL-17a, and TNFα) and inflammatory chemokine CCL-5 in EAE mice. On the other hand, Bacoside-A treated mice showed a nonsignificant effect on promoting the expressions of NCAM, BDNF1, and FOXP3 in acute and chronic models of EAE. Histopathological analysis revealed that the Bacoside-A treated mice at a dose of 10 mg/kg exhibited a significant reduction in cellular infiltrations, cellular changes, and demyelination in cerebral tissues, but unable to protect at a higher dose in both models. In conclusion, Bacoside-A can able to inhibit the progression of EAE may be by the inhibition of inflammatory cytokines and chemokine evolved during active EAE.

Assessment of neuroprotective effects of Gallic acid against glutamate-induced neurotoxicity in primary rat cortex neuronal culture.

Glutamate excitotoxicity plays a crucial role in the pathogenesis behind the development and progression of several neurodegenerative diseases. The study aimed to investigate the neuroprotective activity of Gallic acid (GA) against glutamate-induced neurotoxicity in primary rat cortex neurons (RCN). Treated the RCNs with GA 25 & 50 µg/ml for 2 h and later treated the cells with 100 µM glutamate (GLU) and incubated for 24 h at 37 °C. The results demonstrated that, the GA improved the antioxidant profile in the cortex neurons and inhibited the production of the proinflammatory cytokine. GA also maintained the Ca2+ homeostasis, IGF-1 expression, and protected the neurons from glutamate-induced neuronal toxicity. The neuroprotective activity of GA has further confirmed from the results of N-acetylaspartate and expression of microtubule-associated protein-2 expression. The reports suggest that, GA is significantly attenuated the glutamate-induced neurotoxicity and protected neurons from various chemical events that are involved in the pathogenesis of neurotoxicity.

Asiaticoside counteracts the in vitro activation of microglia and astrocytes: Innuendo for multiple sclerosis.

BACKGROUND: During the development of Multiple Sclerosis (MS) there is a marked activation of microglia and astrocyte, leading to progressive inflammation and degeneration of myelin sheath which results in axonal loss and neuron damage. PURPOSE: In this study, we have explored the action of Asiaticoside A against the activated microglia and astrocytes. METHODS: Primary microglia and astrocyte cultures were used for the study and the activity were evaluated using cell proliferation assay, nitrate assay and TNFα estimation using ELISA. RESULTS: Asiaticoside A inhibited the production of nitric oxide and TNFα in LPS activated primary microglia and astrocyte cultures. CONCLUSION: This study suggests that Asiaticoside A may be effective against the progression of MS.