Protein Kinases and their Inhibitors Implications in Modulating Disease Progression.

Protein phosphorylation plays an important role in cellular pathways, including cell cycle regulation, metabolism, differentiation and survival. The protein kinase superfamily network consists of 518 members involved in intrinsic or extrinsic interaction processes. Protein kinases are divided into two categories based on their ability to phosphorylate tyrosine, serine, and threonine residues. The complexity of the system implies its vulnerability. Any changes in the pathways of protein kinases may be implicated in pathological processes. Therefore, they are regarded as having an important role in human diseases and represent prospective therapeutic targets. This article provides a review of the protein kinase inhibitors approved by the FDA. Finally, we summarize the mechanism of action of protein kinases, including their role in the development and progression of protein kinase-related roles in various pathological conditions and the future therapeutic potential of protein kinase inhibitors, along with links to protein kinase databases. Further clinical studies aimed at examining the sequence of protein kinase inhibitor availability would better utilize current protein kinase inhibitors in diseases. Additionally, this review may help researchers and biochemists find new potent and selective protein kinase inhibitors and provide more indications for using existing drugs.

Exploring Liposomes for Lung Cancer Therapy.

Cancer is referred to as a pleiotropic disease-causing approximately 9.6 million deaths in 2018. Among all cancers, lung cancer was the leading cause of death in 2017, and 12% of fatalities were alone due to lung cancer. The associated risk factors in lung cancer include smoking (80-85%), chronic inflammation in the lungs, COPD, pulmonary fibrosis, environmental and occupational exposure to nickel, arsenic, chromates, etc. Early diagnosed patients' treatment plan includes chemotherapy, immunotherapy, radiotherapy, surgery, and tumor ablation. Many sorts of drug delivery carriers have been used in the past, usually in targeted chemotherapy. Liposomes are spherical shape vesicles containing a lipid bilayer and aqueous core, with potency to encapsulate both hydrophobic and hydrophilic drugs with minimal toxicity. These vesicles have a particle size of 0.02-1000 µm allowing selective passive targeting to the tumor's deeper tissues. Current publications on liposomes highlight their acceptance and best choice among all systems to deliver synthetic and herbal drugs to the lungs. This review focuses on many aspects, which include an in-depth analysis of potential anticancer drugs that have utilized the advantages of liposomes for effective lung carcinomatherapy and devices used to deliver the active agents to the pulmonary tissues. Investigations on ongoing, approved, and failed clinical trials and patents on products related to lung cancer have been highlighted to provide a critical review on the subject.

Cerebroprotective effect of pterostilbene against global cerebral ischemia in rats.

AIM OF THE STUDY: The role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied. MATERIALS AND METHODS: Male SD rats (180-200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study. RESULT: The pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control. CONCLUSION: This work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.

Inhibition of human amylin aggregation by Flavonoid Chrysin: An in-silico and in-vitro approach.

Islet amyloid polypeptide (amylin), consecrated by the pancreatic ß-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the ß-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

Current Pharmacological Trends on Myricetin.

Myricetin is a member of the group of flavonoids called flavonols. Myricetin is obtained from various fruit, vegetables, tea, berries and red wine. Myricetin is characterized by the pysrogallol B-ring, and the more hydroxylated structure is known to be capable for its increased biological properties compared with other flavonols. Myricetin is produced by the Myricaceae, Anacardiaceae, Polygonaceae, Pinaceae and Primulacea families. It is soluble in organic solvent such as ethanol, DMSO (dimethyl sulfoxide), and dimethyl formamide (DMF). It is sparingly soluble in aqueous buffers. Myricetin shows its various pharmacological activities including antioxidant, anti-amyloidogenic, antibacterial, antiviral, antidiabetic, anticancer, anti-inflammatory, anti-epileptic and anti-ulcer. This review article focuses on pharmacological effects of Myricetin on different diseases such as osteoporotic disorder, anti-inflammatory disorder, alzheimer's disease, anti-epileptic, cancer, cardiac disorder, diabetic metabolic disorder, hepatoprotective disorder and gastro protective disorder.

An Overview of Stroke: Mechanism, In vivo Experimental Models Thereof, and Neuroprotective Agents.

BACKGROUND: Stroke is one of the causes of death and disability globally. Brain attack is because of the acute presentation of stroke, which highlights the requirement for decisive action to treat it. OBJECTIVE: The mechanism and in-vivo experimental models of stroke with various neuroprotective agents are highlighted in this review. METHOD: The damaging mechanisms may proceed by rapid, nonspecific cell lysis (necrosis) or by the active form of cell death (apoptosis or necroptosis), depending upon the duration and severity and of the ischemic insult. RESULTS: Identification of injury mediators and pathways in a variety of experimental animal models of global cerebral ischemia has directed to explore the target-specific cytoprotective strategies, which are critical to clinical brain injury outcomes. CONCLUSION: The injury mechanism, available encouraging medicaments thereof, and outcomes of natural and modern medicines for ischemia have been summarized. In spite of available therapeutic agents (thrombolytics, calcium channel blockers, NMDA receptor antagonists and antioxidants), there is a need for an ideal drug for strokes.