Novel Dual COX-2/5-LOX Inhibitory Activity by Chalcone Derivatives: A Safe and Efficacious Anti-Inflammatory Agent.

BACKGROUND: Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cas-cade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflam-matory activity via dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism. METHODS: RAW 264.7 macrophages were collected from NCC, Pune, for in-vitro experiments. The IC50 values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macro-phages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The in-vivo evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney. RESULTS: The present study described the in-vitro and in-vivo biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC50 values 0.092 and 0.136µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selec-tivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. In-vivo carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% com-pared with standard 40.13% granuloma inhibition. CONCLUSION: The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-tri-methoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

Gold Nanoparticle-based Biosensors for Point-of-Care Diagnostics: A Review of Sensing Nanoparticle Applications and Future Prospects.

Point of Care Diagnostics (POCD) is quintessential in hospitals and the healthcare sector as the secants uplift the quality of medical care and the life of a patient by facilitating quick identification of the underlying pathological condition. Nanotechnology can provide opportunities and has potential in the development of new-age sensing/diagnostic tools. Owing to extraordinary features (e.g., higher density, effective catalysis, good conduction, biocompatibility, inertness, and greater surface-to-volume ratio), gold nanoparticles (AuNPs) are frequently employed in POCT (Point-of-Care-Testing). Gold nanoparticles-based colorimetric methods are widely used in the rapid, sensitive, and selective detection of analytes/target molecules. AuNPs description is critical for their possible utility in prophylaxis, diagnostics, and treatment of an ailment. AuNPs interact with organic/inorganic target molecules to generate colorimetric shift that enables the accurate, precise, and subtle recognition of biologicals (e.g., microorganisms, cellular components, and proteins) and metal ions. This review focused on the need for AuNPs-based colorimetric application in prophylaxis, diagnostics, and treatment in healthcare and reviewed the future outlook of these AuNPs for biological applications. Different synthesis methods of AuNPs, their morphology, and characterization, including their surface functionalization, will be discussed in detail. AuNPs are very much preferable nanomaterials owing to exclusive optical, electrical, and photothermal features. AuNPs-based colorimetric biosensors are simple and possess great utility, yet these offer a robust technique to enable visual, quantitative analysis.

Metabolomics: A Tool to Envisage Biomarkers in Clinical Interpretation of Cancer.

BACKGROUND: Cancer is amongst the most dreadful ailments of modern times, and its impact continuously worsens global health systems. Early diagnosis and suitable therapeutic agents are the prime keys to managing this disease. Metabolomics deals with the complete profiling of cells and physiological phenomena in their organelles, thus helping in keen knowledge of the pathological status of the disease. It has been proven to be one of the best strategies in the early screening of cancer. OBJECTIVE: This review has covered the recent updates on the promising role of metabolomics in the identification of significant biochemical markers in cancer-prone individuals that could lead to the identification of cancer in the early stages. METHODS: The literature was collected through various databases, like Scopus, PubMed, and Google Scholar, with stress laid on the last ten years' publications. CONCLUSION: It was assessed in this review that early recognition of cancerous growth could be achieved via complete metabolic profiling in association with transcriptomics and proteomics. The outcomes are rooted in various clinical studies that anticipated various biomarkers like tryptophan, phenylalanine, lactates, and different metabolic pathways associated with the Warburg effect. This metabolite imaging has been a fundamental step for the target acquisition, evaluation of predictive cancer biomarkers for early detection, and outlooks into cancer therapy along with critical evaluation. Significant efforts should be made to make this technique most reliable and easy.

Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022).

INTRODUCTION: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. METHODS: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. CONCLUSION: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

Cardioprotective Activity of Cassia fistula L. Bark Extract in Isoproterenol-Induced Myocardial Infarction Rat Model.

Cassia fistula Linn, generally recognized as Indian laburnum, is one of the ancient trees in the Indian subcontinent used for its ornamental and diverse medicinal properties. It is known for its ethnic medicinal uses in inflammatory and infectious pathologies such as antihelmintic, purgative, carminative, antipyretic, expectorant, analgesic, laxative, antiseptic, and antidote against snake poison. The Cassia bark is rich in anthraquinones, flavanols glycosides, and sitosterols, which renders it cardioprotective properties. The existing experiments were designed to assess the potential of Cassia fistula bark against isoproterenol (ISP)-induced cardiotoxicity in rats, which has not been validated yet. The bark was successively extracted with five different solvents, and each extract was subjected to in vitro antioxidant studies. Further acute oral toxicity assays were carried out preceding in vivo myocardial studies. Cardiotoxicity-inducing agent, ISP, was administrated to the rats for two consecutive days (8th and 9th). Based on in vitro studies, the Cassia fistula methanolic extract (CFME) was administered in two doses: CFME-LD (lower dose 250 mg/kg) and CFME-HD (high dose 500 mg/kg) separately. It was found that CFME produced a substantial decrease in lipid peroxidation and an increase in antioxidants in myocardial tissues. CFME abrogated the levels of triglyceride and total cholesterol with a decrease in alanine transaminase (ALT) and aspartate transaminase (AST) activity in serum at both doses. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and histopathology also revealed the protective effects of CFME against ISP-induced myocardial infarction. The study showed the significant role of the CFME as a strong antioxidant and cardioprotective action in ISP-induced toxicity.