Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.

A marked increase in the global prevalence of ischemic heart disease demands focused research for novel and more effective therapeutic strategies. At present, atherosclerotic cardiovascular disease (ACVD) is the leading cause of the global incidence of heart attacks and a major contributor to many peripheral cardiac diseases. Decades of research have unearthed the complex and multidimensional pathophysiology of ACVD encompassing oxidative stress, redox imbalance, lipid peroxidation, pro-inflammatory signaling, hyperglycemic stress and diabetes mellitus, chronic low-grade inflammation and aging, immune dysregulation, vascular dysfunction, loss of hemostasis, thrombosis, and fluid shear stress. However, the scientific basis of therapeutic interventions using conventional understandings of the disease mechanisms has been subject to renewed scrutiny with novel findings in recent years. This critical review attempts to revise the pathophysiological mechanisms of atherosclerosis using a recent body of literature, with a focus on lipid metabolism and associated cellular and biochemical processes. The comprehensive study encompasses different molecular perspectives in the development and progression of coronary atherosclerosis. The review also summarizes currently prescribed small molecule therapeutics in inflammation and ACVD, and overviews prospective management measures under development including peptides and microRNA therapeutics. The study provides updated insights into the current knowledge of coronary atherosclerosis, and highlights the need for effective prevention, management and development of novel intervention approaches to overcome this chronic epidemic.

Amla (Phyllanthus emblica) has long been used in traditional folk medicine to prevent and cure a variety of inflammatory diseases. In this study, the antioxidant activity (DPPH scavenging and reducing power), anti-inflammatory activity (RBC Membrane Stabilization and 15-LOX inhibition), and anticoagulation activity (Serin protease inhibition and Prothrombin Time assays) of the methanolic extract of amla were conducted. Amla exhibited a substantial amount of phenolic content (TPC: 663.53 mg GAE/g) and flavonoid content (TFC: 418.89 mg GAE/g). A strong DPPH scavenging effect was observed with an IC₅₀ of 311.31 µg/ml as compared to standard ascorbic acid with an IC₅₀ of 130.53 µg/ml. In reducing power assay, the EC₅₀ value of the extract was found to be 196.20 µg/ml compared to standard ascorbic acid (EC₅₀ = 33.83 µg/ml). The IC₅₀ value of the RBC membrane stabilization and 15-LOX assays was observed as 101.08 µg/ml (IC₅₀ of 58.62 µg/ml for standard aspirin) and 195.98 µg/ml (IC₅₀ of 19.62 µg/ml for standard quercetin), respectively. The extract also strongly inhibited serine protease (trypsin) activity with an IC₅₀ of 505.81 µg/ml (IC₅₀ of 295.44 µg/ml for standard quercetin). The blood coagulation time (PTT) was found to be 11.91 min for amla extract and 24.11 min for standard Warfarin. Thus, the findings of an in vitro study revealed that the methanolic extract of amla contains significant antioxidant, anti-inflammatory, and anticoagulation activity. Furthermore, in silico docking and simulation of reported phytochemicals of amla with human 15-LOXA and 15-LOXB were carried out to validate the anti-inflammatory activity of amla. In this analysis, epicatechin and catechin showed greater molecular interaction and were considerably stable throughout the 100 ns simulation with 15-lipoxygenase A (15-LOXA) and 15-lipoxygenase B (15-LOXB) respectively.

Introduction: Garlic (Allium sativum) is widely used as a flavor-enhancing dietary ingredient and exhibits a wide spectrum of pharmacological effects. This study aimed to investigate the therapeutic effects of aqueous garlic extract to explore the bioactivity against 15-lipoxygenase (15-LOX) mediated inflammopathies. Methods: In this study, the antioxidant (DPPH free radical scavenging assay and reducing power assay), anti-inflammatory (hypotonicity-induced hemolysis assay and 15-LOX inhibition assay) and anticoagulation (serine protease inhibition assay and prothrombin time assay) effects of the aqueous garlic extract were investigated. Furthermore, in silico molecular docking and dynamic simulation analysis of reported small compounds of garlic against 15-LOX1 and 15-LOX2 were performed to figure out the most efficient phytochemical ligands and validate the anti-inflammatory potential. Results: The DPPH scavenging effect and the reducing power of the extract were found with the IC50 of 213.87 ± 1.49 μgmL-1 and EC50 of 124.78 ± 3.39 μgmL-1, respectively. In the hypotonicity-induced hemolysis and 15-LOX inhibition assay, the IC50 values were observed as 147.59 ± 2.98 μgmL-1 and 250.05 ± 8.48 μgmL-1, respectively. The extract inhibited serine protease activity with an IC50 of 301.33 ± 1.31 μgmL-1 and prevented blood coagulation for 10.05 ± 0.35 minutes in prothrombin time assay. The in silico study identified Rhamnetin as a potential 15-LOX1 and 15-LOX2 inhibitor, and it exhibited a stable interaction with the targets throughout the 100 ns dynamic simulation. Conclusion: The findings of this study provide molecular insights into garlic’s medicinal properties as well as its bioactive compounds, which can be potential therapeutic interventions for 15-LOX mediated inflammations.