Melatonin is a chronobiotic hormone, which can regulate human diseases like cancer, atherosclerosis, respiratory disorders, and microbial infections by regulating redox system. Melatonin exhibits innate immunomodulation by communicating with immune system and influencing neutrophils to fight infections and inflammation. However, sustaining redox homeostasis and reactive oxygen species (ROS) generation in neutrophils are critical during chemotaxis, oxidative burst, phagocytosis, and neutrophil extracellular trap (NET) formation. Therefore, endogenous antioxidant glutathione (GSH) redox cycle is highly vital in regulating neutrophil functions. Reduced intracellular GSH levels and glutathione reductase (GR) activity in the neutrophils during clinical conditions like autoimmune disorders, neurological disorders, diabetes, and microbial infections lead to dysfunctional neutrophils. Therefore, we hypothesized that redox modulators like melatonin can protect neutrophil health and functions under GSH and GR activity–deficient conditions. We demonstrate the dual role of melatonin, wherein it protects neutrophils from oxidative stress‐induced apoptosis by reducing ROS generation; in contrast, it restores neutrophil functions like phagocytosis, degranulation, and NETosis in GSH and GR activity–deficient neutrophils by regulating ROS levels both in vitro and in vivo. Melatonin mitigates LPS‐induced neutrophil dysfunctions by rejuvenating GSH redox system, specifically GR activity by acting as a parallel redox system. Our results indicate that melatonin could be a potential auxiliary therapy to treat immune dysfunction and microbial infections, including virus, under chronic disease conditions by restoring neutrophil functions. Further, melatonin could be a promising immune system booster to fight unprecedented pandemics like the current COVID‐19. However, further studies are indispensable to address the clinical usage of melatonin.

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Platelets are known for their indispensable role in haemostasis and thrombosis. During oxidative stress, alteration in platelet function contributes towards multiple health complications. To date, various synthesized compounds have shown antiplatelet activity however, their uses are still ambiguous as these compounds display multiple side effects. Commercially used curcumin is a mixture of curcumin, demethoxy curcumin and bisdemethoxy curcumin. Majority of the studies demonstrate the effect of crude curcumin lacking specific understanding on the effect of pure curcumin. Therefore, in this study, curcumin was purified from crude curcumin mixture and examined against oxidative stress-induced platelet apoptosis and activation. Purified curcumin restored the AAPH-induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release from mitochondria to the cytosol, and phosphatidyl serine externalization. Further, it inhibited agonists-induced platelet activation and aggregation, demonstrating its antiplatelet activity. Western blot analysis confirms the protective effect of purified curcumin against oxidative stress-induced platelet apoptosis and activation via down regulation of MAPKs protein activation including ASK1, JNK, p-38. This suggests that purified curcumin could be a potential therapeutic bioactive molecule to treat oxidative stress-induced platelet activation, apoptosis, and associated complications.