Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption.

The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body's own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37's mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed an inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as a potential therapeutic avenue to mitigate disease severity. The combination of niacinamide and LL37 is a potent antiviral formulation that targets viral membranes of various variants and can be an effective strategy to overcome vaccine escape.

The role of Th17/IL-17 on eosinophilic inflammation.

Eosinophilia develops in reactive environment such as allergy, parasitic infections and in hypereosinophilic syndrome [HES]. Activated eosinophils are accompanied by a wide variety of inflammatory response due to release of toxic inflammatory mediators, which may result in severe tissue/organ damage at the site of eosinophilic infiltrations, due to degranulation. The factor responsible for the detrimental effect of activated circulatory eosinophils is an area less explored. In the present study, we determined the serum cytokine milieu of eosinophilic and control subjects, and also investigated the change in the pattern of cytokine released under mitogen stimulation. Increased level of various pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IL-5 and IL-17 was detected in serum and culture supernatants of endotoxin stimulated white blood cells [WBCs] of eosinophilic subjects compared to control population. It was observed that endotoxin exposure in WBCs of eosinophilic subjects, led to increased release of IL-17, produced by TH17 subset of T-cell, contributing towards eosinophilic exuberations, in vitro. We observed non-specific lysis by eosinophils under such inflammatory milieu and synergistic eosinophilic activity in presence of IL-17 and IL-5 in combination. Taken together, our findings provide vital insight on TH17 lymphocyte mediated activation of eosinophils, via differential cytokine regulation, which play an important role in hypereosinophilic systemic inflammation.

L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation.

Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca(2+) and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea.