Tamarixetin Exhibits Anti-inflammatory Activity and Prevents Bacterial Sepsis by Increasing IL-10 Production

Abstract

Sepsis is a systemic inflammatory response to pathogenic infection that currently has no specific pharmaceutical interventions. Instead, antibiotics administration is considered the best available option, despite increasing drug resistance. Alternative strategies are therefore urgently required to prevent sepsis and strengthen the host immune system. One such option is tamarixetin (4'- O-methylquercetin), a naturally occurring flavonoid derivative of quercetin that protects against inflammation. The purpose of this study was to determine whether the anti-inflammatory effects of tamarixetin protect against the specific inflammatory conditions induced in lipopolysaccharide (LPS) or Escherichia coli K1 models of sepsis. Our study showed that tamarixetin reduced the secretion of various inflammatory cytokines by dendritic cells after activation with LPS. It also promoted the secretion of the anti-inflammatory cytokine interleukin (IL)-10 and specifically increased the population of IL-10-secreting immune cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory effects in mouse models of bacterial sepsis and decreased bacteria abundance and endotoxin levels. We therefore conclude that tamarixetin has superior anti-inflammatory properties than quercetin during bacterial sepsis. This effect is associated with an increased population of IL-10-secreting immune cells and suggests that tamarixetin could serve as a specific pharmaceutical option to prevent bacterial sepsis.

Indole-3-guanylhydrazone hydrochloride mitigates long-term cognitive impairment in a neonatal sepsis model with involvement of MAPK and NFκB pathways

“…A common feature of neonatal sepsis is the systemic induction of inflammatory mediators, which can disrupt the blood-brain barrier (BBB) and interact with the brain, thereby causing brain inflammation. Sepsis is associated with the exacerbated production of proinflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-inflammatory cytokines, such as IL-10, which attempt to restore the immunological balance (Cohen, 2002;Park et al, 2018;Schulte et al, 2013). Ours findings corroborate with these findings, we describe that LPS cause a severe neuroinflammation in hippocampus of neonates.…”

Study on Pharmacokinetic and Bioavailability of Tamarixetin after Intravenous and Oral Administration to Rats

“…In addition, researchers have confirmed that tamarixetin has the effect of inhibiting liver cancer in PLC/PRF/5 and HepG2 cells [2]. Tamarixetin has better anti-inflammatory properties compared with quercetin during bacterial sepsis via increased interleukin (IL)-10 production [8]. This property is similar to previous research that PNIPAM nanoparticles of curcuminoids could significantly decrease levels of TNF- α and IL-1 β [12].…”

The Inhibitory Effect of Flavonoid Aglycones on the Metabolic Activity of CYP3A4 Enzyme

“…Interestingly, stimulation of enzyme activity of CYP3A4 was observed with tamarixetin; observed residual activity was 195% ( Table 1 ). Tamarixetin exhibits anti-inflammatory activity, and prevents bacterial sepsis by stimulating immune system and interleukin 10 production [ 62 ]. It also has anticancer properties on human leukemia cells [ 63 ].…”