Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression

Abstract

Background Sepsis is a severe medical condition. Approximately 0.75 million people are diagnosed with sepsis in the USA annually. Several of anti-inflammatory drugs are used to manage sepsis, but with a very low success rate. This study examined the possible protective effects of a naturally occurring flavanone, quercetin, in a rat model of sepsis. Material/Methods The study was carried out using Wistar albino rats. Sepsis was induced by cecal ligation and puncture methods. Histological analysis was performed by hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. Superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities were determined by standard assays. Protein expression was determined by Western blot analysis. Results The results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats. Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels. The activities and the expression of SOD, CAT, and APX were significantly decreased upon administration of quercetin in the septic rats at the dosage of 15 and 20 mg/kg. The effects of quercetin were also examined on the expression of the High mobility group box 1 (HMGB1) protein in septic rats. The results showed that quercetin caused a significant decrease in HMGB1 protein levels. Conclusions The findings of this study suggest that quercetin has therapeutic potential in the treatment of sepsis.

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective

“…Several phytochemicals have been shown to alleviate the sepsis during interfering with the release and action of HMGB1. (I) resveratrol inhibits the cytoplasmic translocation of HMGB1; (II) resveratrol, 56,57 curcumin, 95 quercetin, 42 and glycyrrhizin 24 decrease the level of HMGB1; and (III) glycyrrhizin directly binds HMGB1 and inhibits its binding to RAGE and TLR4 24,25 …”

“…Moreover, YKL‐40 and periostin, biomolecules that are increased in inflammatory conditions such as sepsis, 39–41 were significantly decreased by quercetin treatment 38 . Quercetin was also shown to reduce the levels and expression of HMGB1, as well as the activity of SOD, CAT, and ascorbate peroxidase in CLP‐induced septic rats 42 . Several studies have been conducted to address the mechanisms underlying the biological effects of quercetin in sepsis.…”

Superoxide Dismutase Administration: A Review of Proposed Human Uses

“…Moreover, HMGB1 translocation and release are promoted by H 2 O 2 in hepatocytes [ 235 ], primary human epidermal melanocytes [ 236 ], and neonatal rat cardiomyocytes [ 237 ]. Therefore, the increase in SOD activity and the parallel reduction in HMGB1 levels have been proposed as the mechanisms underlying the protective effects exerted by quercetin in a rat model of sepsis [ 238 ], the amelioration of the cisplatin-induced hepatotoxicity by the Ganoderma lucidum mushroom [ 239 ], and the anti-inflammatory effect of the midazolam–sufentanil combination [ 240 ]. Two cross-talking pathways are involved: Nrf2/HO-1 and the Toll-like receptor (TLR)/NF-κB axis [ 241 ].…”

<p>Effects of Supplementation with Anti-Inflammatory Compound Extracted from Herbs in Healthy and Obese Cats</p>

“…Quercetin exerts an obvious anti-inflammatory activity in many animal species, [25][26][27] and SAA as an inflammatory marker was reduced significantly in the obesity disease cats as well as in the healthy controls. MDA concentrations were not changed in the obesity disease cats, and this phenomenon may indicate insufficiency of anti-oxidant activity of quercetin derivative.…”