Context

Obesity is a chronic low-grade inflammatory state associated with immune cell infiltration into the adipose tissue (AT). We hypothesize that the anti-obesity and anti-inflammatory effects of troxerutin (TX) are mediated through inhibition of elastase.

Objective

To determine the inhibitory effect of TX on elastase in vitro and in tumor necrosis factor alpha (TNFα) induced 3T3-L1 adipocytes and the molecular interaction of TX with human neutrophil elastase (HNE).

Materials and Methods

Differentiated 3T3-L1 adipocytes were pretreated with TX, elastatinal (ELAS) or sodium salicylate (SAL) before exposure to TNFα. Lipid accumulation, reactive oxygen species (ROS) generation and oxidant-antioxidant balance were examined. The mRNA and protein expression of TNFα, interleukin-6, monocyte chemoattractant protein-1, adiponectin, leptin, resistin, chemerin, and elastase were analyzed. Elastase inhibition by TX and ELAS in a cell free system and docking studies for HNE with TX and ELAS were performed.

Results

TX, ELAS or SAL pretreatment had lowered lipid droplets formation and TG content. TX suppressed ROS generation, oxidative stress and improved antioxidant status. The expression of inflammatory cytokines and elastase was downregulated while that of adiponectin was upregulated by TX. The concentration required to produce 50% inhibition in vitro (IC₅₀) was 11.5 μM for TX and 16.9 μM for ELAS. TX showed hydrogen bonding and hydrophobic interactions with elastase.

Discussion

TNFα induces inflammation of 3T3-L1 cells through elastase activation. TX inhibits elastase activity, downregulates expression and binds with elastase.

Conclusion

The antioxidant and anti-inflammatory activities of TX in AT could be of relevance in the management of obesity.

中文翻译：

---

Troxerutin的抗炎作用是通过弹性蛋白酶抑制介导的。

语境

肥胖是与免疫细胞浸润到脂肪组织（AT）相关的慢性低度炎症状态。我们假设troxerutin（TX）的抗肥胖和抗炎作用是通过抑制弹性蛋白酶介导的。

目的

若要确定TX在体外和在肿瘤坏死因子α（TNFα）诱导的3T3-L1脂肪细胞中对弹性蛋白酶的抑制作用以及TX与人中性粒细胞弹性蛋白酶（HNE）的分子相互作用。

材料和方法

在暴露于TNFα之前，先用TX，弹性蛋白（ELAS）或水杨酸钠（SAL）预处理分化的3T3-L1脂肪细胞。检查了脂质的积累，活性氧（ROS）的产生以及氧化剂-抗氧化剂的平衡。分析了TNFα，白介素-6，单核细胞趋化蛋白-1，脂联素，瘦素，抵抗素，凯莫瑞和弹性蛋白酶的mRNA和蛋白表达。在无细胞系统中通过TX和ELAS抑制弹性蛋白酶，并进行了HNE与TX和ELAS的对接研究。

结果

TX，ELAS或SAL预处理降低了脂质滴的形成和TG含量。TX抑制了ROS的产生，氧化应激并改善了抗氧化剂的状态。TX能下调炎症细胞因子和弹性蛋白酶的表达，脂联素则上调。体外产生50％抑制作用所需的浓度（IC ₅₀）对于TX为11.5μM，对于ELAS为16.9μM。TX显示出氢键和与弹性蛋白酶的疏水相互作用。

讨论区

TNFα通过弹性蛋白酶激活诱导3T3-L1细胞的炎症。TX抑制弹性蛋白酶活性，下调表达并与弹性蛋白酶结合。

结论

TX在AT中的抗氧化和抗炎活性可能与肥胖的治疗有关。