A novel spider-toxin-derived anti-gout peptide NCTX14 alleviated NLRP3-mediated pyroptosis in hyperuricemia

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Process Biochemistry Pub Date : 2025-06-16 DOI:10.1016/j.procbio.2025.06.009

Naixin Liu , Yixiang Liu , Junyuan Wang , Yuliu Yang , Yujing Ding , Xiaohan Sun , Mengfan Ma , Xin Yu , Shaoyang Zhang , Jing Tang , Xinwang Yang , Ying Wang

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引用次数: 0

Abstract

Gout is a serious metabolic disorder mainly caused by high levels of serum uric acid (HUA). Due to the limitations of current treatments, it is important to investigate new urate-lowering compounds. In this study, a novel peptide, NCTX14 (CRPPVMLPKCEEFMK), was discovered within the venom gland of Nephila clavata. Research shows that NCTX14 doesn't exhibit cytotoxicity or hemolytic activity in vitro and is non-toxic when administered in vivo. This peptide effectively reduces serum uric acid levels and inhibits xanthine oxidase activity in mice with high uric acid levels. This is achieved through the downregulation of URAT1 and GLUT9, along with the upregulation of OAT1, ultimately enhancing uric acid excretion. Moreover, NCTX14 alleviates kidney damage by inhibiting the expression of inflammatory cytokines, such as IL-6, IL-1β, TNF-α. In HUA nephropathy, NCTX14 alleviates renal injury by inhibiting NLRP3 mediated pyroptosis injury. Additionally, NCTX14 demonstrates anti-inflammatory and pain-relieving effects in mice. The potential of NCTX14 in the treatment of gout suggests its practical application value as an anti-gout medicine candidate molecular.

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一种新型蜘蛛毒素衍生的抗痛风肽NCTX14减轻了nlrp3介导的高尿酸血症热亡

痛风是一种严重的代谢性疾病，主要由高水平的血清尿酸（HUA）引起。由于目前治疗的局限性，研究新的降尿酸化合物是很重要的。在本研究中，我们发现了一种新的肽，NCTX14 (CRPPVMLPKCEEFMK)，存在于蛇舌蛇的毒液腺中。研究表明，NCTX14在体外不表现出细胞毒性或溶血活性，在体内给药时无毒。该肽有效降低血清尿酸水平，抑制高尿酸小鼠黄嘌呤氧化酶活性。这是通过下调URAT1和GLUT9，同时上调OAT1，最终增强尿酸排泄来实现的。此外，NCTX14通过抑制炎症细胞因子如IL-6、IL-1β、TNF-α的表达来减轻肾损伤。在HUA肾病中，NCTX14通过抑制NLRP3介导的焦亡损伤来减轻肾损伤。此外，NCTX14在小鼠中具有抗炎和缓解疼痛的作用。NCTX14在痛风治疗中的潜力提示其作为抗痛风药物候选分子具有实际应用价值。

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来源期刊

Process Biochemistry 生物-工程：化工

CiteScore

8.30

自引率

4.50%

发文量

374

审稿时长

53 days

期刊介绍： Process Biochemistry is an application-orientated research journal devoted to reporting advances with originality and novelty, in the science and technology of the processes involving bioactive molecules and living organisms. These processes concern the production of useful metabolites or materials, or the removal of toxic compounds using tools and methods of current biology and engineering. Its main areas of interest include novel bioprocesses and enabling technologies (such as nanobiotechnology, tissue engineering, directed evolution, metabolic engineering, systems biology, and synthetic biology) applicable in food (nutraceutical), healthcare (medical, pharmaceutical, cosmetic), energy (biofuels), environmental, and biorefinery industries and their underlying biological and engineering principles.