Baishan Alhar, Aikebaier Alifeiye, Dilimulati Dilihuma, Nueraihemaiti Nuerbiye, Paerhati Yipaerguli, Hailati Sendaer, Maihemuti Nulibiya, Zhou Wenting
Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China.
Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumqi 830017, China.
Int J Mol Sci. 2025 Feb 19;26(4):1764. doi: 10.3390/ijms26041764.
(KZMK), derived from traditional Kazakh folk medicine, exhibit a variety of pharmacological properties. Long-term clinical studies have demonstrated their efficacy in clearing heat, detoxifying, promoting qi circulation, and alleviating gonorrhea. However, their specific pharmacological effects on urinary tract infections remain unclear. This study employed UHPLC-MS/MS technology to identify the blood components of KZMK and integrated network pharmacology with bioinformatics analysis for molecular docking validation. The anti-inflammatory activity of KZMK was further evaluated using a rat model of LPS-induced cystitis. A total of 17 components in KZMK were identified as capable of entering the bloodstream. Predictive analysis revealed that its primary targets include Caspase-1, NLRP3, STAT1, TLR4, and TNF, with the NLRP3 inflammasome signaling pathway emerging as the key mechanism. In vivo studies showed that KZMK effectively reduced the white blood cell (WBC) count and bladder index in urine sediments of rats with cystitis. Additionally, KZMK alleviated bladder congestion, edema, and histopathological changes in the animals. Treatment with KZMK led to decreased levels of IL-18 and IL-1β cytokines. KZMK significantly inhibited the expression of NLRP3, GSDMD, and Caspase-1 in LPS-induced cystitis, further confirming its anti-inflammatory effects. These findings indicate that KZMK provides protection against LPS-induced cystitis, primarily by inhibiting the activation of the NLRP3 inflammasome. Collectively, the results suggest that KZMK holds promise as a potential therapeutic option for urinary tract infections.
源自哈萨克族传统民间医学的(KZMK)具有多种药理特性。长期临床研究已证明其在清热、解毒、理气和缓解淋病方面的功效。然而,其对尿路感染的具体药理作用仍不清楚。本研究采用超高效液相色谱-串联质谱技术鉴定KZMK的血液成分,并将网络药理学与生物信息学分析相结合进行分子对接验证。使用脂多糖诱导的膀胱炎大鼠模型进一步评估KZMK的抗炎活性。共鉴定出KZMK中有17种成分能够进入血液循环。预测分析表明其主要靶点包括半胱天冬酶-1、NLRP3、信号转导和转录激活因子1、Toll样受体4和肿瘤坏死因子,其中NLRP3炎性小体信号通路为关键机制。体内研究表明,KZMK可有效降低膀胱炎大鼠尿液沉淀物中的白细胞计数和膀胱指数。此外,KZMK减轻了动物的膀胱充血、水肿和组织病理学变化。KZMK治疗导致白细胞介素-18和白细胞介素-1β细胞因子水平降低。KZMK显著抑制脂多糖诱导的膀胱炎中NLRP3、gasdermin D和半胱天冬酶-1的表达,进一步证实了其抗炎作用。这些发现表明,KZMK主要通过抑制NLRP3炎性小体的激活来预防脂多糖诱导的膀胱炎。总体而言,结果表明KZMK有望成为尿路感染的潜在治疗选择。