Jia Zhichao, Lv Dongfang, Chen Tengfei, Shi Zhuozhuo, Li Xiaolin, Ma Junguo, Gao Zhaowang, Zhong Chongfu
Shandong University of Traditional Chinese Medicine, Shandong Jinan 250000, China.
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Jinan 250000, China.
Heliyon. 2024 Apr 30;10(9):e29975. doi: 10.1016/j.heliyon.2024.e29975. eCollection 2024 May 15.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined.
To reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS.
The concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments.
In this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3 T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue.
The potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.
慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)是一种常见的泌尿系统疾病,易于复发。它通常会导致受影响患者出现不同程度的盆腔疼痛和不适,以及与泌尿系统相关的症状。前列金丹片(QLJD)作为一种中药,在临床实践中已显示出对CP/CPPS有良好的治疗效果,但QLJD治疗CP/CPPS的潜在机制尚未明确。
揭示QLJD治疗CP/CPPS的植物化学特征和多靶点作用机制。
采用超高效液相色谱-四极杆静电场轨道阱高分辨质谱(UHPLC-Q Exactive Orbitrap-MS)测定QLJD的成分浓度。利用网络药理学方法,筛选QLJD治疗CP/CPPS所涉及的潜在成分、靶点和通路。采用分子对接计算评估QLJD成分与潜在靶点之间的亲和力,揭示最佳分子构象和结合位点。最后,通过药理学实验研究QLJD的治疗效果和潜在作用机制。
本研究共鉴定出35种靶向29个与CP相关基因的成分,其中槲皮素、黄芩苷、淫羊藿苷、木犀草素和没食子酸为主要成分。富集分析显示,潜在靶点主要参与细胞因子的调节、细胞增殖和凋亡以及氧化应激反应,主要与细胞因子-细胞因子受体相互作用通路、IL-17信号通路、Th17细胞分化通路和JAK-STAT信号通路相关。体内实验表明,QLJD可有效减轻CP/CPPS模型大鼠前列腺组织中CD3 T细胞的浸润和活性氧(ROS)的表达。此外,通过抑制IL-6和信号转导和转录激活因子3(STAT3)的表达,QLJD减少了Th17细胞的分化,从而改善了前列腺组织的病理损伤和前列腺指数。
QLJD作为一种抗CP/CPPS药物的潜力在于其能够通过多成分、多靶点、多通路的作用,干扰IL-6和STAT3的表达,抑制Th17细胞分化,减少大鼠前列腺组织中的炎性细胞浸润,并减轻氧化应激损伤。