■小金丸(XJP)是一种用于治疗良性前列腺增生(BPH)的中药。它已被证明具有多种效果,比如调节性激素水平,表现出抗肿瘤,抗炎,镇痛药,和抗血小板聚集特性,提高免疫力。然而,XJP对BPH的治疗作用及其体内代谢过程的物质基础仍有待阐明。同时,许多存在于泌尿生殖道的微生物,包括那些与BPH有关的,也会影响宿主的健康。
■使用超高效液相色谱-串联质谱(UPLC-MS/MS),确定了XJP的化学成分。通过双侧睾丸消融和注射丙酸睾酮来创建BPH模型。使用病理ELISA对XJP的疗效进行综合评估,TUNEL,和免疫组织化学技术。此外,UPLC-MS代谢组学和16SrRNA测序揭示了血清代谢谱和肠道菌群组成。我们进行了Spearman相关系数分析,以强调“肠道微生物群-血清因子”和“肠道微生物群-代谢物”之间的相互作用。\"
■XJP含有91种减轻大鼠BPH病变的化合物,降低前列腺重量,索引,和血清二氢睾酮(DHT)水平,前列腺特异性抗原(PSA),表皮生长因子(EGF),碱性成纤维细胞生长因子(bFGF),血管内皮生长因子(VEGF)水平。它抑制前列腺上皮细胞凋亡和下调Bax,caspase-3途径中的TGF-β1和IGF-1蛋白。代谢组学研究表明,在治疗的大鼠中,有10种代谢产物上调和10种代谢产物下调。5-甲基胞嘧啶,尿嘧啶,嘧啶代谢中富含胞嘧啶。L-精氨酸在包括嘧啶代谢的代谢途径中起关键作用,精氨酸生物合成,和哺乳动物雷帕霉素靶蛋白(mTOR)信号通路。16SrRNA测序表明,XJP通过降低拟杆菌/厚壁菌(B/F)比例优化了BPH大鼠肠道菌群的多样性和平衡,增强有益细菌,比如蛋黄科,厌氧科,和Romboutsia,抑制功能失调的细菌,比如天花科,Prevotellaceae_NK3B31_组,Dorea,和Frisingicocus.根据Spearman相关系数分析,发现乳酸杆菌与血清因子最相关,而Romboutsia与代谢物的相关性最高。这一发现表明XJP调节BPH大鼠的嘧啶代谢紊乱,与Romboutsia密切相关的法规,Prevotellaceae_NK3B31_组,乳酸菌,Chujaibacter,和肠道,从而提供有价值的生物学见解。
■总之,这些发现表明XJP通过其多组分具有协同抗BHP作用,多目标,多肠微生物群,和多代谢途径特性。这种效应涉及性激素水平的调节,生长因子,以及抗上皮细胞凋亡过程。宿主对特定肠道微生物群的调节和多种代谢途径的参与可能是XJP治疗BPH的重要机制之一。值得注意的是,嘧啶代谢和肠道微生物生态系统在这个过程中紧密交织在一起。
UNASSIGNED: Xiaojin Pill (XJP) is a traditional Chinese medicine prescribed for treating benign prostatic hyperplasia (BPH). It has been proven to have multiple effects, such as regulating sex hormone levels, exhibiting anti-tumor, anti-inflammatory, analgesic, and anti-platelet aggregation properties, and improving immunity. However, the material basis of XJP\'s therapeutic effect on BPH and its metabolic process in vivo remains to be clarified. At the same time, many microorganisms that exist in the urogenital tract, including those related to BPH, can also affect the health of the host.
UNASSIGNED: Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the chemical components of XJP were identified. A BPH model was created through bilateral testicular ablation and injections of testosterone propionate. A comprehensive evaluation of XJP efficacy was conducted using pathological ELISA, TUNEL, and immunohistochemical techniques. In addition, UPLC-MS metabolomics and 16S rRNA sequencing revealed the serum metabolic profile and intestinal microbiota composition. We performed a Spearman correlation coefficient analysis to highlight the interactions between \"intestinal microbiota-serum factors\" and \"intestinal microbiota-metabolites.\"
UNASSIGNED: XJP contains 91 compounds that alleviate pathologies of BPH in rats, decreasing prostate weight, index, and serum levels of Dihydrotestosterone (DHT), Prostate-Specific Antigen (PSA), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) levels. It inhibits prostatic epithelial cell apoptosis and downregulates Bax, TGF-β1, and IGF-1 proteins in the caspase-3 pathway. Metabolomics studies have revealed 10 upregulated and 10 downregulated metabolites in treated rats, with 5-methylcytosine, uracil, and cytosine enriched in pyrimidine metabolism. L-arginine plays a pivotal role in metabolic pathways encompassing pyrimidine metabolism, arginine biosynthesis, and the mammalian target of rapamycin (mTOR) signaling pathway. 16S rRNA sequencing revealed that XJP optimized the diversity and balance of intestinal flora in BPH rats by decreasing the Bacteroidetes/Firmicutes (B/F) ratio, enhancing the beneficial bacteria, such as Eggerthellaceae, Anaerovoracaceae, and Romboutsia, and suppressing the dysfunctional bacteria, such as Atopobiaceae, Prevotellaceae_NK3B31_group, Dorea, and Frisingicoccus. According to the Spearman correlation coefficient analysis, Lactobacillus was found to be most associated with serum factors, whereas Romboutsia showed the highest correlation with metabolites. This finding suggests that XJP modulates pyrimidine metabolism disorders in BPH rats, a regulation that aligns closely with Romboutsia, Prevotellaceae_NK3B31_group, Lactobacillus, Chujaibacter, and Enterorhabdus, thereby providing valuable biological insights.
UNASSIGNED: In summary, these findings indicate that XJP possesses a synergistic anti-BHP effect through its multi-component, multi-target, multi-gut microbiota, and multi-metabolic pathway properties. The effect involves the regulation of sex hormone levels, growth factors, and the anti-epithelial cell apoptosis process. The modulation of specific gut microbiota by the host and the involvement of multiple metabolic pathways are likely one of the significant mechanisms of XJP in treating BPH. Notably, pyrimidine metabolism and the intestinal microbial ecosystem are closely intertwined in this process.