Chen Lixin, Liang Wei, Zhang Kun, Wang Zishuo, Cheng Wei, Li Wenlan
School of Pharmaceutical Sciences, Harbin University of Commerce, Harbin, Heilongjiang, China.
Front Pharmacol. 2024 May 17;15:1206718. doi: 10.3389/fphar.2024.1206718. eCollection 2024.
The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using "Scrophulariae Radix-Fritillaria." The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of "Scrophulariae Radix-Fritillaria" were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. "Scrophulariae Radix-Fritillaria" mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by "Scrophulariae Radix-Fritillaria." Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of "Scrophulariae Radix-Fritillaria" were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of "Scrophulariae Radix-Fritillaria" involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.
通过代谢组学和血清药物化学分析了“玄参-浙贝母”的药效物质及其治疗甲状腺肿的分子机制。采用丙硫氧嘧啶（PTU）建立大鼠甲状腺肿模型，并用“玄参-浙贝母”对动物进行治疗。从甲状腺组织病理学和血液生化指标方面评价该药物对的疗效。采用超高效液相色谱-四极杆飞行时间质谱联用仪（UPLC-Q-TOF/MS）分析大鼠的血清和尿液样本。进行主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）以筛选尿液中的潜在生物标志物及其相应的代谢途径。还鉴定了“玄参-浙贝母”的血液成分，并分析了它们与尿液生物标志物的相关性，以筛选潜在的生物活性化合物。“玄参-浙贝母”减轻了甲状腺组织损伤，使甲状腺激素FT3、FT4和TSH水平恢复正常。我们还鉴定了22种与甲状腺肿相关的尿液生物标志物，其中19种受“玄参-浙贝母”调节。此外，尿液生物标志物参与色氨酸代谢、类固醇激素生物合成和β-丙氨酸代谢，这些途径可能是该药物对的作用靶点。另外，通过血清药物化学检测到“玄参-浙贝母”的47种化合物，其中9种成分，即丁香酸、丹皮酚、雪松醇、顺式阿魏酸、费替生宁、马钱苷元、亚麻酸、乌苏里啶和5-（甲硫基）戊腈，被鉴定为抗甲状腺肿的潜在有效物质。总之，我们表征了“玄参-浙贝母”治疗甲状腺肿所涉及的化学成分和机制，我们的研究结果为其临床应用提供了实验依据。
