Wang Yang, Yang Rui, Shi Youyang, Liu Sheng
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People's Republic of China.
China Academy of Chinese Medical Sciences, Suzhou, 215100, People's Republic of China.
Drug Des Devel Ther. 2025 Sep 13;19:8213-8236. doi: 10.2147/DDDT.S530516. eCollection 2025.
To analyze the constituents and metabolic products of Xianling Cifang Granules (XLCF) in the serum of mice. The potential targets of XLCF in the treatment of breast cancer (BC) were explored by combining network pharmacology and molecular docking technology.
Serum was collected from mice following oral administration of XLCF and analyzed using UHPLC-Q Exactive Orbitrap-MS. Absorbed prototype constituents and metabolites were identified by comparing retention times, accurate masses, MS/MS fragments, and isotopic patterns. Network pharmacology predicted potential therapeutic targets, and molecular docking (Autodock/Pymol) validated interactions between key constituents and targets.
Our comprehensive metabolomic profiling elucidates the pharmacological basis of XLCF against BC by identifying its absorbed constituents and their potential therapeutic links. It identified 122 prototype constituents of XLCF entering the systemic circulation. Icaritin (a metabolite derived from ) was identified as a pivotal constituent due to its high bioavailability and established anti-BC activity, specifically inducing redox-mediated apoptosis via the SIRT6/NF-κB pathway and modulating the immunosuppressive microenvironment in triple-negative breast cancer (TNBC). Additionally, 62 serum metabolites exhibited significant alterations post-XLCF treatment, indicative of metabolic reprogramming involving carboxylation, hydroxylation, glucuronidation, and sulfation. Network pharmacology implicated inflammation and cellular metabolism pathways in the therapeutic effects of XLCF. Molecular docking confirmed that Icaritin, as the principal bioactive component, formed stable interactions with core targets ADORA1, AKR1B1, and ADORA3.
This integrated approach delineates the anti-BC mechanism of XLCF, 122 absorbed constituents (with Icaritin as key) and 62 altered metabolites drive systemic metabolic reprogramming, acting through ADORA1, AKR1B1 and ADORA3 targets to modulate critical pathways. These findings provide robust pharmacological evidence supporting the clinical application of XLCF against BC and demonstrate the value of combining metabolomics with target prediction for Traditional Chinese Medicine (TCM) research. Experimental validation of the identified targets is warranted.
分析仙灵赐方颗粒（XLCF）在小鼠血清中的成分及代谢产物。结合网络药理学和分子对接技术，探索XLCF治疗乳腺癌（BC）的潜在靶点。
给小鼠口服XLCF后收集血清，采用超高效液相色谱-四极杆-轨道阱高分辨质谱（UHPLC-Q Exactive Orbitrap-MS）进行分析。通过比较保留时间、精确质量数、二级质谱碎片和同位素模式，鉴定吸收的原型成分和代谢产物。网络药理学预测潜在治疗靶点，分子对接（Autodock/Pymol）验证关键成分与靶点之间的相互作用。
我们的综合代谢组学分析通过鉴定XLCF的吸收成分及其潜在治疗联系，阐明了XLCF抗BC的药理基础。它鉴定出122种进入体循环的XLCF原型成分。淫羊藿素（一种源自……的代谢产物）因其高生物利用度和已证实的抗BC活性被确定为关键成分，特别是通过SIRT6/NF-κB途径诱导氧化还原介导的凋亡，并调节三阴性乳腺癌（TNBC）中的免疫抑制微环境。此外，62种血清代谢产物在XLCF治疗后表现出显著变化，表明涉及羧化、羟基化、葡萄糖醛酸化和硫酸化的代谢重编程。网络药理学表明炎症和细胞代谢途径与XLCF的治疗作用有关。分子对接证实淫羊藿素作为主要生物活性成分，与核心靶点ADORA1、AKR1B1和ADORA3形成稳定相互作用。
这种综合方法描绘了XLCF的抗BC机制，122种吸收成分（以淫羊藿素为关键）和62种改变的代谢产物驱动全身代谢重编程，通过ADORA1、AKR1B1和ADORA3靶点发挥作用以调节关键途径。这些发现为支持XLCF临床应用于抗BC提供了有力的药理学证据，并证明了代谢组学与靶点预测相结合在中药研究中的价值。对已鉴定靶点进行实验验证是必要的。
