Abstract：
The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.
摘要：
癌症的高患病率和与许多癌症治疗相关的有害副作用需要寻找有效的替代疗法。天然产物因其潜在的治疗益处而越来越被认可和研究。半枝莲D.唐(SBD)，一种具有有效抗肿瘤特性的植物，引起了肿瘤学研究人员的极大兴趣。其主要类黄酮成分-灯盏乙素和木犀草素-由于吸收不良而具有有限的口服生物利用度。这阻碍了其在癌症治疗中的应用。肠道微生物群，被认为是代谢器官，可以调节化合物的生物转化，从而改变其生物利用度和功效。在这项研究中,我们使用液相色谱串联质谱（LC-MS/MS8060）和离子阱飞行时间（LC-MSn-IT-TOF）分析来研究肠道微生物群对灯盏乙素和木犀草素的离体代谢。鉴定了五种代谢物和一种潜在代谢物。我们总结了先前对其抗肿瘤作用的研究，并进行了体外肿瘤细胞系研究以证明其抗肿瘤活性。通过分子对接和纯酶代谢实验验证了体外肠道菌群代谢的可能关键途径。此外,我们通过网络药理学探索了SBD两种成分的抗肿瘤机制，为后续目标识别提供依据。这些发现扩展了我们对SBD抗肿瘤机制的理解。值得注意的是,这项研究有助于现有的知识关于类黄酮生物转化的肠道微生物群，强调SBD在癌症治疗中的治疗潜力。此外，我们的研究结果为未来的体内药代动力学研究提供了理论基础，旨在优化SBD在肿瘤学应用中的临床疗效。
