Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.

Stephaniae Tetrandrae Radix (STR) is a commonly used herb with a history of thousands of years. Accumulating evidence shows the therapeutic effect on breast cancer (BC) of STR. Here, we aimed to elucidate the active components and mechanisms of STR against BC. The active components and targets were retrieved and screened from the corresponding databases. A target protein–protein interaction (PPI) network was built and Ingenuity Pathway Analysis (IPA) used to analyze and screen key targets and pathways. Subsequently, molecular docking was performed to visualize the patterns of interactions between components and targets. Finally, the main active components of STR in treating BC were confirmed by in vitro experiments, and 34 common targets were obtained. The PPI network and IPA showed that the key targets were TP53, JUN, CASP3, and so on. Additionally, signaling pathways were enriched. Docking verified that the active components have good binding potential with the key targets, especially tetrandrine (Tet) and fangchinoline (Fang). In vitro studies confirmed that they significantly inhibited the viability of MDA-MB-231 cells and increased LDH leakage rate compared to MCF-10A cells. STR participates in many cell processes and regulate multiple targets, thereby playing an anti-breast cancer role. Tet and Fang may be the main active components.