The effects of root decay on the anti-tumor potential of Scutellariae Radix: an investigation using mass spectrometry imaging, network pharmacology and in vitro validation

Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi, is widely used in complementary medicine for its therapeutical effects to treat hepatitis, diarrhea and inflammation. It has been confirmed by modern research that Scutellariae Radix also exhibits anti-tumor properties. As S. baicalensis plants grow into older ages, some of the roots start to decay. The decayed Scutellariae Radix is believed to exhibit different pharmacological effects. It is essential to understand how root decay affects the chemical composition of Scutellariae Radix and, consequently, contributes to the alteration of pharmacological effects. Mass spectrometry imaging (MSI) was adopted to map out the spatial distribution of natural compounds in the decayed roots of Scutellariae Radix. Compounds that showed varied contents between decayed and non-decayed tissues were further identified with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Identified compounds exhibiting high gastrointestinal adsorption values and high drug-likeness values were subjected to network pharmacology analysis. The influence of chemical alteration on pharmacological effects was predicted. Predictions were validated through in vitro assays on cancer cell lines (A-549, BxPC-3, KGN, and SGC-7901). A majority of compounds was observed to show significantly decreased contents in the decayed tissues of Scutellariae Radix. The shared targets of 15 key components and cancer were highly enriched in PI3K-Akt signaling pathway and multiple organ-specific cancer pathways. Apigenin, presenting the highest degree value during the establishment of component-target network, was selected as the representative component for in vitro validation of anti-tumor properties. Apigenin was found to inhibit the proliferation of four different tumor cell lines in a dose-dependent manner. The chemical composition of Scutellariae Radix was closely correlated with root decay. The contents of numerous compounds showed sharp decline within the decayed tissues of roots. It was revealed by network pharmacology analysis and in vitro study that many compounds were potential anti-tumor compounds. These findings emphasized the need for separate quality standards for decayed and non-decayed roots. This research advances current exploration of medicinal plants and highlights the importance of quality control in medicinal plant use, contributing to the development of complementary medicine.