Discovery of metal complexes with antibacterial properties in aqueous extracts of Radix scutellariae and a study of the antibacterial properties of the baicalin–manganese complex

Antimicrobial resistance is a major public health concern. Many drug development strategies focus on metal complexes because they have different inhibitory mechanisms and are less prone to drug resistance than traditional antibiotics. In this study, we investigated the antibacterial properties of Radix scutellariae (Huangqin), a traditional Chinese medicine. Using acid methanol solutions, we identified metal complexes in aqueous extracts of Huangqin, in which baicalin, oroxindin, and scutellarin function as ligands. Mn2+ increased the antibacterial activity of the aqueous extract through metal ion addition. We investigated the mechanism and structure of the baicalin–manganese complex (BCM) obtained by hydrothermal synthesis. Reaction products containing BCM at a ratio of 1 : 1 and 2 : 1 were significantly more effective against bacteria than baicalin alone. The antibacterial activity of the BCM against Staphylococcus aureus was eight times higher than that of baicalin. The antibacterial mechanisms included altering the morphological structure of bacteria, disrupting the integrity of their cell membrane and wall, and causing the cells to produce large amounts of reactive oxygen species. Importantly, after continuous cultivation of S. aureus for 20 generations in drug-containing cultures, the minimum inhibitory concentrations (MIC) of amikacin, azithromycin, and clindamycin were 32, eight, and four times greater than those in the first generation, respectively, whereas the MIC of BCM was maintained. BCM could reverse S. aureus resistance to amikacin and azithromycin. In conclusion, during the decoction of Huangqin, the organic components form complexes with metal ions, producing compounds with good antibacterial activity and a low tendency to cause resistance.