Salvia miltiorrhiza Bge is a medicinal plant (Chinese name “Danshen”) widely used for the treatment of hyperglycemia in traditional Chinese medicine. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a potential target for insulin sensitizing for the treatment of diabetes. In this work, PTP1B was displayed at the surface of E. coli cells (EC-PTP1B) to be used as a bait for fishing of the enzyme’s inhibitors present in the aqueous extract of S. miltiorrhiza. Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC₅₀ value of 23.35 µM. The inhibitory mechanism of salvianolic acid B was further investigated by enzyme kinetic experiments and molecular docking, indicating salvianolic acid B was a non-competitive inhibitor for PTP1B (with Ki and Kis values of 31.71 µM and 20.08 µM, respectively) and its binding energy was −7.89 kcal/mol. It is interesting that in the comparative work using a traditional ligand fishing bait of PTP1B-immobilized magnetic nanoparticles (MNPs-PTP1B), no ligands were extracted at all. This study not only discovered a new PTP1B inhibitor from S. miltiorrhiza which is significant to understand the chemical basis for the hypoglycemic activity of this plant, but also indicated the effectiveness of cell display-based ligand fishing in screening of active compounds from complex herbal extracts.

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7-O-glucoside (1), marein (2), and okanin (3) were found to be the enzyme inhibitors. The IC₅₀ values of quercetagetin-7-O-glucoside (1) and okanin (3) were 79.06 ± 1.08 μM and 30.25 ± 1.11 μM, respectively, which is smaller than 100.21 ± 0.11 μM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein (2) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

Hyaluronidase possesses the capacity to degrade high-molecular-weight hyaluronic acid into smaller fragments, subsequently initiating a cascade of inflammatory responses and activating dendritic cells. In cases of bacterial infections, substantial quantities of HAase are generated, potentially leading to severe conditions such as cellulitis. Inhibiting hyaluronidase activity may offer anti-inflammatory benefits. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has anti-inflammatory properties. However, its effects on skin inflammation are not well understood. This study screened and evaluated the active components of S. miltiorrhiza that inhibit skin inflammation, using ligand fishing, enzyme activity assays, drug combination analysis, and molecular docking. By combining magnetic nanomaterials with hyaluronidase functional groups, we immobilized hyaluronidase on magnetic nanomaterials for the first time in the literature. We then utilized an immobilized enzyme to specifically adsorb the ligand; two ligands were identified as salvianolic acid B and rosmarinic acid by HPLC analysis after desorption of the dangling ligands, to complete the rapid screening of potential anti-inflammatory active ingredients in S. miltiorrhiza roots. The median-effect equation and combination index results indicated that their synergistic inhibition of hyaluronidase at a fixed 3:2 ratio was enhanced with increasing concentrations. Kinetic studies revealed that they acted as mixed-type inhibitors of hyaluronidase. Salvianolic acid B had K_i and K_is values of 0.22 and 0.96 μM, respectively, while rosmarinic acid had values of 0.54 and 4.60 μM. Molecular docking revealed that salvianolic acid B had a higher affinity for hyaluronidase than rosmarinic acid. In addition, we observed that a 3:2 combination of SAB and RA significantly decreased the secretion of TNF-α, IL-1, and IL-6 inflammatory cytokines in UVB-irradiated HaCaT cells. These findings identify salvianolic acid B and rosmarinic acid as key components with the potential to inhibit skin inflammation, as found in S. miltiorrhiza. This research is significant for developing skin inflammation treatments. It demonstrates the effectiveness and broad applicability of the magnetic nanoparticle-based ligand fishing approach for screening enzyme inhibitors derived from herbal extracts.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1–7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer–Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson’s disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson’s disease model of PINK1^B9. Perforalactones G and I (2 and 4) showed a 10–15% increase in cell viability of the model cells at 50 μM, while compounds 2 and 4 (100 μM) significantly improved the climbing ability of PINK1^B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.