Rapid Screening of Chemical Components in Salvia miltiorrhiza with the Potential to Inhibit Skin Inflammation.

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 Ki and Kis 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.

Pharmacokinetics of catechols in human subjects intravenously receiving XueBiJing injection, an emerging antiseptic herbal medicine.

XueBiJing injection, prepared from a five-herb combination, is extensively used as add-on therapy in routine sepsis care in China. Catechols, derived from the component herb Salvia miltiorrhiza roots (Danshen), are probably important because of their reported antiseptic properties. This study was designed to characterize pharmacokinetics of major circulating Danshen catechols in human subjects intravenously receiving the injection at the label doses. A total of 17 Danshen catechols were detected in XueBiJing injection (content level, 0.1-139.3 µmol/L). After dosing, tanshinol and salvianolic acid B exhibited relatively high levels of systemic exposure with mean elimination half-lives of 0.38 and 0.29 h, respectively. The total plasma clearance and apparent volume of distribution at steady state of tanshinol were 1.07 L/h/kg and 0.40 L/kg, respectively, whereas those of salvianolic acid B were 0.43 L/h/kg and 0.13 L/kg, respectively. Protocatechuic acid and five other catechols were also detected in plasma but at low exposure levels. Although protocatechuic aldehyde had the highest content level in the injection, like the remaining eight catechols, it was undetected in plasma. Protocatechuic aldehyde was extensively converted into protocatechuic acid and other metabolites. The information gained here facilitates understanding the roles of Danshen catechols in therapeutic actions of XueBiJing injection.