This study aimed to isolate active compounds from traditional Chinese medicinal Taxillus sutchuenensis to inhibit hepatitis C virus (HCV) NS3 protease activity. Under the guidance of bioassay, 10 compounds were isolated from the EtOAc extract fraction, which were identified as inhibitors of HCV NS3 protease. IC₅₀ values of these compounds were obtained, and a broad degree of anti-HCV activity was observed. The most active compounds were kaempferol-3,7-bisrhamnoside (19.4 μM) and (3S)-3-hydroxy-1,7-bis(4-hydroxy-phenyl)-6E-hepten-5-one (28.7 μM). In conclusion, flavonoids and diarylheptanoids were responsible for the anti-HCV constitution of Taxilli Herba. These inhibitors of HCV NS3 protease might serve as potential candidate of anti-HCV agents.

The glucagon-like peptide-1 (GLP-1) is a peptide with incretin activity and plays an important role in glycemic control as well as the improvement of insulin resistance in type 2 diabetes mellitus (T2DM). However, the short half-life of the native GLP-1 in circulation poses difficulties for clinical practice. To improve the proteolytic stability and delivery properties of GLP-1, a protease-resistant modified GLP-1 (mGLP-1) was constructed with added arginine to ensure the structural integrity of the released mGLP-1 in vivo. The model probiotic Lactobacillus plantarum WCFS1 was chosen as the oral delivery vehicle with controllable endogenous genetic tools driven for mGLP-1 secretory constitutive expression. The feasibility of our design was explored in db/db mice which showed an improvement in diabetic symptoms related to decreased pancreatic glucagon, elevated pancreatic β-cell proportion, and increased insulin sensitivity. In conclusion, this study provides a novel strategy for the oral delivery of mGLP-1 and further probiotic transformation.