No abstract

Apolipoprotein B mRNA‐editing enzyme catalytic polypeptide like (APOBEC) DNA cytidine deaminases convert cytosine to uracil in pathogen‐related single‐stranded DNAs. Aberrant activation of APOBEC enzymes in tumour cells leads to hypermutations that drive heterogeneity and clonal evolution, which results in tumour progression and treatment adaptation. APOBEC3 family member APOBEC3B (A3B) is a promising drug target to combat drug resistance, but the discovery of potent lead compounds remained challenging. Here, we devised a BspH1 restriction enzyme‐based biosensor to measure APOBEC deaminase activity, with superior simplicity and without the need of counter assays. Using this method, we performed a proof‐of‐concept screening using series of flavonoids and dihydrochalcones, from which bona fide inhibitors of recombinant A3B were identified and further validated by isothermal titration calorimetry. Our results demonstrate the capability of the BspH1‐based biosensor as a method for HTS, and prospects of developing potent A3B inhibitors using flavonoid and dihydrochalcone backbones.

Zingiber striolatum Diels (Z. striolatum), a widely popular vegetable in China, is famous for its medicinal and nutritional values. However, the anti-inflammatory effects of essential oil from Z. striolatum (EOZS) remain unclear. In this study, EOZS from seven regions in China were extracted and analyzed by GC–MS. LPS-induced RAW264.7 cells and 12-O-Tetradecanoylphorbol 13-acetate (TPA)-stimulated mice were used to evaluate the anti-inflammatory effects of EOZS. Results show that 116 compounds were identified in EOZS from seven locations. Samples 2, 4 and 5 showed the best capability on DPPH radical scavenging and NO inhibition. They also significantly reduced the production of ROS, pro-inflammatory cytokines, macrophage morphological changes, migration and phagocytic capability. Transcriptomics revealed MAPK and NF-κB signaling pathways may be involved in the anti-inflammatory mechanism, and the predictions were proven by Western blotting. In TPA-induced mice, EOZS reduced the degree of ear swelling and local immune cell infiltration by blocking the activation of MAPK and NF-κB signaling pathways, which was consistent with the in vitro experimental results. Our research unveils the antioxidant capability and potential molecular mechanism of EOZS in regulating inflammatory response, and suggests the application of EOZS as a natural antioxidant and anti-inflammatory agent in the pharmaceutical and functional food industries.