Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation.

CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.

[Suitable planting area of Poria cocos in Jinzhai county of Dabie Mountains region].

Dabie Mountain in Anhui province is a genuine producing area of Poria cocos, commonly known as Anling. Jinzhai county in Anhui province is a traditional producing area of P. cocos, and it is also a key county for poverty alleviation in Dabie Mountains. Poverty alleviation of traditional Chinese medicine producing area is an important measure to implement the major strategic deployment of the central government. The planting of P. cocos is helpful to promote the development of traditional Chinese medicine industry in Dabie Mountains and help poverty alleviation. P. cocos is a saprophytic fungus with special demands on soil and ecological environment, and its planting appears a scattered and irregular distribution. Traditional investigation methods are time-consuming and laborious, and the results are greatly influenced by subjective factors. In order to obtain the suitable planting area of P. cocos in Jinzhai county, according to the field survey, the research team has explored the regional, biological characteristics and cultivation methods of P. cocos in the county, and obtained the altitude distribution area suitable for the growth of P. cocos. Then, the MaxEnt niche model was used to analyze the relationship between ecological factors and distribution areas, and the potential distribution zoning of P. cocos in Jinzhai county was studied. Combined with the characteristics of P. cocos planting pattern, taking ZY-3 remote sensing image as the data source, the maximum likelihood method was used to extract the area that could be used for P. cocos cultivation in Jinzhai county, and the reason why artificial planting P. cocos was mainly distributed in the west of Jinzhai county was analyzed. The suitable regional classification of P. cocos in Jinzhai county was obtained by superposition of suitable altitude distribution area, MaxEnt analysis and area extracted from remote sensing image, which provided data support for the planting planning of P. cocos in Jinzhai county.