Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery

Drug Deliv. 2021 Dec;28(1):2187-2197. doi: 10.1080/10717544.2021.1977422.

Abstract

Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.

Keywords: Huangjing; herbzyme; traditional Chinese medicine.

MeSH terms

  • Cell Enlargement / drug effects
  • Cell Line, Tumor
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Network Pharmacology / methods*
  • Plant Extracts / pharmacology*
  • Polygonatum*
  • Protein Interaction Maps
  • Proto-Oncogene Proteins c-akt / drug effects
  • TOR Serine-Threonine Kinases / drug effects

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported in part from the Nazarbayev University Faculty-Development Competitive Research Grants Program with grant number of 16797152; 15798117 (110119FD4531) to Yingqiu Xie; and Taishanghuangjing Biotechnology Co. Ltd. (previously named as Taian Xianlu Food Co. Ltd.).