Pharmacodynamic Material Basis and Pharmacological Mechanism of Huangqi Guizhi Wuwu Granules in Diabetic Peripheral Neuropathy

Huangqi Guizhi Wuwu Decoction (HGWD) is a traditional Chinese medicine (TCM) formula used to treat diabetic peripheral neuropathy (DPN) in China. Considering that the decoction was not easy to carry and use, we have prepared HGWD into Huangqi Guizhi Wuwu Granules (HGWG). However, the active components of HGWG that can be absorbed into plasma and its mechanism of action for DPN treatment remain unclear. In the present study, UHPLC-Q-TOF-MS and network pharmacology methods were applied to explore the potential pharmacodynamic material basis and pharmacological mechanism of HGWG for the treatment of DPN. A total of 31 absorbed components were detected in rat plasma, including 20 prototype compounds and 11 metabolites. Flavonoid-related metabolites and gingerol-related metabolites were major metabolites. The network pharmacological analysis showed that 31 absorbed constituents regulated 122 pathways through 177 targets; among them, baicalein, paeoniflorin C, and 6-gingerol were the main pharmacodynamic components of HGWG for DPN. It can be concluded that monoterpenoid glycosides, flavonoids, organic acids, gingerols, flavonoid-related metabolites, and gingerol-related metabolites were the main pharmacodynamic material basis of HGWG for DPN, and the mechanism of HGWG for DPN may be related to reducing oxidative stress and inhibiting neuroinflammation by stimulating the phosphorylation of p38 MAPK.