Pharmacokinetic study of Tangwang Mingmu granule for the management of diabetic retinopathy based on network pharmacology

Abstract

Context Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. Objective To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. Materials and methods First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. Results Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. Conclusions The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines.