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.

Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy

“…Furthermore, el-Remessy AB et al proposed that 45 high glucose treatment blocks the pro-survival effect of VEGF and causes accelerated endothelial cell apoptosis via the action of peroxynitrite in causing tyrosine nitration of PI 3-kinase, so as to inhibit activity of Akt-1 kinase and increasing the activity of p38 MAP kinase. In addition, Wang et al also pointed out that 46 MAPK14 was identified gene candidate of potentially involved in DR, which was consistent with the results of this study. Saik OV etc.…”

Stachydrine Relieved the Inflammation and Promoted the Autophagy in Diabetes Retinopathy Through Activating the AMPK/SIRT1 Signaling Pathway

“…Tangwang Mingmu granule is a traditional Chinese medicine, which has been widely applied in the DR treatment. Wang et al 9 performed a pharmacokinetic study and found that STA was the main compound of Tangwang Mingmu granule. This aroused our interest to explore whether STA can play a therapeutic effect on DR?…”

“… 8 Autophagy is a double-edged sword in the growth process of eukaryotic cells, which runs through the normal growth, proliferation, and pathophysiological process. 9 For example, in the physiological state or at the early stage of some diseases, autophagy helps to clear senescent and damaged cells or organelles, while when autophagy is too strong, it has a pathogenic effect on cells, tissues, and organs. 10 Recently, many researches demonstrated that activating autophagy might be a promising therapeutic strategy in DR. 11 , 12 Adenosine monophosphate-activated protein kinase (AMPK) participates in the regulation of energy metabolism, plays a protective role in many diseases including DR. 13 Sirtuin 1 (SIRT1), one of the sirtuins family members, is a nicotinamide adenine dinucleotide (NAD +)-dependent histone deacetylase.…”

“… 19 , 20 Recently, research found that STA was an effective compound of Tangwang Mingmu granule, which was a traditional Chinese medicine and widely used in the DR treatment. 9 However, the potential mechanism of STA in DR and the relationship between STA and AMPK/SIRT1 mediated autophagy have not been reported.…”

Identification of the active compounds and their mechanisms of medicinal and edible Heigen based on UHPLC-Q-Exactive Orbitrap MS and network pharmacology

“…Network pharmacology is an emerging research approach combined with pharmacology, bioinformatics, and network biology (Lin et al, 2022). The compound-target-pathway networks can be predicted the biologically active ingredients and elaborate the compound mechanism of action (Wang et al, 2021). Today, network pharmacology comprehensively and systematically reveals the active ingredients (Jian et al, 2022) and potential mechanisms of action of TCM preparations by integrating multiple networks…”