Network pharmacology strategy for revealing the pharmacological mechanism of pharmacokinetic target components of San-Ye-Tang-Zhi-Qing formula for the treatment of type 2 diabetes mellitus

Xue

et al. 2021

Pharmaceutical Biology

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.

Section: Introductionmentioning

confidence: 97%

“… 2019 ; Liu et al. 2020 ). To understand the pharmacokinetic parameters of absorption, distribution, metabolism, and excretion (ADME) of a drug product, the high-content-ingredients that emigrate into the circulatory system are generally selected as target compounds in a pharmacokinetic study (Jiang et al.…”

Section: Introductionmentioning

confidence: 99%

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

Xue

et al. 2021

Pharmaceutical Biology

“…The re-equilibration time of gradient elution was 5 min. Moreover, the detection wavelength was set at 270 and 230 nm ( Liu et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice

Yao

Huang

et al. 2021

Front. Pharmacol.

Sanye Tablet (SYT) is a patent prescription widely used in treating T2D and pre-diabetes, especially T2D comorbid with hypertriglyceridemia, for many years in China. However, the underlying mechanism that accounts for the anti-diabetic potential of SYT by regulating lipid-related intermediates remains to be elucidated. This study aimed to investigate the mechanism of SYT on lipid metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice by means of combining lipidomics and proteomics. The obese mice models were developed via HFD feeding for 20 consecutive weeks. Mice in the treatment group were given metformin and SYT respectively, and the effects of SYT on body weight, blood glucose, insulin sensitivity, fat accumulation in the organs, and pathological changes in the liver were monitored. Lipid metabolism was examined by lipidomics. Further determination of signaling pathways was detected by proteomics. The biological contributions of the compounds detected in SYT’s chemical fingerprint were predicted by network pharmacology. SYT treatment reduced body weight, inhibited viscera and hepatic steatosis lipid accumulation, and prevented insulin resistance. Furthermore, it was found that circulatory inflammatory cytokines were reduced by SYT treatment. In addition, lipidomics analysis indicated that SYT targets lipid intermediates, including diacylglycerol (DAG) and Ceramide (Cer). Mechanistically, SYT positively affected these lipid intermediates by suppressing liver lipogenesis via downregulation of SREBP1/ACC and the JAK/STAT signaling pathway. Our results predicted that astragalin and rosmarinic acid might regulate the JAK-STAT pathway by targeting PIM2 and STAT1, respectively, while paeoniflorin and rosmarinic acid were likely to regulate inflammatory responses by targeting TNFα, IL-6, and IL-4 during T2D. Overall, our study provides supportive evidence for the mechanism of SYT’s therapeutic effect on dysregulated lipid metabolism in diabesity.

“…Nuciferine, a major aporphine alkaloid found in Lotus ( Nelumbo nucifera leaves), may be a potentially important candidate in the management of insulin resistance and type 2 diabetes. The network pharmacology analysis shows that nuciferine has several biological functions, which may be associated with insulin resistance and dysregulation of lipolysis in adipocytes, which are partly confirmed [ 9 ]. Nuciferine and pronuciferine significantly increase glucose uptake in insulin resistant 3T3-L1 adipocytes, showing the amelioration of glucose metabolism.…”

Section: Prevention Of Insulin Resistance and Type 2 Diabetesmentioning

confidence: 99%

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

et al. 2021

The incidence and prevalence of metabolic syndrome has steadily increased worldwide. As a major risk factor for various diseases, metabolic syndrome has come into focus in recent years. Some natural aporphine alkaloids are very promising agents in the prevention and treatment of metabolic syndrome and its components because of their wide variety of biological activities. These natural aporphine alkaloids have protective effects on the different risk factors characterizing metabolic syndrome. In this review, we highlight the activities of bioactive aporphine alkaloids: thaliporphine, boldine, nuciferine, pronuciferine, roemerine, dicentrine, magnoflorine, anonaine, apomorphine, glaucine, predicentrine, isolaureline, xylopine, methylbulbocapnine, and crebanine. We particularly focused on their impact on metabolic syndrome and its components, including insulin resistance and type 2 diabetes mellitus, endothelial dysfunction, hypertension and cardiovascular disease, hyperlipidemia and obesity, non-alcoholic fatty liver disease, hyperuricemia and kidney damage, erectile dysfunction, central nervous system-related disorder, and intestinal microbiota dysbiosis. We also discussed the potential mechanisms of actions by aporphine alkaloids in metabolic syndrome.