Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease

Abstract

ZeXie Decoction (ZXD) is a traditional Chinese medicine composed of Alisma orientalis (Sam.) Juzep. and Atractylodes macrocephala Koidz. ZXD has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The mechanistic basis for the pharmacological activity of ZXD, however, remains poorly understood. In this study, we used a network pharmacology approach and investigated the association between ZXD and NAFLD. We identified the active ingredients of ZXD and screened the potential targets of these ingredients, after which a database of relevant NAFLD-related targets were constructed and several enrichment analyses were performed. Furthermore, the ethanol and aqueous extracts of ZXD were prepared and experimental pharmacology validation was conducted using RT-qPCR of the non-alcoholic fatty liver disease (NAFLD) model in Sprague-Dawley (SD) rats. As a result, a herb-compound-target-pathway network model was developed, and HMGCR, SREBP-2, MAPK1, and NF-κBp65 targets were validated. The gene expression results of these four targets were consistent with those of the network pharmacology prediction. Using an integration strategy, we revealed that ZXD could treat NAFLD by targeting HMGCR, SREBP-2, MAPK1, and NF-κBp65.

Qualitative Analysis of Drug-Containing Plasma and its Application to Quantitative Analysis and Pharmacokinetic Study of Zexie Decoction Using UPLC-MS/MS

“…Moreover, the lipid-lowing and anti-inflammatory activities of alisol A, alisol B, and alisol A 24-acetate have been broadly reported recently ( Zeng et al, 2016 ; Fei et al, 2018 ; Ho et al, 2019 ). Considering ZXD-mediated treatment of NAFLD and a number of other diseases related to dysregulation of lipid metabolism ( Song et al, 2014 ; Xue et al, 2014 ; Wu et al, 2021b ; Chang et al, 2021 ), alisol A, alisol B and alisol A 24-acetate were selected to analyzed in the present study.…”

“…The results had suggested that the ethanolic extract of ZXD manifested a better hypolipidemic effect than the aqueous extract owing to the different chemical composition ( Chang et al, 2021 ). Afterward, the ethanolic extract of ZXD was proved to have a therapeutic effect on non-alcoholic fatty liver disease in SD rats ( Wu et al, 2021b ). As a result, it was discovered that the ethanolic extract of ZXD had the significantly better potential for future investigation.…”

Intracellular Cholesterol Synthesis and Transport

“…In recent years, additional traditional Chinese medicines have been observed to have cholesterol-lowering effects, including aloe-emodin ( Su et al, 2020 ), apigenin ( Wu et al, 2021b ), Dingxin recipe IV ( Zhang et al, 2021 ), and ZeXie decoction ( Wu et al, 2021a ). The mechanisms of some of these medicines involve SREBP2 transcription and maturation processes.…”

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation

“…By using the keywords “ Davallia mariesii Moore ex Bak.”, 71 herbal compounds were totally identified for the follow-up screening. For these compounds, 18 potential active ingredients were selected with the two key ADME indexes, including oral bio-availability (OB ≥ 30%) and drug similarity (DL ≥ 0.18) ( 14 ). When compared with the related literature and collected two-dimensional (2D) structures of each ingredient from the PubChem database ( ) ( 15 ), 10 flavonoid compounds of TFDR were picked up as the potential candidates.…”