Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation

Abstract

Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB). Pathway and functional enrichment analysis of these putative targets indicated that DGLHD obviously influenced NF-κB and PPAR signaling pathway. Consistently, DGLHD downregulated levels of ALT (alanine transaminase) and AST (aspartate transaminase), reduced production of proinflammatory cytokines-TNF (tumor necrosis factor) -α and IL (Interleukin) -1β in serum and liver from mice with hepatic fibrosis, and inhibited hepatic stellate cell (HSC)-T6 cells proliferation. DGLHD decreased TGF (transforming growth factor) -β1 and α-SMA (smooth muscle actin) expression as well, maintained MMP (matrix metalloprotein) 13-TIMP (tissue inhibitor of metalloproteinases) 1 balance, leading to mitigated ECM (extracellular matrix) deposition in vivo and in vitro. Moreover, our experimental data confirmed that the alleviated inflammation and ECM accumulation were pertinent to NF-κB inhibition and PPAR-γ activation. Overall, our results suggest that DGLHD aims at multiply targets and impedes the progression of hepatic fibrosis by ameliorating abnormal inflammation and ECM deposition, thereby serving as a novel regimen for treating hepatic fibrosis in clinic.

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…The DL index can be useful in optimizing pharmacokinetic and pharmaceutical properties, such as solubility and chemical stability (Christopher et al, 1997). Herein, we assigned an OB value of ≥ 30% or a DL value of ≥ 0.18, as criteria to identify the potential active ingredients (Cao et al, 2018).…”

“…With the rapid development of bioinformatics, network pharmacology has emerged as a powerful tool to explore TCM (Cao et al, 2018;Yu et al, 2018). Based on system-biology, multi-directional pharmacology, and highthroughput analysis, network pharmacology can thoroughly explain the complicated relationship between drugs and diseases by constructing biological network and network visualization analysis of the potential active ingredients, hub targets, signaling pathways and diseases (Yuan et al, 2017;Ning et al, 2018;Huang et al, 2019).…”

Top-100 Most Cited Publications Concerning Network Pharmacology: A Bibliometric Analysis

“…Pathway and network analysis and protein-protein interactions are common methods for NP [6–8, 23]. Oral bioavailability [24] is an essential parameter for drug absorption and utilization; therefore, NP studies commonly use this alone or in combination with other parameters, including drug likeness, Caco-2 permeability, and drug half-life, as filters to select compounds from herbs [6, 7, 25]. Other methods, such as molecular docking, are also used in many NP studies [6, 23].…”

“…The first method, classic NP, involves the downloading of hundreds of herbal compounds from a database, or combining literature, and the mapping of a body of targets [6]. The second method involves the integration of experimental data to validate the computational results [7, 8]. Recently, many studies on NP for TCM have been published in various journals [6–11].…”

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism

“…), Coptis chinensis Franch., Radix Rehmanniae Praeparata (Rehmannia root), Astragalus propinquus (the root of astragalus membranaceus), Chinese skullcap (Scutellaria baicalensis) and Phellodendron amurense (Phellodendron chinense Schneid. ), is used for the treatment of autoimmune diseases and diabetes (Cao et al, 2017;Cao et al, 2018). In a study of ob/ob mice model, it normalized glucose and insulin level, diminished fat accumulation and lipogenesis, increased the expression of adiponectin, and promoted glucose uptake (Cao et al, 2017).…”