Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty Liver Disease in High Fat-diet Mice

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BACKGROUND: Traditional Chinese medicine (TCM) has the advantage of low toxicity of natural ingredients, multiple targets and effects, and low medication costs. It has unique advantages for metabolic and chronic diseases. Huangqin-Huanglian decoction (HQHLD) is composed of Scutellariae Radix, Coptidis Rhizoma, Rehmanniae Radix, and Gentianae Radix Et Rhozima; it has great potential for the treatment of NAFLD with the modern pharmacological research and TCM theory, but there is still a relative lack of research on the potential targets and pharmacological effects of HQHLD.

METHODS: In this work, we have used network pharmacology to predict the targets and signaling pathways of HQHLD, and validated NAFLD-related targets using the HFD model in order to explore more therapeutic drugs and methods for NAFLD. We collected the HQHLD ingredients and NAFLD targets through TCMSP, ETCM, DisGeNET, HGMD, MalaCards, OMIM, and TTD, built ingredients-target networks by Cytoscape, and screened key ingredients in HQHLD. DAVID and Metascape databases were used for GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking of the key ingredients and key targets was performed by AutoDock. We verified the effect of HQHLD on high-fat diet (HFD) mice by measuring the weight, liver weight index, and the level of TG, TC, LDL-C, and HDLC. HE staining and oil-red staining were performed to detect the damage and fat accumulation in the liver. The changes in INSR, PPAR-α, PPAR-γ, TNF-α, and caspase3 were experimented with WB.

RESULTS: With the network pharmacology analysis, we found quercetin, baicalein, sitosterol, wogonin, oroxylin-A, glycyrrhizin, hydroberberine, berberine, sesamin, and carotene to be the main ingredients in HQHLD. According to KEGG pathway analysis, INSR, AKT, JNK1, PPAR-α, PPAR-γ, and the other 16 targets are the main targets of HQHLD in the treatment of NAFLD. We took HFD mice as the in vivo model of NAFLD. Our results showed that HQHLD could reduce liver weight, and TG and LDL-C levels, and increase HDL-C level in serum. By HE and oil red staining, we found that HQHLD could protect the morphology of hepatocytes and reduce fat in the liver. We also found HQHLD to protect the liver by increasing the expression of INSR and PPAR-α, and reducing the expression of PPAR-γ, TNF-α, and caspase3 in the liver.

CONCLUSION: In conclusion, our study has firstly studied the main ingredients and key targets of HQHDL in treating NAFLD by network pharmacology analysis, and preliminarily confirmed that HQHLD could alleviate NAFLD in a multi-target way by lowering fatty acids, and decreasing insulin resistance, inflammation, and apoptosis in the liver.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Endocrine, metabolic & immune disorders drug targets - 24(2024), 6 vom: 01., Seite 691-708

Sprache:

Englisch

Beteiligte Personen:

Yang, Hongying [VerfasserIn]
Wei, Dongyun [VerfasserIn]
Zhang, Yao [VerfasserIn]
Jian, Wenxuan [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis.
Cholesterol, LDL
Drugs, Chinese Herbal
High-fat diet
Huanglian
Huangqin-Huanglian decoction
Inflammation
Journal Article
Network pharmacology
Non-alcoholic fatty liver disease
Peroxisome Proliferator-Activated Receptors
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 22.02.2024

Date Revised 22.02.2024

published: Print

Citation Status MEDLINE

doi:

10.2174/0118715303257018230927182802

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM363517375