Title:Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty
Liver Disease in High Fat-diet Mice
Volume: 24
Issue: 6
Author(s): Hongying Yang, Dongyun Wei, Yao Zhang and Wenxuan Jian*
Affiliation:
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong,
510080, People's Republic of China
Keywords:
Huangqin-Huanglian decoction, non-alcoholic fatty liver disease, high-fat diet, network pharmacology, inflammation, apoptosis.
Abstract:
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.
