Cpd861 Targeting BCL2 to Alleviate Hepatic Fibrosis: Network Pharmacology, Mendelian Randomization, and Molecular Docking Mechanisms


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Abstract

Background:Compound 861 (Cpd861) is a traditional Chinese herbal compound for the treatment of hepatic fibrosis (HF). In the current investigation, Cpd861 has been demonstrated to have an underlying molecular mechanism and material foundation for the treatment of HF through network pharmacology, Mendelian randomization (MR), and molecular docking.

Methods:Public databases were consulted for Cpd861 constituents and HF targets. Protein-protein interactions (PPIs) were established using STRING software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To elucidate the causal relationship between potential targets and liver injury, MR was used as a methodological tool. Finally, a molecular docking analysis was conducted between the active compound and the key target.

Results:We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2.

Results:We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2.

Conclusion:This study made predictions regarding the efficacious components, as well as potential targets and pathways of Cpd861 in the therapy of HF. This will open up a new perspective for further investigation of the molecular mechanism of Cpd861 in the treatment of HF.

About the authors

Yaning Lyu

School of Nursing, Shandong Second Medical University

Email: info@benthamscience.net

Xifeng Liang

School of Nursing, Shandong Second Medical University

Email: info@benthamscience.net

Shuang Gao

School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences

Email: info@benthamscience.net

Jing Li

School of Nursing, Shandong Second Medical University

Email: info@benthamscience.net

Jinming Li

School of Nursing, Jining Medical University

Email: info@benthamscience.net

Shuhan Zhang

School of Nursing, Jining Medical University

Email: info@benthamscience.net

Chenghong Yin

Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital

Author for correspondence.
Email: info@benthamscience.net

Cheng Chi

School of Nursing,, Jining Medical University

Author for correspondence.
Email: info@benthamscience.net

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