Network pharmacology and molecular docking approaches to elucidate the potential compounds and targets of Saeng-Ji-Hwang-Ko for treatment of type 2 diabetes mellitus.

BACKGROUND

Saeng-Ji-Hwang-Ko (SJHK) is a traditional Korean medicine formula derived from Donguibogam, a classic medical textbook, published in 1613. It is described as a general treatment for So-gal (wasting-thirst, ) known as type 2 diabetes mellitus (T2DM) in a modern clinical term. It is necessary to elucidate the potential compounds and targets of SJHK for T2DM treatment by conducting network pharmacology and molecular docking analyses.

METHODS

Information about the chemical constituents of SJHK were collected, and druggable compounds were screened based on oral bioavailability and drug-likeness. Putative target genes of druggable compounds and T2DM-related genes were retrieved from public databases. A compound-target network was constructed to visualize the relationship between the druggable compounds in SJHK and common targets related to T2DM. The constructed network was further investigated through Protein-Protein Interaction, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analyses, and molecular docking.

RESULTS

Compound-target network analysis demonstrated that kaempferol, salicylic acid, estrone, and β-sitosterol were key compounds of SJHK with PTGS2, ESR1, PRKAA2, PRKAB1, and CYP19A1 being its key targets. Estrogen signaling, AGE-RAGE signaling, insulin resistance, non-alcoholic fatty liver disease, and TNF signaling pathway were potential pathways involved in the effect of SJHK on T2DM. Molecular docking simulations revealed that estrone and β-sitosterol had the strong binding energies for all the key target proteins.

CONCLUSIONS

This study demonstrates that network pharmacology and molecular docking analyses help to better understand the potential key compounds and targets of SJHK for treating T2DM as a complementary medicine.

SUMMARY: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder caused by genetic and/or environmental factors. There has been a growing attention to new therapeutic approaches to treat T2DM using traditional medicine as a complementary treatment which is expected to have synergistic effects with few side effects. Saeng-Ji-Hwang-Ko (SJHK) is a traditional Korean medicine (TKM) formula derived from Donguibogam, a classic medical textbook, published in 1613. It is described as a general treatment for So-gal (wasting-thirst, ) known as type 2 diabetes mellitus (T2DM) in a modern clinical term. It is necessary to elucidate the potential compounds and targets of SJHK for T2DM treatment by conducting network pharmacology and molecular docking analyses. Compound-target network analysis demonstrated that kaempferol, salicylic acid, estrone, and β-sitosterol were key compounds of SJHK with PTGS2, ESR1, PRKAA2, PRKAB1, and CYP19A1 being its key targets. Estrogen signaling, AGE-RAGE signaling, insulin resistance, non-alcoholic fatty liver disease, and TNF signaling pathway were potential pathways involved in the effect of SJHK on T2DM. Molecular docking evaluation revealed that estrone and β-sitosterol had the highest binding energies for all key target proteins, suggesting potential key compounds of SJHK. Although additional future studies including further experimental and clinical validation are needed, this study demonstrates that SJHK has a great potential for treating T2DM as a complementary medicine.