Effects and Mechanistic Role of Mulberry Leaves in Treating Diabetes and its Complications.

Diabetes mellitus (DM) has become a surge burden worldwide owing to its high prevalence and range of associated complications such as coronary artery disease, blindness, stroke, and renal failure. Accordingly, the treatment and management of DM have become a research hotspot. Mulberry leaves (Morus alba L.) have been used in Traditional Chinese Medicine for a long time, with the first record of its use published in Shennong Bencao Jing (Shennong's Classic of Materia Medica). Mulberry leaves (MLs) are considered highly valuable medicinal food homologs that contain polysaccharides, flavonoids, alkaloids, and other bioactive substances. Modern pharmacological studies have shown that MLs have multiple bioactive effects, including hypolipidemic, hypoglycemic, antioxidation, and anti-inflammatory properties, with the ability to protect islet [Formula: see text]-cells, alleviate insulin resistance, and regulate intestinal flora. However, the pharmacological mechanisms of MLs in DM have not been fully elucidated. In this review, we summarize the botanical characterization, traditional use, chemical constituents, pharmacokinetics, and toxicology of MLs, and highlight the mechanisms involved in treating DM and its complications. This review can provide a valuable reference for the further development and utilization of MLs in the prevention and treatment of DM.

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 ß-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 ß-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 ß-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 ß-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.