Systematic Evaluation of the Mechanisms of Mulberry Leaf (Morus alba Linne) Acting on Diabetes Based on Network Pharmacology and Molecular Docking

Abstract

Background: Diabetes mellitus is one of the most common endocrine metabolic disorder diseases. The application of herbal medicine to control glucose levels and improve insulin action might be a useful approach in the treatment of diabetes. Mulberry leaves (ML) has been reported to exert important activities of anti-diabetic. Objective: In this work, we aimed to explore the multi-targets and multi-pathways regulatory molecular mechanism of Mulberry leaves (ML, Morus alba Linne) acting on diabetes. Methods: Identification of active compounds of Mulberry leaves using Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Bioactive components were screened by FAF-Drugs4 website (Free ADME-Tox Filtering Tool). The targets of bioactive components were predicted from SwissTargetPrediction website, and the diabetes related targets were screened from GeneCards database. The common targets of ML and diabetes are used for Gene Ontology (GO) and pathway enrichment analysis. The visualization networks were constructed by Cytoscape 3.7.1 software. The construction of biological networks were performed to analyze the mechanisms as follows: (1) Compound-Target network; (2) Common target-Compound network; (3) Common targets protein interaction network; (4) Compound-Diabetes protein-protein interactions (PPI) network; (5) Target-Pathway network; (6) Compound-Target-Pathway network. At last, the prediction results of network pharmacology were verified by molecular docking method. Results: 17 active components were obtained by TCMSP database and FAF-Drugs4 website. 51 potential targets (11 common targets and 40 associated indirect targets) were obtained and used to build the PPI network by String database. Furthermore, the potential targets were used to GO and pathway enrichment analysis. 8 key active compounds (quercetin, Iristectorigenin A, 4-Prenylresveratrol, Moracin H, Moracin C, Isoramanone, Moracin E and Moracin D) and 8 key targets (AKT1, IGF1R, EIF2AK3, PPARG, AGTR1, PPARA, PTPN1 and PIK3R1) were obtained to play major roles in Mulberry leaf acting on diabetes. And the signal pathways involved in the mechanisms mainly include AMPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, insulin signaling pathway and insulin resistance. The molecular docking results show that the 8 key active compounds have good affinity with the key target of AKT1, and the 5 key targets (IGF1R, EIF2AK3, PPARG, PPARA and PTPN1) have better affinity than AKT1 with the key compound of quercetin. Conclusion: Based on network pharmacology and molecular docking of this work provided an important systematic and visualized basis for further understanding the synergy mechanism of ML acting on diabetes.

Protective effects of endothelial progenitor cell microvesicles carrying miR‑98‑5p on angiotensin II‑induced rat kidney cell injury

“…Previous evidence has indicated that miR-98-5p affects apoptosis, inflammation and oxidative stress by regulating the PI3K/Akt signaling pathway (27)(28)(29). Moreover, studies have shown that IGF1R can affect the development of diabetes through the PI3K/Akt/eNOS axis (30)(31)(32).…”

Anti-inflammatory effects of Chaishi Tuire Granules on influenza A treatment by mediating TRAF6/MAPK14 axis

“…Moreover, IL-6 and TNF were inflammatory factors involved in the process of inflammatory response. The production of cytokines such as IL-6 is induced by TNF and is involved in inflammatory responses and oxidative stress processes ( 11 , 12 ). The C-type lectin receptor signaling pathway plays an important role in host fungal infection by coordinating the immune system against infection ( 13 ).…”

Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus

“…Docking study on (4Z, 12Z)-cyclopentadeca- 9) isolated from Grewia hirsuta against target protein GSK-3 has shown that the oxygen atom of the isolated compound reacts with LYS-85 residue of GSK-3 and forms hydrogen bond through a strong hydrophobic interaction [154]. Quercetin ( 22) (Figure 6), iristectorigenin A (38), 4-prenylresveratrol (39), moracin H (40), moracin C (41), isoramanone (42), moracin E (43), and moracin D (44) (Figure 10) isolated from leaves of Morus alba Linne have shown good affinity to AKT-1 target protein [155]. Molecular docking and SAR studies conducted on compounds of different chemical categories are also reported, and these data could be useful in predicting activities of natural compounds with related structures.…”