Network pharmacology analysis reveals neuroprotection of Gynostemma pentaphyllum (Thunb.) Makino in Alzheimer' disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world, but still lack of effective drug treatment. Gynostemma Pentaphyllum (Thunb.) Makino (GpM), a Chinese medicinal herb, plays important roles in anti-inflammation, anti-oxidative stress and anti-tumor, which has been reported to ameliorate cognitive impairment of AD. However, the neuroprotective mechanism of GpM remains unclear. This study aims to investigate the targets and possible signaling pathways of GpM in the treatment of AD. METHODS: Active compounds of GpM and their putative target proteins were selected from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. AD-associated targets were identified from GeneCards, the Online Mendelian Inheritance in Man (OMIM) database and the Therapeutic Target Database (TTD). The intersecting targets of GpM and AD were identified and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to analyze the mechanism of them. Compound-target-pathway (CTP) network and protein-protein interaction (PPI) network were constructed and analyzed to elucidate the correlation between compounds, proteins and pathways. Molecular docking was performed to further demonstrate the possibility of GpM for AD. RESULTS: A total of 13 active compounds of GpM, 168 putative target proteins of compounds and 722 AD-associated targets were identified. Eighteen intersecting targets of GpM and AD were found and the epidermal growth factor receptor (EGFR), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), nitric oxide synthase in endothelial (NOS3) and serum paraoxonase/arylesterase 1 (PON1) were selected as the primary targets of GpM in the treatment of AD. The neuroprotective effect of GPM was related to a variety of pathways, including amoebiasis, HIF-1 signaling pathway, cytokine-cytokine receptor interaction and so on. CONCLUSIONS: Our findings elucidate the active compounds, targets and pathways of GpM involved in effects of anti-AD. The novel mechanism of GpM against AD provides more treatment options for AD.

The Efficacy Mechanism of Epigallocatechin Gallate against Pre-Eclampsia based on Network Pharmacology and Molecular Docking.

Pre-eclampsia (PE), a pregnancy complication, affects 3-5% of all pregnancies worldwide and is the main cause of maternal and perinatal morbidity. However, there is no drug which can clearly slow this disease progression. Epigallocatechin gallate (EGCG), a natural compound extracted from green tea, has been found to enhance the treatment efficacy of oral nifedipine against pregnancy-induced severe PE. This study aims to clarify the potential targets and pharmacological mechanisms of EGCG in treatment of PE. We used Traditional Chinese Medicine Systems Pharmacology database and Gene Cards database to obtain 179 putative target proteins of EGCG, 550 PE-related hub genes and 39 intersecting targets between EGCG and PE. By using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, we got the gene entries and enrichment pathways closely related to the intersecting targets. The top 10 enrichment pathways were pathway in cancer, proteoglycans in cancer, HIF-1 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, bladder cancer, hepatitis B, IL-17 signaling pathway, toxoplasmosis, PI3K-Akt signaling pathway. Furthermore, compound-target-pathway (CTP) and protein-protein interaction (PPI) network analysis were employed to explore the interaction of the top twelve targets for EGCG in treating PE. Molecular docking analysis showed combinations between these targets and EGCG, and the interaction between EGCG and the targets IL-6 and EGFR was confirmed by using molecular dynamic simulation. In conclusion, these findings hint the underlying mechanism of EGCG in the treatment of PE and point out directions in further studies on PE.

A network pharmacology study on mechanism of resveratrol in treating preeclampsia via regulation of AGE-RAGE and HIF-1 signalling pathways.

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy that threatens the lives of millions of pregnant women and their babies worldwide. Without effective medications, there are thousands of maternal and child mortalities every year. Resveratrol (RSV), a non-flavonoid polyphenol extracted from multiple plants, has shown positive effects in treating hypertension, cardiovascular disorders, and even PE. This study aimed to explore the pharmacological mechanism of RSV in treating PE by using network pharmacology and bioinformatics. Methods: With the use of multiple databases, 66 intersecting targets were obtained from the 347 putative targets of RSV and 526 PE-related genes. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to investigate the functions of the intersecting targets. The protein-protein interaction network and target-pathway network were drawn and analyzed to illustrate the correlation between targets and pathways. Finally, molecular docking was conducted to calculate the binding energy between RSV and core targets. Results: The results showed that the core targets of RSV were IL6, TNF, IL1B, VEGFA, STAT3, and EGFR. There existed good binding between RSV and IL6, TNF, IL1B, VEGFA, and EGFR. In addition, we found that RSV mainly functioned in the AGE-RAGE and HIF-1 signaling pathways, which are associated with the occurrence and development of PE. Conclusion: In conclusion, our findings indicated that RSV has the effects of regulating angiogenesis and anti-inflammation and can be a candidate medicine for treating PE.