RESUMEN
Coluria longifolia Maxim (C. longifolia) is a Chinese folk medication commonly used to treat arthritis and joint pain. Literatures have reported that C. longifolia has significant anti-inflammatory, analgesic and antipyretic effects. The aim of this research was to assay the effective fractions of C. longifolia (EFCL) against rheumatoid arthritis (RA) and to elucidate its anti-RA mechanism on a preliminary basis. The rat model of collagen-induced arthritis (CIA) was established. The therapeutic effects of different fractions in vivo were evaluated by body weight changes, a foot swelling score, inflammatory factors and histopathological examination. The mechanism of EFCL was investigated by activity of oxidative stress related enzyme, qPCR and Western blotting tests. In vivo results showed that total extraction (TE) and n-butanol fraction (NF) could significantly alleviate the symptoms of RA, decrease the levels of IL-6 and TNF-α (P < 0.01), and improve histopathological injury. The mechanism study showed that SOD level was significantly increased with MDA level decreased in the NF group. The upregulated proteins and mRNA expression levels of Nrf2, HO1 and NQO1 after TE and NF administration suggested that the anti-arthritic effect may be related to the Nrf2 signaling pathway and downstream HO1 and NQO1. In conclusion, this study confirmed that C. longifolia is capable of treating RA with NF as the main effective fraction. Its anti-RA action may be associated with Nrf2 signaling pathway and downstream HO1 and NQO1.
RESUMEN
To investigate the potential mechanism of ginger in the treatment of triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and in vitro cell experiments. The Traditional Chinese Medicine Systems Pharmacology Database And Analysis Platform, the Bioinformatics Analysis Tool For Molecular Mechanism Of Traditional Chinese Medicine and the HERB database and literature search were used to search for the main active compounds of ginger. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to predict the possible molecular mechanism and signaling pathway of ginger in the treatment of triple negative breast cancer. The key core genes of ginger in the treatment of triple negative breast cancer were docked with the active ingredients of ginger on the Autodock platform, and the mechanism of ginger on triple negative breast cancer was further verified by in vitro cell experiments. As a result, 10 effective components, 27 potential targets and 10 Protein-Protein Interaction core genes were predicted in the treatment of triple negative breast cancer with ginger, involving 287 biological processes, 18 cellular components and 38 molecular functions. Ginger regulated the proliferation, migration and apoptosis of triple negative breast cancer cells by regulating TNF, IL-17, FoxO, MAPK, PI3K/AKT and other signaling pathways. The results of molecular docking showed that the lowest binding potential energy between dihydrocapsaicin (DHC) and EGFR protein was -7.70 kcal·mol-1, followed by that between 6-gingerol and EGFR protein was -7.30 kcal·mol-1 and that between DHC and CASP3 protein was -7.20 kcal·mol-1. In vitro cell experiments showed that ginger could inhibit the proliferation and migration of TNBC MDA-MB-231 cells, increase the mRNA expression of Caspase family CASP9 and the protein expression of CASP3 and BAX. Overall, based on the combination of network pharmacology and in vitro cell experiments, ginger has the characteristics of multi-target in the treatment of TNBC, which may play a regulatory role through the PI3K/AKT family. It provides a reference for the drug development of ginger and the clinical treatment of triple negative breast cancer.