Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) has become one of most frequent bone diseases worldwide with aging population. Lycii Fructus, a common plant fruit with the property of drug homologous food, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of Lycii Fructus against PMOP through using network pharmacology approach. The active ingredients of Lycii Fructus were obtained from Traditional Chinese Medicine System Pharmacology database. Target fishing was performed on these ingredients in UniProt database for identification of the relative targets. Then, we screened the targets related to PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and Lycii Fructus were obtained to perform protein-protein interaction, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis. A total of 35 active ingredients were identified in Lycii Fructus, and fished 158 related targets. Simultaneously, 292 targets associated with PMOP were obtained from GeneCards database and DisGeNET database. By drawing Venn diagram, 41 overlapping genes were obtained, and were considered as therapeutically relevant. Gene ontology enrichment analysis predicted that anti-inflammation and promotion of angiogenesis might be 2 potential mechanism of Lycii Fructus for PMOP treatment. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as IL-17 pathway, TNF pathway, MAPK pathway, PI3K-Akt signaling pathway and HIF signaling pathway were involved in regulating these 2 biological processes. Through the method of network pharmacology, we systematically investigated the mechanisms of Lycii Fructus against PMOP. The identified multi-targets and multi-pathways provide new insights to further determinate its exact pharmacological mechanisms.

Two cardenolide glycosides from the seed fairs of Asclepias curassavica and their cytotoxic activities.

Two cardenolide glycosides, corotoxigenin 3-O-[ß-D-glucopyranosyl-(1→4)-6-deoxy-ß-D-glucopyranoside] (1) and coroglaucigenin 3-O-[ß-D-glucopyranosyl-(1→4)-6-deoxy-ß-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.

Chinese herbal medicines for prevention and treatment of colorectal cancer: From molecular mechanisms to potential clinical applications.

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

Integrating Network Pharmacology and Experimental Validation to Investigate the Effects and Mechanism of Astragalus Flavonoids Against Hepatic Fibrosis.

Hepatic fibrosis (HF) represents the excessive wound healing where an excess amount of connective tissues is formed within the liver, finally resulting in cirrhosis or even hepatocellular carcinoma (HCC). Therefore, it is significant to discover the efficient agents and components to treat HF, thus restraining the further progression of hepatopathy. Astragalus membranaceus (Fisch.) Bunge [also called Astragali Radix (AR)] is a famous herb in traditional Chinese medicine (TCM), which possesses a variety of biological activities and exerts good therapeutic effects in the treatment of HF. Flavonoids account for the major active ingredients related to the AR pharmacological effects. Total AR flavonoids have been proved to exert inhibitory effects on hepatic fibrosis. This study aimed to further undertake network pharmacology analysis coupled with experimental validation and molecular docking to investigate the effects and mechanism of multiple flavonoid components from AR against liver fibrosis. The results of the network pharmacology analysis showed that the flavonoids from AR exerted their pharmacological effects against liver fibrosis by modulating multiple targets and pathways. The experimental validation data showed that the flavonoids from AR were able to suppress transforming growth factor beta 1 (TGF-ß1)-mediated activation of hepatic stellate cells (HSCs) and reduce extracellular matrix deposition in HSC-T6 cells via regulating the nuclear factor kappa B (NF-κB) signal transduction pathway. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for IκB kinase (IKKß) after docking into the crystal structure. The above results indicated that, flavonoids possibly exerted the anti-inflammatory effect on treating HF by mediating inflammatory signaling pathways. The potential mechanism of these flavonoids against liver fibrosis may be related to suppression of the NF-κB pathway through effective inhibition of IKKß. This study not only provides a scientific basis for clarifying the effects and mechanism of AR flavonoids against liver fibrosis but also suggests a novel promising therapeutic strategy for the treatment of liver fibrosis.