A network pharmacology approach to explore and validate the potential targets of ginsenoside on osteoporosis.

Background: Osteoporosis (OP) is determined as a chronic systemic bone disorder to increase the susceptibility to fracture. Ginsenosides have been found the anti-osteoporotic activity of in vivo and in vitro. However, its mechanism remains unknown.Methods: The potential mechanism of ginsenosides in anti-osteoporotic activity was identified by using network phamacology analysis. The active compounds of ginsenosides and their targets associated to OP were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Drug Bank, Pharmmapper, and Cytoscape. The Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis target genes were performed in String, Phenopedia, DisGeNET database, and Metascape software. The protein to protein interaction were created by String database and Cytoscape software. The molecular docking was used to investigate the interactions between active coumpounds and potential targets by utilizing SwissDock tool, UCSF Chimera, and Pymol software. Results: A total of eight important active ingredients and 17 potential targets related to OP treatment were subjected to analyze. GO analysis showed the anti-osteoporosis targets of ginsenoside mainly play a role in the response to steroid hormone. KEGG enrichment analysis indicated that ginsenoside treats OP by osteoblast differentiation signal pathway. Lastly, the molecular docking outcomes indicated that ginsenoside rh2 had a good binding ability with four target proteins IL1B, TNF, IFNG, and NFKBIA. Conclusion: IL1B, TNF, IFNG, and NFKBIA are the most important targets and osteoblast differentiation is the most valuable signaling pathways in ginsenoside for the treatment of OP, which might be beneficial to elucidate the mechanism concerned to the action of ginsenoside and might supply a better understanding of its anti-OP effects.

Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway.

The molecular mechanisms that regulate the proliferation and differentiation of inner ear spiral ganglion cells (SGCs) remain largely unknown. Shikonin (a naphthoquinone pigment isolated from the traditional Chinese herbal medicine comfrey root) has anti-oxidation, anti-apoptosis and promoting proliferation and differentiation effects on neural progenitor cells. To study the protective effect of shikonin on auditory nerve damage, we isolated spiral ganglion neuron cells (SGNs) and spiral ganglion Schwann cells (SGSs) that provide nutrients in vitro and pretreated them with shikonin. We found that shikonin can reduce ouabain, a drug that can selectively destroy SGNs and induce auditory nerve damage, caused SGNs proliferation decreased, neurite outgrowth inhibition, cells apoptosis and mitochondrial depolarization. In addition, we found that shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs, promoting cells proliferation, and inhibiting cells apoptosis by activating the Nrf2/antioxidant response elements (ARE) signal pathway. However, knockdown of Nrf2 rescued the protective effect of shikonin on SGNs and SGSs damage. In addition, we injected shikonin pretreatment into mouse that ouabain-induced hearing loss and found that shikonin pretreatment has a defensive effect on auditory nerve damage. In summary, the results of this study indicate that shikonin could attenuate the level of oxidative stress in SGNs and SGSs through the Nrf2-ARE signaling pathway activated, induce the proliferation and differentiation of SGNs, and thereby improve the neurological hearing damage in mice. Therefore, shikonin may be a candidate therapeutic drug for endogenous antioxidants that can be used to treat neurological deafness.

Network pharmacology reveals the potential mechanism of Baiying Qinghou decoction in treating laryngeal squamous cell carcinoma.

CONTEXT: Baiying Qinghou as a traditional Chinese medicine decoction shows anticancer property on laryngeal squamous cell carcinoma. However, little is known about the precise mechanism of Baiying Qinghou detection against laryngeal squamous cell carcinoma. OBJECTIVE: This study was aimed to explore potential mechanism of therapeutic actions of Baiying Qinghou decoction on laryngeal squamous cell carcinoma. MATERIALS AND METHODS: The active chemical components of Baiying Qinghou decoction were predicted, followed by integrated analysis of network pharmacology and molecular docking approach. The network pharmacology approach included target protein prediction, protein-protein interaction network construction and functional enrichment analysis. RESULTS: Sitosterol and quercetin were predicted to be the overlapped active ingredients among three Chinese herbs of Baiying Qinghou decoction. The target proteins were closely associated with response to chemical, response to drug related biological process and cancer related pathways such as PI3K-Akt signaling, HIF-1 signaling and Estrogen signaling pathway. The target proteins of TP53, EGFR, PTGS2, NOS3 and IL1B as the key nodes in PPI network were cross-validated, among which EGFR, IL1B, NOS3 and TP53 were significantly correlated with the prognosis of patients with laryngeal squamous cell carcinoma. Finally, the binding modes of EGFR, IL1B, NOS3 and TP53 with quercetin were visualized. DISCUSSION AND CONCLUSION: Quercetin of Baiying Qinghou decoction showed therapeutic effect against laryngeal squamous cell carcinoma by regulating TP53, EGFR, NOS3 and IL1B involved with drug resistance and PI3K-AKT signaling pathway. TP53, EGFR, NOS3 and IL1B may be the candidate targets for the treatment of laryngeal squamous cell carcinoma.