Investigation of Ginseng-Ophiopogon Injection on Enhancing Physical Function by Pharmacogenomics and Metabolomics Evaluation.

BACKGROUND: Ginseng-ophiopogon injection (GOI) is a clinically commonly used drug for Qi deficiency syndrome characterized by decreased physical function in China. This study aimed to clarify common pharmacological mechanisms of GOI in enhancing physical function. METHODS: We performed an integrative strategy of weight-loaded swimming tests in cold water (5.5 °C), hepatic glycogen and superoxide dismutase (SOD) detections, GC-TOF/MS-based metabolomics, multivariate statistical techniques, network pharmacology of known targets and constituents, and KEGG pathway analysis of GOI. RESULTS: Compared with the control group, GOI showed significant increases in the weightloaded swimming time, hepatic levels of glycogen and SOD. Additionally, 34 significantly differential serum metabolites referred to glycolysis, gluconeogenesis and arginine biosynthesis were affected by GOI. The target collection revealed 98 metabolic targets and 50 experimentreported drug targets of ingredients in GOI involved in enhancing physical function. Further, the PPI network analysis revealed that 8 ingredients of GOI, such as ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, and notoginsenoside R1, were well-associated with 48 hub targets, which had good ability in enhancing physical function. Meanwhile, nine hub proteins, such as SOD, mechanistic target of Rapamycin (mTOR), and nitric oxide synthases, were confirmed to be affected by GOI. Finally, 98 enriched KEGG pathways (P<0.01 and FDR<0.001) of GOI were obtained from 48 hub targets of the PPI network. Among them, pathways in cancer, Chagas disease, lipid and atherosclerosis, and PI3K-Akt signaling pathway ranked top four. CONCLUSIONS: This study provided an integrative and efficient approach to understanding the molecular mechanism of GOI in enhancing physical function.

Discovery of Taxus chinensis fruit wine as potentially functional food against Alzheimer's disease by UHPLC-QE-MS/MS, network pharmacology and molecular docking.

Nowadays, there is no specific cure for Alzheimer's disease (AD), but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. However, the chemical constituents and molecular mechanisms of TCFW still remain unknown. In this study, chemical profiling with UHPLC-QE-MS/MS, network pharmacology and molecular docking were integrated to fastly explore the potential chemicals and mechanisms of TCFW against AD. A total of 31 chemical components in TCFW were detected and identified compared with the solvent wine of TCFW by UHPLC-QE-MS/MS. Then, 27 potential key targets and 14 chemical compounds of TCFW were uncovered for the improvement of AD by network pharmacology and molecular docking. These 14 compounds were reported to have diverse bioactivities such as neuroprotective activity, antifibrotic activity, anticancer activity, antiviral activity and effectiveness in the treatment of neuronal injury, Alzheimer's disease, etc. Among these 27 targets affected by TCFW predicted by our approach, AKT1, PTGS2, NOS3, NOS2, INS, ESR1, ESR2, BDNF, IL6, IL1B, DRD2 and ACHE were significantly altered in AD. The GO and KEGG enrichment analyses revealed that TCFW mainly acted on oxidative response, inflammatory response, insulin secretion, amyloid fibril formation, neurodegenerative pathway-multiple diseases, Alzheimer's disease, longevity regulation pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc, which were the main pathogenesis of AD. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by cognitive and behavioral dysfunction. Nowadays, there is no specific cure for AD, but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. This study proposed a fastly integrated method to explore the potential chemicals and mechanisms of TCFW against AD by UHPLC-QE-MS/MS, network pharmacology and molecular docking. Here, we found that TCFW may ameliorate AD by reversing many biological events, including oxidative stress, inflammatory response, neuronal apoptosis, insulin secretion, amyloid fibril formation, and T cell co-stimulation, which may provide some insights for the development and research of anti-AD drugs.

Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in the hippocampi of perimenopausal rats induced by immobilization stress.

OBJECTIVE: We wished to study the impact of Chaihushugan San (CSS) on the behavior of perimenopausal rats with liver-Qi stagnation (LQS) and to investigate the effect of CSS on signal transduction of the Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-regulated kinase (ERK) cascade in the hippocampi of rats induced by immobilization. METHODS: Twenty 52-week-old female rats were divided into two groups by the random number table method: model control group (MCG) and CSS group (CSSG), with 10 rats in each group. Ten-week-old female rats were used as the normal control group (NCG). CSS effects were assessed using rats exposed to immobilization stress by measuring body weight and sucrose consumption, serum hormone levels, and observing performance in the open field test (OFT). Molecular mechanisms were examined by measuring the effect of CSS on expression of Raf1, MEK1/2 and ERK1/2 mRNA in hippocampi using quantitative real-time polymerase chain reaction and by measuring levels of these proteins and related phospho-proteins using Western blotting. RESULTS: Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose consumption; and increased serum levels of corticotropin releasing hormone (CRH) and corticosterone (CORT). Activation of hippocampal Raf/MEK/ERK cascade was suppressed significantly in the MCG, and activation was increased after 21 days of CSS treatment. CONCLUSION: CSS has significant effects upon relief of the symptoms of LQS in immobilization-induced rats. The mechanism underlying this action might (at least in part) be mediated by reversal of disruption of the Raf/MEK/ERK pathway.