Mechanism of Eucommiae ulmoides and Radix Dipsaci in prevention and treatment of osteoporosis:An analysis based on network pharmacology and cell experiment / 中国药理学通报

Aim To investigate the effect and mechanism of Eucommiae ulmoides and Radix Dipsaci in the treatment of osteoporosis.Methods The active ingredients of Eucommiae ulmoides and Radix Dipsaci were obtained by TCMSP,BATMAN-TCM platform and the literature.Osteoporosis related genes were collected by GeneCards and OMIM.The compound target network was constructed with Cytoscape 3.7.2 software.The protein interaction network was constructed with STRING online website.DAVID was used to perform gene ontology(GO)enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The synergistic effect of Eucommiae ulmoides and Radix Dipsaci was tested by osteo-blast proliferation,alkaline phosphatase expression and mineralized nodule formation experiments.The protein expressions of BMP2 and Wnt signaling pathway were investigated by Western blotting.Results A total of 44 active components of Eucommiae ulmoides and 17 active components of Radix Dipsaci were screened,and 80 targets were intersected by osteoporosis.GO analysis showed that the action mechanism of Eucommiae ulmoides and Radix Dipsaci in the treatment of osteoporosis was involved with 52 items of biological process,8 items of cell composition and 16 items of molecular function.The KEGG enrichment pathway was dominated by 6 major signaling pathways.Compared with the control group,the osteoblast proliferation,alkaline phosphatase expression and mineralized nodule formation significantly increased in Eucommiae ulmoides or Radix Dipsaci group(P<0.01).Western blotting showed that Eucommiae ulmoides mainly regulated the expression levels of Wnt signaling pathways(P<0.05 or P<0.01),and Radix Dipsaci up-regulated the expression levels of BMP2 signaling pathways(P<0.01).Meanwhile,Eucommiae ulmoides and Radix Dipsaci significantly enhanced these effects,respectively(P<0.01).Conclusions Although Eucommiae ulmoides and Radix Dipsaci have different active components,their main targets and pathways are the same in the treatment of osteoporosis.Eucommiae ulmoides and Radix Dipsaci can regulate the function of osteoblasts through BMP2 and Wnt signaling pathways,and the combination of the two drugs in the treatment of osteoporosis has synergistic effect.

Mangiferin inhibited neuroinflammation through regulating microglial polarization and suppressing NF-κB, NLRP3 pathway / 中国天然药物

Inflammation plays important roles in the progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Microglia is responsible for the homeostasis of the central nervous system (CNS), and involved in the neuroinflammation. Therefore, it could be potential in treatment of neurodegenerative diseases to suppress the microglia-mediated neuroinflammation. Mangiferin, a major glucoside of xanthone in Anemarrhena Rhizome, has anti-inflammatory, anti-diabetes, and anti-oxidative properties. However, the effect of mangiferin on the inflammatary responses of microglia cells are still poorly understand. In this study, we investigated the mechanism by which mangiferin inhibited inflammation in LPS-induced BV

Synthesis and antifatigue activities of new benzamide derivatives / 药学学报

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

Effects of naringin on proliferation, differentiation and maturation of rat calvarial osteoblasts in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of naringin on the proliferation, differention and maturaion of rat calvarial osteoblasts (ROB).</p><p><b>METHOD</b>Segregated neonatal SD rat skull, enzyme digestion to obtain ROB. The culture medium was replaced every three days. Serial subcultivation proceeded when cells covered with 80% culture dish. Naringin supplemented into the culture at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) respectively. MTT method was adopted in proliferation analysis and the activity of ALP was examined after induced 9 days. Search the best concentration and supplemented into the medium, then the osteogenic differentiation markers including the secretion amount of osteocalcin, osteopontin and bone morphogenetic protein-2 were compared between the naringin-supplemented group and the control. Total RNA was isolated and the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERa and ERbeta was investigated by Real time RT-PCR. Total protein also was isolated and the expression ERa, ERbeta and collagen I was examined by Western blot. After the addition of ICI 182.780, an inhibitor of the estrogen signal pathway, these index also was examined and the changes were compared.</p><p><b>RESULT</b>The ROB proliferation was motivated by naringin dose-dependently. And it evidently leads to osteogenic process and maturation. 1 x 10(-5) mol x L(-1) is the best concentration. Naringin improved the secretion of osteocalcin, osteopontin, bone morphogenetic protein-2 and collagen I significantly. Besides, it can also enhanced the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERalpha and ERbeta. While all these effects can be restrained by ICI 182.780.</p><p><b>CONCLUSION</b>The naringin with final concentration of 1 x 10(-5) mol x L(-1) enhances the osteogenic differentiation and maturation of ROB significantly, while the promoting effects vanished after the addition of ICI 182.780. These results suggesting that naringin is one of the phytoestrogens and have the activity of bone formation may via estrogen signal pathway, it can be developed into a new drug for osteoporosis therapy.</p>