Mechanisms and Molecular Targets of the Tao-Hong-Si-Wu-Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
Authors: Fu, Fanyu; Huang, Zeqing; Ye, Hengli; Tan, Biao; Wang, Rongtian; Chen, Weiheng
Abstract
The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-kappa B, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.
An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome-A SYSDIET Sub-Study
NUTRIENTS
Authors: Ulven, Stine M.; Holven, Kirsten B.; Rundblad, Amanda; Myhrstad, Mari C. W.; Leder, Lena; Dahlman, Ingrid; de Mello, Vanessa D.; Schwab, Ursula; Carlberg, Carsten; Pihlajamaki, Jussi; Hermansen, Kjeld; Dragsted, Lars O.; Gunnarsdottir, Ingibjorg; Cloetens, Lieselotte; Akesson, Bjorn; Rosqvist, Fredrik; Hukkanen, Janne; Herzig, Karl-Heinz; Savolainen, Markku J.; Riserus, Ulf; Thorsdottir, Inga; Poutanen, Kaisa S.; Arner, Peter; Uusitupa, Matti; Kolehmainen, Marjukka
Abstract
A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.
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