Goniothalamin prevents lipopolysaccharide-induced acute lung injury and inflammation via TLR-4/NF-κB signaling pathway.

Goniothalamin (GTN) is a natural compound isolated from Goniothalamus species. It is a potent anti-inflammatory agent. However, there is a paucity of scientific data about its toxicity. This study investigated GTN's anti-inflammatory mechanism and lipopolysaccharide (LPS)-induced lung injury in mice. Mice were distributed into four groups and injected with GTN intraperitoneally (Dosage-50 and 100 mg/kg). We analyzed the wet/dry weight ratio, infiltrated inflammatory cell count, myeloperoxidase (MPO) activity, and histopathological changes in the lung tissues of the mice. Results revealed GTN alleviated LPS-induced inflammation in mice. Western Blot and enzyme-linked immunosorbent assay techniques were used to investigate the effect of GTN on pro-inflammatory cytokines and proteins involved in the MAPK and nuclear factor-B (NF-κB) signaling pathways. Cytokines (macrophage migration inhibitory factor, interleukin [IL]-13, IL-6, TNF-α, and IL-1ß) were inhibited by GTN. However, IL-10 was upregulated. Western blot analysis indicated that GTN suppressed the phosphorylation of jun N-terminal kinase, nuclear factor NF-kappa-B p65, I-kappa-B, extracellular signal-regulated kinases, NF-κB, and p38. GTN also suppressed the expression of TLR-4 protein, thereby, inhibiting MAPK and NF-κB signaling pathways. Thus, GTN can effectively prevent and cure acute lung injury.

Gene-gene and gene-environment interactions on cord blood total IgE in Chinese Han children.

BACKGROUND: IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene-gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene-gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. METHODS: 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene-gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. RESULTS: A four-way gene-gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10-4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10-3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10-2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10-2). CONCLUSIONS: Gene-gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.