Oleuropein is one of the primary phenolic compounds present in olive leaf. In this study, the anti-inflammatory effect of oleuropein was investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 and a zebrafish model. The inhibitory effect of oleuropein on LPS-induced NO production in macrophages was supported by the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, our enzyme immunoassay showed that oleuropein suppressed the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). Oleuropein inhibited the translocation of p65 by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Oleuropein also decreased activation of ERK1/2 and JNK, which are associated with LPS-induced inflammation, and its downstream gene of AP-1. Furthermore, oleuropein inhibited LPS-stimulated NO generation in a zebrafish model. Taken together, our results demonstrated that oleuropein could reduce inflammatory responses by inhibiting TLR and MAPK signaling, and may be used as an anti-inflammatory agent.

The medicinal herbal plant has been commonly used for prevention and intervention of disease and health promotions worldwide. Brazilein is a bioactive compound extracted from Caesalpinia sappan Linn. Several studies have showed that brazilein exhibited the immune suppressive effect and anti-oxidative function. However, the molecular targets of brazilein for inflammation prevention have remained elusive. Here, we investigated the mechanism underlying the inhibitory effect of brazilein on LPS-induced inflammatory response in Raw264.7 macrophage cells. We demonstrated that brazilein decreased the expression of IRAK4 protein led to the suppression of MAPK signaling and IKKβ, and subsequent inactivation of NF-κB and COX2 thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1β, MCP-1, MIP-2, and IL-6 in LPS-induced Raw264.7 macrophage cells. Moreover, we observed that brazilein reduced the production of nitrite compared to the control in LPS-induced Raw264.7. Thus, we suggest that brazilein might be a useful bioactive compound for the prevention of IRAK-NF-κB pathway associated chronic diseases.

Increases in temperature cause a proliferation of heat-stress-related disorders by disrupting the body's homeostasis system, particularly when excessive levels of reactive oxygen species disrupt the balance of antioxidant defence systems. Thus, controlling oxidative stress is important for the regulation of body homeostasis. Schisandra chinensis (SC) has a potential effect on antioxidants and is resistant to high temperatures. However, the mechanism of SC during heat stress is unclear. Therefore, we evaluated the effect of SC on heat stress by performing several bioactive genetic assays on Sprague Dawley (SD) rats. The results demonstrated that heat stress significantly increased in heat-stress-related gene expression whereas it was dramatically reduced in the gene expression of the SC group. The genes related to oxidative stress were also significantly suppressed in the SC group compared with those of the heat stress group. Furthermore, there was a greater decrease in the MDA content of the SD rats in the orally administered SC group than in the heat exposure group. Thus, we demonstrate that SC has a protective effect on heat stress as a result of its strong antioxidant properties and the prevention of lipid peroxidation.

Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPβ expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans.

Brazilin, is a bioactive compound extracted from Caesalpinia sappan Linn, has been reported the protective effect of the immune system. Particular attention is now devoted to better understanding of the molecular basis of bazilin anti-inflammatory activity. In the present study, we studied the effect of brazilin on the Raw264.7 macrophage cell lines by a nutrigenomics approaches. Raw264.7 cells were treated with braziln, then treated with LPS to cause inflammation. The nuclear transcription κB (NF-κB) promoter activity were analyzed with dual luciferase assay kit. The gene expression and production levels of pro-inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 were evaluated with semi-quantitative RT-PCR and with ELISA, respectively. We also examined inflammatory signaling, including mitogen-activated protein kinase (MAPK) pathway, iNOS, COX2, and IRAK4. Our findings demonstrated that brazilin down-regulated the expression of IRAK4 protein lead to suppress of c-Jun NH 2 terminal kinase (JNK) signaling, and subsequently inactivation of nuclear transcription κB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1β, TNFα and IL-6 in LPS stimulated Raw264.7 macrophage cell. Thus, brazilin showed anti-inflammatory activity in Raw264.7 macrophage cell targeting IRAK4 mediated signaling pathway.

Campylobacter species have developed resistance to existing antibiotics. The development of alternative therapies is, therefore, a necessity. This study evaluates the susceptibility of Campylobacter strains to selected natural products (NPs) and frontline antibiotics. Two C. jejuni strains (ATCC® 33560TM and MT947450) and two C. coli strains (ATCC® 33559TM and MT947451) were used. The antimicrobial potential of the NPs, including plant extracts, essential oils, and pure phytochemicals, was evaluated by broth microdilution. The growth was measured by spectrophotometry and iodonitrotetrazolium chloride. Antibiotic resistance genes (tet(O) and gyrA) were characterized at the molecular level. The minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) ranged from 25 to 1600 µg/mL. Cinnamon oil, (E)-Cinnamaldehyde, clove oil, eugenol, and baicalein had the lowest MIC and MBC values (25–100 µg/mL). MT947450 and MT947451 were sensitive to erythromycin and gentamicin but resistant to quinolones and tetracycline. Mutations in gyrA and tet(O) genes from resistant strains were confirmed by sequencing. The findings show that NPs are effective against drug-sensitive and drug-resistant Campylobacter strains. The resistance to antibiotics was confirmed at phenotypic and genotypic levels. This merits further studies to decipher the action mechanisms and synergistic activities of NPs.

Thermophilic Campylobacter species are among the major etiologies of bacterial enteritis globally. This study aimed at assessing the antimicrobial resistance (AMR) profiles, virulence genes, and genetic diversity of thermophilic Campylobacter species isolated from a layer poultry farm in South Korea. One hundred fifty-three chicken feces were collected from two layer poultry farms in Gangneung, South Korea. The Campylobacter species were isolated by cultural techniques, while PCR and sequencing were used for species confirmation. Antimicrobial susceptibility testing for six antimicrobials [ciprofloxacin (CIP), nalidixic acid (NAL), sitafloxacin (SIT), erythromycin (ERY), tetracycline (TET), and gentamicin (GEN)] was carried out by broth microdilution. Three AMR and nine virulence genes were screened by PCR. Genotyping was performed by flaA-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Of the 153 samples, Campylobacter spp. were detected in 55 (35.9%), with Campylobacter jejuni and Campylobacter coli being 49 (89.1%) and six (10.9%), respectively. High-level resistance was observed for CIP (100%), NAL (100%), and TET (C. jejuni, 93.9%; C. coli: 83.3%). No resistance was observed for SIT. The missense mutation (C257T) in gyrA gene was confirmed by sequencing, while the tet(O) gene was similar to known sequences in GenBank. The rate of multidrug-resistant (MDR) strains was 8.2%, and they all belonged to C. jejuni. All Campylobacter isolates possessed five virulence genes (cdtB, cstII, flaA, cadF, and dnaJ), but none possessed ggt, while the rates for other genes (csrA, ciaB, and pldA) ranged between 33.3 and 95.9%. The flaA-RFLP yielded 26 flaA types (C. jejuni: 21 and C. coli: five), while the MLST showed 10 sequence types (STs) for C. jejuni and three STs for C. coli, with CC-607 (STs 3611) and CC-460 (ST-460) being predominant. Among the 10 STs of C. jejuni, three were newly assigned. The findings of this study highlight the increased resistance to quinolones and TET, the virulence potential, and the diverse genotypes among Campylobacter strains isolated from the layer poultry farm.

Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent.