Inflammation is a biological response of the immune system to defend the body from negative stimulation. However, the excessive inflammatory response can damage host tissues and pose serious threats. Exopolysaccharide (EPS), one of the postbiotics, is secreted from lactic acid bacteria. Although many studies have described the beneficial effects of EPS, such as its anti-inflammatory and anti-oxidant effects, its underlying mechanisms have remained to be poorly understood. Thus, we identified that EPS obtained from Lactobacillus plantarum L-14 was a homogeneous polysaccharide primarily comprised of glucose. To examine these anti-inflammatory effects, an inflammatory response was induced by lipopolysaccharide (LPS) administration to mouse macrophage RAW 264.7 cells that were pretreated with EPS. The anti-inflammatory effects of EPS were identified by analyzing the changes within inflammatory markers at the molecular level. We demonstrate here that EPS suppressed proinflammatory mediators, such as cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β, and downregulated the expression of an inducible nitric oxide synthase known to lead to oxidative stress. It was also confirmed that EPS had anti-inflammatory effects by blocking the interaction of LPS with Toll-like receptor 4 (TLR4), as demonstrated by using the known TLR4 inhibitor TAK-242. In addition, we found that EPS itself could suppress the expression of TLR4. Consequently, our data suggest that EPS can be a potential target for the development of natural product-derived medicine for treating inflammatory diseases related to TLR4.

We investigated the potential probiotic properties of Limosilactobacillus fermentum KGC1601 isolated from Panax ginseng. Ginseng cultivated in an experimental field of the Korea Ginseng Research Institute was fermented, followed by single colony selection from MRS agar. We performed 16s-rRNA sequencing and whole-genome analysis to identify L. fermentum and evaluate the biosafety parameters of this strain, respectively. We confirmed this strain was susceptible to six antibiotics, as proposed by the European Food Safety Authority, did not produce biogenic amines, and did not exhibit any hemolytic activity. Acid resistance and bile salt tolerance, which are essential properties of a probiotic agent, were investigated. Notably, distinguishing properties of this strain were that it exhibited excellent bile salt tolerance and anti-inflammatory effects. The excellent bile salt tolerance was confirmed by scanning electron microscopy. Through qRT-PCR and ELISA studies, it was revealed that L. fermentum KGC1601 pre-treatment up-regulates anti-inflammatory cytokines and down-regulates pro-inflammatory cytokines in RAW 264.7 cells. Consequently, we suggested that L. fermentum KGC1601 can be safely used as a potential anti-inflammatory functional probiotic agent.

Obesity and associated metabolic disorders, including cardiovascular disease and diabetes, are rapidly becoming serious global health problems. It has been reported that Lactobacillus plantarum (L. plantarum) extracts have the beneficial activities of antiobesity and antidiabetes, although few studies have compared the beneficial effects among various L. plantarum extracts. In this study, three new L. plantarum (named LP, LS, and L14) strains were identified, and the antiobesogenic and diabetic effects of their extracts were investigated and compared using 3T3‐L1 cells in vitro. Lipid accumulation in maturing 3T3‐L1 cells was significantly decreased by the addition of LS and L14 extracts. The mRNA expression levels of Pparγ, C/ebpα, Fabp4, Fas, and Dgat1 were significantly decreased by the addition of LP, LS, and L14 extracts. Interestingly, the protein expression levels of PPARγ, C/EBPα, FABP4, and FAS were downregulated in mature 3T3‐L1 cells with the addition of the L14 extract. Moreover, the LS and L14 extract treatments stimulated glucose uptake in maturing adipocytes. The L14 extract treatments exhibited a significant reduction in TNF‐α protein expression, which is a key factor of insulin resistance in adipocytes. Of the three extracts, L14 extract markedly reduced adipogenic differentiation and insulin resistance in vitro, suggesting that the L14 extract may be used as a therapeutic agent for obesity‐associated metabolic disorders.

In this study, we determined the probiotic properties and safety of Limosilactobacillus reuteri KGC1901 isolated from Korean Panax ginseng root. This strain was identified based on its 16s rRNA sequence, and the absence of genes related to antibiotic resistance and virulence was confirmed through whole genome analysis in terms of safety. Moreover, this strain had no antibiotic resistance to eight antibiotics as proposed by the European Food Safety Authority, did not show hemolytic activity on blood agar, and did not produce biogenic amines. L. reuteri KGC1901 also showed the capability to survive at low pH and in presence of bile salts and sufficiently adhered to HT-29 cells and mucin. The adhesion ability to HT-29 was confirmed by immunofluorescence staining. These results indicated the excellent viability of L. reuteri KGC1901 in the human gastrointestinal tract. Additionally, L. reuteri KGC1901 had antimicrobial activity against Clostridium difficile, and the presence of the reuterin (3-HPA) biosynthetic gene cluster in the genome was revealed. Furthermore, the cell-free supernatant of KGC1901 had DPPH scavenging activity and reduced the nitric oxide production in LPS-stimulated RAW 264.7 cells. Based on these results, it was confirmed that L. reuteri KGC1901 derived from ginseng has sufficient potential to be used as a probiotic.

Etoposide, an anticancer drug that inhibits topoisomerase II, is commonly used in combination chemotherapy. However, the impact of O-GlcNAcylation regulation on etoposide’s anticancer effects has rarely been investigated. This study evaluated the effect of etoposide on cellular O-GlcNAcylation and whether modulating this process enhances etoposide-induced apoptosis. O-GlcNAc expression was measured after 24 h of etoposide treatment, and the effect of O-GlcNAc transferase (OGT) inhibition by OSMI-1 on etoposide’s anticancer activity in HepG2 human liver cancer cells was quantitatively analyzed. Additionally, molecular analyses were used to confirm that the observed effects were mediated by p53-induced apoptosis. Etoposide reduced O-GlcNAcylation in a dose-dependent manner without directly interacting with OGT. Cotreatment with 20 μM of OSMI-1 lowered the IC₅₀ value for cell viability by approximately 1.64-fold to 60.68 μM and increased the EC₅₀ value for cytotoxicity by around 4.07-fold to 43.41 μM. Furthermore, this synergistic effect was linked to the activation of the p53/caspase-3/PARP1 pathway. These findings suggest that downregulating O-GlcNAcylation may enhance the efficacy of etoposide-based chemotherapy and help overcome tumor resistance.