Anti-Inflammatory Effect of Fermented Cabbage Extract Containing Nitric Oxide Metabolites with Silica.

The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in the ear after DNFB sensitization on the dorsal skin of mice. FCS alleviated the severity of atopic dermatitis-like skin lesions. In addition, epidermis thickness of the ear and penetration of inflammatory cells in atopic dermatitis-like skin lesions were decreased after topical application of FCS. The serum levels of TNF-α and IL-4 were measured in atopic dermatitis mice using ELISA kits, which were observed to be significantly decreased after topical application of FCS. This study demonstrates that the FCS can be used as a potential therapeutic for the treatment and prevention of AD.

Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype.

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels-similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment.

Fermented Lettuce Extract Containing Nitric Oxide Metabolites Attenuates Inflammatory Parameters in Model Mice and in Human Fibroblast-Like Synoviocytes.

Lettuce (Lactuca sativa L.) contains various bioactive compounds that can reduce the severity of inflammatory diseases. This study aimed to identify therapeutic effects and underlying mechanisms of fermented lettuce extract (FLE) containing stable nitric oxide (NO) on collagen-induced arthritis (CIA) in mice and fibroblast-like synoviocytes (MH7A line) from patients with rheumatoid arthritis (RA). DBA/1 mice were immunized with bovine type II collagen and orally administered FLE for 14 days. On day 36, mouse sera and ankle joints were collected for serological and histological analysis, respectively. Consuming FLE inhibited RA development, suppressing pro-inflammatory cytokine productions, synovial inflammation, and cartilage degradation. The therapeutic effects of FLE in CIA mice were similar to those of methotrexate (MTX), which is typically used to treat RA. In vitro, FLE suppressed the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in MH7A cells. We also demonstrated that FLE inhibited TGF-ß-induced cell migration, suppressed MMP-2/9 expression, inhibited MH7A cell proliferation, and increased the expression of autophagy markers LC3B and p62 in a dose-dependent manner. Our data suggest that FLE could induce autophagosome formations in the early of stages of autophagy while inhibiting their degradation in the later stages. In conclusion, FLE is a potential therapeutic agent for RA.

Antidiabetic Effect of Noodles Containing Fermented Lettuce Extracts.

The aim of the current study was to examine the antidiabetic effect of noodle containing fermented lettuce extract (FLE) on diabetic mice as a pre-clinical study. The γ-aminobutyric acid (GABA) content, antioxidant capacity, and total polyphenol content of the FLE noodles were analyzed and compared with those of standard noodles. In addition, oral glucose and sucrose tolerance, and fasting blood glucose tests were performed using a high-fat diet/streptozotocin-mediated diabetic mouse model. Serum metabolite profiling of mice feed standard or FLE noodles was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) to understand the mechanism changes induced by the FLE noodles. The GABA content, total polyphenols, and antioxidant activity were high in FLE noodles compared with those in the standard noodles. In vivo experiments also showed that mice fed FLE noodles had lower blood glucose levels and insulin resistance than those fed standard noodles. Moreover, glycolysis, purine metabolism, and amino acid metabolism were altered by FLE as determined by GC-TOF-MS-based metabolomics. These results demonstrate that FLE noodles possess significant antidiabetic activity, suggesting the applicability of fermented lettuce extract as a potential food additive for diabetic food products.