Modulating effect of Eunkyo-san on expression of inflammatory cytokines and angiotensin-converting enzyme 2 in human mast cells.

Eunkyo-san is widely used in the treatment of severe respiratory infections. Mast cells not only serve as host cells for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but also they also exacerbate Coronavirus disease in 2019 (COVID-19) by causing a cytokine storm. Here we investigated whether Eunkyo-san and its active compound naringenin regulate the expression of inflammatory cytokines and factors connected to viral infection in activated human mast cell line, HMC-1 cells. Eunkyo-san and naringenin significantly reduced levels of inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, thymic stromal lymphopoietin, and tumor necrosis factor-α without impacting cytotoxicity. Eunkyo-san and naringenin reduced levels of factors connected to SARS-CoV-2 infection such as angiotensin-converting enzyme 2 (ACE2, SARS-CoV-2 receptor), transmembrane protease/serine subfamily member 2, and tryptase in activated HMC-1 cells. Treatment with Eunkyo-san and naringenin considerably reduced expression levels of ACE2 transcription factor, AP-1 (C-JUN and C-FOS) by blocking phosphatidylinositide-3-kinase and c-Jun NH2-terminal kinases signaling pathways. In addition, Eunkyo-san and naringenin effectively suppressed activation of signal transducer and activator of transcription 3, nuclear translocation of nuclear factor-κB, and activation of caspase-1 in activated HMC-1 cells. Furthermore, Eunkyo-san and naringenin reduced expression of ACE2 mRNA in two activated mast cell lines, RBL-2H3 and IC-2 cells. The overall study findings showed that Eunkyo-san diminished the expression levels of inflammatory cytokines and ACE2, and these findings imply that Eunkyo-san is able to effectively mitigating the cytokine storm brought on by SARS-CoV-2 infection.

Euscaphic acid relieves fatigue by enhancing anti-oxidative and anti-inflammatory effects.

BACKGROUND: Oxidative stress and inflammation are involved in chronic fatigue. Euscaphic acid (EA) is an active compound of Eriobotrya japonica (Loquat) and has anti-oxidative effect. METHODS: The goal of present study is to prove whether EA could relieve fatigue through enhancing anti-oxidant and anti-inflammatory effects in in vitro/in vivo models. RESULTS: EA notably improved activity of superoxide dismutase (SOD) and catalase (CAT), while EA reduced levels of malondiadehyde (MDA) and inflammatory cytokines without cytotoxicity in H2O2-stimulated in myoblast cell line, C2C12 cells. EA significantly reduced levels of fatigue-causing factors such as lactate dehydrogenase (LDH) and creatin kinase (CK), while EA significantly incresed levels of anti-fatigue-related factor, glycogen compared to the H2O2-stimulated C2C12 cells. In treadmill stress test (TST), EA significantly enhanced activities of SOD and CAT as well as exhaustive time and decreased levels of MDA and inflammatory cytokines. After TST, levels of free fatty acid, citrate synthase, and muscle glycogen were notably enhanced by oral administration of EA, but EA decreased levels of lactate, LDH, cortisol, aspartate aminotransferase, alanine transaminase, CK, glucose, and blood urea nitrogen compared to the control group. Furthermore, in forced swimming test, EA significantly increased levels of anti-fatigue-related factors and decreased excessive accumulations of fatigue-causing factors. CONCLUSIONS: Therefore, the results indicate that potent anti-fatigue effect of EA can be achieved via the improvement of anti-oxidative and anti-inflammatory properties, and this study will provide scientific data for EA to be developed as a novel and efficient component in anti-fatigue health functional food.

Surfactin exerts an anti-cancer effect through inducing allergic reactions in melanoma skin cancer.

Surfactin is a mast cell degranulator, that increases the immune response via the degranulation of mast cells. Recently, numerous studies reported that allergic reactions play an important role in the reduction of melanoma development. So, this study aimed to investigate the anti-cancer effects of surfactin in a melanoma skin cancer in vivo model and a melanoma cell line, B16F10. Oral administration of surfactin significantly increased survival rate and reduced tumor growth and tumor weight on melanoma skin cancer in vivo model. Surfactin significantly increased infiltration of mast cells and levels of histamine. Surfactin significantly enhanced levels of IgE and immune-enhancing mediators, such as interferon-γ, interleukin (IL)-2, IL-6, IL-12, and tumor necrosis factor-α in serum and melanoma tissues. Activities of caspase-3, 8, and 9 were significantly enhanced by oral administration of surfactin. In vitro model, surfactin significantly increased B16F10 cell death via activation of caspase-3, 8, and 9 in a dose-dependent manner. Overall, our results indicate that surfactin has a significant anti-cancer effect on melanoma skin cancer through indirectly or directly inducing apoptosis of B16F10 melanoma cells. Also, these findings suggest that it will contribute to a novel perception into the role of allergic reactions in melanoma.