Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis.

Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation. Female C57BL/6 mice were immunized with MOG35-55. Clinical scores and other parameters were monitored daily for the 21days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T cell differentiation was evaluated via flow cytometry. The results demonstrated that hesperidin inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. Hesperidin increased Treg cells production of interleukin IL-10 and transforming growth factor (TGF)-ß, but concurrently resulted in a significant reduction in production of IL-17 and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of Th17 cells, as well as significant increase in percentages of Treg cells in the spleen and lymph nodes. Real-time PCR results indicated hesperidin treatment reduced ROR-γt factor expression, but enhanced Foxp3 expression. Collectively, these results demonstrated that hesperidin could reduce the incidence and severity of disease.

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice.

Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased TH2 and Treg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-ß, but concurrently resulted in a significant reduction in production of interferon (IFN)-γ, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of TH1 and TH17 cells, as well as significant increase in percentages of Treg and TH2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high- and medium-dose estrogen treatments reduced T-bet and ROR-γt factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen - similar to a pregnancy level of estrogen - could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.

Effects of probiotic Lactobacillus acidophilus and Lactobacillus casei on colorectal tumor cells activity (CaCo-2).

BACKGROUND: The probiotic microorganisms are live normal flora that provide nutritional benefits. When probiotic administered in adequate amounts, they also confer a health benefit on the host. Different mechanisms of probiotic effects include the following: stimulating the immune system, modifying the composition of normal intestinal flora and preventing the carcinogenic activity of fecal enzymes. In this study, direct effects of probiotic lactobacilli on tumor cells were investigated. METHODS: Supernatants and bacterial extracts of two standard Lactobacillus species (L. acidophilus and L. casei) were prepared and CaCo-2 cells were treated with them. Probiotic effects on cell proliferation, necrosis, apoptosis, migration and invasion were assessed. RESULTS: The supernatants of Lactobacilli decreased cell proliferation and increased cell apoptosis, however, no significant effect on cell necrosis was reported. In contrast, Lactobacilli extract, reduced cell proliferation and increased cell apoptosis. Lactobacilli extract also led to cell necrosis. Furthermore, both supernatants and cell extracts of the probiotic agents resulted in decreased cells' migration and invasion. CONCLUSION: In this study, it was shown that Lactobacilli probiotics useful effects are not confined to the enhancement of the immune system; however, they effectively suppress the malignant phenotypes of colorectal cancer cells.