Effect of Momordica charantia polysaccharide on immunomodulatory activity in mice.

Momordica charantia polysaccharides (MCPs) have been reported to exert beneficial roles, such as disease healing, in medicine and pharmacy. However, little is known about their effects on immunomodulation. The present study aimed to explore the possible effects of Momordica charantia polysaccharide (MCP) on the immunomodulatory activity of mice lymphocytes. To this aim, male BALB/c mice aged 6-8 weeks were assigned to the following six experimental groups: i) Normal (NG); ii) model (MG); iii) positive (PG); iv) MCP low-dose (MLG); v) MCP medium-dose (MMG); and vi) MCP high-dose (MHG). An immunosuppressive model was established by the intraperitoneal injection of cyclophosphamide in all groups apart from NG. The NG and MG mice were fed with distilled water, whereas the PG mice were administered with levamisole and the MLG, MMG and MHG mice were fed on low, medium and high (100, 200 and 300 mg/kg, respectively) doses of MCP for 21 consecutive days. Subsequently, the mice underwent surgical procedure and were analysed using a range of procedures, including measurement of the thymus index (TI) and spleen index (SI), assessment of the lymphocyte proliferation rate and cell phagocytosis of peritoneal macrophages, lymphocyte proliferation, secretion and mRNA expression of cytokines IFN-γ, IL-6 and IL-12. The mice divided into six groups as mentioned above and treated for 7 days, in the first 6 days, except NG group, mice in each group were desiccated in the abdominal cavity and sensitized by 1% dinitrofluorobenzene (DNFB). On day 6, mice were sensitized with 20 µl DNFB/acetone/olive oil solution behind the right ear and in front of the right ear. Compared with those in the NG mice (not injected with 80 mg/kg cyclophosphamide), the TIs and SIs of the PG, MLG, MMG and MHG mice were increased. In addition, the inhibitory rate of ear swelling and the phagocytic activity of peritoneal macrophages in the PG, MLG, MMG and MHG mice were increased compared with those of MG. Furthermore, the lymphocyte proliferation rate, the secretion and relative mRNA expression levels of cytokines IFN-γ, IL-6 and IL-12 were significantly increased in the PG, MMG and MHG mice compared with those in the NG mice. The results from the present study suggest that treatment with MCP led to an upregulation of the organ indices of immunosuppressed mice, reduced their delayed allergic reaction indicated by the differential cytokine levels, improved the phagocytic activity of peritoneal macrophages, enhanced the proliferation rate of lymphocytes, increased the secretion and expression of IFN-γ, IL-6 and IL-12. Therefore, MCP may improve the immune function of the immunosuppressed mice.

Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways.

Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 µg/mL) and capsaicin (25, 50, 75, or 100 µg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 µg/mL, tumor necrosis factor (TNF)-α level was 860 µg/mL, and nitric oxide (NO) level was 19.8 µg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.

Vitexin-2-O-rhamnoside improves immunosuppression, oxidative stress, and phosphorylation of PI3K/Akt signal pathway in cyclophosphamide treated mice.

Vitexin-2-O-rhamnoside (VR) is an important active substance in hawthorn, which is widely used as a food or functional food raw material; however, its immunomodulatory activities have not been extensively studied. In this study, BALB/c mice immunocompromised by cyclophosphamide (CY) were used as models to explore the effects of VR on the immunity and antioxidant capacity of mice. The results revealed that VR can restore weight to the immunosuppressed mice to varying degrees, improve spleen and thymus injury, and restore peripheral blood levels. Furthermore, it can effectively promote the proliferation of T and B lymphocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) cell activities, and the secretion and mRNA expression of cytokines IFN-γ, IL-2, IL-6, and IL-12 to 0.36, 0.34, 50.25%, 45.74%, 28.36 pg/mL or 0.68, 31.81 pg/mL or 0.74, 20.40 pg/mL or 0.75, and 19.81 pg/mL or 0.55, respectively. Moreover, it can upregulate the phosphorylation level of PI3K/Akt signaling pathway in mice immunosuppressed by CY, increase the activities of glutathione peroxidase (GSH-Px), chloramphenicol acetyltransferase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and decrease the level of malondialdehyde (MDA). This study provides a theoretical and experimental basis for the research and development of health products with targeted efficacy, and the development of diversified products in the hawthorn deep-processing industry.

Cadmium stimulates mouse skin fibroblast apoptosis by affecting intracellular homeostasis.

CONTEXT: Cadmium (Cd2+) is an important industrial and environmental pollutant and has been shown to induce apoptosis in a variety of cell types and tissues. OBJECTIVE: To assess the specific effects of low-dose Cd2+ on the skin. This organ is easily exposed to Cd2+, but how it damages cells is not fully understood. MATERIALS AND METHODS: Mouse skin fibroblasts were treated with low doses of Cd2+ (0.4, 0.8 or 1.6 µM) for 12-48 h, and we observed cell morphological alterations, measured DNA damage and quantified cell viability changes. RESULTS: Cd2+-treated fibroblasts exhibited morphological changes and evidence of DNA damage, as well as higher numbers of apoptotic and necrotic cells. There were increased caspase -3, -8 and -9 activities when fibroblasts were treated with 0.4, 0.8 and 1.6 µM CdCl2 for 24 h. Higher intracellular calcium (Ca2+) and reactive oxygen species (ROS) levels, and enhanced efflux of extracellular Ca2+ and potassium (K+). The mitochondrial membrane potential was lowered in treated cells, and the cell cycle arrested in the G0/G1 phase. Bax and Fas gene expression increased and Bcl-2 gene expression decreased. DISCUSSION: The results demonstrate that Cd2+ exerts typical apoptotic effects in mouse skin fibroblasts. It strongly inhibited proliferation and induced apoptosis in a dose- and duration-dependent manner. Ca2+ homeostasis was disturbed by oxidative stress, mitochondrial dysfunction and caspase-mediated apoptosis. CONCLUSION: K+ efflux and Bax, Bcl-2 and Fas gene expression regulation play important roles in Cd2+-induced dysfunction by disrupting intracellular homeostasis in mouse skin fibroblasts.

One-dimensional infinite chain structures of [Al2(OH)4(H2O)4]X2 (X = I, Br, Cl): an aggregate of Al2 species and a precursor of Al(OH)3.

By a combination of the Rietveld full-profile fitting technique based on powder X-ray diffraction data and the single-crystal structure solving and refining method, one-dimensional infinite zigzag chain structures were observed in the structures of [Al2(OH)4(H2O)4]X2 (X = I, Br, Cl). These crystallize in the same monoclinic system and the same C2/c space group with different unit cell parameters from spontaneously hydrolyzed solutions of AlX3. Each chain is composed of a significant number of AlO6 octahedra that fall into two groups with reverse orientations and connect to each other by edge-sharing. Furthermore, the counterions intersperse among the chains forming strong van der Waals interactions. It was also discovered that each chain was an aggregate formed from the further hydrolysis of the Al2 species (Al2(OH)2(H2O)8(4+), a dimer formed by two octahedral Al(H2O)6(3+) monomers sharing an edge) and a building unit for constructing the infinite hexameric ring sheet in nordstrandite and gibbsite. These are three new structures, rarely solved from powder XRD data, of polyaluminum compounds, and they provide the first direct evidence of the aggregation processes of Al2 species and their subsequent evolution into an infinite zigzag chain as well as further evolution into an infinite hexameric ring layer as found in nordstrandite and gibbsite. Furthermore, they also represent the first three examples in which each polyaluminum species possesses a one-dimensional infinite chain structure formed by AlO6 octahedra via edge-sharing only.