Zingerone protects keratinocyte stem cells from UVB-induced damage.

The epidermis, the outermost layer of the skin, is a stratified epithelium that protects the body from the external environment. Keratinocyte stem cells (KSCs) are involved in epidermis homeostasis by maintaining epidermal integrity through a process of constant regeneration. Ultraviolet B (UVB) radiation is a major inducer of cellular damage in the epidermis. In this study, we investigated the effects of zingerone (a phenolic compound derived from spices) on UVB-induced cellular damage in KSCs. We found that zingerone significantly inhibited cellular senescence of KSCs in response to UVB irradiation. These effects were confirmed by the senescence-associated ß-galactosidase and comet assays. Zingerone decreased the production of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in UVB-irradiated KSCs. Moreover, UVB-induced expression of p21, a cell cycle arrest-related gene, was reduced by zingerone treatment, whereas zingerone upregulated the expression of proliferation-related genes such as proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF), in addition to anti-senescence-related genes including telomerase reverse transcriptase (TERT), histone deacetylase 1 (HDAC1), and DNA (cytosine-5)-methyltransferase 1 (DNMT1). The UVB-protective effects of zingerone were mediated by inhibition of p42/44 MAPK and p38 MAPK. Therefore, zingerone could potentially be used to protect the epidermis from UVB-induced damage.

Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthritis.

Advancements in rheumatoid-arthritis-(RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential agents with relative safety and efficacy continues and natural compounds have been considered as alternatives to identify new entities. Since previous in-vivo data and our in-vitro findings showed that torilin has a strong anti-inflammatory property, we further investigated its effect against collagen-induced-arthritis-(CIA) in mice. CIA-induced DBA/1J mice were treated with torilin or methotrexate (MTX) for 5-weeks. Arthritis severity was evaluated by arthritic score and joint histopathology. Draining lymph node (dLN), joint and peripheral-blood mononuclear-cell (PBMC) counts, and activation/localization of T-/B-lymphocytes, dendritic cells (DCs) and neutrophils were examined by FACS analysis. Serum anti-type-II-collagen-(CII) antibody levels and cultured-splenocyte and serum cytokines were also evaluated. Torilin markedly reduced CIA-induced arthritic score, histopathology and leukocyte counts. Besides, torilin suppressed CIA-activated T-cells including CD3+, CD3+/CD69+, CD8+, CD4+ and CD4+/CD25+ in dLNs or joints. It also modified CD19+ or CD20+/CD23+ (B-cells), MHCII+/CD11c+ (DCs) and Gr-1+/CD11b+ (neutrophil) subpopulations. It further depressed total anti-CII-IgG, anti-CII-IgG1 and anti-CII-IgG2a antibody productions. Moreover, while IFN-γ and IL-10 were not affected, torilin suppressed CIA-induced serum TNF-α, IL-1ß and IL-6 levels. Interestingly, torilin also blocked IFN-γ, IL-17 and IL-6 cytokines while it did not affect IL-10 but enhanced IL-4 in splenocytes. These results show that torilin attenuated arthritis severity, modified leukocyte activations in dLNs or joints, and restored serum and splenocyte cytokine imbalances. Torilin may have immunomodulatory and anti-inflammatory properties with the capacity to ameliorate the inflammatory response in CIA-mice.

Cordyceps pruinosa extracts induce apoptosis of HeLa cells by a caspase dependent pathway.

AIM OF THE STUDY: Cordyceps is a parasitic fungus and has long been used as a traditional Chinese medicine to treat illnesses, promote longevity, increase athletic power, and relieve exhaustion and cancer. In this study, we reveal the mechanisms underlying apoptosis induced by Cordyceps pruinosa butanol fraction (CPBF) in the human cervical adenocarcinoma cell line, HeLa. MATERIALS AND METHODS: Proliferation and apoptosis of cells were examined by MTT assay, DNA fragmentation, phosphatidyl serine distribution assay, Western blot analysis, and immunocytochemistry. To determine the association between CPBF related apoptosis and ROS, electron spin resonance (ESR) trapping experiments were used. RESULTS: CPBF inhibited proliferation and induced apoptosis in HeLa cells in a dose-dependent manner using a MTT assay, DNA fragmentation, and a phosphatidyl serine distribution assay. Western blot analysis showed that apoptosis in HeLa cells was caspase-3- and -9-dependent. Proteolytic cleavage of PARP and the release of cytochrome c from the mitochondria into the cytosol were significantly increased and the Bcl-2/Bax protein ratio was decreased. Apoptosis induced by CPBF was not prevented by various antioxidants. CONCLUSIONS: These results indicate that apoptotic effects of CPBF on HeLa cells are mediated by mitochondria-dependent death-signaling pathway independent of reactive oxygen species, suggesting that CPBF might be effective as an anti-proliferative agent for cancer.

The opposite correlation between calcium ion and cyclic-AMP regarding the activation of microsomal triglyceride transfer protein in rat liver.

In this study, the effects of Ca(2+) and cyclic adenosine monophosphate (cAMP) on microsomal triglyceride (TG) transfer protein (MTP) activity were investigated in rat liver. MTP activity was high when liver contained low levels of cAMP, which was induced by administration of glucose, or high levels of total Ca(2+) and TG. However, MTP activity increased by high levels of Ca(2+) and TG was reduced in a dose-dependent manner by treatment with dibutyryl-cAMP (db-cAMP), a cAMP analogue. Conversely, when homogenates of liver from normal rats, with low levels of total Ca(2+) and high levels of cAMP, were incubated with thapsigargin, a Ca(2+)-inducer, MTP activity was increased in a dose-dependent manner compared to control. Therefore, our results suggest that high levels of Ca(2+) cause hypertriglyceridemia through the elevation of MTP activity, as opposed to high levels of cAMP, which suppress MTP activity and inhibit hypertriglyceridemia.

Inhibitory effects of fermented nutraceuticals on NO production and T cell proliferation in juvenile atopic dermatitis.

As the most common inflammatory skin disease in children, atopic dermatitis begins in infancy or early childhood, with about 90% of cases appearing under age of 5. The prevalence of atopic dermatitis has rapidly increased among children in recent years. Physiological and psychological abnormalities and social impact are also well known in children with atopic dermatitis and in their families. Atopic dermatitis not only seriously affects the quality of life of the children and their families but also is leading chronic disease in children with hard-to-cure.Recently, we found that the fermented extract of several plants had considerable potential to treat juvenile atopic dermatitis. This extract therefore is now under investigation to find the underlying immunopathological mechanism by determining its inhibitory effects on nitric oxide (NO) release and T cell proliferation. The fermented extract dose dependently blocked NO production. In particular, the inhibitory effect of the extract was maximized up until 80-fold dilution of the original extract. This extract did not induce cytotoxic effects up to 80-fold dilution. Interestingly, doses between 320- and 80-fold dilution significantly protected cell death mediated by LPS-induced NO production. The fermented extract also significantly suppressed CD3 induced T cell proliferation in a dose dependent manner.

Surfactin C inhibits the lipopolysaccharide-induced transcription of interleukin-1beta and inducible nitric oxide synthase and nitric oxide production in murine RAW 264.7 cells.

The anti-inflammatory activity of the surfactin C derived from Bacillus subtilis isolate was investigated in lipopolysaccharide (LPS, 1 microg ml(-1))-treated mouse RAW 264.7 cells. LPS increased mRNA transcription of cyclooxygenase (COX)-2, interleukin (IL)-1beta and inducible nitric oxide synthase (iNOS). However, surfactin C at 50 microg ml(-1 )inhibited the LPS-induced increase in the transcription of IL-1beta and iNOS and nitric oxide (NO) production in a dose-dependent manner.