Background: Epigallocatechin-3-gallate (EGCG) is a major form of tea catechin and has a variety of biological activities. In the present study, we investigated the effect of EGCG on the secretion of TNF-α, IL-6 and IL-8, as well as its possible mechanism of action by using the human mast cell line (HMC-1). Methods: EGCG was treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187). To investigate the effect of EGCG on PMA+A23187-stimulated HMC-1 cells, ELISA, Western blot analysis, electrophorectic mobility shift assay and luciferase assay were used in this study. Results: EGCG (100 µM) inhibited PMA+A23187-induced TNF-α, IL-6 and IL-8 expression and production. EGCG inhibited the intracellular Ca2+ level. EGCG attenuated PMA+A23187-induced NF-ĸB and extracellular signal-regulated kinase (ERK1/2) activation, but not that of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. Conclusion: EGCG inhibited the production of TNF-α, IL-6 and IL-8 through the inhibition of the intracellular Ca2+ level, and of ERK1/2 and NF-ĸB activation. These results indicate that EGCG may be helpful in regulating mast-cell-mediated allergic inflammatory response.
Benign prostate hyperplasia (BPH) is a common disease in elderly men, characterized by proliferated prostate and urinary tract symptoms. The hormonal cascade starting by the action of 5-alpha-reductase (5AR) is known to be one of the pathways responsible for the pathogenesis of BPH. Present investigation evaluated the capacity of berberine (BBR), a nature-derived compound abundant in Coptis japonica, in testosterone-induced BPH rats. Experimental BPH was induced by inguinal injection with testosterone propionate (TP) for 4 weeks. BBR or finasteride, a 5AR inhibitor as positive control, was treated for 4 weeks during BPH. BPH induced by TP evoked weight gaining and histological changes of prostate and BBR treatment improved all the detrimental effects not only weight reduction and histological changes but also suppression of prostate-specific antigen (PSA), which is elevated during BPH. Additionally, BBR suppressed TP-associated increase of 5AR, androgen receptor (AR) and steroid coactivator-1 (SRC-1), the key factors in the pathogenesis of BPH. To evaluate the underlying molecular mechanisms responsible for beneficial effects of BBR, we investigated whether these effects were associated with the mitogen-activated protein kinase pathway. BPH induced by TP showed increased phosphorylation of extracellular signal-regulated kinase (ERK), whereas this was suppressed by BBR treatment. On the other hand, c-jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase was not changed in BPH rats. In in vitro study using RWPE-1 cells, a human prostate epithelial cell line. TP increased cell proliferation and BPH-related key factors such as PSA, AR, and 5AR in RWPE-1 cells, and those factors were significantly decreased in the presence of BBR. Furthermore, these proliferative effects in RWPE-1cells were attenuated by treatment with U0126, an ERK inhibitor, confirming BBR can relieve overgrowth of prostate via ERK-dependent signaling. The cotreatment of U0126 and BBR did not affect the change of 5AR nor proliferation compared with U0126 alone, suggesting that the effect of BBR was dependent on the action of ERK. In conclusion, this study shows that BBR can be used as a therapeutic agent for BPH by controlling hyperplasia of prostate through suppression of ERK mechanism.
Spirulina is a true puree of a filamentous, spiral-shaped blue alga and exerts the useful properties as a source of many biochemicals. This study investigated the antidepressant-like effect of hydrolyzed Spirulina by malted barley on the forced swimming test in mice. After the forced swimming test, we examined the levels of several blood biochemical parameters in mice. The effect of the hydrolyzed Spirulina by malted barley-treated group for 2 weeks on the immobility time was significantly reduced in comparison with the control group (p < .05). Plasma level of blood urea nitrogen and lactate dehydrogenase was significantly decreased in the hydrolyzed Spirulina by malted barley-treated group compared with the control group (p < .05). It had no effect on the variation of creatine kinase, glucose, total protein, and albumin levels. Therefore, these results suggest that hydrolyzed Spirulina by malted barley might be a candidate among antidepressant agents.
Danggwibohyeoltang (DGBHT) is an oriental herbal prescription consisting of two herbs: Astragali Radix and Angelicae gigantis Radix. We examined the immune-enhancing effect of DGBHT in mice using the forced swimming test (FST) and in vitro tests in peritoneal macrophages. After daily oral administration of DGBHT, blood biochemical parameters related to fatigue were measured after the FST. The immobility time in the FST was significantly decreased in the DGBHT-treated group (200 mg/kg) on the 10th and 14th days. DGBHT (100~~200 mg/kg) treatment significantly increased glucose levels, acting as an energy source. Lactic dehydrogenase levels, which are accurate indicators of muscle damage, tended to decline after DGBHT administration (100~200 mg/kg). When DGBHT (200 mg/kg) was orally administered to mice, creatine kinase levels tended to decrease; however, this decrease was not significant. DGBHT did not have any effects on the variation of total protein and blood urea nitrogen levels. Further, we examined how DGBHT regulates cytokine production, nitric oxide (NO) production, and nuclear factor-kappa B (NF-κB) activation in mouse peritoneal macrophages. When DGBHT was used in combination with recombinant interferon-gamma (rIFN-γ), there was a noticeable cooperative induction of NO production and NF-κB activation. Moreover, rIFN-γ plus DGBHT treatment of peritoneal macrophages significantly increased the production of tumor necrosis factor-alpha (TNF-α) and interleukin-12 (IL-12). These results suggest that DGBHT improves immune function through the changes in indicators related to fatigue and the regulatory effects on immunological parameters, such as TNF-α, IL-12, NO production, and NF-κB activation.
Proteinase-activated receptor 2 (PAR2) is cleaved and activated by trypsin or mast cell tryptase, and may play an important role in inflammation. We have investigated the potential of PAR2 agonists to modulate TNF-alpha secretion from human astrocytoma cell line CCF-STTG1. We found that CCF-STTG1 expresses PAR2 by RT-PCR and Western blot analysis. Agonists such as trypsin, the peptide SLIGKV-NH(2) (corresponding to the PAR2 tethered ligand), or mast cell tryptase directly signal to CCF-STTG1 to stimulate secretion of TNF-alpha but do not stimulate in the presence of soybean trypsin inhibitor (SBTI) or VKGILS-NH(2) (reverse peptide). The secretion of TNF-alpha by trypsin was significantly blocked by pretreatment with either 50 microM PD98059 or 1 microM SB203580. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase homologue in CCF-STTG1 without any detectable activation of c-Jun N-terminal kinase (JNK). These results show that trypsin may induce TNF-alpha secretion following activation of ERK and p38 via PAR2 in CCF-STTG1.
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