RESUMO
Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.
Assuntos
Alérgenos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Extratos Vegetais/farmacologia , Rhus/química , Caspases/metabolismo , Feminino , Humanos , Proteínas I-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fosforilação/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Receptores do Fator de Necrose Tumoral/metabolismo , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/antagonistas & inibidoresRESUMO
OBJECTIVES: This study was designed to evaluate the efficacy and the safety of constitutional herbal tea for treating chronic fatigue with no diagnosed cause, which is called Mibyeong in Korea. METHODS: Males and females with ages between 40 and 59 years who had complained of fatigue for 1 month consistently or for 6 months intermittently without a definite cause were recruited. At the same time, a Chalder fatigue scale (CFS) score of 19 was essential for participation in this study. Sixty five subjects completed the entire process, including blood tests and tests with medical devices. Five assessments of health status were accomplished over 8 weeks by using the CFS and the visual analogue scale (VAS). To ensure that the constitutional herbal tea was being safely used, we conducted and analyzed renal function and liver function tests. For the diagnosis of the Sasang constitution, the Sasang Constitutional Analysis Tool (SCAT) was used, and a specialist in Sasang constitutional medicine made the final diagnosis based on the SCAT result. Constitutional herbal tea was served four weeks after the first visit. The subjects took the constitutional herbal tea twice a day for one month. RESULTS: The results are as follows: The CFS and the VAS scores were significantly improved for the subjects in the constitutional herbal tea. No abnormalities were found on the blood tests to evaluate safety after taking the constitutional herbal tea. The improvements in the CFS and the VAS scores due to the constitutional herbal tea had no significant differences according to the Sasang constitution. CONCLUSION: Constitutional herbal tea may be used to reduce fatigue and improve health and has no adverse effect on either the kidney or the liver.
RESUMO
OBJECTIVES: This study was designed to investigate the effects of Calculus Bovis-Fel Uris-Moschus pharmacopuncture(BUM) on the regional cerebral blood flow (rCBF) and the mean arterial blood pressure (MABP) in normal and cerebral ischemic rats and to investigate a possible pathway involved in the effects of BUM. METHODS: The changes in the rCBF and the MABP following BUM into Fengfu (GV16) were determined by using a laser-Doppler flow meter and a pressure transducer, respectively. RESULTS: BUM significantly increased the rCBF and decreased the MABP in normal rats in a dose-dependent manner. The effect on the rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, intraperitoneal), an inhibitor of guanylate cyclase, but was not affected by pretreatment with indomethacin (1 mg/kg, intraperitoneal), an inhibitor of cyclooxygenase. The BUM-induced decrease of the MABP was changed neither by methylene blue nor by indomethacin pretreatment. In the cerebral ischemic rats, the rCBF was stably increased upon cerebral reperfusion in the BUM group in contrast to the rapid and marked increase in the control group. CONCLUSION: This study demonstrated that BUM into Fengbu (GV16) increased the rCBF in a dose-dependent manner in the normal state; furthermore, it improved the stability of the rCBF in the ischemic state upon reperfusion. Also, the effects of BUM on the rCBF were attenuated by inhibition of guanylate cyclase, suggesting that the effects involved the guanylate cyclase pathway.
RESUMO
OBJECTIVES: This study was designed to investigate the effect of four pharmacopuncture drugs (scolopendrid, Calculus Bovis-Fel Uris-Moschus (BUM), bee venom 25%, and sweet bee venom 10%) on the cerebral hemodynamics, including changes in the regional cerebral blood flow (rCBF) and in the mean arterial blood pressure (MABP). METHODS: The changes in the rCBF and the MABP were determined by using a laser-Doppler flowmeter and a pressure transducer, respectively. RESULTS: Scolopendrid (0.3 ml, 1 ml/kg) caused no significant changes in the rCBF and the MABP, whereas BUM (0.3 ml, 1 ml/kg) decreased the rCBF and the MABP, bee venom 25% (0.3 ml, 1 ml/kg) increased the rCBF and lowered the MABP, and sweet bee venom 10% (0.3 ml, 1 ml/kg) increased the rCBF and had no significant effect on the MABP. CONCLUSIONS: The rCBF and the MABP were influenced differently by the administration of various pharmacopunctures. Further studies are needed to elucidate the underlying mechanism.
RESUMO
We have isolated a complementary deoxyribonucleic acid clone that encodes the protein disulfide isomerase of Bombyx mori (bPDI). This protein has a putative open reading frame of 494 amino acids and a predicted size of 55.6 kDa. In addition, 2 thioredoxin active sites, each with a CGHC sequence, and an endoplasmic reticulum (ER) retention signal site with a KDEL motif were found at the C-terminal. Both sites are typically found in members of the PDI family of proteins. The expression of bPDI messenger ribonucleic acid (mRNA) was markedly increased during ER stress induced by stimulation with calcium ionophore A23187, tunicamycin, and dithiothreitol, all of which are known to cause an accumulation of unfolded proteins in the ER. We also examined the tissue distribution of bPDI mRNA and found pronounced expression in the fat body of insects. Hormonal regulation studies showed that juvenile hormone, insulin, and a combination of juvenile hormone and transferrin (although not transferrin alone) affected bPDI mRNA expression. A challenge with exogenous bacteria also affected expression, and the effect peaked 16 hours after infection. These results suggest that bPDI is a member of the ER-stress protein group, that it may play an important role in exogenous bacterial infection of the fat body, and that its expression is hormone regulated.