Biofactors - Volume 30, issue 2

Authors: Reiter, Elke | Azzi, Angelo | Zingg, Jean-Marc

Article Type: Research Article

Abstract: The tocopherols (α, β-, γ-, and δ-tocopherol) and resveratrol are phytochemicals with alleged beneficial effects against atherosclerosis, vascular diseases and different cancers. They both can act as antioxidants, but they also modulate signal transduction and gene expression by non-antioxidant mechanisms. Here we wanted to determine whether the combined treatment of mast cells with the two compounds inhibits cell proliferation more efficiently when compared to individual treatments. Both compounds inhibit HMC-1 mastocytoma cell …proliferation and reduce the activity of Protein Kinase B (PKB/Akt) by inhibiting its Ser473-phosphorylation. The combination of 50 μM δ-tocopherol and 50 μM resveratrol inhibits proliferation of HMC-1 cells more efficiently when compared to single treatments. In line with this, PKB Ser473-phosphorylation is inhibited best by δ-tocopherol and resveratrol combinatory treatment. Resveratrol acts more efficiently as an inhibitor of PKB phosphorylation than α-, β-, γ-tocopherols, whereas δ-tocopherol shows a stronger inhibition possibly as a result of its apoptotic secondary effects. Our data suggest that δ-tocopherol and resveratrol can act additively in reducing cell proliferation and PKB phosphorylation. The combination of phytochemicals with relatively broad specificity on enzymes involved in signal transduction and gene expression may increase their activity in disease prevention by modulating several different molecular targets. Show more

Keywords: Mast cells, tocopherol, resveratrol, Akt, proliferation

Citation: BioFactors, vol. 30, no. 2, pp. 67-77, 2007

Authors: Heo, Buk-Gu | Park, Yong-Seo | Chon, Sang-Uk | Lee, Sook-Young | Cho, Ja-Yong | Gorinstein, Shela

Article Type: Research Article

Abstract: The aim of this investigation was to determine the content of total phenolics, antioxidant activity and cytotoxicity of methanol extracts from the aerial parts of 11 Korean medicinal salad plants. The highest total phenolic content of the methanol extracts was found in Aster scaber (17.1 mg 100 g^{-1}) , followed by Ixeris dentate (16.4 mg 100 g^{-1}) , Aster yomena (12.0 mg 100 g^{-1}) and Sedum sarmentosum (9.1 mg …100 g^{-1}) of FW. Methanol extracts of Ixeris dentate and Aster scaber at 50 μg mL^{-1} exhibited the highest DPPH radical scavenging activity by 86.4 and 83.3%, respectively. It was registered a dose-dependent increase of DPPH free radical scavenging activity. Total phenolic content of the studied plant extracts was correlated with the DPPH radical scavenging activity. It was found by means of MTT assay, that cytotoxicity of the methanol extracts was the highest against HCT-116. Methanol extracts from Petasites japonicus (IC_{50} < 25.0 μg mL^{-1}) showed the highest activity against HCT-116, following by Angelica gigas (34.75 μg mL^{-1}) , Erythronium japonicum (44.06 μg mL^{-1}) , and Aster scaber (54.87 μg mL^{-1}) . In conclusion, the studied salad plants have high total phenolics content and high antioxidant activity. These plants dose-dependently increased DPPH free radical scavenging activity. The total phenolics level was highly correlated with the free radical scavenging activity. Most of the studied salad plants have potent cytotoxicity activity. The results of this investigation suggest that the extracts of studied salad plants could be an addition to basic medicine for some diseases. Show more

Keywords: Aerial parts of Korean medicinal salad plants, methanol extracts, natural antioxidants, total phenolic content, DPPH radical scavenging activity, cytotoxicity

Citation: BioFactors, vol. 30, no. 2, pp. 79-89, 2007

Authors: Minamiyama, Yukiko | Takemura, Shigekazu | Tsukioka, Takuma | Shinkawa, Hiroji | Kobayashi, Fumiko | Nishikawa, Yuriko | Kodai, Shintaro | Mizuguchi, Shinjiro | Suehiro, Shigefumi | Okada, Shigeru

Article Type: Research Article

Abstract: Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen …activator inhibitor-1 (PAI-1) were significantly higher in OLETF rats than in non-diabetic control Long--Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29–33 weeks of diabetic phase in OLETF rats. OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacylgycerol, low density lipoprotein, cholesterol and PAI-1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal. Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator-stimulated phosphoprotein, an index of the NO-cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus. Show more

Keywords: diabetes, fermented grain food, GLUT4, NO-cGMP, OLETF rats

Citation: BioFactors, vol. 30, no. 2, pp. 91-104, 2007

Authors: Mizuha, Yoko | Yamamoto, Hironori | Sato, Tadatoshi | Tsuji, Mitsuyoshi | Masuda, Masashi | Uchida, Masayuki | Sakai, Kentaro | Taketani, Yutaka | Yasutomo, Koji | Sasaki, Hajime | Takeda, Eiji

Article Type: Research Article

Abstract: It has been reported that Cordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract of Cordyceps sinensis (WECS) on osteoclast differentiation in vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose-dependently inhibited the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. In fact, cytotoxic …effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF-κB through the prevention of IκBα phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL-induced osteoclast differentiation through a mechanism involving the NF-κB pathway. Show more

Keywords: Water extract of Cordyceps sinensis (WECS), osteoclast, differentiation, receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL), nuclear factor kappa B (NF-κB), inhibitor of the κB (IκB)

Citation: BioFactors, vol. 30, no. 2, pp. 105-116, 2007

Authors: Tsukioka, Takuma | Takemura, Shigekazu | Minamiyama, Yukiko | Nishiyama, Noritoshi | Mizuguchi, Shinjiro | Okada, Shigeru | Suehiro, Shigefumi

Article Type: Research Article

Abstract: The pleural cavity is normally in a state of negative pressure and low oxygen tension. It is exposed to the atmosphere during thoracic surgery. However, no reports of pathophysiological investigation of the effects of pleural oxygen exposure involved in thoracotomy are available. In this study, the effects of pleural oxygen exposure on systemic and pleural inflammation were investigated. Male Wistar rats (9 weeks old) were placed on mechanical ventilation and underwent thoracotomy with lipopolysaccharide (LPS) …administration, which simulates latent inflammatory condition. The pleural cavity was exposed to nitrogen (N_{2} thoracotomy group), air (20% oxygen, air thoracotomy group), or 100% oxygen (O_{2} thoracotomy group) under mechanical ventilation for 2 h. Animals were sacrificed 2 h or 8 h after LPS administration, and inflammatory indices (plasma tumor necrosis factor-α and interleukin-6, histology) were examined. For examination of inflammatory mediators, pleural effusion was added to cultured RAW264 cells, a murine macrophage cell line, and tumor necrosis factor-α levels in supernatant were measured. The capacity of pleural superoxide generation was investigated without LPS administration. Results showed increases in plasma interleukin-6 concentration and lung injury in the air and O_{2} thoracotomy groups. Pleural oxygen exposure stimulated pleural superoxide generation, and increased pleural 4-hydroxy-2-nonenal and lung lipid peroxide concentrations. Tumor necrosis factor-α levels in cell culture supernatants were increased by the addition of pleural effusion from the air and O_{2} thoracotomy groups. In conclusion, pleural oxygen exposure induced pleural oxidative injury and aggravated latent systemic inflammatory response. Show more

Keywords: Oxidative injury, pleural cavity, systemic inflammatory response, thoracic surgery

Citation: BioFactors, vol. 30, no. 2, pp. 117-128, 2007

Authors: Cimino, Francesco | Cristani, Mariateresa | Saija, Antonina | Bonina, Franco Paolo | Virgili, Fabio

Article Type: Research Article

Abstract: UV light is considered one of the major etiological factor in skin aging, cancer and also to systemic impairment such as immunosuppression. Increased production of reactive oxygen species (ROS) and oxidative stress condition are known to play a central role in initiating and driving the signalling events that lead to cellular response following UV irradiation. In the present study we have investigated the photoprotective activity of a standardized extract from red orange (ROE), obtained from three …red orange varieties and containing as main active principles phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) and ascorbic acid. The aim of this study was to evaluate the efficacy of ROE in modulating cellular responses to UVB in human keratinocytes (HaCaT). Our data indicate that ROE is potentially able to efficiently counteract UVB-induced response, and in particular some events associated to inflammation and apoptosis, such as NF-kB and AP-1 translocation and procaspase-3 cleavage. This activity is probably due to a block of cellular oxidative stress-related events. Thus we can propose ROE as a useful natural standardised extract in skin photoprotection with promising applications in the field of dermatology. Show more

Keywords: Red orange extract, UVB, skin, inflammation, apoptosis, keratinocyte

Citation: BioFactors, vol. 30, no. 2, pp. 129-138, 2007