High-efficiency generation of induced pluripotent stem cells from human foreskin fibroblast cells using the Sagunja-tang herbal formula.

BACKGROUND: Sagunja-Tang (SGT-4) is a traditional herbal formula in Korean medicine that is used to treat anti-metabolic syndrome, and has antioxidant activity. In this study, we evaluated the effects of SGT-4 on the formation efficiency of induced pluripotent stem cells (iPSCs) from human foreskin fibroblasts (HFFs) by four reprogramming transcription factors: Oct4, Sox2, KIf4, and c-Myc (OSKM). METHODS: SGT-4 contained four different herbal medicines that are composed of Ginseng Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Rhizoma Alba, and Poria Sclerotium. The composition of SGT-4 was analyzed by high-performance liquid chromatography (HPLC). HFFs were transfected with episomal vectors contained by four OSKM. Western blotting, RT-PCR, immunofluroescence, and in vitro differentiation were used to assess the pluripotency of the iPSC cells. RESULTS: SGT-4 exhibited antioxidant activity against the generation of intracellular reactive oxygen species (ROS) as well as promoted the activation of superoxide dismutase 1 (SOD1), catalase, gluthathione peroxidase 1 (GPX1), and glutathione (GSH). Moreover, the ATP level was not significantly fluctuated depending on the concentration of SGT-4 in the hiPSCs. CONCLUSION: Our results indicate that the SGT-4, herbal formula significantly increases the efficiency of human iPSC generation via the transcription factors (Oct4, Sox2, KIf4, and c-Myc).

5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone exerts its anticancer and antiangiogenesis effects through regulation of the Akt/mTOR signaling pathway in human lung cancer cells.

5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone (DHTMF) is one of the constituents of Vitex rotundifolia, a medicinal herb that is used for the treatment of various disorders in China and Korea. In this study we evaluated the antitumor and antiangiogeneic activities of DHTMF. DHTMF significantly suppressed growth and induced apoptosis in lung carcinoma cells in a dose-dependent manner, as indicated by a decrease in Bcl-2 levels and increases in Bax and cleaved caspase-3 levels. In addition, DHTMF treatment significantly reduced the phosphorylation of Akt and mammalian target of rapamycin (mTOR), accompanied by reductions in the protein level of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), which are key angiogenic molecules in H522 lung cancer cells. Furthermore DHTMF inhibited VEGF-induced angiogenesis, as indicated by reduced expression of CD34, tube formation and migration in human umbilical vein endothelial cells (HUVECs), as well as reduced neovascularization in an in vivo mouse Matrigel plug assay. DHTMF also inhibited phosphorylation of Akt, mTOR, and p70S6K in HUVECs and lung cancer cells. Taken together, our finding indicated that DHTMF inhibits Akt/mTOR signaling and reduces the expression of HIF-1 α and VEGF in tumor cells, which in turns inhibits endothelial cell-mediated angiogenesis. These results suggest that DHTMF inhibits angiogenesis as well as induces apoptosis via the Akt/mTOR pathway and might elicit pharmacological effects that are useful for treatment of lung cancer.

Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma.

Sulforaphane (1-isothiocyanato-4-(methylsulfinyl)-butane), belonging to a family of natural compounds that are abundant in broccoli, has received significant therapeutic interest in recent years. However, the molecular basis of its effects remains to be elucidated. In this study, we attempt to determine whether sulforaphane regulates the inflammatory response in an ovalbumin (OVA)-induced murine asthma model. Mice were sensitized with OVA, treated with sulforaphane, and then challenged with OVA. Sulforaphane administration significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Additionally, sulforaphane suppressed the increase in the levels of SOCS-3 and GATA-3 and IL-4 expression in the OVA-challenged mice. Collectively, our results demonstrate that sulforaphane regulates Th2 immune responses. This sutdy provides novel insights into the regulatory role of sulforaphane in allergen-induced Th2 inflammation and airway responses, which indicates its therapeutic potential for asthma and other allergic diseases.

RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction.

In asthma, T helper 2 (T(H)2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated CD4(+) T cells. Dendritic cells played an important role in determining the fate of naive T cells into either T(H)1 or T(H)2 cells. We determined whether RG-II regulates the T(H)1/T(H)2 immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon- gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.