The HIF-1α transcriptional factor and the BH-3 only protein BNIP3 are known to play fundamental roles in response to hypoxia. The objective of this research is to investigate the molecular mechanisms and the correlation of HIF-1α, BNIP3 and IGFBP-3 in hypoxia-induced cardiomyocytes injuries. Heart-derived H9c2 cells and neonatal rat ventricular myocytes (NRVMs) were incubated in normoxic or hypoxic conditions. Hypoxia increased HIF-1α expression and activated the downstream BNIP3 and IGFBP-3 thereby triggered mitochondria-dependent apoptosis. Moreover, IGF1R/PI3K/Akt signaling was attenuated by HIF-1α-dependent IGFBP-3 expression to enhance hypoxia-induced apoptosis. Autophagy suppression with 3-methyladenine or siATG5 or siBeclin-1 significantly decreased myocardial apoptosis under hypoxia. Knockdown of FoxO3a or BNIP3 significantly abrogated hypoxia-induced autophagy and mitochondria-dependent apoptosis. Moreover, prolonged-hypoxia induced HIF-1α stimulated BNIP3 and enhanced IGFBP-3 activation to inhibit IGF1R/PI3K/Akt survival pathway and mediate mitochondria-dependent cardiomyocyte apoptosis. HIF-1α and FoxO3a blockage are sufficient to annul the change of excessive hypoxia of hearts.
Green tea is a widely consumed beverage known for its beneficial anti-inflammatory, anti-oxidative, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. Here, we administered epigallocatechin gallate fraction of green tea extract (EGTE) to mice for 6 weeks and examined the effects on the innate and adaptive immune responses by measuring phagocytic and natural killer (NK) cell activity, as well as antigen-specific proliferation, cytolysis, cytokine secretion, and antibody production. Our data show that EGTE administration increased NK cell cytolysis and peritoneal cell phagocytosis, as well as splenocyte proliferation and secretion of IL-2 and IFN-γ. Of note, EGTE treatment decreased the production antigen-specific IgE via increased the proportion of CD4+ CD25+ regulatory T lymphocytes in the spleen, suggesting that EGTE may play a role in regulating the allergic response.
Adaptogens are harmless herbs which have pharmaceutical benefits due to their balancing, regulative and tonic functions. However, despite these medicinal effects, the antioxidant potential of adaptogens is rarely mentioned. This study investigated the antioxidant potential of 3 adaptogen extracts, Rhodiola rosea (golden root), Eleutherococcus senticosis (Siberian ginseng) and Emblica officinalis (Indian gooseberry, Amla). The results of this study showed that R. rosea had the highest potential for singlet oxygen scavenging, hydrogen peroxide scavenging, ferric reducing, ferrous chelating and protein thiol protection than either of the other 2 extracts. E. senticosis, on the other hand, showed the best potential for hypochlorite scavenging. In addition, the polyphenol content in the 3 adaptogen extracts followed the order: R. rosea, E. officinalis and E. senticosis. Our data suggest that the antioxidant potential of the 3 adaptogen extracts was proportional to their respective polyphenol content. The supplementation of adaptogen extracts containing high levels of polyphenols may not only have adaptogen properties, but may decrease the risk of complications induced by oxidative stress.
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