Abstract. Baicalein, a herbal medicine, is a natural flavonoid isolated from the roots of Scutellaria baicalensis Georgi. It is known for its anticancer, anti-inflammatory and neuroprotective properties. Despite these well-known properties, it is not yet clear what effect baicalein has on tumor progression. Therefore, in the present study, we used B16F10 cells, Lewis lung carcinoma (LLC) cells, and human umbilical vein endothelial cells (HUVECs) to investigate the effect of baicalein on cell proliferation and viability, migration and tube formation in vitro. In addition, an experimental animal model was used to observe the growth rate and metastasis of tumors and tumor vessel formation in vivo. Our results showed that baicalein decreased the proliferation and migration and induced tumor cell death via caspase-3 activation in the B16F10 and LLC cells, and strongly inhibited tube formation and cell migration in HUVECs. Furthermore, mouse models showed that baicalein reduced the tumor volume and greatly reduced the tumor growth rate in the early stages of tumor progression, and the baicalein-treated groups had significantly reduced expression of CD31 (endothelial cell marker) and α-SMA (mural cell marker) in the tumors, indicating that baicalein inhibits tumor angiogenesis by disrupting tumor vasculature development. Comparison of the lymph node and lung samples collected from the baicalein-treated group, and the untreated group showed that baicalein reduced metastasis of the tumor to these tissues. In summary, baicalein reduced tumor progression and metastasis, directly induced tumor cell death, and inhibited tumor angiogenesis. Our results strongly demonstrate that baicalein is a potential chemotherapeutic agent.
Prion diseases are a family member of neurodegenerative disorders caused by the accumulation of misfolded-prion proteins (scrapie form of PrP, PrP(Sc)). The accumulation of PrP(Sc) in the brain leads to neurotoxicity by the induction of mitochondrial-apoptotic pathways. Recent studies implicated gingerol in protection against neurodegeneration. However, the basis of the neuroprotection in prion disease remains unclear. Thus, we investigated the influence of gingerol on prion peptide-induced neuronal damage. Gingerol blocked PrP(106-126)-mediated neurotoxicity by protecting mitochondrial function. Moreover, the protective effect of gingerol against PrP(106-126)-induced mitochondrial damage was associated with hypoxia-inducible factor 1 alpha (HIF-1α) expression. Gingerol-induced HIF-1α expression inhibited the PrP(106-126)-induced mitochondrial dysfunction. On the other hand, inhibition of gingerol-induced HIF-1 α expression attenuated the gingerol-mediated neuroprotective effect. Here, we demonstrate for the first time that treatment with gingerol prevents prion peptide-mediated neuronal cell death and that the neuroprotection is induced by HIF-1α-mediated signals. This study suggests that treatment with gingerol may provide a novel therapeutic strategy for prion-mediated neurotoxicity.
Prion disorder-related neurodegenerative diseases are characterized by the accumulation of prion protein (PrP) scrapie isoform (PrPsc) within the central nervous system. PrPsc induces neuronal cell death by increasing intracellular generation of reactive oxygen species (ROS). Lactoferrin (LF) is an 80 kDa protein, which has antioxidant abilities due to the scavenging of ROS. The effects of LF treatment on PrP (106-126)-mediated neurotoxicity and ROS generation were the focus of this study. LF treatment protected against PrP (106-126)-induced neuronal cell death and decreased ROS generation. The reduced ROS generation prevented PrP (106-126)-induced mitochondrial dysfunction. Moreover, PrP (106-126)-induced protein activation including c-Jun N-terminal kinase and caspase-3 were blocked by LF treatment. These results demonstrated that LF protects neuronal cells against PrP (106-126)-mediated neurotoxicity through the scavenging of ROS and provide evidence that LF treatment prevents neuronal cell death caused by PrP (106-126).
Sigesbeckia pubescens (SP) is a traditional Chinese medicine, possessing antioxidant and anti-inflammatory activities. In this study, we evaluate the neuroprotective activities of SP extract on glutamate-induced oxidative stress in HT22 cells and the molecular mechanism underlying neuroprotection. We applied 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), crystal violet, reactive oxygen species (ROS), lactate dehydrogenase (LDH), quantitative real-time polymerase chain reaction (qPCR), and western blot analyses for assessing the neuroprotective effects of SP extract. The experimental study revealed that SP considerably increased the cell viability, and reduced the oxidative stress promoted ROS and LDH generation in HT22 cells in a dose-dependent manner. Additionally, the morphology of HT22 cells was effectively improved by SP. Upregulated gene expressions of mitogen-activated protein kinase (MAPK) were markedly attenuated by SP. Similarly, SP notably suppressed the ROS-mediated phosphorylation of MAPK (pERK1/2, pJNK, and pp38) cascades and activation of apoptotic factor caspase-3 signaling pathway that overall contributed to the neuroprotection. Taken together, SP may exert neuroprotective effects via alteration of MAPK and caspase-3 pathways under oxidative stress condition. Therefore, SP is a potential agent for preventing oxidative stress-mediated neuronal cell death.
Insulin-like growth factor-1 (IGF-1) is one of the most important components of bovine colostrum. It exhibits antiapoptotic and antioxidative activities. Prion diseases are neurodegenerative disorders caused by cell death through mitochondrial dysfunction and increasing generation of reactive oxygen species (ROS). This study examined the protective effect of IGF-1 on residues 106-126 of the cellular prion protein [PrP (106-126)]-mediated mitochondrial neurotoxicity and oxidative stress. In SH-SY5Y human neuronal cells, treatment with PrP (106-126) decreased the cell viability and IGF-1 pretreatment markedly blocked the PrP (106-126)-induced neuronal cell death. IGF-1 inhibited PrP (106-126)-induced intracellular ROS generation and mitochondrial oxidative stress. In addition, IGF-1 blocked the translocation of the Bax protein to the mitochondria induced by PrP (106-126). These results demonstrate that IGF-1 protects neuronal cells against PrP (106-126)-mediated neurotoxicity through an antioxidative effect and blockage of mitochondrial Bax translocation. The results also suggest that regulation of IGF-1 secretion may have a therapeutic potential in the management of mitochondrial dysfunction and oxidative stress-induced neurodegeneration.
during pregnancy, the uterus undergoes intense neovascularization and vascular remodeling to supply oxygen and nutrients to the embryo. during this period, progesterone secreted from the ovary has effects on vascular remodeling in the endometrium and interacts with angiogenic factors. However, the exact mechanism of uterine vascular remodeling during pregnancy is poorly understood. Therefore, the aim of the present study was to investigate the association between angiopoietin-2 (ang-2), one of the angiopoietins, and intrauterine vessel remodeling during pregnancy, and to determine the effect of progesterone on ang-2 levels. changes in ang-2 expression were observed according to quantitative modification of progesterone using pregnant mice and human uterine microvascular endothelial cells. as a result, ang-2 was observed mainly in the mesometrial region (Mr) of the uterus during the period between implantation and placentation. Furthermore, a substantial amount of ang-2 also appeared in endothelial cells, particularly of the venous sinus region (VSr). interestingly, ang-2 expression was increased by progesterone, whereas estrogen had limited effects. To confirm the association between ang-2 and progesterone, the function of the progesterone receptor (Pr) was inhibited using ru486, a blocker of Pr. ang-2 expression and vascular remodeling of the VSr in the uterus were decreased when the functions of progesterone were inhibited. overall, the regulation of ang-2 by progesterone/Pr was associated with vascular remodeling in the VSr during pregnancy. The present study proposed a solution to prevent pregnancy failure due to a lack of vascularity in the uterus in advance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.