Complement component 3 inhibition by an antioxidant is neuroprotective after cerebral ischemia and reperfusion in mice.

Oxidative stress after stroke is associated with the inflammatory system activation in the brain. The complement cascade, especially the degradation products of complement component 3, is a key inflammatory mediator of cerebral ischemia. We have shown that pro-inflammatory complement component 3 is increased by oxidative stress after ischemic stroke in mice using DNA array. In this study, we investigated whether up-regulation of complement component 3 is directly related to oxidative stress after transient focal cerebral ischemia in mice and oxygen-glucose deprivation in brain cells. Persistent up-regulation of complement component 3 expression was reduced in copper/zinc-superoxide dismutase transgenic mice, and manganese-superoxide dismutase knock-out mice showed highly increased complement component 3 levels after transient focal cerebral ischemia. Antioxidant N-tert-butyl-α-phenylnitrone treatment suppressed complement component 3 expression after transient focal cerebral ischemia. Accumulation of complement component 3 in neurons and microglia was decreased by N-tert-butyl-α-phenylnitrone, which reduced infarct volume and impaired neurological deficiency after cerebral ischemia and reperfusion in mice. Small interfering RNA specific for complement component 3 transfection showed a significant increase in brain cells viability after oxygen-glucose deprivation. Our study suggests that the neuroprotective effect of antioxidants through complement component 3 suppression is a new strategy for potential therapeutic approaches in stroke.

Safety and efficacy of basic fibroblast growth factors for deep second-degree burn patients.

INTRODUCTION: Burn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. MATERIALS AND METHODS: A total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1630 patients with deep second-degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. RESULTS: AEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average day to application (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). CONCLUSION: Our study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second-degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second-degree burn patients.

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus.

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for hERα and hERß with IC50 values of 1.20 ×10(-7) g/ml and 1.00×10(-7) g/ml, respectively. LNE induced 17ß-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on hER α and ß than other fractions. Our results indicate that LNE had higher binding affinities for hERß than hERα, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia.

In this study, we examined the estrogenic activity of bavachin, a component of Psoralea corylifolia that has been used as a traditional medicine in Asia. Bavachin was purified from ethanolic extract of Psoralea corylifolia and characterized its estrogenic activity by ligand binding, reporter gene activation, and endogenous estrogen receptor (ER) target gene regulation. Bavachin showed ER ligand binding activity in competitive displacement of [(3)H] E2 from recombinant ER. The estrogenic activity of bavachin was characterized in a transient transfection system using ERα or ERß and estrogen-responsive luciferase plasmids in CV-1 cells with an EC50 of 320 nM and 680 nM, respectively. Bavachin increased the mRNA levels of estrogen-responsive genes such as pS2 and PR, and decreased the protein level of ERα by proteasomal pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells transiently transfected with the corresponding receptor and hormone responsive reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen by binding and activating the ER.