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Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on brain injury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-κB (NF-κB) protein expression was analyzed by western blotting. IL-1β and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reduced brain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-κB activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1β and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism.

Heparin is well known to suppress vascular smooth muscle cell (VSMC) proliferation, and attempts to exploit this therapeutically have led to recognition of multiple pathways for heparin's anti-mitogenic actions. At low concentrations (ca. 1 µg · ml−1), these suppressive effects may reflect physiological activities of endogenous heparan sulfates, and appear to be rapid responses to extracellular or cell surface-associated heparin. Because heparin has been shown to influence expression of caveolin proteins, and caveolae/lipid rafts are critical structures modulating cell signaling, we examined the effect of heparin on signaling involving cholesterol-rich membrane microdomains. The VSMC line PAC-1 activates the MAP kinase Erk in response to the cholesterol-sequestering agents methyl-β-cyclodextrin and nystatin. This follows a temporal sequence that involves Ras-GTP activation of MEK, and is independent of PKC, Src, and PI3 kinase. However, ligand-independent phosphorylation of the EGF receptor (EGFR) by removal of cholesterol precedes Ras activation, and the EGFR kinase inhibitor AG1478 blocks Erk phosphorylation, supporting occurrence of the signaling sequence EGFR-Ras-MEK-Erk. Phosphorylation of EGFR occurs predominantly in caveolin-rich microdomains as identified by Western blotting of fractions from density gradient centrifugation of membranes prepared under detergent-free conditions. In these situations, heparin inhibits phosphorylation of EGFR on the Src-dependent site Tyr845, but not the autophosphorylation of Tyr1173, and decreases Ras activation and Erk phosphorylation. We conclude that heparin can suppress Erk signaling in VSMC with effects on site-specific phosphorylation of EGFR localized in caveolin-enriched lipid rafts. J. Cell. Physiol. 211: 205–212, 2007. © 2007 Wiley-Liss, Inc.

Type 1 diabetes (T1D) is an insulin-dependent diabetes because of insufficient insulin pro‐ duction by the pancreatic islet β cells. Although the pathogenic mechanism of T1D is not yet completely clear, the current view of T1D pathogenesis is that under certain genetic back‐ ground, exogenous and/or endogenous factors trigger autoimmunity against islet β cells in the pancreas causing β cell damage and subsequent insufficiency of insulin production [1, 2]. About two decades ago, it was first demonstrated that T cells specific to β cell antigens were activated and participated in the pathogenesis of T1D [3, 4]. A great deal of work fol‐ lowing these reports in both animal models and humans has provided convincing data fur‐ ther supporting T1D is a T cell-mediated autoimmune disease. On the other hand, the evidence showing that majority of T1D patients have high titers of autoantibodies against islet β cells [5, 6] suggests that self-reactive B cells must also be involved in the autoimmune process. The role of B cells in the pathogenesis of T1D was further supported by the recent research and clinical data demonstrating B cell depletion by anti-CD20 antibodies delayed the disease process.

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Toll-like receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR4 gene have been shown to be associated with impaired inflammatory response. Here, we investigated the association of TLR4 polymorphisms with T2DM. Four TLR4 polymorphisms (+986A/G, +1196C/T, +3725G/C, and +11367G/C) were genotyped in a total number of 822 T2DM patients and 835 healthy controls. Results showed that the +986A/G and +1196C/T polymorphisms did not exist in the Han Chinese population. The prevalence of TLR4 +3725GC and CC genotypes were significantly decreased in T2DM cases than in controls (odds ratio (OR) = 0.62, 95 % confidence interval (CI) = 0.50-0.78, p = 3.48 × 10(-5), and OR = 0.36, 95 % CI = 0.22-0.59, p = 1.55 × 10(-5), respectively). Also, the frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p = 2.46 × 10(-9)). When analyzing the TLR4 +11367G/C polymorphism, the +11367CC genotype revealed lower numbers in patients compared to healthy controls (OR = 0.46, 95 % CI = 0.27-0.78, p = 0.0032). Analysis of the clinical features on the control subjects demonstrated no correlations between these TLR4 polymorphisms and sex, age, body mass index, etc. (p > 0.05). In conclusion, these data indicate that TLR4 +3725G/C and +11367G/C polymorphisms may be novel protective factors against T2DM in the Chinese population.

Lipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.