BackgroundExcessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2)-induced cytotoxicity in a normal human hepatocyte cell line, HL7702.MethodsWe analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH) release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS) levels, activities and protein expressions of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) formation. Expressions of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test.ResultsThe results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1) and acyl-CoA oxidase (ACOX) induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886.ConclusionsTaken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the antioxidative effect and the regulation of PPAR-alpha also play an important part in the protective effect.

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In this study, we sought to elucidate whether protocatechuic acid contributes to induce angiogenesis as well as its mechanisms. To this end, we examined the role of protocatechuic acid on human brain microvascular endothelial cell line (HBMEC) proliferation, invasion and tube formation in in vitro. For the study of mechanisms involved, the phosphoinositide 3 kinase (PI3K)-Akt inhibitor LY294002, the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME, vascular endothelial growth factor (VEGF), antagonist sFlt-1 and VEGF receptor blocker SU-1498 were used. Proliferation of HBMEC was tested by MTT. Scratch adhesion test was used to assess the ability of invasion. A Matrigel tube formation assay was performed to test capillary tube formation ability. PI3K-Akt-eNOS-VEGF pathway activation in HBMEC was tested by Western blot. Our data suggested that protocatechuic acid induces angiogenesis in vitro by increasing proliferation, invasion and tube formation. VEGF expression was increasing by protocatechuic acid and counteracted by VEGF antagonist sFlt-1, LY294002 and L-NAME in HBMEC. Tube formation was increased by protocatechuic acid and counteracted by VEGF receptor blocker-SU1498, LY294002 and L-NAME. These data suggest that protocatechuic acid may be a candidate therapy for stroke recovery by promoting angiogenesis via a programmed PI3K/Akt/eNOS/VEGF signalling axis.Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Re-establishment of functional microvasculature promotes stroke recovery. Signals and substrates of neurogenesis and neuroplasticity are tightly co-regulated with angiogenesis and vascular remodelling [1]. After stroke, promotion of angiogenesis enhances neurogenesis and functional recovery [2]. Neurovascular responses have a central role as the damaged central nervous system transitions from initial injury into repair [3]. Hence, therapies that enhance neurovascular remodelling should provide new opportunities for stroke recovery [4].Vascular endothelial growth factor (VEGF) is the most important mitogen in the process of angiogenesis. The lack of a single VEGF allele shows already abnormal blood vessel development and leads to embryonic lethality [5,6]. The angiogenic effects of this pathway are primarily mediated through the interaction of VEGF-A with VEGFR2. The binding of VEGF to its receptors on the surface of endothelial cells activates intracellular tyrosine kinases, triggering multiple downstream signals that promote angiogenesis, including PI3K/Akt and eNOS signals [7].Protocatechuic acid is a major benzoic acid derivative found in vegetables, nuts, brown rice, fruits and herbal medicines. Numerous pharmacological effects, such as antioxidative, antibacterial, anti-inflammatory effects and antitumour promotion activities, have been attributed to protocatechuic acid [8][9][10][11].In the present study, we therefore investigated the hypothesis that protocatechuic acid promoted angiogenesis in cerebral endothelial cell, acti...

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