Trans-Cinnamaldehyde Increases Random Pattern Flap Survival Through Activation of the Nitric Oxide Pathway.

BACKGROUND: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide. MATERIALS AND METHODS: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7. RESULTS: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide-gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF. CONCLUSION: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.

Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury.

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain.

Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures.