Low-Molecular-Weight Fucoidan Attenuates Mitochondrial Dysfunction and Improves Neurological Outcome After Traumatic Brain Injury in Aged Mice: Involvement of Sirt3.

Traumatic brain injury (TBI) is a leading cause of death and long-term disability. Fucoidan, a sulfated polysaccharide extracted from brown algae, possesses potent anti-oxidative and anti-inflammatory effects. Considering TBI happens frequently in adults, especially in aged individuals, we herein sought to define the protective effects of low-molecular-weight fucoidan (LMWF) in the aged mice. 16- to 18-month-old mice administered with LMWF (1-50 mg/kg) or vehicle were subjected to TBI using a controlled cortical impact (CCI) model. LMWF at the doses of 10 and 50 mg/kg significantly reduced both cortical and hippocampal lesion volume. This protection was associated with reduced neuronal apoptosis, as evidenced by TUNEL staining. Importantly, LMWF was effective even when administered up to 4 h after TBI. Treatment with LMWF improved long-term neurobehavioral outcomes, including sensorimotor function, and hippocampus-associated spatial learning and memory. In addition, LMWF significantly suppressed protein carbonyl, lipid peroxidation, reactive oxygen species (ROS) generation, as well as mitochondrial dysfunction, which was evidenced by mitochondrial cytochrome c release and collapse of mitochondrial membrane potential (MMP). To evaluate the underlying molecular mechanisms, the expression of sirtuin 3 (Sirt3) was detected by RT-PCR and Western blot. The results showed that TBI significantly increased the expression of Sirt3, which was further elevated by LMWF treatment. Knockdown of Sirt3 using intracerebroventricular injection of small interfering RNA (siRNA) partially prevented the therapeutic effects of LMWF. Collectively, these findings demonstrated that LMWF exerts neuroprotection against TBI in the aged brain, which may be associated with the attenuation of mitochondrial dysfunction through Sirt3 activation.

Effect of Colquhounia root tablet on IL-2 and IFN-γ mRNA expression in rats with experimental allergic encephalomyelitis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of Colquhounia root tablet on IL-2 and IFN-γ mRNA expression in experimental allergic encephalomyelitis (EAE) of rats.</p><p><b>METHODS</b>The allergic encephalomyelitis model was established in Wistar rats by immunization with myelin basic protein of spinal cord of guinea pig and complete Freund's adjuvant. The rats in treatment group received Colquhounia root tablet (300 mg*kg(-1), BID). The symptom of EAE was observed; pathological feature and myelin of brain and spinal cord were detected with HE stain and Loyez's stain, respectively. The expressions of IL-2 and IFN-γ mRNA were assayed by RT-PCR.</p><p><b>RESULTS</b>No EAE symptoms were developed in treatment group, the expressions of IL-2 and IFN-γ mRNA were 0.345 ± 0.032 and 0.353 ± 0.023, which were significantly lower than those of model group (P<0.01). The histopathologic examinations revealed that less inflammation cells around vessels and demyelination in white matter of brain and spinal cords were observed in treatment group than in model group.</p><p><b>CONCLUSION</b>Colquhounia root tablets are effective in treatment of EAE of rats, which may be associated with inhibition of the expression of IL-2 and IFN-γ mRNA.</p>