Kaempferol is a novel antiviral agent against channel catfish virus infection through blocking viral attachment and penetration in vitro.

Channel catfish virus (CCV, Ictalurid herpesvirus 1) is the causative pathogen of channel catfish virus disease, which has caused high mortality and substantial economic losses in the catfish aquaculture industry. Due to the lack of licensed prophylactic vaccines and therapeutic drugs, the prevention and control of CCV infection seem to remain stagnant. Active compounds from medicinal plants offer eligible sources of pharmaceuticals and lead drugs to fight against endemic and pandemic diseases and exhibit excellent effect against viral infection. In this study, we evaluated the antiviral ability of 12 natural compounds against CCV with cell models in vitro and found kaempferol exhibited the strongest inhibitory compound against CCV infection among all the tested compounds. Correspondingly, kaempferol decreased transcription levels of viral genes and the synthesis of viral proteins, as well as reduced proliferation and release of viral progeny, the severity of the CPE induced by CCV in a dose-dependent manner, based on quantitative real-time PCR (RT-qPCR), western blotting, viral cytopathic effects (CPE) and viral titer assessment. Moreover, time-of-drug-addition assays, virus attachment, and penetration assays revealed that kaempferol exerted anti-CCV activity probably by blocking attachment and internalization of the viral entry process. Altogether, the present results indicated that kaempferol may be a promising candidate antiviral agent against CCV infection, which shed light on the development of a novel and potent treatment for fish herpesvirus infection.

Efficacy of Long-term Selenium Supplementation in the Treatment of Chronic Keshan Disease with Congestive Heart Failure.

Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.

The neuroprotective effects of tanshinone IIA on ß-amyloid-induced toxicity in rat cortical neurons.

Oxidative stress caused by amyloid ß-peptide (Aß) may play an important role in the pathogenesis of Alzheimer disease (AD). Aß is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. Tanshinone IIA (Tan IIA) is extracted from a traditional herbal medicine Salvia miltiorrhiza BUNGE, which has been shown to protect against oxidative stress and cell death. In this study, we investigated the neuroprotective effect of Tan IIA against Aß25₋35-induced cell death in cultured cortical neurons. Exposure of cortical neurons to 30µM Aß25₋35 caused a significant viability loss, cell apoptosis and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA) production. In parallel, Aß25₋35 significant increased the intracellular ROS elevation and decreased mitochondrial membrane potential (MMP). However, pretreatment of the cells with Tan IIA prior to Aß25₋35 exposure suppressed these Aß25₋35-induced cellular events noticeably. In addition, Tan IIA reduced the Aß25₋35-induced increase of caspase-3 activity, and reduced cytochrome c translocation into the cytosol from mitochondria. Furthermore, Tan IIA also ameliorated the Aß25₋35-induced Bcl-2/Bax ratio reduction in cortical neurons. Taken together, these data indicate that Tan IIA protected cultured cortical neurons against Aß25₋35-induced neurotoxicity through its antioxidative potential. Our results strongly suggest that Tan IIA may be effective in treating AD associated with oxidative stress.

Neuroprotective effects of emodin in rat cortical neurons against beta-amyloid-induced neurotoxicity.

Accumulation of beta-amyloid protein (Abeta) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). In this study, the neuroprotective effect of emodin extracted from the traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc against Abeta(25-35)-induced cell death in cultured cortical neurons was investigated. We found that pre-treatment with emodin prevented the cultured cortical neurons from beta-amyloid-induced toxicity. The preventive effect of emodin was blocked by pre-treatment with a phosphatidylinositol-3-kinase (PI3K) pathway inhibitor LY294002 or an estrogen receptor (ER) specific antagonist ICI182780, but not by pre-treatment with an extracellular signal-related kinases (ERK) inhibitor U0126. Furthermore, we found that emodin exposure induced the activation of the Akt serine/threonine kinase and increased the level of Bcl-2 expression. Moreover, the application of emodin for 24h was able to induce the activation of Abeta(25-35)-suppressed Akt and decrease the activation of the Jun-N-terminal kinases (JNK), but not of ERK. Interestingly, the up-regulation of Akt and Bcl-2 did not occur in the presence of LY294002 or ICI182780, suggesting that emodin-up-regulated Bcl-2 is mediated via the ER and PI3K/Akt pathway. Taken together, our results suggest that emodin is an effective neuroprotective drug and is a viable candidate for treating AD.

[Evaluation of hepatocellular function influenced by Chinese drug Dahuang Zhechong pill].

OBJECTIVE: To evaluate the influence of Chinese drug Dahuang Zhechong pill on the hepatocellular function. METHOD: Thirty-seven patients with hepatocirrhosis and twelve normal controls were performed the hepatobiliary scintgraphy with Tc-99m labeled ethylene hepatobiliary iminodiacetic acid (99 mTc-EHIDA), and the biochemical examination of hepatic function. There was 19 cases repeated the imaging after 6 months treated with chineses drug. By the three compartmental model configurations, the function parameters of hepatocellular extraction and excretion were calculated. RESULT: In the hepatocirrhosis groups, the hepatocellular uptake peak time and mean residence index were higher than those in normal controls (P < 0.01). Compared to normal controls, the uptake index, uptake speed index and descendent speed index were decreased markedly (P < 0.05). After treatment for 6 months with Chinese drug, the level of serum transaminase, globulin and bilirubin was lower than that before treatment. The uptake peak time and mean residence index decreased notably after treatment for 6 months (P < 0.01), and the uptake index increased, (P < 0.05). CONCLUSION: Chinese drug Dahuang Zhechong pill may improve the hepatocellular function and liver function status in patients with hepatocirrhosis.

Neuroprotective effects of ebselen are associated with the regulation of Bcl-2 and Bax proteins in cultured mouse cortical neurons.

There is little information available on the mechanisms underlying the neuroprotective actions of the organoselenium compound ebselen. In this study, we sought to determine the relationship between alterations in the expression of Bcl-2 and Bax proteins and intracellular levels of calcium and the protective effects of ebselen with a concentration range of 0.01-20 microM against glutamate toxicity in cultured mouse cortical neurons. Pretreatment with ebselen at moderate doses (4-12 microM), but not at lower or higher doses, significantly improved glutamate-induced suppression of cell viability. Pretreatment with ebselen (8 microM) also prevented apoptotic alterations, completely reversed the suppression of Bcl-2 expression, and significantly inhibited Bax overexpression, but did not alter elevated intracellular concentrations of calcium induced by glutamate. Pre-, co-, and post-treatment with ebselen (8 microM) had similar potency in improving the decreased viability of glutamate-exposed cells. These results indicate that the neuroprotective effects of ebselen at low doses are associated with the regulation of Bcl-2 and Bax proteins but appear to be independent of glutamate-mediated elevation of intracellular calcium, suggesting that different mechanisms are involved in the actions of low and high dose regimens. Ebselen may be an effective agent used for early treatment of acute brain injuries.

[Experimental study of mailuoning injection on therapy of hemifacial spasm].

OBJECTIVE: To investigate the protective effect of Mailuoning on the facial nerve demyelination of Hemifacial spasm and provide the data for therapy of Hemifacial spasm. METHOD: 24 New Zealand white rabbits were divided into control group, Saline group and Mailuoning group, on the latter two groups the models of Hemifacial spasm were made by the temporal superficial artery closely contacting the main trunk of facial nerve at stylomastoid foramen. From the 5th week, the Saline and Mailuoning were injected intravenously into ear margin for 2 weeks on Saline and Mailuoning group respectively. At the 7th week, the MDA and SOD in serum were measured, mean while the microstructure and ultrastructure of facial nerve were observed on 3 animal groups. RESULT: The MDA decreased obviously (P < 0.05) and SOD increased significantly (P < 0.01) in Mailuoning group comparing with that of Saline group, while the MDA and SOD showed insignificant changes of Mailuoning group and control group. The facial nerve severely demyelinated and axons retrogressively changed in Saline group but mild in Mailuoning group. CONCLUSION: Mailuoning injection has a significant protective effect on the facial nerve demyelination of Hemifacial spasm and the very important applied value for therapy of Hemifacial spasm.

The effects of the total saponin of Dipsacus asperoides on the damage of cultured neurons induced by beta-amyloid protein 25-35.

According to the pathogenesis of Alzheimer's disease (AD), beta-amyloid protein (A beta) was directly toxic to neurons, leading to neurodegeneration. Total saponin of Dipsacus asperoides (tSDA) is one of the main ingredients of Dipsacus asperoide, a traditional Chinese medicine. To explore the effects of tSDA on neuronal damage induced by A beta in vitro, biochemical analysis combining primary cultured neurons were adopted. Neurons were treated with 35 mmol/L A beta for 24 h, and tSDA at concentrations of 1-300 mg/L were added to A beta-treated cultures 24 h in advance, A beta for 24 h, the survival rate of neurons decreased closely by 50%. Lactate dehydrogenase release and the Malondialdehyde (MDA) level increased substantially. However, if neurons were pretreated with tSDA, the survival rate of neurons was higher than A beta-treated alone. Lactate dehydrogenase release and the MDA level decreased distinctly. Results demonstrated that tSDA possessed a neuroprotective action and that tSDA protected neurons against the toxicity of A beta, most likely by relieving oxidative stress or inhibiting the process of A beta, inducing free radical generation.