Fafeng Cheng

Refined Qingkailing Protects MCAO Mice from Endoplasmic Reticulum Stress-Induced Apoptosis with a Broad Time Window.

In the current study, we are investigating effect of refined QKL on ischemia-reperfusion-induced brain injury in mice. Methods. Mice were employed to induce ischemia-reperfusion injury of brain by middle cerebral artery occlusion (MCAO). RQKL solution was administered with different doses (0, 1.5, 3, and 6 mL/kg body weight) at the same time of onset of ischemia, and with the dose of 1.5 mL/kg at different time points (0, 1.5, 3, 6, and 9 h after MCAO). Neurological function and brain infarction were examined and cell apoptosis and ROS at prefrontal cortex were evaluated 24 h after MCAO, and western blot and intracellular calcium were also researched, respectively. Results. RQKL of all doses can improve neurological function and decrease brain infarction, and it performed significant effect in 0, 1.5, 3, and 6 h groups. Moreover, RQKL was able to reduce apoptotic process by reduction of caspase-3 expression, or restraint of eIF2a phosphorylation and caspase-12 activation. It was also able to reduce ROS and modulate intracellular calcium in the brain. Conclusion. RQKL can prevent ischemic-induced brain injury with a time window of 6 h, and its mechanism might be related to suppress ER stress-mediated apoptotic signaling.

Baicalin's Therapeutic Time Window of Neuroprotection during Transient Focal Cerebral Ischemia and Its Antioxidative Effects In Vitro and In Vivo

We investigated the effects of baicalin on an ischemia-reperfusion-induced brain injury model in rats and its antioxidative activities in vitro and in vivo. An ischemia-reperfusion injury of the brain via a middle cerebral artery occlusion (MCAO) was induced in rats. Baicalin was injected at different time points (0, 2, 4, and 6 h) after the MCAO was induced. Baicalin can improve neurological function and significantly decrease brain infarction within a time window of 4 h. Moreover, baicalin was able to reduce cell apoptosis and had the strong antioxidative effect of reducing reactive oxygen species production and malondialdehyde generation. In contrast, baicalin interfered with superoxide dismutase and nicotinamide adenine dinucleotide 2′-phosphate oxidase activities. Moreover, baicalin also exhibited strong neuroprotective effects against H2O2-mediated injury and improved the SOD activity of neurons. Furthermore, baicalin demonstrated good scavenging of hydroxyl radicals, superoxide anions, and DPPH radicals and exerted an additional effect of inhibiting xanthine oxidase. Baicalin showed beneficial effects against MCAO-induced injury within a 4 h time window, and its antioxidative effects both in vitro and in vivo may partly elucidate its mechanism of action.

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

Chinese medicine injection qingkailing for treatment of acute ischemia stroke: a systematic review of randomized controlled trials.

Qingkailing (QKL) injection was a famous traditional Chinese patent medicine, which was extensively used to treat the acute stages of cerebrovascular disease. The aim of this study was to assess the quantity, quality and overall strength of the evidence on QKL in the treatment of acute ischemic stroke. Methods. An extensive search was performed within MEDLINE, Cochrane, CNKI, Vip and Wan-Fang up to November 2011. Randomized controlled trails (RCTs) on QKL for treatment of acute stroke were collected, irrespective of languages. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards, and RevMan5 was used for data analysis. Results. 7 RCTs (545 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that QKL combined with conventional treatment was more effective in effect rate, and the score of MESSS and TNF-α level compared with conventional treatment alone, but there was no significant difference in mortality of two groups. Only one trial reported routine life status. There were four trials reported adverse events, and no obvious adverse event occurred in three trials while one reported adverse events described as eruption and dizziness.

Synergistic neuroprotective effects of Geniposide and ursodeoxycholic acid in hypoxia‑reoxygenation injury in SH‑SY5Y cells

Endoplasmic reticulum stress (ERS) and autophagy activation play important roles in the process of cerebral ischemia/reperfusion (I/R) injury. The synergistic protective effects of Geniposide and ursodeoxycholic acid against cellular apoptosis caused by oxygen-glucose deprivation-reoxygenation (OGD/R) were investigated using a Cell Counting Kit-8 assay, lactate dehydrogenase (LDH) assay, flow cytometry, quantitative polymerase chain reaction (qPCR), and western blotting to examine cellular viability, apoptosis, reactive oxygen species (ROS) levels, mRNA and protein levels, respectively, in relation to ERS and autophagy. We found that pretreatment with Geniposide improved cellular viability. Moreover, treatment with a combination of Geniposide and Tauroursodeoxycholic acid (TUDCA) (GT) protected injured cells better than Geniposide alone. Further studies showed that the increase in cellular ROS levels, and the overexpression of mRNA and proteins related to OGD/R-induced ERS and autophagy, were both counteracted by GT. Our study indicates that the protective effects of GT on OGD/R-induced apoptosis in SH-SY5Y cells are associated with the inhibition of ERS and autophagy.

New Perspectives on Specific Immune-Depletion Technique Using Monoclonal Antibodies against Small Active Molecules in Herbs

One of the main focuses in Chinese Medicine research is the identification of efficacious components in Chinese herbal medicine (CHM). Studies in such area are difficult due to the complexity and the synergistic characteristics of CHM. Current methods to track and separate active components are not adequate to meet the needs of revealing effects and identify substances and pharmacological mechanisms, which directly restrict the modernization and globalization of CHM. In this paper, a new methodology to deplete a single active component via immunoassay was introduced. The specific active component in a CHM mixture can then be identified and studied through comparative analyses of the pharmacological effects before and after immune depletion. With this new methodology, degree of contribution of a particular component to the whole complex herbal mixture can be elucidated, and its synergistic property with other components can be determined. The new method can reflect not only the overall combined pharmacological effects of CHM but also the effect of individual component. It is an effective way to explain the degree of contribution of one specific component to the overall activity of a CHM prescription.

Mechanisms of non-alcoholic fatty liver disease and its correlation with chronic stress

With the increase in the incidence of nonalcoholic fatty liver disease(NAFLD), the distributions of area and age have gradually expanded, and it has become a hot topic in the field of medical and scientific research. Previous studies often attributed the reason of NAFLD to unhealthy diet and lifestyle. However, recent studies have shown that chronic stress is one of the main factors for the development of NAFLD. In this paper, we present the latest research achievements on the mechanism of NAFLD caused by chronic stress, with an aim to provide a theoretical basis for the prevention and treatment of NAFLD.

P01.04. Attenuation of neurological dysfunction and brain infarction with a chinese herbal formula in ischemia-reperfusion induced brain injury of mice

Purpose Stroke is one of the most common diseases in China, especially ischemic stroke. Although there are significant advances in treatment of stroke in Western medicine, traditional Chinese medicine also plays an important role in treatment of patients suffering from acute ischemic stroke in China. One Chinese herbal formulation named Qingkailing solution is derived from an ancient formulation of Angongniuhuangwang and has been documented to reduce ischemic injury of the brain. However, due to significant side effects associated with Qingkailing solution, we reconstituted components of Qingkailing solution and formed a new solution named JZQKL. In the study, we are investigating the effect of different concentrations of JZQKL on ischemia induced brain injury.