Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats / 中国中药杂志

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Study on Protective Effects of Drug-contained Serum of Xiaoxuming Decoction on Astrocyte of Oxygen and Glucose Deprivation Model Rats / 中国药房

OBJECTIVE：To investigate the protective effects of drug-contained serum of Xiaoxuming decoction （XXM）on astrocyte of oxygen and glucose deprivation model rats ，and to explore its mechanisms. METHODS ：The astrocytes of rats were randomly divided into control group ，model group and XXM low-dose ，middle-dose，high-dose groups. The cells in the control group were not treated ；after 2.5 h of OGD ，model group and XXM low-dose ，middle-dose，high-dose groups were reoxygenated for 0，3，6，12 h in 0（i.e. the model group was not added with drugs ），2.5％，5％，10％ of XXM ，respectively. The content of lactate dehydrogenase （LDH）was detected by colorimetry. The reactive oxygen species （ROS）level was detected by fluorescence probe method ，and the expression of Manganese superoxide dismutase （MnSOD）was determined by immunofluorescence double staining method in control group ，model group and XXM high-dose group after 12 h of reoxygenation following OGD. RESULTS ： The content of LDH in the control group was always kept at a low level ；LDH content in the model group gradually increased from （110.99±17.06）U/L to （436.64±55.29）U/L after 0-12 h of reoxygenation following OGD ，which was significantly higher than that in the control group （P＜0.05）. Compared with model group at the same time point after reoxygenation following OGD ，the contents of LDH in the cells of XXM low-dose ，medium-dose and high-dose groups were decreased to different extents ，and showed a time-and dose-dependent trend. The contents of LDH in XXM groups at 6 and 12 h after reoxygenation following OGD were significantly lower than that of the model group （P＜0.05）. At 12 h after reoxygenation following OGD ，the levels of ROS in model group were significantly higher than control group ， while the level of MnSOD was significantly lower than control group（P＜0.05）. The level of ROS in XXM high-dose group hospital.sh.cn was significantly lower than model group ，while the level of MnSOD was significantly higher than model group （P＜0.05）.. CONCLUSIONS：XXM can protect astrocyte by up-regulating sh.cn levels of MnSOD ，scavenging excessive oxygen free radicals ， to relieve the OGD induced astrocytic injury ，with protective effect.

Conotation of ancient "stroke" and Qianyin Yaofang Xiaoxuming Decoction treating cerebral infarction and cerebral hemorrhage / 中国中药杂志

Xiaoxuming Decoction is the ancient classic herbal formulae for the treatment of stroke. Before the Han and Tang Dynasties, Xiaoxuming Decoction was highly praised by doctors of all dynasties as the "No.1 prescription of internal medicine". However, it was gradually declined in later generations and even abandoned by doctors of all dynasties. The reason why Xiaoxuming Decoction was anybody to care for it and the changes of physicians' understanding of the pathogenesis of "stroke" in the ancient times. In ancient times, the connotation of stroke was very extensive, including facial neuritis, acute cerebral infarction, acute cerebral hemorrhage, sequelae of cerebral hemorrhage, unexplained weakness of limbs, cervical spondylosis, acute myelitis, acute radiculitis, Guillain Barre syndrome, multiple sclerosis, myasthenia gravis, motor neuron disease, dermatomyositis, hypokalemic paralysis peripheral neuritis. According to studies, in the treatment of cerebral infarction and cerebral hemorrhage, Xiaoxuming Decoction can significantly shorten the course of acute stage and promote the recovery of hemiplegia, and its mechanism is consistent with the treatment principle of modern medicine for cerebrovascular diseases. In addition, this prescription is forbidden for patients with red face, fast heart rate, high blood pressure, blocked stool, red tongue, yellow fur, rapid pulse string or strong pulse string, and strong pulse on the wrist.

Experience of treating facial neuritis, unexplained limb weakness, cervical spondylosis, acute myelitis, acute radiculitis, Guillain Barre syndrome, multiple sclerosis, myasthenia gravis, motor neuron disease, dermatomyositis with Xiaoxuming Decoction / 中国中药杂志

Xiaoxuming Decoction is an ancient classic herbal formula for the treatment of stroke. In ancient times, the connotation of stroke was very extensive, including facial neuritis, acute cerebral infarction, acute cerebral hemorrhage, sequelae of cerebral hemorrhage, unexplained weakness of limbs, cervical spondylosis, acute myelitis, acute radiculitis, Guillain Barre syndrome, multiple sclerosis, myasthenia gravis, motor neuron disease, dermatomyositis, hypokalemic paralysis peripheral neuritis. It has been identified that: ①Xiaoxuming Decoction is very common in the treatment of cerebrovascular diseases, such as cerebral infarction, cerebral hemorrhage and other cerebrovascular diseases, facial neuritis, acute myelitis, acute radiculitis, Guillain Barre syndrome, unexplained limb weakness, multiple sclerosis, motor neuron disease, myasthenia gravis, and rheumatic and immune system diseases, such as dermatomyositis, and can not only alleviate symptoms, but also improve prognosis and the long-term survival rate. ②Sudden limb failure, facial paralysis, and hypoalgesia without heat syndrome are the key indications of Xiaoxuming Decoction. ③This is a special prescription for the treatment of acute facial neuritis, and can cure in one week in the combination with moxibustion. ④In the treatment of facial neuritis complicated with hypertension or acute cerebrovascular disease, Xiaoxuming Decoction generally has a certain antihypertensive effect, without any hypertensive effect, which reflected its two-way regulatory effect for blood pressure. ⑤In the treatment of unknown limb weakness, acute myelitis, acute radiculitis, Guillain Barre syndrome, Xiaoxuming Decoction can rapidly alleviate the symptoms. ⑥This is the basic formula for multiple sclerosis and motor neuron disease. Long term use of Xiaoxuming Decoction can alleviate the symptom of limb weakness, reduce the occurrence of complications and delay the progress of the disease, but with a poor long-term prognosis. ⑦In the treatment of myasthenia gravis, Xiaoxuming Decoction can significantly improve muscle strength, and gradually help stop hormone reduction. After thymoma surgery, Xiaoxuming Decoction is also applicable to some patients with recurrent myasthenia gravis. ⑧Xiaoxuming Decoction also plays a role in the treatment of dermatomyositis and cervical spondylopathy. ⑨Raw ephedra is the monarch drug of Xiaoxuming Decoction, which is the key to the effect. The dosage starts with 6 g is titrated in a small dose and increases gradually. In addition, this formula is forbidden for those with red face, fast heart rate, high blood pressure, blocked stool, red tongue, yellow fur, wiry and rapid pulse or powerful pulse, and spout pulse.

Network pharmacology study of Xiaoxuming Decoction based on vasodilatory and vasoconstrictory related GPCR targets / 中国中药杂志

In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction (XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors (GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors (5-HT1AR, 5-HT1BR), AT1R, β2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0. The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.

Effects of active components group of Xiaoxuming decoction on brain mitochondria in cerebral ischemia/reperfusion rats during early recovery period / 中国中药杂志

To observe the effect of active components group of Xiaoxuming decoction (XXMD) on brain mitochondria in cerebral ischemia/reperfusion rats during early recovery period, and study its protective mechanism for nerves in cerebral ischemia/reperfusion rats during early recovery period. Cerebral ischemia model of middle cerebral artery occlusion in rats was established by suture method, and reperfusion was conducted 2 h later. The degree of cerebral ischemia in rats was evaluated by using Zea-Longa's standard grading method, and the model rats were randomly divided into model group, Xiaoxuming decoction active components low, medium and high dose groups and positive drug Ginaton group, with sham operated rats as control group. Gradient centrifugation was used to extract the mitochondria from rat brain after 5 days of drug administration. Then the mitochondrial respiratory function was measured by Clark oxygen electrode method; mitochondrial membrane potential and the mitochondrial reactive oxygen species(ROS) level were detected by fluorescence probe methods; and the activity of mitochondrial succinodehydrogenase (SDH) and the content of ATP in the ischemic region of MCAO rats were measured by spectrophotometric method. The results showed that as compared with the model group, XXMD could significantly improve mitochondrial respiratory activity, increase the activity of SDH, reduce the level of ROS, increase mitochondrial membrane potential and obviously promote the synthesis of ATP in brain tissues. The results indicated that XXMD active components group could alleviate the energy metabolism disorders, protect brain mitochondrial damage and improve mitochondrial function in MCAO rats, which may be the mechanism of its neuroprotection activity.

Chemical Constituents in Groups of Effective Components Extracted fromXiaoxuming Decoction / 世界科学技术-中医药现代化

This article was aimed to study the chemical constituents in groups of effective components extracted from Xiaoxuming Decoction. Twelve compounds were isolated and purified by dynamic axial compression column chromatography. Their chemical structures were identified by spectral analysis. The results showed that twelve compounds were isolated and identified as octacosanoic acid(1), cetanol(2), oroxylin A(3), wogonin(4), baicalein(5), tetrandrine(6), fangchinoline(7), wogonoside(8), baicalin(9), paeoniflorin(10), amygdalin(11), manntol(12). It was concluded that all compounds were isolated from this compound prescription for the first time.

Effective components combination of Xiaoxuming Decoction on anti-Alzheimer’s disease / 中成药

AIM: To apply high throughput screening methods to research Xiaoxuming Decoction's effective components combination and its action mechanism. METHODS: We studied the effects of 240 sequential components of Xiaoxuming Decoction (L1-L120,A1-A120) on anti-A? neurotoxicity、anti-H_2O_2 damage、anti-glutamic acid damage and ?-secretase activity. RESULTS: We evaluated these results of screening comprehensively,and found several components of Xiaoxuming Decoction (L1-L40,A30-A60,A100-A120) had the potential effects of listed before.So the combination of these components was regarded as the effective components combination of Xiaoxuming Decoction for anti-Alzheimer's disease. CONCLUSION: Xiaoxuming Decoction had effective protection against Alzheimer's disease through multi-component and multi-target.High throughput screening methods will push the development of Chinese traditional compound prescription greatly.