[Study on therapeutic mechanism of Rehmanniae Radix Praeparata- Corni Fructus in sequelae of ischemic stroke based on network pharmacology technology].

In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.

Effects of Tianqijiangtang capsule on survival, self-renewal and differentiation of hippocampal neural stem cells of embryonic rats cultured in high glucose medium.

OBJECTIVE: This study aims to investigate the effects of Tianqijiangtang capsule on the survival, self-renewal and differentiation of hippocampal neural stem cells (NSCs) of embryonic rats cultured in high glucose medium. MATERIALS AND METHODS: A cell model of diabetic encephalopathy was established. Cell viability was assessed to screen the optimal concentration of glucose for the cell model of diabetic encephalopathy. Then, the effects of Tianqijiangtang capsule on the proliferation and differentiation of NSCs, and the expression of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in the culture medium and cells were detected. RESULTS: High glucose significantly reduced the ability of survival, proliferation and differentiation of NSCs, which was statistically significant, when compared to the control group (P < 0.05 or 0.01). Tianqijiangtang capsule significantly enhanced the survival, proliferation and differentiation of NSCs cultured in high glucose medium, which was statistically significant, when compared with the high glucose group (P < 0.05 or 0.01). The high glucose culture resulted in a significant decrease in VEGF and BDNF levels in culture medium and cells of NSCs. Tianqijiangtang capsule significantly increased the level of VEGF nuclear BDNF in cells and the culture medium, which was significantly higher, when compared to that in the high glucose group (P < 0.05 or 0.01). CONCLUSION: Tianqijiangtang capsule enhances the level of neurotrophic factor synthesized and secreted by hippocampal NSCs cultured with high glucose through the autocrine and paracrine pathway, promotes the NSC survival, replication and differentiation of new neurons and astrocytes, and reduces the degeneration and necrosis of nerve cells.

Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing Kidney Herbs on Hippocampal Cholinergic System in Alzheimer's Disease Model Rat Induced by Aß 1-42.

BACKGROUND: Therapy of nourishing kidney has been used for treating memory deficits of Alzheimer's disease (AD) for thousands of years based on traditional Chinese medicine. However, we found the therapy of dredging the bowels could alleviate both memory deficits and mental symptoms of AD in clinic. OBJECTIVE: To determine whether the therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs for treating AD rats, and to explore the underlying mechanism of the combination of nourishing kidney and dredging the bowels (NKDB) herbs. METHODS: 60 rats were randomly divided into sham-operated group (SOG), model group (MG), nourishing kidney group (NKG), dredging the bowels group (DBG), nourishing kidney and dredging the bowels group (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was performed by injecting Aß 1-42 into the hippocampal CA1 region. Animals received aqueous solution of Chinese herbal medicine or western medicine while SOG received only distilled water. Ability of learning and memory were assessed by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase (ChAT) activity and positive cells in the hippocampus were detected by the biochemical and immunofluorescent assay. RESULTS: All rats were in the same baseline. While after model establishment, ability of learning and memory of MG, NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were significantly improved compared with MG. Additionally, AChE activity of NKG, DBG, and NKDBG was significantly decreased, meanwhile ChAT activity showed an increased tendency. The number of AChE-positive cells and ChAT-positive cells of both NKDBG and DHG were significantly decreased and increased respectively, superior to those when compared with NKG and DBG. What's more, there was no significant difference between NKDBG and DHG. CONCLUSION: Therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs by reversing morphological damage of hippocampal cholinergic system. Furthermore, treatment with NKDB herbs could be effectively against AD, providing a practical therapeutic strategy in clinic.

Evidence of alterations in the expression of orphan receptors GPR26 and GPR39 due to the etiology of the metabolic syndrome.

AIMS: Metabolic syndrome (MS) is composed of several metabolic abnormalities that increase the risk of cardiovascular diseases and diabetes. Although there are treatments for the components of MS, this pathology maintains a high mortality, suggesting that there are other mechanisms in which orphan receptors such as GPR26 and GPR39 may be involved. For this reason, the aim of this work was to evaluate the expression of GPR26 and GPR39 orphan receptors in two models of MS (diet and genetics). MATERIALS AND METHODS: We used male Wistar rats, which received 70% fructose in drinking water for 9 weeks, and obese Zucker rats. We measured weight, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol to determine the MS and the expression of the orphan receptors GPR26 and GPR39 in brain, heart, aorta, liver, and kidney by RT-PCR. RESULTS: The analysis of the expression of the orphan receptors GPR26 and GPR39 showed that the receptors are expressed in some tissues, but the expression of the GPR26 tends to decrease in the heart and aorta, whereas in the brain, no changes were observed, this receptor is not expressed in the liver and kidney of both strains. The expression of GPR39 isoforms depends on the tissue and MS model. CONCLUSIONS: We conclude that the orphan receptors GPR26, GPR39v1, and GPR39v2 are expressed in different tissues and their profile expression is dependent on the etiology of the MS.

Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats.

We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair.

The Role of Chinese Herbs and Acupuncture on the Inflammation Reaction After Cerebral Ischemia.

As a complex pathological process, immune inflammatory reaction plays an important role in the injury by cerebral ischemia. Inflammatory mediators can promote each other to coregulate the immune inflammatory reaction. Inflammatory cytokines play a pivotal role in regulating the immune inflammatory reaction process. Chinese herbs and acupuncture can exert a protective effect against neuronal damage by cerebral ischemia by inhibiting the production and expression of inflammatory cytokines and adhesion molecules, effectively blocking the inflammatory reaction and reducing the apoptosis of nerve cells.

Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells.

Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury.

Effects of Panax notoginseng saponins on proliferation and differentiation of rat hippocampal neural stem cells.

We aimed to investigate the effects of Panax notoginseng saponins (PNS) on proliferation, differentiation and self-renewal of rat hippocampal neural stem cells (NSCs) in vitro. Rat hippocampal NSCs were isolated from post-natal day 1 (P1) rats and cultured in a serum-free medium. The neurospheres were identified by the expressions of nestin, class III ß-tublin (Tuj-1) and glial fibrillary acid protein (GFAP). The cells were given PNS and subjected to oxygen glucose deprivation (OGD) as an in vitro model of brain ischemia reperfusion. The proliferation of NSCs was determined by MTT colorimetry, nestin/BrdU immunofluorescent double-labeling and RT-PCR. Differentiation of NSCs was assessed by immunofluorescent double-labeling of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1. The primary cells and the first two passages of cells formed certain amount of neurospheres, the cells derived from a single cell clone also formed neurospheres. Nestin, BrdU, GFAP and Tuj-1-positive cells appeared in those neurospheres. Compared to the control group, PNS significantly promoted NSC proliferation and the expression of nestin/BrdU, and also enhanced Tuj-1, vimentin, and nestin mRNA expressions in hippocampal NSCs. PNS significantly increased area density, optical density and numbers of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1 positive cells following OGD. These results indicate that PNS can promote proliferation and differentiation of hippocampus NCSs in vitro after OGD, suggesting its potential benefits on neurogenesis and neuroregeneration in brain ischemic injury.

[A new opinion on detection methods for pulse shape and pulse force].

Pulse shape and pulse force are difficult to detect in pulse taking study. But the application of visualized technology extends the space acquisition of pulse taking information, and it is possible to realize the objective detection of pulse shape and pulse force. Rational research thoughts and strategies could be informed by combining image information and other data, and it is a necessary method in implementing the objective detection of pulse.

[Effect of Bnxia Xexin Decoction and its disassembled recipes on somatostatin in rats with stress gastric ulcer].

OBJECTIVE: To explore the acting mechanism of Banxia Xiexin Decoction (BXD) and its disassembled recipes on stress gastric ulcer, for providing references to the scientific researches on the assembling rule of BXD. METHODS: The rat model of acute gastric ulcer was established by water immersion-restraint stress. The experimental rats were divided into the normal group, the model group and the treated groups treated with BXD and its disassembled recipes respectively to observe the therapeutic efficacy and the changes of somatostatin (SS) expression in brain and gastric tissues. RESULTS: In the model group, the SS expression was 0.0237 +/- 0.0056 in brain and 0.0171 +/- 0.0053 in gastric tissue respectively, which was significantly lower than those in the normal group (0.0305 +/- 0.0024 and 0.0282 +/- 0.0037) respectively. Compared to the model group, the two indexes in rats treated with full BXD were 0.0294 +/- 0.0050 and 0.0288 +/- 0.0027, treated with sweet flavor portion were 0.0314 +/- 0.0027 and 0.0219 +/- 0.0059, all showed increase of SS expression, and the increment was more significant in the former. CONCLUSION: BXD can increase the expression of SS to realize its therapeutic efficacy, and the recipe was assembled rationally.

[A review of experimental designs of compound compatibility law of traditional Chinese medicine].

The paper discussed a variety of experimental designs of compound compatibility law of traditional Chinese medicine (TCM): study of whole formula and different ingredients of formula. The latter includes study of single ingredient, study of functional ingredient group, orthogonal design, clustering analysis, homogeneous design, factorial analysis and so on. It was proposed that experimental designs of formula should be based on the theory of TCM, and combined with modern sciences.