[Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining].

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

Mesenchymal Stem Cell-Mediated Mitochondrial Transfer: a Therapeutic Approach for Ischemic Stroke.

Stroke is the leading cause of death and adult disability worldwide. Mitochondrial dysfunction is one of the hallmarks of stroke-induced neuronal death, and maintaining mitochondrial function is essential in cell survival and neurological progress following ischemic stroke. Stem cell-mediated mitochondrial transfer represents an emerging therapeutic approach for ischemic stroke. Accumulating evidence suggests that mesenchymal stem cells (MSCs) can directly transfer healthy mitochondria to damaged cells, and rescue mitochondrial damage-provoked tissue degeneration. This review summarizes the research on MSCs-mediated mitochondrial transfer as a therapeutic strategy against ischemic stroke.

SIRT1-mediated deacetylation of NF-κB inhibits the MLCK/MLC2 pathway and the expression of ET-1, thus alleviating the development of coronary artery spasm.

Coronary artery spasm (CAS) is an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion. The cardioprotective effect of sirtuin-1 (SIRT1) has been extensively highlighted in coronary artery diseases. The aims within this study include the investigation of the molecular mechanism by which SIRT1 alleviates CAS. SIRT1 expression was first determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in an endothelin-1 (ET-1)-induced rat CAS model. Interaction among SIRT1, nuclear factor-kappaB (NF-κB), myosin light chain kinase/myosin light chain-2 (MLCK/MLC2), and ET-1 was analyzed using luciferase reporter assay, RT-qPCR, and Western blot analysis. After ectopic expression and depletion experiments in vascular smooth muscle cells (VSMCs), contraction and proliferation of VSMCs and expression of contraction-related proteins (α-SMA, calponin, and SM22α) were measured by collagen gel contraction, 5-ethynyl-2'-deoxyuridine (EdU) assay, RT-qPCR, and Western blot analysis. The obtained results showed that SIRT1 expression was reduced in rat CAS models. However, overexpression of SIRT1 inhibited the contraction and proliferation of VSMCs in vitro. Mechanistic investigation indicated that SIRT1 inhibited NF-κB expression through deacetylation. Moreover, NF-κB could activate the MLCK/MLC2 pathway and upregulate ET-1 expression by binding to their promoter regions, thus inducing VSMC contraction and proliferation in vitro. In vivo experimental results also revealed that SIRT1 alleviated CAS through regulation of the NF-κB/MLCK/MLC2/ET-1 signaling axis. Collectively, our data suggested that SIRT1 could mediate the deacetylation of NF-κB, disrupt the MLCK/MLC2 pathway, and inhibit the expression of ET-1 to relieve CAS, providing a theoretical basis for the prospect of CAS treatment and prevention.NEW & NOTEWORTHY Rat coronary artery spasm models exhibit reduced expression of SIRT1. Overexpression of SIRT1 inhibits contraction and proliferation of VSMCs. SIRT1 inhibits NF-κB through deacetylation to modulate VSMC contraction and proliferation. NF-κB activates the MLCK/MLC2 pathway. NF-κB upregulates ET-1 to modulate VSMC contraction and proliferation.

Effects of velvet antler polypeptides on Alzheimer's disease cell model via miR-613 HDAC6 pathway.

To study the effect of velvet antler polypeptides (VAP) on Alzheimer's disease (AD) cell model, Aß25-35 was used to induce SK-N-SH cells to obtain AD cell model. The MDA, SOD, GSH-Px levels were determined using relevant kits. Flow cytometry was conducted to detect apoptosis, Western blot was employed to measure Bcl-2, Bax, HDAC6 protein expression, and qPCR was used to assay microRNA (miR)-613 and HDAC6 mRNA levels. Target Scan prediction combined with dual luciferase reporting experiments was conducted to analyze the targeting relationship between miR-613 and HDAC6. miR-613 was transfected in SK-N-SH cells; Alternatively, anti-miR-613 was transfected, followed by Aß25-35 and 80 mg/L of VAP. The AD model cells showed increased MDA content, apoptosis rate, Bax protein expression, HDAC6 mRNA and protein expression, but lower SOD, GSH-Px activities, Bcl-2 protein level, and miR-613 expression (p<0.05). VAP reduced MDA content, apoptosis rate, Bax protein expression, HDAC6 mRNA and protein expression, but enhanced SOD, GSH-Px activities, Bcl-2 protein level, and miR-613 expression (p<0.05). Over-expression of miR-613 increased SOD, GSH-Px activities, and Bcl-2 protein expression in AD model cells, but reduced HDAC6 protein levels, MDA content, apoptosis rate, and Bax protein levels (p<0.05). VAP may regulate Aß25-35-induced apoptosis so as to treat Alzheimer's disease.

Osteoblast-derived lipocalin-2 regulated by miRNA-96-5p/Foxo1 advances the progression of Alzheimer's disease.

Aim: Alzheimer's disease (AD) is the most frequent cause of dementia and characterized by the accumulation of ß-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.

Downregulation of microRNA-135b promotes atherosclerotic plaque stabilization in atherosclerotic mice by upregulating erythropoietin receptor.

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA-135b (miR-135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR-135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR-135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR-135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR-135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR-135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR-135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR-135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.

Medicine in Future and Advantages of Integrated Chinese and Western Medicine.

The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.

Effects of microRNA-10a on synapse remodeling in hippocampal neurons and neuronal cell proliferation and apoptosis through the BDNF-TrkB signaling pathway in a rat model of Alzheimer's disease.

The aim of this study was to research the effects of microRNA-10a (miR-10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF-TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR-10a mimics, miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT-qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR-10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR-10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a inhibitors group presented an opposite trend to the miR-10a mimics and K252a groups. The synapse was complete and abundant in the miR-10a inhibitors group while disappeared in the miR-10a mimics and K252a groups. The results indicated that miR-10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway.

[Experimental study on effect of anhydroicaritin phytosomes in preventing and treating bone loss and enhancing bone quality in ovariectomized osteoporosis rats].

OBJECTIVE: To explore the effect of anhydroicaritin phytosomes (AIP) in preventing and treating bone loss and enhancing bone quality in ovariectomized osteoporosis rats. METHOD: Seventy-two SD female rats were randomly divided into 6 groups: the sham group, the model group, the estrogen group and AIP groups (low, middle, high). The sham group was only sham operated, and the remaining five groups were ovariectomized. One week after the ovariectomy, the rats were given 17 beta-estrogen and AIP (15, 30, 60 mg x kg(-1)) for consecutively three months, during which period their serum calcium (s-Ca), serum phosphorus(s-P), alkaline phosphate (ALP), urine calcium (u-Ca), urine phosphorus(u-P), urinary deoxypyridinoline (D-Pyr) and creatinine (Cr) were detected. Subsequently, rats were sacrificed, and their thighbone, second lumbar vertebrate and forth lumbar vertebrate were collected to detect bone mineral density (BMD), bone calcium (b-Ca) and phosphorus (b-P), biomechanical properties and bone histomorphometric parameters. RESULT: Compared with the sham group, the model group showed a significant increase in serum ALP, u-Ca and D-Pyr /Cr, and reduction in BMD of femur, b-Ca and b-P, biomechanical properties (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/ TV), with metratrophia. Compared with the model group, ALP high and middle-dose groups and the estrogen group showed a decrease in serum ALP, u-Ca and D-Pyr/Cr, and growth in BMD of femur, b-Ca and b-P, biomechanical properties of the forth lumbar vertebrae (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/TV). The beta-estrogen group showed endometrial hyperplasia, whereas AIP groups showed no hyperplastic change. CONCLUSION: AIP could inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus.

Combined treatment with a traditional Chinese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) and alendronate improves bone microstructure in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis. AIM OF THE STUDY: The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats. MATERIALS AND METHODS: Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers. RESULTS: This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone. CONCLUSIONS: We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.

Effects of total flavonoids of Epimedium sagittatum on the mRNA expression of the estrogen receptor α and ß in hypothalamus and hippocampus in ovariectomized rats.

OBJECTIVE: To explore the effect of total flavonoids of Epimedium sagittatum (TFE) on the mRNA expressions of the estrogen receptor alpha (ERα) and estrogen receptor beta(ERß) in hippocampus and hypothalamus in ovariectomized (OVX) Sprague-Dawley(SD) rats, and the mechanism of TFE against postmenopausal osteoporosis. METHODS: Forty-eight female SD rats,aged 10-11 months old, were randomly divided into 4 groups: a sham group, an ovariectomy group (rats were bilaterally ovariectomized), a TFE group, and a 17ß-estradiol group (rats were fed with TFE and 17ß-estradiol for 4 months, respectively). The RT-PCR was performed to determine the mRNA expression of ERα and ERß in hypothalamus and hippocampus. RESULTS: Serum estradiol level, bone mineral density (BMD) of vertebra,wet weight of uterus, and the mRNA expressions of ERα and ERß in hypothalamus and hippocampus were markedly decreased in OVX rats, all of which were reversed by 17ß-estradiol treatment except the mRNA expression of ERß. Similar results were achieved by TFE treatment except the wet weight of uterus. CONCLUSION: TFE can improve BMD of vertebra in the OVX rats without side effects on the uterus. The mechanism may be related to increasing the mRNA expressions of ERα and ERß in hypothalamus and hippocampus.

[Research on relationship between tissue quantitative distribution of 3H-Achyranthes bidentata ecdysterone and channel-tropism of herbal drugs in mice].

OBJECTIVE: To study the relationship between tissue quantitative distribution and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and the channel-tropism of herbal drugs in mice. METHOD: 3H-achyranthes bidentata ecdysterone was used as a tracer agent and injected into mice by the caudal vein. In 36 hours, the contents of the tracer agent of samples involving 9 different tracing phases and organ or tissue were determined in order to observe the dynamic quantitative distribution and excretion and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and to understand the channel-tropism of herbal drugs achyranthes bidentata. RESULT: 3H-achyranthes bidentata ecdysterone of same organs in different tracing phases and the contents of 3H-achyranthes bidentata ecdysterone in same tracing phases of different organs were significantly different (P<0.01). 3H-achyranthes bidentata ecdysterone was mainly distributed, in the liver, kidney, adrenal gland, small intestine and lung. The concentration-time profiles of achyranthes bidentata ecdysterone in rats injected into mice by the caudal vein were shown to fit a two-compartment open model with half-lives of (778.65 +/- 12.36) min, the elimination of achyranthes bidentata ecdysterone from plasma was found to be in accord with linear kinetics. CONCLUSION: The above mentioned selective distribution of 3H-achyranthes bidentata ecdysterone basically coincides with the meridian affinity and zang fu selection of the traditional Chinese medicine drug Achyranthes bidentata. This study will provide a scientific basis for the channel-tropism of A. bidentata.

[The influence of the different components of nourishing kidney herbs on osteoporosis rats].

OBJECTIVE: To observe the influent of the different components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with Dexamethasona(DXM). METHOD: Models of three-month old SD female rats with osteoporosis here made by being fed with low calcium diet (containing calcium 0.2%) and distilled water, and injected with DXM 0.1 mg/100 g weight intramuscularly, twice a week. Then the osteoporosis rats were treated with different components of nourishing kidney herbs, and the change of calcium, phosphate, alkaline phosphatase(ALP), calcitonin(CT), PTH, CT/PTH, estrogen(E2), testosterone(T), T/E2 and bone section and bone quantitative morphology in these osteoporosis rats were observed. RESULT: The total components of nourishing kidney herbs could improve the general condition of osteoporosis rats, decrease PTH, increase CT, estrogen, testosterone, CT/PTH and T/E2. The total components of nourishing kidney herbs could improve osteoporotic state, promote bone formation, and inhibite bone resorption. But no effect of the A, B, C, D components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with DXM was found. CONCLUSION: It is possible that the purification and separation of these herbs weaken or destroy the integrative effect of nourishing kidney herbs or destroy effective components of nourishing kidney herbs during the process of purification and separation.