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This study investigates the protective role of IMM-H004, a novel coumarin derivative, on hepatic ischemia-reperfusion injury (HIRI) in mice. All animal experiments in this paper have been approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The experimental animals were divided into three groups, including sham group, model group, and IMM-H004 treatment group. Serum biochemical indicators were detected and H&E staining was used to assess liver damage. Real-time quantitative PCR (qPCR) was performed to analysis the mRNA content of inflammatory factors. Immunohistochemistry and immunofluorescence were used to observe neutrophil infiltration. Western blot was used to examine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and interleukin-1β (IL-1β). The results showed that IMM-H004 could significantly reduce the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH). H&E results showed IMM-H004 could alleviate liver damage caused by HIRI. The mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-6 (IL-6) were decreased by IMM-H004 administration. Meanwhile, IMM-H004 could markedly inhibit neutrophil infiltration. Furthermore, IMM-H004 could significantly down-regulate the protein expression of NLRP3, ASC, caspase-1, and IL-1β, inhibiting the activation of NLRP3 inflammasome pathway. Our results confirmed that IMM-H004 could protect mice from HIRI and provide a theoretical foundation for IMM-H004 application for treating HIRI.
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A mouse model of cholestatic liver fibrosis was established by bile duct ligation (BDL) method. The effect of ginsenoside Rg1 in the disease progress and the mechanism of cholestatic liver fibrosis are investigated in this mouse model. All animal experiments in this paper have been approved by the Unit Ethics Committee. Analysis of serum biochemical indicators and pathological sections assessed liver function, liver damage and fibrosis in mice. Immunohistochemistry and Western blot assays were used to detect vascular cell adhesion molecule-1 (VCAM-1) in BDL-induced mice. Nuclear factor-κB (NF-κB) and inflammatory factors were detected to investigate related mechanism of Rg1. The results showed that expression of VCAM-1 was up-regulated and peaked at 7 days, followed by decreased expression, but still efficiently expressed compared to the sham-operated group. Compared with the model group, 40 mg·kg-1·d-1 Rg1 treatment reduced serum aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin (T.Bili) levels (P<0.05 or P<0.01) and liver function damage,alleviated BDL-induced liver fibrosis, significantly down-regulated the expression of VCAM-1 (P<0.05), and inhibited the inflammatory response. In addition, Rg1 significantly reduced NF-κB p65 level in the cellular nucleus (P<0.05). This study demonstrates that VCAM-1 is dynamically altered during BDL-induced liver fibrosis. Rg1 could dampen inflammation and alleviate cholestatic liver fibrosis via regulation of the NF-κB/VCAM-1 pathway. The results provide an experimental basis for Rg1 application for treating liver fibrosis.
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Objective:Stems,petioles,stem sections with axillary and leaves of Scrophularia ningpoensis were taken as the material in vitro to screen out the suitable plantlet regeneration system and optimal exercising seedling conditions. Method:Different explants,hormones and concentrations on the induction and proliferation of cluster bud were studied by L16(45) orthogonal test. One factor analysis of variance (ANOVA) was made on the induction of adventitious buds rooted with different concentrations of hormones. At the same time,different substrates,watering cycles and transition modes were selected to optimize key technologies of exercising seedlings of S. ningpoensis. Result:Stem sections with axillary was the best explant,which was followed by stems,leaves and petioles. The suitable media for the induction of adventitious buds was MS+6-BA 0.5 mg·L-1+NAA 0.2 mg·L-1,with the induction rate of 100.0% and the proliferation multiple of 9.84.The suitable media for root induction was 1/2 MS+IBA 0.2 mg·L-1,with the rooting rate of 100.0% and the number of roots of 39.45.For matrix,they were transplanted with nutrient soil,vermiculite and perlite (5:2:1) as the media,to keep proper matching of fertility,permeability and water retention. The container seedlings can grow well,and the survival rate was more than 95% when they were watered every 2 days,the acclimatization of plantlets took 20 days indoor and 10 days in shaded greenhouses. Conclusion:The clonal propagation system of S. ningpoensis was established to provide an effective way for the efficient,rapid and steady plantlet regeneration,the breeding of high-quality seedlings and the suitable exercising seedling conditions of S. ningpoensis.
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Polygalae Radix and Acori Tatarinowii Rhizoma were first recorded in Shennong's Herbal Classic. Both of them can "improve people's memory". Long-term administration can make body light and macrobian. They have often been used as couplet medicines and the core combination of nootropic and memory improvement prescriptions. At present, traditional Chinese medicine clinicians believes that the principle of Polygalae Radix and Acori Tatarinowii Rhizoma in improving memory or intelligence is to supplement the deficiency, remove phlegm and unblock nine orifices, with sufficient evidences for the traditional theory. However, its material basis and mechanism for improving memory have not been fully elucidated. In this paper, we searched the literatures about pharmacological and pharmacodynamics mechanism of Polygalae Radix,Acori Tatarinowii Rhizoma and their chemical components on nervous system in recent ten years from Pubmed database and CNKI. The main material basis for improving memory of Polygalae Radix-saponins, oligosaccharides and alone, the main material basis for improving memory of Acori Tatarinowii Rhizoma-α-asarone,β-asarone and eugenol, the changes of the quality and quantity of the active substances after combination, and the mechanism of improving memory of the single drugs and their couplet medicines, such as scavenging free radicals, regulating cholinergic system, clearing β-amyloid protein(Aβ), decreasing the level of phosphorylation of Tau protein, improving the rate of apoptosis and regulating synaptic plasticity, were systematically collected, analyzed and summarized. In view of the current research situation, this paper points out the possible shortcomings, with the aim to further explore the mechanism of Polygalae Radix combined with Acori Tatarinowii Rhizoma with the mechanism of "1+1>2".
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Stroke is the leading cause of death in Chinese currently, characterized by high incidence, high morbidity and high mortality, of which ischemic stroke accounted for 87%. However, it still lacks the ideal treatment. Stem cells are a class of cells with self-renewal ability and high differentiation potential. Stem cell transplantation breaks the irreversibility of nerve injury to post-stroke infarct area. However, stem cells also requiring specific chemokines to promote their directional migration to the injured tissue site after transplanted. Stromal cell-derived factor-1α (SDF-1α) is one of the typical chemokines. SDF-1α and its specific receptor CXCR4 can induce its migration, increase its proliferation and promote angiogenesis. In this paper, the role of SDF-1α/CXCR4 axis in the treatment of ischemic stroke in stem cells is reviewed in order to provide a theoretical basis for enhancing the efficacy of stem cell transplantation in the treatment of ischemic stroke.
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The main ingredient of extractable petroleum ether of Polyrhachis vicina Roger (EPPR) is octadecene unsaturated fatty acids. Mounting evidence supports that N-3 polyunsaturated fatty acids can attenuate neuroinflammation, reduce oxidative stress, then protect neurons. In order to explore the effect of EPPR on the inflammatory response of depressed rats, the model of depression was established by chronic unpredictable mild stress (CUMS). Sucrose preference test, forced swimming test were employed to investigate the anti-depressive effect of EPPR in rat. The activation of glial cells and astrocytes in the prefrontal cortex of depressed rats was observed by immunofluorescence. The levels of inflammatory factors were measured by Quantitative Real-time PCR. NF-κB was detected by immunoblotting. EPPR could significantly improve the depressive behavior of rats, decrease NF-κB translocation to the compartment of nucleus, down-regulate the pro-inflammatory cytokines IL-1β, TNF-α and indoleamine 2,3-dioxygenase (IDO) gene expression levels, inhibit the activation of microglia and astrocytes in depressed rats. These results suggest that EPPR could notably ameliorate inflammation induced by chronic stress, and the protective effect might be linked to the regulation of NF-κB p65.
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Ginsenoside Rg1 is a common component of a variety of stroke and diabetes medications, but its anti-stroke effect in diabetic patients is unclear. The aim of this research is to test the therapeutic effect of Rg1 on ischemic stroke in diabetic rats, and elucidate the effect of Rg1 on post-stroke neuro-inflammation. Rg1 significantly reduced the infarct area percent, increased the behavioral score, and reduced the brain water content in diabetic rats after stroke in the diabetic rats. Rg1 reduced the post-stroke inflammatory response and decreased the expression of high mobility group box1 (HMGB1) protein significantly. Elevated level of HMGB1 activity by supplementing exogenous HMGB1 protein abolished the anti-stroke effect of Rg1, which suggests that HMGB1 is involved into the anti-stroke effect of Rg1 in the diabetic rats.
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The impact of Rg1 in the disease progress and pathology of amyotrophic lateral sclerosis (ALS) was investigated in mouse model (SOD1 G93A). Body weight and survival rate were monitored to check the course of disease. Rotarod test was used to evaluate the coordination of muscle movement. Toluidine blue staining and immunofluorescence were used to check the effect of Rg1 on motor neuron and microglia. The expression of oxidative stress related protein Nrf2 and the miRNA were tested to investigate the mechanism of Rg1. We found that 20 mg·kg-1·d-1 Rg1 significantly postponed the disease onset and process, improved the motor syndrome, reduced the loss of motor neuron and inhibited the activation of microglia cells. Rg1 inhibited the aggregation of miR-153 in the spinal cord of ALS mice, which relieved the inhibition of Nrf2 and contributed to its up-regulation in the activation of HO-1 anti-oxidative signal pathway. Our study confirmed that Rg1 could protect ALS mice from oxidative damage through the up-regulation of miR-153/Nrf2/HO-1, which provides a theoretical foundation for Rg1 application to the ALS treatment.
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This study was designed to test the effect of short-term high-fat diet feeding on the cognitive impairment in a rat model of Alzheimer's disease. After establishment of Alzheimer's disease model, the rats were fed on a high-fat diet, and subjected to water maze (Morris water maze, MWM) behavioral test for learning and memory ability. Western blot was used to detect the expression of caspase-1 pathway. The results showed that short-term high-fat diet could alleviate the damage of okada acid in Morris water maze. The mechanism may be mediated by the regulation of the NLRP3/caspase-1 signaling pathway, which alleviates neuronal damage, resulting in a protective effect.
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Ginsenoside Rg1 is one of the main active components of ginseng with various pharmacological activities including anti-inflammatory, anti-oxidation, anti-aging, anti-tumor and anti-apoptosis. Ginsenoside Rg1 plays a protective role in multiple tissues and organs, which shows the multiple targeting properties of the pharmacological effects. Recently, a number of studies have demonstrated that ginsenoside Rg1 has a protective role in the liver due to its multiple pharmacological effects. In chemical liver injury models, or in other liver injury models, ginsenoside Rg1 can alleviate liver necrosis induced by oxidative stress and inflam-mation. This article provides a review of the recent studies on the efficacy of ginsenoside Rg1 in the treatment of various liver damage and the molecular mechanism.
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Aspirin (AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun-dred million,but many persons were died from interned bleeding.We found salvianolic acids (salvianolic acid B 57％,salvianolic acid A 1％,rosmarinic acid,35％,SA)was much better than AS in preventing in-cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows: (1) both AS and AS have same anti-platelet aggregation ef-fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2only;(2)For established thrombosis,SA could dissolved it, AS showed no effect. The thrombolytic mechanism of SA has been elucidated. (3) In SHRSP rats, the incidence of stroke and death rate in SA group was distinct less that of AS group;(4)In MCAO rats,SA and Sal B decreased stroke index and neural im-pairment. AS showed no such ability; (5) There is microcirculatory disturbance in cardio-cerebral isch-emic disease. SA could improve circulatory disturbance induced by LPS, adrenaline, ROS and I/r. there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis-turbance models;(6)Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease. SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin)and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7)Thereis overproduc-tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro-bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8)According to literatures,1/3 patients who take AS for long time will have hemorrhage, we found in normal rats and mice (coagulating and hemodynamics) SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases; (9) As well known, neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation, inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre-ventive effect on cardio-cerebral vascular diseases. SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in-hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.
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OBJECTIVE To study the differentiation of PC12 cells induced by total salvianolic acid (Tsa) and the mechanism. METHODS MTT assay was used to detect the effect of Tsa 0.01, 0.1 and 1.0 μg·L-1on proliferation of PC12 cells and on the cells damaged by oxygen and glucose deprivation (OGD).The number of projections of PC12 cells was statistically analyzed.Western blotting was applied to detect the levels of microtubule-associated protein2 (MAP-2), extracellular signal-regulated kinase1/2 (ERK1/2), phosphorylated ERK1/2(p-ERK1/2), mitogen-activated protein kinase kinase1/2(MEK1/2) and p-MEK1/2 proteins.MEK inhibitor U0126 was examined for its effect on expressions of p-ERK1/2 and ERK1/2 protein in PC12 cells induced by Tsa 1.0 μg·L-1.RESULTS Compared with normal control group, Tsa 1.0 μg·L-1could promote PC12 cell proliferation, and the survival rate was increased by 90%, but the survival rate of PC12 cells was not affected by Tsa 0.01 or 0.1 μg·L-1. Compared with OGD injured group,PC12 cells injured by OGD could be repaired by Tsa 0.1 or 1.0 μg·L-1,and the survival rate was increased to (47.7±1.8)% and (63.2±13.0)%, respectively (P<0.05, P<0.01). Compared with normal control group,Tsa 0.01,0.1 and 1.0 μg·L-1could promote the growth of PC12 cell projections (P<0.01). Western blotting results showed that Tsa could promote the expressions of MAP-2, p-ERK1/2 and p-MEK1/2 proteins, and this effect could be blocked by U0126 inhibitor (P<0.01). CONCLUSION Tsa can induce the proliferation and differentiation of PC12 cells, the mechanism of which is possibly the activation of p-MEK and p-ERK1/2.
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Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.
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Clausenamide (clau) is one of seven novel compounds isolated from Clausena lansium (Lour) skeels. Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers. After identification of the configuration of these enantiomers, the synthesis of 16 enantiomers, including optically active clau and (+) and (-)clau was carried out. During this study, many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated. Production scale is now sufficient to meet the needs of clinical practice. In a pharmacological study numerous models and indicators showed that (-)clau is the active enantiomer, while (+)clau is inactive and elicits greater toxicity than (-)clau. The principal pharmacological effects of (-)clau are to increase cognition, demonstrated in ten models of memory impairment, as well as to inhibit β-amyloid (Aβ) toxicity, blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein. This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia. (-)Clau is considered to be a promising drug candidate for treatment of Alzheimer׳s disease and other neurodegenerative disorders.
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To observe the effect of various doses of oil of Piper longum unsaponifiable matter (OPUM) to cholesterol gallstones in experimental mice. C57BL/6 mice (n = 60) were randomly divided into 6 groups: control group, model group, OPUM (15, 30 and 60 mg x kg(-1)) group and ursodeoxycholic acid (UDCA, 60 mg x kg(-1)) group, administered for 10 weeks. The level of serum lipid and liver function enzymes were tested. The gallbladder was removed and bile was obtained by centrifugation. Next, the levels of the bile total cholesterol (TC), phospholipid (PL) and bile acid (TBA) were measured. The indicators of lipid peroxidation were determined and cholesterol saturation index (CSI) was calculated. The liver histological changes were observed by HE staining. The results showed that serum TC, TG (triglycerides) and AST (aspartate transaminase) contents, gallbladder cholesterol crystallization and CSI increased significantly (P < 0.05). In addition, the activity of SOD decreased significantly and MDA content increased significantly in liver (P < 0.05). HE staining results showed that the hepatic cord disorder and intracellular lipid droplets increased significantly. All results indicate that lithogenic diet lead to the formation of cholesterol gallstones. In OPUM (30 and 60 mg x kg(-1)) group, serum TC, TG and AST content, gallbladder cholesterol crystallization and CSI decreased significantly, the activity of SOD increased significantly and MDA content decreased significantly. HE staining results showed that OPUM can improve the morphology of liver cell, reduce the degree of hepatic cord disorders and restore the cell morphology close to normal. The cause of OPUM prevents cholesterol gallstone formation maybe due to protect the integrity of the liver cells, lower CSI, and reduce cholesterol crystal formation and hence prevent cholesterol gallstone formation.
Subject(s)
Animals , Male , Mice , Aspartate Aminotransferases , Blood , Bile , Chemistry , Cholesterol , Blood , Gallbladder , Gallstones , Metabolism , Liver , Metabolism , Pathology , Malondialdehyde , Metabolism , Mice, Inbred C57BL , Piper , Chemistry , Plant Oils , Pharmacology , Plants, Medicinal , Chemistry , Random Allocation , Superoxide Dismutase , Metabolism , Triglycerides , BloodABSTRACT
This study is to investigate the influence and the expression of CMTM family of testosterone on spermatogenesis suppression in the male rats treated by gossypol and cyclophosphamide. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) were administered to male rats to induce spermatogenesis suppression. Testosterone propionate was administrated at the dose of 5 mg kg(-1) every other day for 6 times. Sperm was collected from the left caudal epididymis, the count and motility of sperm were analyzed by CASA. Morphological change of testis tissue was observed with HE staining. The expression of CMTM family was examined by Western blotting assay. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) decreased the count and motility of sperm, and the pathological change of testis tissue was also observed. But, testosterone (5 mg kg(-1)) had positive effect. Furthermore, CMTM4 down-expressed remarkably in the gossypol and cyclophosphamide treated rats, the expression of the CMTM4 was up-expressed after testosterone administration. On the contrary, the expression of CMTM2 increased significantly only in gossypol treated male rats, but not in cyclophosphamide treated male rats. The expression of CMTM2 was down-expressed after testosterone administration. However, no obvious change of CMTM2 was observed in cyclophosphamide treated rats. Testosterone did not influence the expression of CKLF1, CMTM3 and CMTM5, the CMTM6, CMTM7 and CMTM8 of CMTM family were not detected in testis tissue. These demonstrated that the spermatogenesis effect of testosterone (5 mg kg(-1)) was associated with the expression of CMTM family, and CMTM2 and CMTM4 may take part in the spermatogenesis process.
Subject(s)
Animals , Male , Rats , Cyclophosphamide , Toxicity , Gene Expression Regulation , Gossypol , Toxicity , Membrane Proteins , Metabolism , Rats, Wistar , Sperm Count , Sperm Motility , Spermatogenesis , Testis , Metabolism , Pathology , Testosterone , PharmacologyABSTRACT
In recent decades, scientists in Asian and Western countries have been paying great attention to ginseng research. Today, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. Ginsenosides show biological activities only after being deglycosylated by intestinal bacteria. Aglycone protopanaxadiol and protopanaxatriol show the highest bioactivities. According to literature, the noticeable action of ginseng is that of delaying aging and especially increasing the nootropic effect, and it was found for the first time that Rg1 could increase hippocampal neurogenesis in vitro and in vivo under physiological and pathological circumstances. This is one of primary mechanisms underlying many of its pharmacological actions on the central nervous system. Rg1 was further shown to improve learning and memory in normal rats and mice. The nootropic signaling pathway has also been carried out in normal rats, and the Rg1-induced signaling pathway is similar to the memory formation that occurs in mammals, suggesting that Rg1 may have a potential effect in increasing intellectual capacity in normal people. Comparisons of chemical structures and pharmacologic functions between Panax ginseng and Panax quiquefolium were carried out by many scientists. The conclusion is that each has its own characteristics. There is no superiority or inferiority to the other.