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Chemokines play pleiotropic roles in the pathology of Alzheimer′s disease(AD),a chronic inflammatory disease of central nervous system.The neuropathological features of AD include neurofibrillary tangles,amyloid plaques,neuroinflammation,and neuronal synaptic loss.Chemokines are involved in the pathogenesis of AD by activating or regulating inflammatory cells or glial cells,playing dual key roles of the pro-and anti-inflammatory properties in AD.The levels of chemokines in serum,cerebrospinal fluid and brain tissue of AD patients are changed accordingly.This review summarizes the role of chemokines and their receptors in AD in the biological activities and unveils the changing rules,aiming to provide new strategies for clinical treatment of AD.
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Aim To research the synergistic effect of hyperlipoproteinemia and Aβ in the processing of Alzheimer′s disease.Methods Seventy SD rats were randomly divided into seven groups, and dealt with D-gal(hypodermic injection), hyperlipemia diet, microinjection into both side of CA1 section in hippocampus, independently.Morris water maze(MWM) test was used to evaluate the spatial memory impairments.Tau and tau(pThr181) pathology in the hippocampus were detected using Western blot and immunohistochemistry.Nissl′s staining was used to detect cell apoptosis.Results Aβ25-35-treated rats showed significant impairments of spatial memory in MWM test, especially in the group of D-gal+Aβ25-35+HLD(P<0.01).Furthermore, these rats treated with Aβ25-35, D-gal, and hyperlipemia diet, exhibited significantly increased phosphorylation of tau, particularly in the Thr181 site.Conclusion Hyperlipoproteinemia is the risk factor for older person, which could strengthen the toxic effect of Aβ, and promote phosphorylation of tau.
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Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity (>0.995) within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80-120%. The excretion recoveries of Rg1, ginsenoside Rh1 (Rh1), and protopanaxatriol (Ppt) in bile, urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were 40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile. Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.
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Aim To investigate the antidepressive-like effect of ethyl alcohol extract of Polyrhachis vicina Rog-er(EAPR),and its mechanism.Methods EAPR was prepared by ethanol extraction.Its anti-depressive effect was investigated by tail suspension test (TST) and forced swimming test (FST).Furthermore,repeated doses of reserpine was used for preparing the depres-sive rats.Results EAPR has definitely anti-depres-sive effect,as evidenced by the decreased immobility time in FST and TST at the doses of 8 and 4 g·kg -1 (P <0.05).In the repeated reserpine evoked depres-sive rats,EAPR antagonized the symptoms induced by monoamines depletion and attenuated the anhedonia, as manifested by reversed hypothermia,akinesia and sucrose consumption at the doses of 8 and 2 g·kg -1 (P <0.05,P <0.01).Neuro-chemical studies showed that AFPR significantly increased the concentration of monoamines,including 5-hydroxytryptamine (5-HT) and noradrenaline(NA)at the dose of 8 g·kg -1 (P <0.05),and had no effect on normal rats .Furthermore, EAPR increased the activity of superoxide dismutase (SOD)in serum,hippocampus and cerebral cortex at the dose of 8 g·kg -1 (P <0.05).Conclusion EA-PR possesses the definite antidep ressive properties, connected with the regulation of neurotransmitter me-tabolism and the nerve cells antioxidant effect.
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Pyk2(Proline-rich tyrosine kinase 2) is an important member of focal adhesion kinase family. Pyk2 is highly ex-pressed in the central nervous system and the hematopoietic sys-tem . Pyk 2 can trigger a variety of SH 2 domain-containing pro- teins to phosphorylate their substrates, thus it can participate in the regulations including ion channel activation, stress response, cell adhesion, cytoskeleton reorganization, vesicle transport and so on. Through the regulations above, the ability of cell migra-tion, survival, proliferation changes accordingly, suggesting that Pyk2 in many important regulatory processes may become a tar-get for clinical effects. Current drug development for Pyk2 main- ly focuses on cancer, osteoporosis and immune response. This review illustrates the domain structure, regulatory mechanisms, potential drug targets, and the drug development of Pyk2 based on the above three fields, which will provide a theoretical basis for clinical treatment.
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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.
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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.
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Aim To elucidate the biochemical mechanism of gossypol in inducing the decline of sperm quality.Methods Gossypol was administered orally at the dose of 50 mg?kg-1/2 d for two weeks.Then,the sperm was collected from the left caudal epididymis and was analysed by CASA.The morphological changeand the concentration of nitric oxide(NO)in testes as well as the level of hormone〔follicle-stimulating hormone(FSH)〕,luteotrophic hormone(LH),testosterone(T)in serum were assayed.Results Gossypol could induce the decrease of sperm number and sperm quality.The concentration of NO in testes increased significantly.Among the three kind of hormone,only the concentration of T showed decrease after the oral administration of gossypol.NA1108 could antagonize the decline of sperm quality damaged by gossypol and decrease the content of NO in testes.Conclusions The concentration of NO in testes beyond normal value was one of the toxic mechanism of gossypol that contributed to the inhibition of spermatogenesis.Some drugs with the ability to reduce NO content in testes could also increase sperm quality.