Effects of harpagide on nerve cell and caspase-independent apoptotic signaling pathway in MCAO mice / 中国药理学通报

Aim To study the effects of harpagide on hippocampal neurons, mitochondrial function and caspase-independent apoptosis pathway after cerebral ischemia in mice. Methods The middle cerebral ar-tery occlusion (MCAO ) was employed to establish MCAO model. After that,the mice were given harp-agide (4,8,12 mg·kg - 1 )and edaravone (3. 2 mg ·kg - 1 )by tail vein injection after MCAO immediate-ly,and the model and control mice were given equal a-mounts of saline by the same way. After MCAO for 6 h,the apoptosis rate of hippocampal neuron and the mitochondrial membrane potential (MMP)of MCAO mice were detected by flow cytometry. We observed the clarity of inner and outer membrane of the hipp-ocampal neuronal mitochondrial,the integrity of the mitochondrial cristae,the changes of matrix electron density of mitochondria,and mitochondria swelling by transmission electron microscopy. Western blot was employed to determine the expression of apoptosis in-duced factor (AIF)and endonuclease G (Endo G)in mitochondrion and pro-caspase-3 in endochylema. qPCR was employed to determine the expression of AIF and Endo G. Results Compared with control group, the apoptosis rate of hippocampal neuron of MCAO mice significantly increased(P < 0. 01),the MMP of hippocampal neuron significantly decreased and the mi-tochondrial ultrastructure of cerebral ischemic area was severely damaged, loosely arranged and obviously swollen;the expression of AIF and Endo G in mito-chondria of cerebral tissue of MCAO mice significantly decreased,and the releases of AIF and Endo G signifi-cantly increased(P < 0. 01);the expressions of AIF, Endo G mRNA were evidently up-regulated (P <0. 01). Compared with model group,each dose of harpagide could significantly decrease the apoptosis rate of hippocampal neurons of mice brain (P < 0 . 05 ,P < 0. 01);MMP markedly increased in hippocampal nerve cells(P < 0. 01);the ultrastructure of neuronal mitochondria was obviously improved. Compared with model group,harpagide (8,12 mg·kg - 1 )could sig-nificantly increase the expression of AIF and Endo G protein in mitochondria of mouse brain,and the release of mitochondrial AIF and Endo G protein decreased(P< 0. 05,P < 0. 01);harpagide (4 mg·kg - 1 )could significantly increase the expression of Endo G protein in mitochondria of mouse brain,and the release of En-do G protein markedly decreased (P < 0. 05);harp-agide (8,12 mg·kg - 1 )could significantly decrease the expression of AIF and Endo G mRNA in hippocam-pus of mice(P < 0. 05,P < 0. 01). Conclusion The protective effect of harpagide on MCAO may be related to the protective effects on cerebral nerve cells,the ac-tivity of the mitochondria and the inhibition of caspase-independent apoptotic signaling pathways.

Effects of spironolactone towards rabbit atrial remodeling with rapid pacing

This study aimed to observe the effects of spironolactone towards the rabbit atrial remodeling with rapid atrial pacing [RAP]. 30 rabbits were randomly divided into control group, RAP group and spironolactone group, with 10 rabbits in each group. RAP was performed at the speed of 800 beats/min for 8 h, atrial effective refractory period [AERP] was determined before and at the 1[st], 2[nd], 4[th], 6[th] and 8[th] of the pacing, the expressions of atrial muscular calcium channel alpha 1C subunit and beta 1 subunit mRNA were performed the RT-PCR detection, and ultrastructural changes of atrial myocytes were observed. AERP of RAP group shortened, with poor frequency adaptability; the expressions of calcium channel alpha 1C subunit and beta 1 subunit mRNA decreased 22% and 26%, respectively, when compared with the control group; ultrastructure of atrial myocytes changed significantly. AERP of spironotlactone group shortened less that RAP group, and the frequency adaptability was maintained, the decreased expressions of calcium channel alpha 1C subunit and beta 1 subunit mRNA significantly reduced. RAP could cause atrial remodeling, while spironolactone could inhibit RAPinduced atrial remodeling

Two new phenylpropanoids from Micromelum integerrimum / 中国天然药物

AIM@#To investigate the chemical and bioactive constituents from the stems and leaves of Micromelum integerrimum.@*METHOD@#The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and HPLC. Their structures were mainly elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. Their cytotoxicity and antimicrobial activities were tested by the SRB and turbidimetric methods, respectively.@*RESULTS@#Two new phenylpropanoids and two known coumarins were obtained, and their structures were identified as microintegerrin A (1), microintegerrin B (2), scopoletin (3), and scopolin (4). All of the compounds were tested for their cytotoxicity against three cancer cell lines (HeLa, A549, and BGC-823) and for antimicrobial activity against the fungus Candida albicans and the bacterium Staphylococcus aureus.@*CONCLUSION@#Two new phenylpropanoids 1 and 2 were isolated and identified from the stems and leaves of M. intgerrimum. None of the compounds showed cytotoxic or antimicrobial activity at the tested concentration of 20 μg·mL(-1).

Association between polymorphisms of CD28/ICOS gene in chromosome 2q33 region and both susceptibility to and severity of multiple sclerosis in Han people of south China / 中华神经医学杂志

Objective To investigate the polymorphisms of CD28 and COS genes in chromosome 2q33 region and susceptibility to and severity of multiple sclerosis (MS).Methods Eighty-three patients diagnosed as having MS from Han population of South China were studied; one hundred and ten patients with non-autoimmune diseases or healthy volunteers were selected as controls.DNA was obtained from peripheral venous blood; the polymorphisms of amplified productions (CD28 and ICOS genes) were detected by PCR-RFLP and analyzed by agarose gel electrophoresis.Immunofluorescent two-color flow cytometry was used to study the expressions of CD28 and ICOS genes of lymphocytes in the peripheral blood of these 2 groups. Results The genotype frequency of TT at ICOS-2394 site in patients with MS (33.7%) was significantly higher than that in controls (10.9%,P＜ 0.05), and the allele frequency of T in patient group (56.0%) was obviously higher than that in the controls (30.9%, P＜0.05). No marked combined effects were noted in the 3 SNPs (CD28-372, ICOS-2349 and ICOS-2119). TT genotype in the polymorphic site of ICOS-2394 was correlated to primary progressive MS, while CT genotype in the polymorphic site of ICOS-2394 was not correlated to secondary progressive MS. The genotype and allele frequencies of the 3 SNPs had no marked association with the severity of MS (P＞0.05). The levels of CD28 and ICOS gene expressions in lymphocytes of peripheral blood of patients with MS were significantly higher in patients than that in control group (P ＜ 0.05). Conclusion ICOS polymorphisms might be related to MS in Han population of South China,which suggests that ICOS might be one of genes having susceptibility to MS. No association between CD28 gene polymorphisms and susceptibility to MS is noted.

Effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigat the effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats.</p><p><b>METHOD</b>The rats were equally and randomly divided into six groups. Control, Tianwang Buxin decoction, P. grandiflorum-absenced Tianwang Buxin decoction, Radix S. miltiorrhizae, Radix S. miltiorrhizae and P. grandiflorum, P. grandiflorum. The effect on brain meninx vascullosa in rats were observed through an inverted microscope, doppler perfusion imager and blood reheology measurement meter.</p><p><b>RESULT</b>The effect of Tianwang Buxin decoction was best among the six groups in dilatation of the diameter of arterial and venule, and velocity of blood flow. The effect of Radix Salviae miltiorrhizae was postponed and decreased when P. grandflorum was removed of from this prescription. However, it was minimal advance of blood apparent-viscosity for Tianwang Buxin decoction.</p><p><b>CONCLUSION</b>It is indeed that P. grandiflorum leads S. miltiorrhizae to main and collaterall channel, goes up like the boat and oar and aims to reinforce affection for the other drugs of Tianwang Buxin decoction to mprove the microcirculation of brain meninx vascullosa of rats.</p>