Objective: To explore the effects of ligustrazine on proteinuria, serumcreati-nine, urinary thromboxane A_2(TxA_2), metabolism of prostacyclinI_2(PGI_2)―6-keto-PGF_(1α), and renal pathological changes of SD rats wit...Objective: To explore the effects of ligustrazine on proteinuria, serumcreati-nine, urinary thromboxane A_2(TxA_2), metabolism of prostacyclinI_2(PGI_2)―6-keto-PGF_(1α), and renal pathological changes of SD rats with passive Hermannnephritis (PHN). Methods: The PHN model was induced by intravenous injection of rabbit anti-ratrenal tubular epithelial antigen (Tub―Ag) an-tiserum to SD rats. I. P. administration ofligustrazine to rats was given every 2 d for 1 to 5 weeks. The proteinuria, creatinine, TxA_2 and6-keto-PGF_(1α) were measured by sulfosaticylic acid, picric acid, and direct radioimmunoassayrespectively. The renal pathological changes were observed under light microscope, electronicmicroscope and by direct immunofluorescence staining rabbit and rat IgG. Results: The PHN ratstreated with ligustrazine had significantly less proteinuria, serum creatinine, urinary TxA_2 andpathological changes of kidney, and more urinary 6-keto-PGF_(1α) than those without administrationof ligustrazine. Conclusion: Ligustrazine decreases proteinuria, urinary TxA_2, and renal tissueinjury and increases urinary 6-keto-PGF_(1α). These data indicate that ligustrazine may modulatethe balance of TxA_2 and PG I_2 in rat PHN model and can be used for preventing and treatingmembranous glomerulonephritis.展开更多
Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustraz...Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.展开更多
BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to exp...BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.展开更多
To search for potent anti-ischemic stroke agents,a series of tetramethylpyrazine(TMP)/resveratrol(RES)hybrids 6 a-t were designed and synthesized.These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(...To search for potent anti-ischemic stroke agents,a series of tetramethylpyrazine(TMP)/resveratrol(RES)hybrids 6 a-t were designed and synthesized.These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,6 d,6 g-i,6 o and 6 q were more active than TMP.The most active compound 6 h exhibited more potent antiplatelet aggregation activity than TMP,RES,as well as positive control ticlopidine(Ticlid)and aspirin(ASP).Furthermore,6 h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide(H2 O2)or hydroxyl radical(·OH).Importantly,6 h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation(OGD/R)injury,comparable to an anti-ischemic drug edaravone(Eda).Together,our findings suggest that 6 h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.展开更多
Ligustrazine,an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort,has been clinically applied to treat the cerebrovascular diseases.Hyperhomocystcincmia(Hhcy)is an independent ...Ligustrazine,an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort,has been clinically applied to treat the cerebrovascular diseases.Hyperhomocystcincmia(Hhcy)is an independent risk factor for Alzheimer's disease(AD).Memory deficits can be caused by Hhcy via pathologies of Aβ-like tau and amyloid-β(Aβ)in the hippocampus.Here,we investigated whether homocysteine(Hey)can induce Aβ-like pathologies and the effects of ligustrazine on these pathologies.The Hey rat model was constructed by 14-day Hey injection via vena caudalis,and rats were treated with daily intragastric administration of ligustrazine at the same time.We found that the pathologies of tau and Aβ were induced by Hey in the hippocampus,while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment.Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced Aβ-like pathologies.展开更多
BACKGROUND: Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate t...BACKGROUND: Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6% ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood flow was determined by the radioactive microsphere technique (RMT). RESULTS: The blood flow in the P group was significantly lower than that of the C group, while the blood flow in the T group was significantly higher than that of the P group but showed no significant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were significantly increased, but there was no significant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was significant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion; the longer the time, the more severe this became. The pulmonary pathological changes wereaggravated significantly in the P group. Histopathological scores were higher in the P group than in the C group throughout the experimental course. Histopathological scores in the T group were lower than those in the P group at 6 and 12 hours. CONCLUSIONS: Microcirculatory disorder is an important factor of lung injury in ANP. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the lung.展开更多
AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups...AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA2/PGI2 and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT).RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA2 to PGI2 was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA2 to PGI2 was decreased at 6 and 12 h in T group.CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.展开更多
Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the ...Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency （PWL） to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion （DRG） neurons. Results Intraplantar injection of ligustrazine （0.5 mg in 25 μl） significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion （DRG） neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin （TTX） -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.展开更多
BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore t...BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS： Ligustrazine parenteral solution （Qiqihar Pharmaceutical Factory, China） and gentamicin sulfate （Shenyang First Pharmaceutical Factory, China） were used in this experiment.METHODS： White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection ＋ saline, gentamicin sulfate injection ＋ ligustrazine, and ligustrazine ＋ saline, respectively.MAIN OUTCOME MEASURES： Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS： Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 （P〉0.05）. Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION： Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.展开更多
Objective: To study the effect of adjuvant therapy with salviae miltiorrhizae and ligustrazine injection on neural function injury, degree of oxidative stress reaction, chemotactic factor and adhesion molecule in pati...Objective: To study the effect of adjuvant therapy with salviae miltiorrhizae and ligustrazine injection on neural function injury, degree of oxidative stress reaction, chemotactic factor and adhesion molecule in patients with ischemic stroke. <br> Methods: Patients with ischemic stroke admitted in our hospital from August 2013 to October 2015 were retrospectively analyzed and divided into conventional treatment (CT) group receiving conventional treatment and traditional Chinese medicine auxiliary (TCMA) group receiving adjuvant therapy with salviae miltiorrhizae and ligustrazine injection. After the treatment of the first month and the third month, serum was collected to detect the contents of nerve injury molecules, oxidative stress parameters, chemotactic factor and adhesion molecule. <br> Results: After the 4-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1,CD40,CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients ofTCMA group were all significantly lower than those of CT group, and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. After the 8-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1,CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients ofTCMA group were all significantly lower than those of CT group and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. <br> Conclusions: Adjuvant therapy with salviae miltiorrhizae and ligustrazine injection can alleviate the neural function injury, inhibit oxidative stress reaction and the generation of chemotactic factor and adhesion molecule in patients with ischemic stroke, which is an effective medicine for treating ischemic stroke.展开更多
To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation injured group and...To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation injured group and Ligustrazine group. After irradiation by 6.0 Gy 60 Co γ ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono nuclear cells (BMMNC) were counted, and the expression levels of bFGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group ( P <0.05 or P <0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group ( P <0.05 or P <0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.展开更多
BACKGROUND： Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expressi...BACKGROUND： Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expression of heat shock protein-70 and Bcl-2, thus alleviating brain tissue injury caused by cerebral ischemia/reperfusion. This study aimed to address the question of whether ligustrazine can protect the membrane structure of neurons. OBJECTIVE： To establish rat models of cerebral ischemia/reperfusion, observe the membrane structure and main organelles of neurons with electron microscope after ligustrazine intervention, and to analyze the dose-dependent effects of ligustrazine on neuronal changes. DESIGN： A randomized controlled study. SETTING： Department of Anatomy Research and Electron Microscopy, Hebei North University. MATERIALS： Forty Wistar rats of SPS grade, weighing 180-250 g and equal proportion of female and male, were provided by Hebei Medical University Animal Center （No. 060126）. The ligustrazine injection （40 g/L, No. 05012） was produced by Beijing Yongkang Yaoye. LKB4 Ultramicrotome was purchased from LKB Company in Sweden. JEM100CXII electron microscope was purchased from JEOL in Japan. METHODS： The experiment was performed in the Laboratory of the Department of Anatomy and Electron Microscopy, Hebei North University from June to August 2006. （1） Wistar rats were allowed to adapt for 3 days, and were then randomly divided into four groups, according to the numeration table method： normal group, model group, low-dose ligustrazine group, and high-dose ligustrazine group. There were 10 rats in each group. （2）Rats in the model group, low-dose ligustrazine group, and high-dose ligustrazine group underwent cerebral ischemia/reperfusion model, according to Bannister＇s method. The carotid artery was opened for reperfusion after 90 minutes of cerebral ischemia. Samples were collected from the cerebral cortex after 24 hours. Animals from the ligustrazine low-dose group and ligustrazine high-dose group received ligustrazine injections, 50 mg/kg and 100 mg/kg, respectively. Samples were collected at the same time as the model group. MAIN OUTCOME MEASURES： Alterations of the neuronal ultrastructure and main organelles were observed by electron microscopy. RESULTS： Forty Wistar rats were included in the final analysis. Plentiful ribosome and rough endoplasmic reticulum existed in the cytoplasm of cortical neurons in the normal group. Edema existed in the nucleus and cytoplasm of neurons in the model group. The cell membrane was damaged, resulting in the external eruption of certain cellular organelles. In the low-dose ligustrazine group, neuronal swelling was decreased in the cytoplasm, whereas cellular organelles were relatively increased. However, the mitochondria remained swollen. The double layer structure disappeared in parts of the mitochondrial membrane. The caryotheca was still broken, and neuronal damage was significantly decreased in the high-dose ligustrazine group. In addition, cytoplasmic swelling was reduced andmost part of caryotheca was complete. Fragmentation of the cellular membrane was not detected. Mitochondrial cristae and the lysosome could also be detected. The number of rough endoplasmic reticulum and free ribosomes was increased, and the structure of great part of caryotheca was clear. In addition, the number of nuclear pore was increased. However, the nuclear heterochromatin was relatively reduced. CONCLUSION： In the rat, the protective effects of ligustrazine were significant on neuronal membrane structures and main organelles after cerebral ischemia/reperfusion. There was a dose-dependent effect between neuronal changes and Ligustrazine.展开更多
A series of novel derivatives of ligustrazine linked with substituted benzoyl guanidine were synthesized. These compounds have not been reported in literature, and their chemical structures were confirmed by IR, ^1H N...A series of novel derivatives of ligustrazine linked with substituted benzoyl guanidine were synthesized. These compounds have not been reported in literature, and their chemical structures were confirmed by IR, ^1H NMR and MS. The results of NHE1 inhibitory activity test showed that compounds I2, I3, I4, I6, and I7 possess more potent NHE1 inhibitory activity than cariporide.展开更多
[Objective] This study aimed to investigate the combination effects of ligustrazine and cis-dichlorodiamine platinum （DDP） on anti-proliferation, cell cycle and apoptosis of SGC-7901 cell lines in vitro. [Methed] SG...[Objective] This study aimed to investigate the combination effects of ligustrazine and cis-dichlorodiamine platinum （DDP） on anti-proliferation, cell cycle and apoptosis of SGC-7901 cell lines in vitro. [Methed] SGC-7901 cells were treat- ed with ligustrazine and DDP alone or combined for 48 h for morphology assay. Anti-proliferative effects with the same treatment for 24, 48 and 72 h were assayed by MTT method, respectively. Cell cycle distribution and apoptosis assay of treated cells were performed in flow cytometry. Zhengjun Jin＇s protocol was used to assay the effect of drug combination. [Result] Ligustrazine significantly increased the prolif- eration inhibition rate of DDP on SGC-7901 cells in combination with DDP, com- paring with the effects of ligustrazine or DDP alone, and exhibited synergistic antitu- mor effect. The combination drug treatment induced cell cycle arrest occurred in S and G2 phase of the cell cycle and increased the apoptosis rate significantly. [Conclusion] Our results indicate that ligustrazine, as a low-toxic and natural herbal component, can significantly increase the anti-proliferative effect and apoptosis rate of antitumor drug DDP on human gastric carcinoma SGC：.-7901 cells.展开更多
To evaluate the possibility of employing ligustrazine in the prevention of restenosis, the effects of ligustrazine on the intimal thickening of air injured carotid artery of rats were investigated, and the effects of...To evaluate the possibility of employing ligustrazine in the prevention of restenosis, the effects of ligustrazine on the intimal thickening of air injured carotid artery of rats were investigated, and the effects of ligustrazine on the proliferation of rabbit aortic median smooth muscle cells (SMCs) cultivated in vitro were examined. Artery injury model of 18 rats of about 3 months old was established by Fishman air dry method. Fourteen days after operation, the maximal artery intimal and medial thickness of the control and ligustrazine group was measured on the image analysis system. Using cell counting and thymidine ( 3H TdR) up take method, we also examined the effects of ligustrazine on the proliferation of aortic median SMC from 4 rabbits. Ligustrazine was found to inhibit the proliferation and 3H TdR up take of SMC in a dose dependent manner in vitro ( P <0.05 or P <0.01 vs control). It also inhibited the intimal thickening of rat arteries after deendothelialization. The maximal intimal thickness of ligustrazine group was much thinner than that of the control (35.9±3.8 μm vs 80.2±23.4 μm, P <0.01). It was showed that ligustrazine could be used for prevention of restenosis in clinical practice.展开更多
Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral artery occlusion with a suture. Two ...Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral artery occlusion with a suture. Two hours later, injection of Ligustrazine (80mg/kg, 1 time/d) was performed peritoneally. Four hours after the ischemia, 5-bromodeoxyuridine (BrdU) (50mg/kg, 1 time/d) was injected peritoneally. At 7d, 14d and 21d after ischemia, BrdU positive cells in the cortex were observed by immunohistochemical staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ-Ⅵ layers of the ipsilateral cortex, with a band-like distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased. In Ligustrazine group, BrdU positive cells were also observed in the Ⅱ-Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7d, 14d and 21d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.展开更多
Summary: Mice with immune induced aplastic anemia (AA) were given 5 mg ligustrazine intraperitoneally twice a day. On the 14th day, the expression of CD 49d , CD 49e , cyclinD 2 in bone marrow mononuclear ...Summary: Mice with immune induced aplastic anemia (AA) were given 5 mg ligustrazine intraperitoneally twice a day. On the 14th day, the expression of CD 49d , CD 49e , cyclinD 2 in bone marrow mononuclear cells (MNC) was examined by flow cytometry, and VCAM 1 on stromal cells was immunohistochemically measured by Strept Avidin Biotin Complex (SABC). The expression of CD 49d , CD 49e , VCAM 1 and cyclinD 2 in ligustrazine treated group was significantly higher than that in AA group ( P <0 01), but the ratio of G 0+G 1 phase cells was significantly lower than that in AA group ( P <0.01).The results showed that ligustrazine could improve the expression of adherent molecule and cyclin D 2 in the bone marrow of mice with immune induced aplastic anemia, thereby promoting the growth of hematopoietic cells.展开更多
BACKGROUND： Studies have shown that both salviae miltiorrhizae and ligustrazine can promote protein expression of nerve growth factor （NGF） and regeneration of peripheral nerve. OBJECTIVE： To verify the effect of ...BACKGROUND： Studies have shown that both salviae miltiorrhizae and ligustrazine can promote protein expression of nerve growth factor （NGF） and regeneration of peripheral nerve. OBJECTIVE： To verify the effect of salviae miltiorrhizae and ligustrazine hydrochloride injection on axonal regeneration and NGF protein expression in a rat model of sciatic nerve injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Traditional Chinese Medicine and the Institute of Bioengineering of Jinan University from July to December 2008. MATERIALS： Salviae miltiorrhizae and ligustrazine hydrochloride injection （containing 20 mg salviae miJtiorrhizae and 100 mg ligustrazine per 100 mL injection） was provided by Guizhou Baite Pharmaceutical, China; salviae miltiorrhizae and ligustrazine decoctions （containing 1 g raw drug per 1 mL decoction） were provided by Guangzhou Baiyunshan Factory for Traditional Chinese Medicine, China; rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Biosynthesis Biotechnology, China. METHODS： A total of 80 healthy, male, Sprague Dawley rats were used to establish a sciatic nerve injury model via neurotomy, and were then randomly assigned to 4 groups： salviae miltiorrhizae and ligustrazine hydrochloride injection group （intraperitoneal injection of 35 mL/kg per day salviae miltiorrhizae and ligustrazine hydrochloride injection）, saIviae miltiorrhizae group （intragastric peffusion of 2 mL salviae miltiorrhizae）, ligustrazine group （intragastric peffusion of 2 mL ligustrazine）, and model group （intraperitoneal injection of 35 mL/kg per day saline）, with 20 rats in each group. Thereafter, rats in each group were then divided into 4 subgroups according to varying time points of 1, 2, 4, and 8 weeks post-surgery, with 5 rats in each subgroup. MAIN OUTCOME MEASURES： Axons were quantified using chromotrope 2R-brilliant green and silver staining combined with image analysis to calculate the axonal regeneration rate; NGF expression was detected using immunohistochemistry and Western blot analysis; toe interspace was measured by behavior at 4 and 8 weeks. RESULTS： With increasing time after sciatic nerve expression, and toe interspace gradually increased njury, the axonal regeneration rate, NGF protein At 4 and 8 weeks post-surgery, axonal regeneration rate and NGF protein expression were significantly increased in the injured tissue of the salviae miltiorrhizae and ligustrazine hydrochloride injection, salviae miltiorrhizae, and ligustrazine groups, compared with the model group （P 〈 0.05 or P 〈 0.01）, and toe interspace was remarkably enlarged （P 〈 0.05 or P 〈 0.01）, especially in the salviae miltiorrhizae and ligustrazine hydrochloride injection group. CONCLUSION： Salviae miltiorrhizae and ligustrazine hydrochloride injection promoted axonal regeneration and NGF protein expression in the injured sciatic nerve, and also enhanced neurofunctional recovery. Its effect was superior to salviae miltiorrhizae or ligustrazine alone.展开更多
To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT ) mice. The syngeneic BMT mice model was established. T...To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT ) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine treated group, the diameter of center veins and the area of micro vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT ( P <0.01). In addition, Ligustrazine significantly increased the number of CFU S on day 10 and the number of CFU GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.展开更多
The present study was to investigate changes of free radicals in the whole rat liver, changes of ATP levels of hepatic cells, ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the ...The present study was to investigate changes of free radicals in the whole rat liver, changes of ATP levels of hepatic cells, ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the effects of ligustrazine and salvia compound. The results indicated that : 1 ) the free radical levels increased by 8. 3-fold and 9.0-fold in the groups with 30 and 60 min ischemia after 40 min reperfusion, as compared with the group with ischemia only (P<0.01, P<0.01, respectively). 2) The levels of ATP returned to normal in the group with 30 min ischemia after reperfusion for 40 min and 3 d , remained low in the group with 90 min ischemia and fell again after a mild increase in the group with 60 min ischemia. 3) The hepatic and endothelial cell damage after ischemia became more severe after reperfusion, as revealed by electron microscopy. The presenet study also showed that ligustrazine and salvia compound have protective effects against reperfusion injury. They can be used to scavenge free radicals, improve hepatic microcirculation and alleviate hepatic and endothelial cell damage.展开更多
文摘Objective: To explore the effects of ligustrazine on proteinuria, serumcreati-nine, urinary thromboxane A_2(TxA_2), metabolism of prostacyclinI_2(PGI_2)―6-keto-PGF_(1α), and renal pathological changes of SD rats with passive Hermannnephritis (PHN). Methods: The PHN model was induced by intravenous injection of rabbit anti-ratrenal tubular epithelial antigen (Tub―Ag) an-tiserum to SD rats. I. P. administration ofligustrazine to rats was given every 2 d for 1 to 5 weeks. The proteinuria, creatinine, TxA_2 and6-keto-PGF_(1α) were measured by sulfosaticylic acid, picric acid, and direct radioimmunoassayrespectively. The renal pathological changes were observed under light microscope, electronicmicroscope and by direct immunofluorescence staining rabbit and rat IgG. Results: The PHN ratstreated with ligustrazine had significantly less proteinuria, serum creatinine, urinary TxA_2 andpathological changes of kidney, and more urinary 6-keto-PGF_(1α) than those without administrationof ligustrazine. Conclusion: Ligustrazine decreases proteinuria, urinary TxA_2, and renal tissueinjury and increases urinary 6-keto-PGF_(1α). These data indicate that ligustrazine may modulatethe balance of TxA_2 and PG I_2 in rat PHN model and can be used for preventing and treatingmembranous glomerulonephritis.
基金supported by a grant from the Health and Family Planning Commission of Heilongjiang Province Research Project in China,No.2014-195the Education Department Science and Technology Foundation of Heilongjiang Province in China,No.12531741the Natural Science Foundation of Heilongjiang Province of China,No.H2015083
文摘Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.
基金This study was supported by grants from the Zhenjiang Science and Technology Committee(No.SH2002015and No.SH2005044).
文摘BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.
基金supported by the National Natural Science Foundation of China(Nos.8182204181773573+5 种基金21977116and 81673305)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09711002-006-013)the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZCX201824)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2018-1)part of the work was supported by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX18_0795)。
文摘To search for potent anti-ischemic stroke agents,a series of tetramethylpyrazine(TMP)/resveratrol(RES)hybrids 6 a-t were designed and synthesized.These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,6 d,6 g-i,6 o and 6 q were more active than TMP.The most active compound 6 h exhibited more potent antiplatelet aggregation activity than TMP,RES,as well as positive control ticlopidine(Ticlid)and aspirin(ASP).Furthermore,6 h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide(H2 O2)or hydroxyl radical(·OH).Importantly,6 h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation(OGD/R)injury,comparable to an anti-ischemic drug edaravone(Eda).Together,our findings suggest that 6 h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.
基金grants from Changzhou Sci&Tech Program(No.CJ20190063,No.CJ20200090)Young Talent Development Plan of Changzhou Health Commission(No.CZQM2020078,and No.CZQM2020063)+3 种基金China Postdoctoral Science Foundation(No.2020M670012ZX)National Natural Science Foundation of China(No.81803498)Jiangsu Planned Projects for Postdoctoral Research Funds(No.2019K157)"Mass Entrepreneurship and Innovation Plan"of Jiangsu Province(No.QT201919).
文摘Ligustrazine,an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort,has been clinically applied to treat the cerebrovascular diseases.Hyperhomocystcincmia(Hhcy)is an independent risk factor for Alzheimer's disease(AD).Memory deficits can be caused by Hhcy via pathologies of Aβ-like tau and amyloid-β(Aβ)in the hippocampus.Here,we investigated whether homocysteine(Hey)can induce Aβ-like pathologies and the effects of ligustrazine on these pathologies.The Hey rat model was constructed by 14-day Hey injection via vena caudalis,and rats were treated with daily intragastric administration of ligustrazine at the same time.We found that the pathologies of tau and Aβ were induced by Hey in the hippocampus,while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment.Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced Aβ-like pathologies.
基金This study was supported by grants from the Zhenjiang Science and Technology Committee, China (No. SH2002015 and NO. SH 2005044).
文摘BACKGROUND: Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6% ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood flow was determined by the radioactive microsphere technique (RMT). RESULTS: The blood flow in the P group was significantly lower than that of the C group, while the blood flow in the T group was significantly higher than that of the P group but showed no significant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were significantly increased, but there was no significant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was significant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion; the longer the time, the more severe this became. The pulmonary pathological changes wereaggravated significantly in the P group. Histopathological scores were higher in the P group than in the C group throughout the experimental course. Histopathological scores in the T group were lower than those in the P group at 6 and 12 hours. CONCLUSIONS: Microcirculatory disorder is an important factor of lung injury in ANP. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the lung.
基金Supported by Zhenjiang Science and Technology Committee, No. SH2002015
文摘AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA2/PGI2 and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT).RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA2 to PGI2 was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA2 to PGI2 was decreased at 6 and 12 h in T group.CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.
文摘Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency （PWL） to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion （DRG） neurons. Results Intraplantar injection of ligustrazine （0.5 mg in 25 μl） significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion （DRG） neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin （TTX） -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.
基金the National Natural Science Foundation of China,No. 30672739the Scientific Research Program of Education Department of Liaoning Province,No. 2008722the Science and Technology Foundation of Liaoning Province,No. 20031032
文摘BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS： Ligustrazine parenteral solution （Qiqihar Pharmaceutical Factory, China） and gentamicin sulfate （Shenyang First Pharmaceutical Factory, China） were used in this experiment.METHODS： White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection ＋ saline, gentamicin sulfate injection ＋ ligustrazine, and ligustrazine ＋ saline, respectively.MAIN OUTCOME MEASURES： Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS： Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 （P〉0.05）. Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION： Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.
文摘Objective: To study the effect of adjuvant therapy with salviae miltiorrhizae and ligustrazine injection on neural function injury, degree of oxidative stress reaction, chemotactic factor and adhesion molecule in patients with ischemic stroke. <br> Methods: Patients with ischemic stroke admitted in our hospital from August 2013 to October 2015 were retrospectively analyzed and divided into conventional treatment (CT) group receiving conventional treatment and traditional Chinese medicine auxiliary (TCMA) group receiving adjuvant therapy with salviae miltiorrhizae and ligustrazine injection. After the treatment of the first month and the third month, serum was collected to detect the contents of nerve injury molecules, oxidative stress parameters, chemotactic factor and adhesion molecule. <br> Results: After the 4-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1,CD40,CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients ofTCMA group were all significantly lower than those of CT group, and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. After the 8-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1,CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients ofTCMA group were all significantly lower than those of CT group and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. <br> Conclusions: Adjuvant therapy with salviae miltiorrhizae and ligustrazine injection can alleviate the neural function injury, inhibit oxidative stress reaction and the generation of chemotactic factor and adhesion molecule in patients with ischemic stroke, which is an effective medicine for treating ischemic stroke.
基金ThisprojectwassupportedbyagrantfromtheNationalNatu ralScienceFoundationofChina (No .39870 92 6 )
文摘To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation injured group and Ligustrazine group. After irradiation by 6.0 Gy 60 Co γ ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono nuclear cells (BMMNC) were counted, and the expression levels of bFGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group ( P <0.05 or P <0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group ( P <0.05 or P <0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
基金the Grant from Zhangjiakou Science and Technology Department(No.061160)
文摘BACKGROUND： Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expression of heat shock protein-70 and Bcl-2, thus alleviating brain tissue injury caused by cerebral ischemia/reperfusion. This study aimed to address the question of whether ligustrazine can protect the membrane structure of neurons. OBJECTIVE： To establish rat models of cerebral ischemia/reperfusion, observe the membrane structure and main organelles of neurons with electron microscope after ligustrazine intervention, and to analyze the dose-dependent effects of ligustrazine on neuronal changes. DESIGN： A randomized controlled study. SETTING： Department of Anatomy Research and Electron Microscopy, Hebei North University. MATERIALS： Forty Wistar rats of SPS grade, weighing 180-250 g and equal proportion of female and male, were provided by Hebei Medical University Animal Center （No. 060126）. The ligustrazine injection （40 g/L, No. 05012） was produced by Beijing Yongkang Yaoye. LKB4 Ultramicrotome was purchased from LKB Company in Sweden. JEM100CXII electron microscope was purchased from JEOL in Japan. METHODS： The experiment was performed in the Laboratory of the Department of Anatomy and Electron Microscopy, Hebei North University from June to August 2006. （1） Wistar rats were allowed to adapt for 3 days, and were then randomly divided into four groups, according to the numeration table method： normal group, model group, low-dose ligustrazine group, and high-dose ligustrazine group. There were 10 rats in each group. （2）Rats in the model group, low-dose ligustrazine group, and high-dose ligustrazine group underwent cerebral ischemia/reperfusion model, according to Bannister＇s method. The carotid artery was opened for reperfusion after 90 minutes of cerebral ischemia. Samples were collected from the cerebral cortex after 24 hours. Animals from the ligustrazine low-dose group and ligustrazine high-dose group received ligustrazine injections, 50 mg/kg and 100 mg/kg, respectively. Samples were collected at the same time as the model group. MAIN OUTCOME MEASURES： Alterations of the neuronal ultrastructure and main organelles were observed by electron microscopy. RESULTS： Forty Wistar rats were included in the final analysis. Plentiful ribosome and rough endoplasmic reticulum existed in the cytoplasm of cortical neurons in the normal group. Edema existed in the nucleus and cytoplasm of neurons in the model group. The cell membrane was damaged, resulting in the external eruption of certain cellular organelles. In the low-dose ligustrazine group, neuronal swelling was decreased in the cytoplasm, whereas cellular organelles were relatively increased. However, the mitochondria remained swollen. The double layer structure disappeared in parts of the mitochondrial membrane. The caryotheca was still broken, and neuronal damage was significantly decreased in the high-dose ligustrazine group. In addition, cytoplasmic swelling was reduced andmost part of caryotheca was complete. Fragmentation of the cellular membrane was not detected. Mitochondrial cristae and the lysosome could also be detected. The number of rough endoplasmic reticulum and free ribosomes was increased, and the structure of great part of caryotheca was clear. In addition, the number of nuclear pore was increased. However, the nuclear heterochromatin was relatively reduced. CONCLUSION： In the rat, the protective effects of ligustrazine were significant on neuronal membrane structures and main organelles after cerebral ischemia/reperfusion. There was a dose-dependent effect between neuronal changes and Ligustrazine.
文摘A series of novel derivatives of ligustrazine linked with substituted benzoyl guanidine were synthesized. These compounds have not been reported in literature, and their chemical structures were confirmed by IR, ^1H NMR and MS. The results of NHE1 inhibitory activity test showed that compounds I2, I3, I4, I6, and I7 possess more potent NHE1 inhibitory activity than cariporide.
基金Supported by the Fund for Excellent Young Teachers by Education Department of Henan(2010DDJS-224)Natural Science Fund of Education Department of Henan(2010C320001)
文摘[Objective] This study aimed to investigate the combination effects of ligustrazine and cis-dichlorodiamine platinum （DDP） on anti-proliferation, cell cycle and apoptosis of SGC-7901 cell lines in vitro. [Methed] SGC-7901 cells were treat- ed with ligustrazine and DDP alone or combined for 48 h for morphology assay. Anti-proliferative effects with the same treatment for 24, 48 and 72 h were assayed by MTT method, respectively. Cell cycle distribution and apoptosis assay of treated cells were performed in flow cytometry. Zhengjun Jin＇s protocol was used to assay the effect of drug combination. [Result] Ligustrazine significantly increased the prolif- eration inhibition rate of DDP on SGC-7901 cells in combination with DDP, com- paring with the effects of ligustrazine or DDP alone, and exhibited synergistic antitu- mor effect. The combination drug treatment induced cell cycle arrest occurred in S and G2 phase of the cell cycle and increased the apoptosis rate significantly. [Conclusion] Our results indicate that ligustrazine, as a low-toxic and natural herbal component, can significantly increase the anti-proliferative effect and apoptosis rate of antitumor drug DDP on human gastric carcinoma SGC：.-7901 cells.
文摘To evaluate the possibility of employing ligustrazine in the prevention of restenosis, the effects of ligustrazine on the intimal thickening of air injured carotid artery of rats were investigated, and the effects of ligustrazine on the proliferation of rabbit aortic median smooth muscle cells (SMCs) cultivated in vitro were examined. Artery injury model of 18 rats of about 3 months old was established by Fishman air dry method. Fourteen days after operation, the maximal artery intimal and medial thickness of the control and ligustrazine group was measured on the image analysis system. Using cell counting and thymidine ( 3H TdR) up take method, we also examined the effects of ligustrazine on the proliferation of aortic median SMC from 4 rabbits. Ligustrazine was found to inhibit the proliferation and 3H TdR up take of SMC in a dose dependent manner in vitro ( P <0.05 or P <0.01 vs control). It also inhibited the intimal thickening of rat arteries after deendothelialization. The maximal intimal thickness of ligustrazine group was much thinner than that of the control (35.9±3.8 μm vs 80.2±23.4 μm, P <0.01). It was showed that ligustrazine could be used for prevention of restenosis in clinical practice.
文摘Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral artery occlusion with a suture. Two hours later, injection of Ligustrazine (80mg/kg, 1 time/d) was performed peritoneally. Four hours after the ischemia, 5-bromodeoxyuridine (BrdU) (50mg/kg, 1 time/d) was injected peritoneally. At 7d, 14d and 21d after ischemia, BrdU positive cells in the cortex were observed by immunohistochemical staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ-Ⅵ layers of the ipsilateral cortex, with a band-like distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased. In Ligustrazine group, BrdU positive cells were also observed in the Ⅱ-Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7d, 14d and 21d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.
文摘Summary: Mice with immune induced aplastic anemia (AA) were given 5 mg ligustrazine intraperitoneally twice a day. On the 14th day, the expression of CD 49d , CD 49e , cyclinD 2 in bone marrow mononuclear cells (MNC) was examined by flow cytometry, and VCAM 1 on stromal cells was immunohistochemically measured by Strept Avidin Biotin Complex (SABC). The expression of CD 49d , CD 49e , VCAM 1 and cyclinD 2 in ligustrazine treated group was significantly higher than that in AA group ( P <0 01), but the ratio of G 0+G 1 phase cells was significantly lower than that in AA group ( P <0.01).The results showed that ligustrazine could improve the expression of adherent molecule and cyclin D 2 in the bone marrow of mice with immune induced aplastic anemia, thereby promoting the growth of hematopoietic cells.
基金Supported by: the Natural Science Foundation of Guangdong province, No. 5300544High-Tech Research and Development Program of Guangdong Province, No. 2009B030801238+3 种基金2006B35602009the Grants from Guangdong Province Administration of Traditional Chinese Medicine, No. 2008092 1060114the Science and Technology Foundation of Guangzhou,No.2009Z1-E091
文摘BACKGROUND： Studies have shown that both salviae miltiorrhizae and ligustrazine can promote protein expression of nerve growth factor （NGF） and regeneration of peripheral nerve. OBJECTIVE： To verify the effect of salviae miltiorrhizae and ligustrazine hydrochloride injection on axonal regeneration and NGF protein expression in a rat model of sciatic nerve injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Traditional Chinese Medicine and the Institute of Bioengineering of Jinan University from July to December 2008. MATERIALS： Salviae miltiorrhizae and ligustrazine hydrochloride injection （containing 20 mg salviae miJtiorrhizae and 100 mg ligustrazine per 100 mL injection） was provided by Guizhou Baite Pharmaceutical, China; salviae miltiorrhizae and ligustrazine decoctions （containing 1 g raw drug per 1 mL decoction） were provided by Guangzhou Baiyunshan Factory for Traditional Chinese Medicine, China; rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Biosynthesis Biotechnology, China. METHODS： A total of 80 healthy, male, Sprague Dawley rats were used to establish a sciatic nerve injury model via neurotomy, and were then randomly assigned to 4 groups： salviae miltiorrhizae and ligustrazine hydrochloride injection group （intraperitoneal injection of 35 mL/kg per day salviae miltiorrhizae and ligustrazine hydrochloride injection）, saIviae miltiorrhizae group （intragastric peffusion of 2 mL salviae miltiorrhizae）, ligustrazine group （intragastric peffusion of 2 mL ligustrazine）, and model group （intraperitoneal injection of 35 mL/kg per day saline）, with 20 rats in each group. Thereafter, rats in each group were then divided into 4 subgroups according to varying time points of 1, 2, 4, and 8 weeks post-surgery, with 5 rats in each subgroup. MAIN OUTCOME MEASURES： Axons were quantified using chromotrope 2R-brilliant green and silver staining combined with image analysis to calculate the axonal regeneration rate; NGF expression was detected using immunohistochemistry and Western blot analysis; toe interspace was measured by behavior at 4 and 8 weeks. RESULTS： With increasing time after sciatic nerve expression, and toe interspace gradually increased njury, the axonal regeneration rate, NGF protein At 4 and 8 weeks post-surgery, axonal regeneration rate and NGF protein expression were significantly increased in the injured tissue of the salviae miltiorrhizae and ligustrazine hydrochloride injection, salviae miltiorrhizae, and ligustrazine groups, compared with the model group （P 〈 0.05 or P 〈 0.01）, and toe interspace was remarkably enlarged （P 〈 0.05 or P 〈 0.01）, especially in the salviae miltiorrhizae and ligustrazine hydrochloride injection group. CONCLUSION： Salviae miltiorrhizae and ligustrazine hydrochloride injection promoted axonal regeneration and NGF protein expression in the injured sciatic nerve, and also enhanced neurofunctional recovery. Its effect was superior to salviae miltiorrhizae or ligustrazine alone.
文摘To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT ) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine treated group, the diameter of center veins and the area of micro vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT ( P <0.01). In addition, Ligustrazine significantly increased the number of CFU S on day 10 and the number of CFU GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.
文摘The present study was to investigate changes of free radicals in the whole rat liver, changes of ATP levels of hepatic cells, ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the effects of ligustrazine and salvia compound. The results indicated that : 1 ) the free radical levels increased by 8. 3-fold and 9.0-fold in the groups with 30 and 60 min ischemia after 40 min reperfusion, as compared with the group with ischemia only (P<0.01, P<0.01, respectively). 2) The levels of ATP returned to normal in the group with 30 min ischemia after reperfusion for 40 min and 3 d , remained low in the group with 90 min ischemia and fell again after a mild increase in the group with 60 min ischemia. 3) The hepatic and endothelial cell damage after ischemia became more severe after reperfusion, as revealed by electron microscopy. The presenet study also showed that ligustrazine and salvia compound have protective effects against reperfusion injury. They can be used to scavenge free radicals, improve hepatic microcirculation and alleviate hepatic and endothelial cell damage.
