In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The...In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.展开更多
Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly c...Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.展开更多
BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of T...BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial. SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi’an Jiaotong University. MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi’an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). METHODS: The experiments were carried out in School of Medicine of Xi’an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.50±3.80), (31.38±3.72), (61.60±3.61) s, P < 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11±1), (10±1), (8±1), (8±1), (4±1) times, P < 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm2, P < 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups (P > 0.05). CONCLUSION: TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.展开更多
BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurren...BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer,and thus novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay,and cell apoptosis and cell cycle were assessed by flow cytometry.RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose-and time-dependent manner.In addition,flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase.TMP treatment caused early stage apoptosis in SW480 cells,whereas it caused late stage apoptosis in HCT116 cells.CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose-and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase.Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.展开更多
Tetramethylpyrazine (TMP) is a herb used widely in Traditional Chinese Medicine (TCM) as an antianginal drug. The exact mechanism whereby TMP treat ischemic heart disease is still not fully understood. The purpose of ...Tetramethylpyrazine (TMP) is a herb used widely in Traditional Chinese Medicine (TCM) as an antianginal drug. The exact mechanism whereby TMP treat ischemic heart disease is still not fully understood. The purpose of this study is to examine the anti-inflammatory effect of TMP in patients with acute coronary syndromes (ACS). Methods Thirty-two patients with acute myocardial infarction or unstable angina were randomly assigned to TMP group or control group. All patients received the same standard treatment. Patients in TMP group received TMP 3mg/kg every 12 hours for 5 days. Plasma concentrations of high-sensitivity Creactive protein (CRP), serum amyloid A (SAA) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and after 5 days of therapy. Results Both CRP and SAA concentrations increased significantly in control group (P＜0.05) whilst in TMP group, only SAA had a significant increase (P＜0.05); the absolute increase of CRP, SAA, and PAI-1 were significantly less in TMP group than in control group (P＜0.05). Conclusion TMP has an anti-inflammatory and profibrinolytic effect in patients with ACS. These effects may contribute to the clinical benefits of TMP in ischemic heart disease.展开更多
The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutama...The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutamate-induced neurotoxicity in mice and its possible mechanism. Mice, except for controls, received simultaneously intragastric (ig) administration of monosodium glutamate [MSG, 4.0 g/(kg·d)] or/and intraperitoneal (ip) administration of TMP [10, 20, 40 mg/(kg·d)] for 10 d, and then behavioral tests, as well as histopathological and immunohistochemical examination of hippocampi were performed to analyze the glutamate-induced functional and morphological changes and the possible protective effect of TMP. The results showed that ip administration of TMP countered the effects of ig administration of MSG on behavior and histopathology, suggesting that TMP was a neuroprotective agent. This study provides evidence that TMP possesses obviously neuroprotection against glutamate-induced neurotoxicity, and the neuroprotection effect may result from its inhibiting expression of NMDARs, consequently blocking-up Ca2+ influx through the receptor’s associated ion channel, which can be neurotoxic.展开更多
The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, a...The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, and its mechanism of the antidepressant-like action. Forced-swimming, tail-suspension, reserpine-induced hypothermia, akinesia and ptosis, 5-hydroxytryptophan (5-HTP)-induced head-twitch, and potentiation of noradrenaline (NE) toxicity tests, were per-formed to assess the potential antidepressant-like activity of TMP and to study the mechanism by which TMP exerts the antidepressant-like action. Intragastric (ig) administration of TMP markedly reduced the duration of immobility during forced-swimming tests and tail-supension test in rats and mice. TMP partialy reversed reserpine-induced hypothermia, ptosis and akinesia, and potentiated NE toxicity in mice, and these are similar to those of clomipramine;however, TMP did not potentiate 5-HTP-induced head-twitch response (HTR) in mice, and this is different from that of fluoxetine (FLU). The present data provide evidences that TMP possesses potent antidepressant-like activity, and it might be an adrenergic component of pharmacological activity, and its mechanism of antidepressant-like action is similar to that of clomipramine, and different from that of FLU.展开更多
The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, i...The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, in chronic mild stress (CMS)-induced rat model of depression. Male Sprague-Dawley (SD) strain rats were divided into six matched groups (n = 13 or 14 in each group) based on their sucrose consumption: control, CMS, CMS + fluoxetine (FLU), and CMS + TMP groups. The rats except control were housed separately in different rooms, and the rat model of depression was established by exposing to an unpredictable sequence of stressors for 28 days;the rats in CMS + FLU were exposed to CMS and received administration of FLU (2.0 mg/kg/d, ig) for 28 days;the rats in CMS + TMP groups were exposed to CMS and received administration of TMP (10, 20, 40 mg/kg/d, ig), respectively, for 28 days. The rats in control group were given ordinary daily care, and the rats in control and CMS groups received ig administration of normal saline instead of FLU or TMP. The body weight, food intake and fluid consumption were measured, and the behaviors were examined by open field test before and after CMS, and forced-swimming test was performed 1 day after last unpredictable stressor. Chronic administration of TMP partially reversed the effects of CMS on consumption of sucrose solution and locomotion and exploration behavior, and potently shortened the immobility time during forced-swimming test following CMS in rats. The results showed that long-term administration of TMP partially reversed the effects of CMS on the body weight gain, the consumption of sucrose solution, the squares crossin gand rearing in open field test, and the immobility time during forced-swimming test in rats. The present data provide evidences that TMP possesses obvious antidepressant-like activity in CMS-induced rat model of depression.展开更多
Objective To observe the effects or the ramethylpyrazine (TMP ) on ret Ina to find o ut whe ther it can protect retlna from glaucomatous damage. Methods Twenty-four rabblts were randomIy dlvided lnto rour groups.one e...Objective To observe the effects or the ramethylpyrazine (TMP ) on ret Ina to find o ut whe ther it can protect retlna from glaucomatous damage. Methods Twenty-four rabblts were randomIy dlvided lnto rour groups.one eye or each rabblt was model eye lnduced by 2% methyicelluious, and the other was control eye. Normal saline,TMP, timolol and a cobolnation or tlmolol and TMP were admlnlstrated to group A, B, C and D respectlvely. At the end of 4th week, eyes were excavated for Iight and electron microscoplc study. ResuIts The numbers of ganglion cells (P <o. o1) and bipolar cells (P <o. o1) ln model eye were different slgnif1cantly between group A and B. in group A, tke modeI eye gangIlon cells were karyopyknosls, chromatln marglnatlon and nucIear membrane rupture; some inner nuclear cells dcveloped marked lytlc changes l’ outer segmentaweared 4lsorganlzed i but ’group B changed sllghtly. Concndlon The results suggest that TMP may protect retlna from gIaucomatous damage.展开更多
Angiogenesis in atherosclerosis(AS)promotes plaque destabilization.miR-126 has a significant role in angiogenesis.Tetramethylpyrazine(TMP)and paeoniflorin(PF)have anti-atherosclerotic effects.However,the miR-126-relat...Angiogenesis in atherosclerosis(AS)promotes plaque destabilization.miR-126 has a significant role in angiogenesis.Tetramethylpyrazine(TMP)and paeoniflorin(PF)have anti-atherosclerotic effects.However,the miR-126-related mechanisms of TMP and PF combination(TMP-PF)on angiogenesis in AS have not been understood.To explore the mechanism of TMP-PF on angiogenesis in AS targeting miR-126.Human umbilical vein endothelial cells(HUVECs)were assigned into the control,model,TMP-PF,TMP-PF+miR-126 inhibitor,and simvastatin groups.HUVECs were transfected with miR-126 inhibitor or negative control,incubated with oxidized low-density lipoprotein(ox-LDL)to establish AS model,and then treated with TMP-PF or simvastatin.Cell proliferation,migration,and tube formation assays are conducted,and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The expression level of miR-126 was confirmed by polymerase chain reaction(PCR).0x-LDL promoted HUVECs proliferation,migration,and tube formation,downregulated miR-126 expression,and increased the expression of VEGF,VEGFR2,bFGF,and FGFR1.TMP-PF inhibited proliferation,migration,and tube formation,upregulated miR-126 expression and decreased the expression of VEGF,VEGFR2,bFGF,and FGFR1 in ox-LDL-induced HUVECs.However,the effects of TMP-PF on angiogenesis and the expression of miR-126,VEGF,VEGFR2,and FGFR1 were abolished by miR-126 inhibitor.TMP-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway,which might elucidate the underlying mechanism of TMP-PF in alleviating AS.展开更多
Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine(TMP), one of the most widely used medicinal compound isolated from traditional Chinese her...Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine(TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, antilipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.展开更多
The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),i...The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)administration.After i.n.,i.g.and i.v.administration of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals.The concentration of TMPP in the samples was analyzed by HPLC.The area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration.After i.n.administration,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between i.n.route and i.v.injection was 0.68,which was greater than that obtained after i.g.administration(0.43).The systemic bioavailability obtained with i.n.administration was greater than that obtained by the i.g.route(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral cortex.Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.展开更多
Tetramethylpyrazine(TTMP),an important aroma compound,was produced by Bacillus amyloliquefaciens XJB-104 with distillers’grains as raw material.The yield of TTMP under optimized fermentation procedure was 3176.52 mg/...Tetramethylpyrazine(TTMP),an important aroma compound,was produced by Bacillus amyloliquefaciens XJB-104 with distillers’grains as raw material.The yield of TTMP under optimized fermentation procedure was 3176.52 mg/L.TTMP in the fermentation broth was purified and the purity(>99%)was measured by gas chromatography-mass spectrometry.Furthermore,the hepatoprotective activity of TTMP in ethanol-water system was evaluated by biochemical indicators of liver injury,parameters of antioxidant defense system and inflammatory response,and liver histopathological assessment in mice.Ethanol treatment increased serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phos-phatase and lactate dehydrogenase,suggesting liver damage.Both high and low dose of TTMP significantly decreased levels of these indicators.Furthermore,the reduction in the activities or concentrations of superoxide dismutase,catalase,reduced glutathione and malondialdehyde in liver tissue caused by ethanol was significantly alleviated by TTMP.Increased inflammatory cytokines including transcription factor,tumor necrosis factor,interleukin-1beta,interleukin,macrophage chemoattractant protein,inducible nitric oxide synthase and cyclooxygenase were also suppressed by TTMP treatment.It is concluded that TTMP in ethanol-water system has potential liver-protective activity,especially when ethanol is consumed at low doses for short periods of time.展开更多
Objective: To further explore the function of combine use of tetramethylpyrazine(TMP) and cisplatin(DDP) in lung carcinoma. Methods: We used the combination drug to treat Lewis lung cancer mice, investigated the expre...Objective: To further explore the function of combine use of tetramethylpyrazine(TMP) and cisplatin(DDP) in lung carcinoma. Methods: We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor(VEGF), Kruppel-like factor 4(KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. Results: The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. Conclusion: KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways.展开更多
基金supported by the Program from Shanghai Uni-versity of Traditional Chinese Medicine(B201725)
文摘In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.
文摘Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.
基金the National Natural Science Foundation of China, No. 30170300 30300109
文摘BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial. SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi’an Jiaotong University. MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi’an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). METHODS: The experiments were carried out in School of Medicine of Xi’an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.50±3.80), (31.38±3.72), (61.60±3.61) s, P < 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11±1), (10±1), (8±1), (8±1), (4±1) times, P < 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm2, P < 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups (P > 0.05). CONCLUSION: TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.
文摘BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer,and thus novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay,and cell apoptosis and cell cycle were assessed by flow cytometry.RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose-and time-dependent manner.In addition,flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase.TMP treatment caused early stage apoptosis in SW480 cells,whereas it caused late stage apoptosis in HCT116 cells.CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose-and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase.Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.
文摘Tetramethylpyrazine (TMP) is a herb used widely in Traditional Chinese Medicine (TCM) as an antianginal drug. The exact mechanism whereby TMP treat ischemic heart disease is still not fully understood. The purpose of this study is to examine the anti-inflammatory effect of TMP in patients with acute coronary syndromes (ACS). Methods Thirty-two patients with acute myocardial infarction or unstable angina were randomly assigned to TMP group or control group. All patients received the same standard treatment. Patients in TMP group received TMP 3mg/kg every 12 hours for 5 days. Plasma concentrations of high-sensitivity Creactive protein (CRP), serum amyloid A (SAA) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and after 5 days of therapy. Results Both CRP and SAA concentrations increased significantly in control group (P＜0.05) whilst in TMP group, only SAA had a significant increase (P＜0.05); the absolute increase of CRP, SAA, and PAI-1 were significantly less in TMP group than in control group (P＜0.05). Conclusion TMP has an anti-inflammatory and profibrinolytic effect in patients with ACS. These effects may contribute to the clinical benefits of TMP in ischemic heart disease.
文摘The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutamate-induced neurotoxicity in mice and its possible mechanism. Mice, except for controls, received simultaneously intragastric (ig) administration of monosodium glutamate [MSG, 4.0 g/(kg·d)] or/and intraperitoneal (ip) administration of TMP [10, 20, 40 mg/(kg·d)] for 10 d, and then behavioral tests, as well as histopathological and immunohistochemical examination of hippocampi were performed to analyze the glutamate-induced functional and morphological changes and the possible protective effect of TMP. The results showed that ip administration of TMP countered the effects of ig administration of MSG on behavior and histopathology, suggesting that TMP was a neuroprotective agent. This study provides evidence that TMP possesses obviously neuroprotection against glutamate-induced neurotoxicity, and the neuroprotection effect may result from its inhibiting expression of NMDARs, consequently blocking-up Ca2+ influx through the receptor’s associated ion channel, which can be neurotoxic.
文摘The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, and its mechanism of the antidepressant-like action. Forced-swimming, tail-suspension, reserpine-induced hypothermia, akinesia and ptosis, 5-hydroxytryptophan (5-HTP)-induced head-twitch, and potentiation of noradrenaline (NE) toxicity tests, were per-formed to assess the potential antidepressant-like activity of TMP and to study the mechanism by which TMP exerts the antidepressant-like action. Intragastric (ig) administration of TMP markedly reduced the duration of immobility during forced-swimming tests and tail-supension test in rats and mice. TMP partialy reversed reserpine-induced hypothermia, ptosis and akinesia, and potentiated NE toxicity in mice, and these are similar to those of clomipramine;however, TMP did not potentiate 5-HTP-induced head-twitch response (HTR) in mice, and this is different from that of fluoxetine (FLU). The present data provide evidences that TMP possesses potent antidepressant-like activity, and it might be an adrenergic component of pharmacological activity, and its mechanism of antidepressant-like action is similar to that of clomipramine, and different from that of FLU.
文摘The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, in chronic mild stress (CMS)-induced rat model of depression. Male Sprague-Dawley (SD) strain rats were divided into six matched groups (n = 13 or 14 in each group) based on their sucrose consumption: control, CMS, CMS + fluoxetine (FLU), and CMS + TMP groups. The rats except control were housed separately in different rooms, and the rat model of depression was established by exposing to an unpredictable sequence of stressors for 28 days;the rats in CMS + FLU were exposed to CMS and received administration of FLU (2.0 mg/kg/d, ig) for 28 days;the rats in CMS + TMP groups were exposed to CMS and received administration of TMP (10, 20, 40 mg/kg/d, ig), respectively, for 28 days. The rats in control group were given ordinary daily care, and the rats in control and CMS groups received ig administration of normal saline instead of FLU or TMP. The body weight, food intake and fluid consumption were measured, and the behaviors were examined by open field test before and after CMS, and forced-swimming test was performed 1 day after last unpredictable stressor. Chronic administration of TMP partially reversed the effects of CMS on consumption of sucrose solution and locomotion and exploration behavior, and potently shortened the immobility time during forced-swimming test following CMS in rats. The results showed that long-term administration of TMP partially reversed the effects of CMS on the body weight gain, the consumption of sucrose solution, the squares crossin gand rearing in open field test, and the immobility time during forced-swimming test in rats. The present data provide evidences that TMP possesses obvious antidepressant-like activity in CMS-induced rat model of depression.
文摘Objective To observe the effects or the ramethylpyrazine (TMP ) on ret Ina to find o ut whe ther it can protect retlna from glaucomatous damage. Methods Twenty-four rabblts were randomIy dlvided lnto rour groups.one eye or each rabblt was model eye lnduced by 2% methyicelluious, and the other was control eye. Normal saline,TMP, timolol and a cobolnation or tlmolol and TMP were admlnlstrated to group A, B, C and D respectlvely. At the end of 4th week, eyes were excavated for Iight and electron microscoplc study. ResuIts The numbers of ganglion cells (P <o. o1) and bipolar cells (P <o. o1) ln model eye were different slgnif1cantly between group A and B. in group A, tke modeI eye gangIlon cells were karyopyknosls, chromatln marglnatlon and nucIear membrane rupture; some inner nuclear cells dcveloped marked lytlc changes l’ outer segmentaweared 4lsorganlzed i but ’group B changed sllghtly. Concndlon The results suggest that TMP may protect retlna from gIaucomatous damage.
基金supported by the National Natural Science Foundation of China(82004193)CACMS Innovation Fund(CI 2021A00914)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ14-YQ-007).
文摘Angiogenesis in atherosclerosis(AS)promotes plaque destabilization.miR-126 has a significant role in angiogenesis.Tetramethylpyrazine(TMP)and paeoniflorin(PF)have anti-atherosclerotic effects.However,the miR-126-related mechanisms of TMP and PF combination(TMP-PF)on angiogenesis in AS have not been understood.To explore the mechanism of TMP-PF on angiogenesis in AS targeting miR-126.Human umbilical vein endothelial cells(HUVECs)were assigned into the control,model,TMP-PF,TMP-PF+miR-126 inhibitor,and simvastatin groups.HUVECs were transfected with miR-126 inhibitor or negative control,incubated with oxidized low-density lipoprotein(ox-LDL)to establish AS model,and then treated with TMP-PF or simvastatin.Cell proliferation,migration,and tube formation assays are conducted,and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The expression level of miR-126 was confirmed by polymerase chain reaction(PCR).0x-LDL promoted HUVECs proliferation,migration,and tube formation,downregulated miR-126 expression,and increased the expression of VEGF,VEGFR2,bFGF,and FGFR1.TMP-PF inhibited proliferation,migration,and tube formation,upregulated miR-126 expression and decreased the expression of VEGF,VEGFR2,bFGF,and FGFR1 in ox-LDL-induced HUVECs.However,the effects of TMP-PF on angiogenesis and the expression of miR-126,VEGF,VEGFR2,and FGFR1 were abolished by miR-126 inhibitor.TMP-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway,which might elucidate the underlying mechanism of TMP-PF in alleviating AS.
基金Supported by the National Natural Science Foundation of China(No.81804098,81673982)Natural Science Foundation of Jiangsu Province(No.BK20180219)+1 种基金Young Talents in Jiangsu Province(No.QNRC2016255)Youth Project of Suzhou Traditional Chinese Medicine Hospital(No.YQN2016003)
文摘Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine(TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, antilipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.
基金The authors gratefully acknowledge the financial support by Department of Science and Technology,Guangdong,China(2010B03070009).
文摘The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)administration.After i.n.,i.g.and i.v.administration of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals.The concentration of TMPP in the samples was analyzed by HPLC.The area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration.After i.n.administration,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between i.n.route and i.v.injection was 0.68,which was greater than that obtained after i.g.administration(0.43).The systemic bioavailability obtained with i.n.administration was greater than that obtained by the i.g.route(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral cortex.Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.
基金This work was supported by the Xuanjiu Group Co.(W2016JSKF0081).
文摘Tetramethylpyrazine(TTMP),an important aroma compound,was produced by Bacillus amyloliquefaciens XJB-104 with distillers’grains as raw material.The yield of TTMP under optimized fermentation procedure was 3176.52 mg/L.TTMP in the fermentation broth was purified and the purity(>99%)was measured by gas chromatography-mass spectrometry.Furthermore,the hepatoprotective activity of TTMP in ethanol-water system was evaluated by biochemical indicators of liver injury,parameters of antioxidant defense system and inflammatory response,and liver histopathological assessment in mice.Ethanol treatment increased serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phos-phatase and lactate dehydrogenase,suggesting liver damage.Both high and low dose of TTMP significantly decreased levels of these indicators.Furthermore,the reduction in the activities or concentrations of superoxide dismutase,catalase,reduced glutathione and malondialdehyde in liver tissue caused by ethanol was significantly alleviated by TTMP.Increased inflammatory cytokines including transcription factor,tumor necrosis factor,interleukin-1beta,interleukin,macrophage chemoattractant protein,inducible nitric oxide synthase and cyclooxygenase were also suppressed by TTMP treatment.It is concluded that TTMP in ethanol-water system has potential liver-protective activity,especially when ethanol is consumed at low doses for short periods of time.
基金supported by the Key Project of Medical Science of Hebei Province(No.20170185)
文摘Objective: To further explore the function of combine use of tetramethylpyrazine(TMP) and cisplatin(DDP) in lung carcinoma. Methods: We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor(VEGF), Kruppel-like factor 4(KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. Results: The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. Conclusion: KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways.
