Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Research Progress on the Anti-Atherosclerotic Effect and Mechanism of Tetramethylpyrazine

Atherosclerosis is a chronic vascular disease and the most common pathological change of cardiovascular disease.Its pathogenesis is closely related to inflammation,oxidative stress,lipid accumulation,and calcinosis.Tetramethylpyrazine plays an anti-atherosclerotic role by regulating lipid metabolism,inhibiting foam cell formation,alleviating inflammation,inhibiting vascular calcification and abnormal platelet activation,and has a cardiovascular protective effect.Therefore,this paper summarized the research progress of the anti-atherosclerosis effect and mechanism of tetramethylpyrazine.

Simultaneous Determination of Tetramethylpyrazine and Aspirin in a New Compound Formulation by Liquid Chromatography

Aim To establish a reversed-phase liquid chromatographic (LC) method forsimultaneous determination of tetramethylpyrazine (TMP) and aspirin in a new compound formulation.Methods Chromatographic separation of the two drugs was achieved on a Diamonsil C_(18) column, usinga binary mixture of methanol-1.5% acetic acid (35:65, V/V, pH = 3.1) as mobile phase at a flow rateof 1.0 mL·min^(-1). Results Separation was completed in less than 12 min. Benzoic acid was used asthe internal standard. Recoveries at levels corresponding to 80 % to 120 % of the label claim ofthe formulation ranged from 99.6 to 100.3 % for aspirin and from 99.9 to 101.3% for TMP. The linearrange was 12.6 - 150.9 μg·mL^(-1)(r= 0.9997, n = 5) for aspirin and 25.0- 300.0 μg·mL^(-1) (r =0.9999, n = 5) for TMP. Conclusion The method developed can be used for the simultaneousdetermination of TMP and aspirin in pharmaceutical preparations.

Tetramethylpyrazine在视网膜色素上皮细胞变性及脉络膜血流和RPE细胞氧化应激中的作用(英文)

目的:研究1%Tetramethylpyrazine(TMP)在视网膜色素上皮细胞(RPE)变性,脉络膜血流和RPE细胞氧化应激中的作用。方法:在碘酸钠诱导的大鼠RPE变性研究中,1%TMP滴眼液预先处理1wk,3次/d,1wk后予碘酸钠舌下静脉注射,在2wk和4wk末,视网膜电图(ERG)测量c波。色素微球体技术分析高眼压状态下TMP对脉络膜血流的影响。Methylthiazoltetrazolium(MTT)分析TMP在各种氧化应激中对RPE的保护作用。结果:碘酸钠注射后2wk,碘酸钠组ERG的c波下降至对照组的36%(P<0.01)。4wk后,碘酸钠组下降至对照组的46%(P<0.01),而1%TMP+碘酸钠组下降至对照组的77%(P<0.01)。与碘酸钠组比较,1%TMP+碘酸钠组控制了67%的c波下降(P<0.05)。在脉络膜血流的测量中,30,60,和120min的结果显示,TMP显著增加脉络膜血流。在氧化应激部分,不同浓度的TMP在各种氧化应激损伤中,对RPE都有各种程度的保护作用。结论:浓度为1%Tetramethylpyrazine可以显著保护碘酸钠和氧化应激诱导的RPE变性,增加脉络膜血流,并可能在AMD的治疗中发挥作用。

PROTECTIVE EFFECT OF TETRAMETHYLPYRAZINE ON LEARNING AND MEMORY FUNCTION IN D-GALACTOSE-LESIONED MICE

To explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice. Methods C57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg·kg-1·d-1). Normal saline, TMP, and Huper-zine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined. Results In this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice. Conclusion TMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

Intra-articular delivery of tetramethylpyrazine microspheres with enhanced articular cavity retention for treating osteoarthritis

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.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system

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.

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

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.

Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria 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 tria 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 15^th 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 mm^2, 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.

Anti-inflammatory and profibrinolytic effect of tetramethylpyrazine in acute coronary syndromes

Background and Objectives 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 C-reactive 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.

Protective Effects of Tetramethylpyrazine on Glutamate-Induced Neurotoxicity in Mice

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.

Antidepressant-Like Effect of Tetramethylpyrazine in Mice and Rats

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.

Antidepressant-Like Activity of Tetramethylpyrazine Measured by Chronic Experimental Method in Rat Model of Depression

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.

Catalytic Hydrogenation of Diacetyl Monoxime to Tetramethylpyrazine with the Soluble Transition Metal Catalysts

Catalytic hydrogenation of diacetyl monoxime to tetramethylpyrazine, by the homogeneous catalysts generated in situ from some transition metal chlorides with triphenylphosphine in ethanol under H-2 pressure of 0.6 similar to 4.6 MPa at 100 similar to 150 degrees C, has been studied. The optimum H-2 partial pressure was observed at about 1.3 MPa. The maximum conversion of diacetyl monoxime and yield of tetramethylpyrazine were 97% and 90%, respectively.

EXPERIMENTAL STUDY ON THE EFFECT OF ACUPUNCTURE ON TROPISM-DISTRIBUTION OF TETRAMETHYLPYRAZINE AND THE CONTENT OF cAMP IN ARTHRITIS RATS

Objective： To verify two hypotheses： 1 ） Acupuncture can increase the re-distribution of tetramethylpyrazine （ligustrazine） hydrochloride （TMPH） to the target organs in adjuvant arthritic rats. 2） Cyclic Adenosine-3＇, 5＇-menophesphete （cAMP） is one of the guidance cues involved in this event. Methods： A total of 40 Wistar rats were randomized into blank control （BC）, model （MO）, medication （ME）, Acupuncture （Acu） and Acu＋ ME groups, with 8 cases in each group. Arthritis model was established by subcutaneous injection of complete Freund＇ s adjuvant （0.1 mL） into the rat＇ s foot pad. Electrcacupuncture （ 15 Hz, 0.2-0.3V） was applied to bilateral “Daling”（大陵 PC 7）, “Taichong” （太冲 LR 3） and “Xiguan” （膝关 LR 7） for 20 min, and the contents of TMPH in the heart, liver, kidney and the foot （affected focus） tissues and the contents of cAMP in the heart and liver tissues were determined with high performance liquid chromatography and radioimmunoassay techniques respectively. Results： Oornpared with medication group, the TMPH contents in the heart, liver, kidney and the affected foot tissues in Acu-ME group was obviously higher （ P〈0.05, P〈0.01 ）. In comparison with ME and Acu groups, the cAMP contents in the heart and liver in Acu＋ ME group was also significantly higher （P〈 0.05, P 〈 0.01 ）. No significant differences were found between ME and Acu ＋ ME groups in TMPH content of kidney and between Acu＋ ME and BC groups in cAMP contents in both liver and heart tissues. Conclusion： Acupuncture may promote the target-tropism distribution of ligustrazine, and cAMP may play an important role in it.

EFFECTS OF TETRAMETHYLPYRAZINE ON RETINA OF RABBITS WITH EXPERIMENTAL GLAUCOMA

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.

INFLUENCE OF ACUPUNCTURE ON BRAIN-TAXIS OF TETRAMETHYLPYRAZINE IN ACUTE CEREBRAL INFARCTION RATS

Purpose: To observe the effect of acupuncture on the brain-taxis of tetramethylpyrazine (TMP) and to explore into the underlying mechanisms of combined action of acupuncture and medicine in the treatment of acute cerebral ischemia. Methods: 37 male Wistar rats were randomly divided into normal control group (n=10), sham-operation group (n=10), acute cerebral ischemia (ACI) + drug group (model group, n=8)and ACI+drug+acupuncture group (acupuncture group, n=9). Rat ACI model was established by using photochemical method. "Neiguan"(PC 6) and "Shuigou"(GV 26) were punctured and stimulated with both hand manipulation and electroacupuncture, 30 min and 16hrs after ACI. TMP was given to the rats of the later 2 groups using gastric perfusion method. High pressure chromatography (HPLC) was used to detect the target absorption level of TMP in the brain. Results: The content of TMP in the brain in acupuncture group was significantly higher than that in model group (P<0.01), suggesting that acupuncture can strengthen the brain-taxis of TMP in ACI rats, and combined administration of acupuncture and Chinese drug maybe work better for treatment of acute cerebral infarction. Conclusion: Acupuncture can strengthen the chemo-taxis of TMP to the brain in ACI rats.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)inhibits angiogenesis in atherosclerosis via miR-126/VEGF/VEGFR2 signaling pathway

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.

Tetramethylpyrazine Improves Postoperative Tissue Adhesion: A Drug Repurposing

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.