Research progress on the role of transient receptor potential canonical 6 in ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca2+ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca2+ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

Determination of bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride by UPLC-MS/MS / 药学学报

An UPLC-MS/MS method was established for the quantification of the genotoxic impurities bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride. The chromatographic separation of the two genotoxic impurities was performed on Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) at 20 ℃. A mixture of 5 mmol·L-1 ammonium hydrogen carbonate aqueous solution and acetonitrile at a flow rate of 0.3 mL·min-1 in gradient elution mode was employed as mobile phase. The UPLC-MS/MS was equipped with electrospray ionization in positive ionization mode and adopted multiple reaction monitoring mode. We found that the calibration curves of the two genotoxic impurities were linear in the range of 0.1-10 ng·mL-1. The limit of detection was 0.10 ng·mL-1 for bis(2-chloroethyl)amine hydrochloride and the average recovery was 101.53% (RSD = 4.06%). The limit of detection was 0.01 ng·mL-1 for 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride and the average recovery was 97.95% (RSD = 1.27%). The sample solution was stable for 24 h. No bis(2-chloroethyl)amine hydrochloride was detected in the samples, and the content of 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in the samples was within the limit. This research provides a method to improve the quality control standards of trazadone.

Synthesis and protein tyrosine kinases inhibitory activity of substituted benzyl piperazine derivatives / 国际药学研究杂志

Objective Using substituted benzyl piperazine as the raw material to design and synthesize new piperazine deriva-tives with protein tyrosine kinase(PTK)inhibitory activity. Methods Benzoic acid was used as starting compound to synthesize a key intermediate,2-chloroethyl benzoate,and the target compounds were synthesized by further reaction of the key intermediate with different substituted benzyl piperazine derivatives.Enzyme-linked immunosorbent assay(ELISA)was used to test the PTK inhibitory activity of the compounds.Results Fifteen new compounds were synthesized and their structures were verified by IR,1H NMR,MS, and elemental analysis.The PTK inhibitory activity of 3h and 3o was stronger than that of the other compounds.Conclusion The syn-thetic method is simple,and the raw materials are cheap and readily available.Compounds 3h and 3o showed relatively higher PTK in-hibitory activities.

Determination of Related Substances in Piperazine Ferulate by HPLC / 中国药师

Objective:To establish an HPLC method for the determination of related substances in piperazine ferulate. Methods:An HPLC method was used to determine the related substances in piperazine ferulate. The separation was performed on an Xtimate C18 column (250 mm × 4. 6 mm, 5 μm). The mobile phase was 0. 5% acetic acid-methanol-acetonitrile with gradient elution. The flow rate was 1. 0 ml·min-1 and the column temperature was 30℃. The detection wavelength was 286 nm and the injection volume was 20μl. Results:Ferulic acid had a good linear relationship within the range of 5-30 μg·ml-1(r=1.0000). The detection limit was 0. 02 ng. Conclusion:The method is reliable, simple, accurate, stable and durable, and suitable for the determination of related sub-stances in piperazine ferulate.

Synthesis and inhibitory activities on vascular smooth muscle cell proliferation of furan-acrylic acyl group piperazine derivatives / 中国生化药物杂志

Objective To synthesis,nine N-[3-(2-furanyl)-acryloyl]-N'-substituted benzyl piperazine derivatives were synthesized and evaluated for their primary biological activities.Methods First, the furylacrylic acid was synthesized, Then the target compounds could be obtained by direct furylacrylic acid with the different substituted benzyl piperazine derivatives.In the biological active experiments, taking the different concentrations, comparing with the blank test, the inhibitory effect of the target compounds on VSMC proliferation was investigated by MTT.Results The successful synthesis of nine new compounds.The method was mild and get high yields.The structures of these compounds were confirmed by IR 1 H-NMR, MS, and elemental analysis.The results of preliminary activity test showed that the synthesized products exhibited inhibitory activity at different concentrations , and the highest inhibitory rate was 15μg/mL.Pharmacological results showed that the compounds 3e, 3f and 3 g showed the moderate inhibitory activities against vascular smooth muscle cells proliferation were higher than other compounds , and were worth further studying.Conclusion The synthesized compounds have inhibitory activities and could very well lead to the development of novel types of treat atherosclerosis drug .

Effects of piperazine ferulate tablets combined with Huangqi injection on β2-microglobulin, NGAL and clinical efficacy in patients with acute renal failure / 中国生化药物杂志

Objective To investigate the effects of piperazine ferulate tablets combined with Huangqi injection on β2-microglobulin,NGAL and clinical efficacy in patients with acute renal failure.Methods A total of 56 patients with acute renal failure from June 2012 to October 2015 in our hospital were collected and randomly divided into the experimental group and the control group with 28 cases in each group.All patients before the treatment of conventional care,diuretics and vasodilators to increase the patient's serum protein and vitamins,so that patients with the body's pH,moisture and electrolyte balance,and gave hemodialysis and low molecular heparin anticoagulant therapy.Patients in the control group were treated on the base of the conventional therapy withastragalus injection 20mL/time,one time a day,intravenous drip,treatment of four weeks; patients in the experimental group were treated on the base of the control group with piperazine ferulate tablet 200mg/time,three times/day,treatment of four weeks.After treatment,compared patients' β2 microsphere protein,NGAL and KIM-1 levels.Results There was no significant difference in the survival rate between the two groups.Compared with before treatment,β2 microsphere protein,NGAL and KIM-1 levels in two groups were lower(P<0.05);Compared with control group,β2 microsphere protein,NGAL and KIM-1 levels in the experimental group were lower(P<0.05).Conclusion Piperazine ferulate tablets combine with astragalus injection in the treatment of patients with acute renal failure have a better clinical curative effect,speculate that the mechanism is relate to reduce β2 microsphere protein,NGAL and KIM-1 levels.

Determination of Residual Organic Solvents in Piperazine Ferulate by GC / 中国药师

Objective:To establish a method for the determination of benzene, chlorine alcohol and pyridine residues in piperazine ferulate. Methods:GC was used with a DB-624 (30 m × 0. 53 mm, 1. 0 μm) elastic quartz capillary column. The flame ionization detector was used with nitrogen as the carrier gas. The initial temperature was 50℃, maintaining for 5 min, and raised to 80℃ at the rate of 10℃·min-1 , and then raised to 200℃ at the rate of 50℃·min-1 , and maintaining for 4 minutes. The inlet temperature was 200℃, and the detector temperature was 220℃. The split ratio was 1 ∶1 and the injection volume was 1μl. The flow rate was 3 ml· min-1. Results:The linear range of benzene was 0.16-0.96 μg·ml-1(r=0.999 5), the average recovery was 95.7% (RSD =2.1, n=9), and the detection limit was 0.16 ng. The linear range of chlorine alcohol was 16.11-96.65 μg·ml-1(r=0.999 7), the average recovery was 97. 8% (RSD=2. 1, n=9), and the detection limit was 0. 62 ng. The linear range of pyridine was 15. 87-95. 23 μg·ml-1(r=0. 999 8), the average recovery was 99. 2% (RSD=1. 3, n=9), and the detection limit was 0. 15 ng. Con-clusion:The method is reliable, simple, accurate and stable, and suitable for the determination of benzene, chlorine alcohol and pyri-dine residues in piperazine ferulate.

Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 µM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 µM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents.

Clinical Observation of Piperazine Ferulate Combined with Glutathione in the Treatment of Diabetic Ne-phropathy / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of piperazine ferulate combined with glutathione in the treatment of diabetic nephropathy. METHODS:80 patients with diabetic nephropathy in our hospital were divided into observation group and control group according to random number table,with 40 cases in each group. Both groups was given general treatment as blood glucose,blood lipid and blood pressure control. Control group was additionally given Reduced glutathione tablets 400 mg, tid,on the basis of general treatment. Observation group was additionally given Piperazine ferulate tablets 100 mg,tid,on the ba-sis of control group. Both groups were treated for 12 weeks. The fasting plasma glucose(FPG),2 h postprandial plasma glucose(2 hPG),blood pressure,blood lipid,serum creatinine (Scr),blood urea nitrogen (BUN),24 h urinary total protein and albumin, urine β2 microglobulin(β2-MG)and N-acetyl-β-glucosaminidase(NAG)of 2 groups were detected before and after treatment. The occurrence of ADR was observed. RESULTS:Before treatment,there was no statistical significance in FPG,2 hPG,blood pres-sure,blood lipid,Scr,BUN,24 h urinary total protein and albumin,urine β2-MG and NAG between 2 groups(P>0.05). After treatment,above indexes of 2 groups were improved significantly,and the observation group was better than the control group, with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:In the treatment of diabetic ne-phropathy,piperazine ferulate combined with glutathione can improve blood glucose,blood pressure,blood lipid levels and renal function with good safety.

Effects of alcoholic extract of Curcuma longa on Ascaridia infestation affecting chicken.

Ascaridia galli, the common intestinal nematode, remains a major cause of economic loss in the poultry industry in developing countries. Treatments using chemicals are not only expensive but also affect host health. Plant extracts as better alternative is gaining significance. Here, we have studied the effects of alcoholic extract of turmeric, Curcuma longa L. (Zingiberaceae) roots, against A. galli infection in chicken. Different concentrations of C. longa root extract were tested in vitro on 5 groups of adults A. galli worms and in vivo on 6 groups of chicks. The results showed that the turmeric root extract @ 60 mg mL-1 in vitro significantly (P < 0.001) proved paralytic and fatal against worms (16.80±1.28 h). In vivo, chicken groups (G2-G6) were infected with an average of 300±12 embryonated eggs of A. galli. The G2 was not given any treatment while G3 was treated with piperazine (@ 200 mg kg-1 body wt.); and Groups 4, 5 and 6 were given turmeric @ 200, 400 and 600 mg kg-1 body wt., respectively. The mean number of worms extracted at the end of the trial in G2 (untreated) was 18.10±2.42, while the G3 treated with piperazine had no worms. Groups 4 and 5 did not show any significant difference compared to G2. However, G6 that had 3.20±1.33 worms was statistically significant. Higher concentrations of turmeric given to infected chickens significantly reduced the length and weight of worms. The study showed that the worm infestation damaged the intestinal villi, and treatment with high concentration of C. longa had healing effects and restored the integrity of intestinal mucosa. The results have demonstrated the ameliorating effect of C. longa turmeric on A. galli infested chickens.

Piperazine derivate ofβ-elemene(DX2) induces human hepatoma HepG2 cell apoptosis through mitochondrial pathway / 国际药学研究杂志

Objective To study the antiproliferative effect of DX2, a piperazine derivate of β-elemene, on human hepatoma HepG2 cells. Methods Cell viability was measured by MTT method. Morphological changes were observed by phase contrast microscopy and acridine orange staining. Apoptotic cell ratio was measured by flow cytometric analysis. Protein level was detected by Western blot analysis. Results DX2 Induced apoptotic morphological changes in HepG2 cells and increased the ratio of apoptotic cells. Treatment of HepG2 cells with DX2 increased the Bax/Bcl-2 ratio, induced the activation of caspase-9 and caspase-3 and caused the degradation of ICAD which was the substrate of capase-3. Conclusion DX2 Induces HepG2 cell death via activation of intrinsic mitochondrial pathway.

Piperazine derivate of β-elemene (DX2) induces human hepatoma HepG2 cell apoptosis through mitochondrial pathway / 国际药学研究杂志

Objective To study the antiproliferative effect of DX2, a piperazine derivate of P-elemene, on human hepatoma HepG2 cells. Methods Cell viability was measured by MTT method. Morphological changes were observed by phase contrast microscopy and acridine orange staining. Apoptotic cell ratio was measured by flow cytometric analysis. Protein level was detected by Western blot analysis. Results DX2 Induced apoptotic morphological changes in HepG2 cells and increased the ratio of apoptotic cells. Treatment of HepG2 cells with DX2 increased the Bax/Bcl-2 ratio, induced the activation of caspase-9 and caspase-3 and caused the degradation of ICAD which was the substrate of capase-3. Conclusion DX2 Induces HepG2 cell death via activation of intrinsic mitochondrial pathway.

Piperazine constituents in fruits of Physalis alkekengi var. francheti / 中草药

Objective: To study the chemical constituents in the fruits of Physalis alkekengi var francheti. Methods: The piperazine constituents were isolated and purified with repeated silica gel column chromatography and RP-preparative HPLC. Their structures were determined by NMR spectroscopy. Results: Thirteen compounds were isolated and elucidated as (3S, 6R)-3-isopropyl-6-(2- methyl propyl)-2, 5-piperazine diketone (1), (3S, 6S)-3-isobutyl-6-isopropyl-2, 5-piperazine diketone (2), (3S, 6S)-3, 6-two(2-methyl propyl)-2, 5-piperazine diketone (3), (3S, 6S)-3, 6-di-isopropyl-2, 5-piperazine di-ketone (4), (3S, 6R)-3-(2-methyl propyl)-6-benzyl- 2, 5-piperazine diketone (5), (3S, 6S)-3-isobutyl-6-benzyl-2, 5-piperazine diketone (6), (3S, 6S)-3-isopropyl-6-(p-hydroxy benzyl)-2, 5-piperazine diketone (7), (3S, 6R)-3-isopropyl-6-(p-hydroxy benzyl)-2, 5-piperazine diketone (8), (3S, 6R)-3-(2-methyl propyl)-6- (p-hydroxy benzyl)-2, 5-piperazine diketone 9), (3S, 6S)-3-isobutyl-6-(p-hydroxy benzyl)-2, 5-piperazine diketone (10), (3S, 6S)-3- isopropyl-6-benzyl-2, 5-piperazine diketone (11), (3S, 6R)-3-isobutyl-6-(2-methyl propyl)-2, 5-piperazine diketone (12), and (3S, 6S)-3-benzyl-6-(p-hydroxy benzyl)-2, 5-piperazine diketone (13). Conclusion: Compounds 1-13 are firstly obtained from this plant.

Implicaciones mttabólicas y clínicas de algunas drogas de diseño / Metabolic and ciinical implications of some designe ddrugs

Antecedentes: Las drogas de diseño del tipo anfetamina, o de benzil y fenil piperazina, o del tipo pirrolidinfenona, producen sentimientos de euforia, energía y deseos de socializar, por eso son conocidas como rave drugs o drogas de club. A pesar de que los consumidores aducen que son drogas seguras, estudios experimentales en biomodelos y de tipo epidemiológico en humanos, indican riesgos potenciales para quien las usa. Materiales y Métodos: El presente artículo de revisión analiza, cualitativamente, la literatura científica disponible en las bases de datos Science Direct y PUBMED, relacionada con el metabolismo de estas drogas recreacionales y sus implicaciones en salud. Resultados: Se obtuvo información pertinente relacionada con los objetivos propuestos, por lo cual puede clasificarse en 2 secciones a saber: metabolismo de las drogas de diseño e implicaciones clínicas de su consumo. Conclusión: Las vías metabólicas que involucran isoenzimas P450 son responsables de la degradación hepática de las drogas de diseño. Existen riesgos potenciales para quien las consume, entre los que se encuentran el síndrome de serotonina, hepatotoxicidad, neurotoxicidad y psicopatología.

Background: Designer drugs of the amphetamine, benzyl, phenyl piperazine, or pyrrolidinophenone type produce feelings of euphoria and energy and a desire to socialize, reason why they are known as "rave drugs" or "club drugs". Although consumers adduce that these are safe drugs, experimental studies using bio models and epidemiological studies in humans, indicate potential risks for users. Materials and Methods: The review article analyses quantitatively scientific literature from Science Direct and PUBMED data bases related to metabolism of these drugs and their implications in health. Results: Relevant information related to the objectives proposed in the present review was found and it can be classified in 2 sections as follows: metabolism of designer drugs and clinical implications of consumption of designer drugs. Conclusion: The metabolic pathways which involve P450 isoenzymes are responsible for hepatic degradation of designer drugs. There are potential risks for consumers such as serotonin syndrome, hepatotoxicity, neurotoxicity, and psychopathology.

Anthelmintic activity of methanolic extract of rhizomes of picrorrhiza kurroa royal ex. Benth.

The objective of this study is to evaluate and compare the Anthelmintic activity of methanolic extract of Picrorrhiza kurroa Royle ex. Benth (Scrophhulariaceae). Picrorrhiza kurroaia a small perennial herb growing in the hilly parts of the North-western Himalayan region in India and Nepal. Earth worms were used for Anthelmintic activity. Piperazine citrate was used as standard drug. Time required for paralysis and death of the earth worms were noted for each sample.

The applicated value of Gui piperazine strange maleate in the treatment of patients with acute cerebral infarction / 中国基层医药

Objective To explore the influence of Gui piperazine strange maleate on the high sensitive C-reactive protein(hs-CRP) and S100B in the serum of patients with acute cerebral infarction.Methods 90 patients with acute cerebral infarction were randomly divided into two groups,the control group(45 cases) and the treatment group (45 cases).The patients in the control group were treated through the conventional treatment,while the patients in the treatment group were treated plus Gui piperazine strange maleate.They were treated for fourteen days.The hs-CRP and S100B in the serum were detected before and after treatment.Results The total effective rates were 93.3％ in the treatment group and 84.4％ in the control group.There was a significant difference between two groups(x2 =4.0125,P ＜ 0.05).The hs-CRP and S100B were decreased after treatment in both groups (all P ＜ 0.05),and there was a significant difference between two groups after treatment (all P ＜ 0.05).Conclusion Gui piperazine strange maleate can improve acute cerebral infarction through mitigating inflammation.

Bioactivity of indolylpiperidine-piperazine derivatives on α1 -adrenoceptor-mediated inotropic response / 中国药理学与毒理学杂志

OBJECTIVE To investigate the blocking activities of a series of potential α1-adrenoceptor (α1-AR) antagonists (Compounds B1 -B9) on α1-AR.METHODS ① A series of potential α1-adrenoceptor (α1-AR) antagonists,indolylpiperidine derivative (IPD) and Compounds B1 -B9,with indolylpiperidine moiety and different substitutes were synthesized through the coupling of indolylpiperidine and piperazine derivatives.② Inotropic responses experiment was used to examine blocking effects of IPD and Compounds B1 - B9 in isolated rat atria by phenylephrine (PE) stimulation.③ Blocking effect of IPD and Compounds B1 - B9 on phosphorylation level of extracellular signal-regulated kinase (ERK) in PE treated HEK293 cells was tested by Western blotting.RESULTS ① Potential α1-adrenoceptor (α1-AR) antagonists with indolylpiperidine moiety and different substitutes were synthesized successfully.② PE caused a dose-dependent inotropic response which was inhibited by pre-incubation of phentolamine (Phen),a non-selective α1-AR antagonist,IPD and Compounds B1,B3,B4,B7,B8 and B9,respectively; IPD and Compounds B4 and B8 caused an obvious rightward shift of inotropic response-curve,the pA2 values for IPD and Compounds B4 and B8 were 6.72 ± 0.21,6.86 ± 0.29 and 6.67 ± 0.19,respectively.③ Phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B1,B2,B3,B5,B6,B7,B8 and B9 or IPD in PE treated α1A-AR stably expressed HEK293 cells; PE-stimulated phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B2,B4,B7 or B8 in α1B-AR stably expressed HEK293 cells.CONCLUSION Compound B4 has a selective blocking activity on α1B-AR,and Compounds B1,B3,B5,B6 and B9 or IPD have a selective blocking activity on the phosphorylation level of ERK1/2.

Rapid analysis of piperazine ferulate tablets by optic-fiber sensing technology and the similarity of ultraviolet spectra / 药物分析学报

A rapid analysis method of piperazine ferulate tablets by optic-fiber sensing technology with UV-vis absorption spectrum was established.Qualitative and quantitative data were obtained and compared by maximum and minimum wavelength,absorbance and contrast spectra.Similarity method was used to identify authenticity of drugs.The difference of contents measured by this method and UV determination method in China Pharmacopoeia showed no statistical significance (P＞0.05),while the similarity can be used as a parameter to identify the authenticity of drugs.

Anthelmintic activity of aqueous and ethanolic extract of Trikatu Churna.

The present study was done with the aim to evaluate anthelmintic activity of Trikatu churna containing traditionally user herbs viz., Piper nigrum L. (Piperaceae), Piper longum L. (Piperaceae) and rhizome of Zingiber officinale Roscoe using adult earthworm Pheritima posthuma. All these three ingredients are spicy, commonly used in our daily diet, also well known for their tremendous therapeutic potential, since from the Vedic period. The aqueous and ethanolic extract of Trikatu churna and its ingredients were also screened for preliminary phytochemical studies. Piperazine citrate was used as standard and it was found that the TCEE activity is higher than TCAE.

A simple and straightforward synthesis of antihistaminic drug cetirizine.

The anti-histaminc drug cetirizine was synthesized in five linear steps with an overall yield of 50%. All the reactions were very clean and the isolation of products also very easy. Our synthetic strategy was applicable to large scale preparation of cetirizine.