scholarly journals Effect of cyanopyrrolidine derivatives on the activity of prolylendopeptidase, acute exudative inflammation and visceral pain in mice

2020 ◽  
Vol 66 (1) ◽  
pp. 77-82
Author(s):  
E.A. Ivanova ◽  
N.N. Zolotov ◽  
V.F. Pozdnev ◽  
T.A. Voronina
Keyword(s):  
Acetic Acid ◽  
Visceral Pain ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Writhing Test ◽  
Tert Butyl

Cyanopyrrolidine derivatives benzyloxycarbonyl-methionyl-cyanopyrrolidine (ZMetPrdN), benzyloxycarbonylphenylalanyl- cyanopyrrolidine (ZPhePrdN), tert-butyl-hydroxycarbonyl-glycyl-cyanopyrrolidine (BocGlyPrdN), tert-butyl-hydroxycarbonyl-methionyl-cyanopyrrolidine (BocMetPrdN) are inhibitors of prolylendopeptidase (PREP; EC 3.4.21.26) with an IC50 of 2 nM to 12 nM. ZMetPrdN, ZPhePrdN and BocMetPrdN additionally inhibited dipeptidyl peptidase IV (DPP-4; EC 3.4.14.5) with an IC50 of 1100 nM to 3200 nM. All the compounds have antinociceptive properties in the acetic acid writhing test in mice. But only cyanopyrrolidine derivatives with aromatic substituents decrease exudative inflammation. The cyanopyrrolidine derivatives also increase PREP activity and compensatorily reduce DPP-4 activity in the serum of mice three hours after the induction of inflammation. Thus, cyanopyrrolidine derivatives exhibit antinociceptive and antiexudative properties in part via their effect on PREP.

scholarly journals Alteration of dipeptidyl peptidase IV activity in rodents with exudative inflammation

2018 ◽  
pp. 51-57
Author(s):  
Е.А. Иванова ◽  
Н.Н. Золотов ◽  
В.Ф. Позднев ◽  
Т.А. Воронина
Keyword(s):  
Acetic Acid ◽  
Blood Serum ◽  
Immune Cells ◽  
Inflammatory Process ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Paw Edema ◽  
Inflammation Mediators ◽  
Severe Inflammation

Известно, что участие дипептидилпептидазы IV (ЕС 3.4.14.5, CD26, ДПП-4) в воспалительном процессе обусловлено ее влиянием на хемотаксис, пролиферацию и накопление иммунных клеток в тканях и ферментативным воздействием на ряд медиаторов воспаления. Целью данной работы являлось изучение изменения активности растворимой формы ДПП-4 при экссудативном воспалении у грызунов и оценка влияния ингибиторов ДПП-4 на его выраженность. Методы. Активность ДПП-4 в перитонеальном выпоте у крыс с моделью уксусного перитонита и мышей с моделью гликоген-индуцированного перитонита, а также в сыворотке крови крыс с моделью уксусного перитонита и с моделью вызванного каррагенаном отека лапы оценивали спектрофлуориметрически. Результаты. Установлено, что при экспериментальных перитонитах в экссудате мышей и крыс значимо увеличивается активность ДПП-4. Кроме того, при уксусном перитоните активность ДПП-4 достоверно возрастает и в сыворотке крови. У крыс с отеком лапы достоверного увеличения активности ДПП-4 в сыворотке крови не выявлено, что может быть обусловлено меньшей тяжестью воспалительного процесса. Введение мышам ингибиторов ДПП-4, отличающихся параметрами ингибирования фермента - ситаглиптина (IC = 25,0 ± 9,0 нмоль/л) и AlaPrdN (2-S-аланина цианопирролидин, IC = 2,0 ± 0,3 нмоль/л), не привело к достоверному изменению выраженности экссудации при уксусном перитоните у мышей. Заключение. Полученные данные позволяют полагать, что повышение активности ДПП-4 при остром экссудативном воспалении является следствием начавшегося воспалительного процесса. The role of dipeptidyl peptidase IV (ЕС 3.4.14.5., CD26, DPPIV) in inflammation is based on its effects on chemotaxis, proliferation, and accumulation of immune cells in tissues, and proteolysis of some inflammation mediators. The goal of this study was to evaluate the activity of soluble DPPIV in rodents with exudative inflammation and effects of DPPIV inhibitors on exudation. Methods. DPPIV activity was measured using the fluorometric assay in peritoneal exudate from rats with acetic acid-induced peritonitis and mice with glycogen-induced peritonitis as well as in serum of rats with acetic-induced peritonitis and carrageenan-induced paw edema. Results. The DPPIV activity was significantly increased in the exudate from mice and rats with experimental peritonitis. Furthermore, the DPPIV activity was significantly higher in blood serum of rats with acetic acid-induced peritonitis. Absence of a significant increase in the serum DPPIV activity in rats with paw edema could be due to less severe inflammation. DPPIV inhibitors with different ICs, sitagliptin (IC = 25.0 ± 9.0 nmol/l) and AlaPrdN (2-S-alanine cyanopyrrolidine, IC = 2.0 ± 0.3 nmol/l), did not significantly change the exudation intensity in mice with acetic acid-induced peritonitis. Conclusion. The increased DPPIV activity in acute exudative inflammation results from inflammatory process onset.

Phytochemical and Pharmacological Activity of Myristica fragrans Houtt (Myristicaceae)

2017 ◽  
Vol 9 (01) ◽  
Author(s):  
Md Arifur Rahman Chowdhury ◽  
Manirujjaman . ◽  
Md Mazedul Haq
Keyword(s):  
Acetic Acid ◽  
Phenolic Content ◽  
Methanolic Extract ◽  
Radical Scavenging ◽  
Antioxidant Property ◽  
Free Radical Scavenging ◽  
Total Phenolic ◽  
Writhing Test ◽  
Myristica Fragrans ◽  
Myristica Fragrans Houtt

Objective: Myristica fragrans Houtt commonly used as traditional medicine for alleviating of various disorders. The purpose of our study was to map out the in vitro antioxidant property and in vivo anti-hyperglycemic and analgesic effect of the methanolic extract of Myristica fragrans Houtt. (Seed and mace) (Myristicaceae) on Swiss albino mice. Methods: The processed powder of Myristica fragrans Houtt (seed and mace) were subjected to methanolic extraction by soxhlet filtration methods, and the desiccated extract was used for screening of antioxidant by DPPH free radical scavenging assessment as well as total phenolic content by using folin-ciocalteu reagent.Anti-hyperglycemic effect and analgesic action tested through alloxan induced antidiabetics test and acetic acid-tempted writhing test on mice. Results: In DPPH free radical scavenging assessment, free radicals neutralization expressed as % of inhibition 49.69±0.06% also by IC50 values as 68.43 µg/ml surmise middle level of antioxidant property. The total phenolic content expressed as 186.25 mg/g equivalent of gallic acid indicates, active phenolic content. Oral administration of 200 and 400 mg/kg of extract dose and reference drug vildagliptin (50 mg/kg) for the duration of the 4-day study period, and initiated % of inhibition the blood glucose level measured as 22.48%, 44.78% and 62.02% regard as the significant anti-hyperglycemic properties. The analgesic activity was investigated by using the acetic acid-induced writhing test in mice, at the dose of 200 mg/kg body and 400mg/kg weight, and resulting 50.4% and 68.10% correspondingly, which was considerably significant with a standard drug. Conclusion: The present study suggests that methanolic extract of seed and mace of Myristica fragrans Houtt can manage moderate oxidative stress as well as perform the painkilling action. Besides, prolong medication may enhance the new dimension of anti-hyperglycemic activity.

Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine

2017 ◽  
pp. 4-12
Author(s):  
Н.Н. Хлебникова ◽  
Н.А. Крупина
Keyword(s):  
Forced Swimming Test ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Forced Swimming ◽  
Face Validity ◽  
Neonatal Exposure ◽  
Depressive State ◽  
Serum Corticosterone ◽  
Old Rats ◽  
Swimming Test

В наших предыдущих исследованиях было показано, что ингибитор пролинспецифической пептидазы дипептидилпептидазы-IV (ДП-IV, EC 3.4.14.5) трипептид дипротин А, введенный крысам в 5-18 постнатальные дни, приводит к развитию у крыс подросткового возраста и взрослых животных эмоционально-мотивационных расстройств. Такие расстройства можно рассматривать как модель смешанного тревожно-депрессивного состояния. Однако специальных исследований по валидности данной модели проведено не было. Цель настоящей работы состояла в проверке влияния трициклического антидепрессанта имипрамина (ИМИ) на депрессивноподобное поведение крыс и уровень кортикостерона в сыворотке крови животных на модели смешанного тревожно-депрессивного состояния. Методика. У крыс в возрасте одного и двух мес. определяли уровень тревожности в автоматизированном тесте «Приподнятый крестообразный лабиринт» и оценивали депрессивноподобное поведение в тесте принудительного плавания. ИМИ вводили взрослым животным в течение 10 дней (20 мг/кг/день, интрагастрально). Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Неонатальное действие дипротина А приводило к повышению тревожности у крыс в возрасте 1 мес. Депрессивноподобное поведение обнаружено у животных в возрасте одного и двух мес. ИМИ нормализовал поведение животных в тесте принудительного плавания и снижал уровень кортикостерона в сыворотке крови крыс. Кроме того, ИМИ снижал вес крыс. Заключение. Результаты исследования свидетельствуют в пользу адекватности модели смешанного тревожно-депрессивного расстройства, возникающего у крыс вследствие действия ингибитора ДП-IV дипротина А на второй-третьей неделях постнатального развития, клиническому прообразу заболевания по критериям «внешней схожести», прогностической и конструкционной валидности. Previously, we have shown that the inhibitor of proline-specific peptidase, dipeptidyl peptidase-IV (DP-IV, EC 3.4.14.5), tripeptide diproptin A administered on postnatal days 5-18 induced emotional and motivational disorders in adolescent and adult rats. These disorders can be considered a model of a mixed anxiety-depression-like disorder. However, validation studies of this model are not available. The aim of this work was to test the effect of the tricyclic antidepressant, imipramine (IMI), on depressive-like behavior in rats and the level of serum corticosterone using the model of mixed anxiety-depressive state. Methods. The level of anxiety was assessed by the automated Elevated Plus Maze test and the depressive-like behavior was evaluated by the forced swimming test in one- and two-month old rats. IMI was administered to adult animals for ten days (20 mg/kg a day, intragastrically). Serum corticosterone concentrations were measured using ELISA. Results. The neonatal exposure to diprotin A increased anxiety in one-month old rats. The depressive-like behavior was observed in animals aged one and two months. IMI normalized behavior of animals in the forced swimming test and reduced serum levels of corticosterone. Also, IMI reduced body weight of rats. Conclusion. The results of the study evidenced adequacy of the model of mixed anxiety-depressive state induced by the DP-IV inhibitor, diprotin A, on the second and third postnatal weeks to the clinical prototype of disease according to criteria of face validity, predictive and construct validity.

Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

2020 ◽  
Vol 16 ◽  
Author(s):  
Lucas Ribeiro dos Santos ◽  
Marcio Luis Duarte ◽  
Maria Stella Peccin ◽  
Antônio Ricardo de Toledo Gagliardi ◽  
Tamara Melnik
Keyword(s):  
Hepatic Steatosis ◽  
Grey Literature ◽  
Specific Treatment ◽  
Reducing Power ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Cochrane Library ◽  
Vast Number ◽  
Dpp Iv ◽  
Dipeptidyl Peptidase Iv Inhibitors

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

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