pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2023-11-5-422-431pmedpharm-1395Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEПротивовоспалительные и антирезорбтивные эффекты ацилзамещенных производных хромона в условиях экспериментального ревматоидного артритаAnti-inflammatory and antiresorptive effects of acyl substitution chromone derivatives in experimental model of rheumatoid arthritishttps://orcid.org/0000-0002-5595-8182ПоздняковД. И.PozdnyakovD. I.

кандидат фармацевтических наук, доцент, заведующий кафедрой фармакологи с курсом клинической фармакологии ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России.

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

Candidate of Sciences (Pharmacy), Assistant Professor, Head of the Department of Pharmacology with a course of Clinical Pharmacology of Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University. 

11, Kalinin Ave., Pyatigorsk, Russia, 357532

pozdniackow.dmitry@yandex.ruhttps://orcid.org/0000-0003-1571-9301КоряноваК. Н.KoryanovaK. N.

кандидат фармацевтических наук, доцент кафедры фармакологии с курсом клинической фармакологии ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России. 

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

 

Candidate of Sciences (Pharmacy), Associate Professor of the Department of Pharmacology with a Course of Clinical Pharmacology, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532

kskor-16@mail.ruhttps://orcid.org/0009-0009-9892-0326АрустамянК. К.ArustamyanK. K.

студентка 5-го курса лечебного факультета ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России. 

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

5th year student of the Medical Faculty of Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University. 

11, Kalinin Ave., Pyatigorsk, Russia, 357532

pozdniackow.dmitry@yandex.ruhttps://orcid.org/0009-0007-5838-3154МаргушевЧ. М.MargushevCh. M.

студент 5-го курса лечебного факультета ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России.

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

5th year student of the Medical Faculty of Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532

Funny.day.15@mail.ruhttps://orcid.org/0009-0003-8909-7389БаскаеваВ. С.BaskaevaV. S.

студентка 6-го курса лечебного факультета ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России.

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

6th year student the Medical Faculty of Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532

baskaevavaleria@yandex.ruhttps://orcid.org/0000-0003-4104-9217РуковицинаВ. М.RukovitsinaV. M.

кандидат фармацевтических наук, старший преподаватель кафедры органической химии ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России.

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

Candidate of Sciences (Pharmacy), Senior Lecturer of the Department of Organic Chemistry of Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University. 

11, Kalinin Ave., Pyatigorsk, Russia, 357532

rucovitcinavika@mail.ruhttps://orcid.org/0000-0001-6011-370XНасрулаеваХ. Н.NasrulayevaH. N.

кандидат фармацевтических наук, доцент кафедры фармакологии ФГБОУ ВО ДМУ Минздрава России. 

367000, Россия, г. Махачкала, пл. Ленина, д. 1

Candidate of Sciences (Pharmacy), Assistant Professor of the Department of Pharmacology of Dagestan State Medical University. 

1, Lenin Sq., Makhachkala, Russia, 367000

lisst32@mail.ruhttps://orcid.org/0000-0001-6605-6814ОлоховаЕ. А.OlokhovaE. A.

ассистент кафедры фармакологии и фармацевтического консультирования с курсом ПО, ФГБОУ ВО КМУ им. проф. В.Ф. Войно-Ясенецкого» Минздрава России.

660005, Россия, г. Красноярск, ул. Партизана Железняка, д. 1

Assistant of the Department of Pharmacology and Pharmaceutical Consulting with a course PO of Krasnoyarsk State Medical University n.a. Prof. V.F. Voino-Yasenetsky. 

1, Partizan Zheleznyak Str., Krasnoyarsk, Russia, 660005

tabletka@yandex.ruПятигорский медико-фармацевтический институт – филиал федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияPyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Дагестанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияDagestan State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииРоссияKrasnoyarsk State Medical University named after Professor V.F. Voino-YasenetskyRussian Federation202329012024115422431Copyright © Поздняков Д.И., Корянова К.Н., Арустамян К.К., Маргушев Ч.М., Баскаева В.С., Руковицина В.М., Насрулаева Х.Н., Олохова Е.А., 20242024Поздняков Д.И., Корянова К.Н., Арустамян К.К., Маргушев Ч.М., Баскаева В.С., Руковицина В.М., Насрулаева Х.Н., Олохова Е.А.Pozdnyakov D.I., Koryanova K.N., Arustamyan K.K., Margushev C.M., Baskaeva V.S., Rukovitsina V.M., Nasrulayeva H.N., Olokhova E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1395

Ревматоидный артрит (РА) – системное воспалительное заболевание, поражающее преимущественно мелкие и крупные суставы. Поиск новых лекарственных средств для лечения РА ведется постоянно, при этом перспективным направлением для создания новых противоревматических средств можно считать целенаправленный синтез политаргетных малых молекул.

Цель

Цель. Оценить противовоспалительное и антирезорбтивное действие ацилзамещенных производных хромона в условиях экспериментального ревматоидного артрита у крыс.

Материалы и методы

Материалы и методы. РА моделировали у крыс путем введения суспензии человеческого коллагена II типа и полного адъюванта Фрейнда (в соотношении 1:1) под подошвенный апоневроз задней конечности животного. Анализируемые вещества с шифрами Х3А7 и Х3А9 в дозе 20 мг/кг и препарат сравнения дексаметазон в дозе 3 мг/кг вводили внутрибрюшинно на протяжении 28-ми дней с момента воспроизведения РА. На 7-й, 14-й, 21-й и 28-й день эксперимента определяли выраженность клинических проявлений РА. По истечении 28-ми дней у крыс в сыворотке крови оценивали изменение содержания цитокинов: фактора некроза опухоли альфа (ФНО-α), интерлейкинов (ИЛ-1, ИЛ-6, ИЛ-10 и ИЛ-12). В синовиальных тканях определяли изменение активности миелопероксидазы и концентрации матриксных металлопротеназ (ММП) 2-го и 9-го типа.

Результаты

Результаты. В ходе исследования было показано, что применение анализируемых соединений Х3А7 и Х3А9, а также препарата сравнения способствовало уменьшению выраженности клинических проявлений РА, начиная с 14-го дня эксперимента. В дальнейшем было продемонстрировано, что у животных, получавших дексаметазон, содержание цитокинов в сыворотке крови уменьшилось по отношению к нелеченым животным: ФНО-α – на 57,8% (p <0,05), ИЛ-1 – 64,1% (p <0,05), ИЛ-6 – 59,1% (p <0,05) и ИЛ-12 – 72,3% (p <0,05), при повышении уровня ИЛ-10 – на 75,4% (p <0,05). Аналогично изменялся цитокиновый профиль сыворотки крови при введении животным исследуемых соединений. Также стоит отметить, что на фоне введения дексаметазона, веществ Х3А7 и Х3А9 активность миелопероксидазы снизилась на 41,7 (p <0,05), 61,7 (p <0,05) и 65,0% (p <0,05) соответственно, тогда как концентрация ММП2 уменьшилась на 24,0 (p <0,05), 38,5 (p <0,05) и 34,4% (p <0,05) соответственно, а ММП9 – на 13,5 (p <0,05), 37,9 (p <0,05) и 35,6% (p <0,05).

Заключение

Заключение. Проведенное исследование показало, что введение анализируемых производных хромона Х3А7 и Х3А9 подавляет реакции воспаления и резорбтивные процессы в синовиальных тканях, что может служить основанием для их дальнейшего изучения в качестве противоревматических средств.

Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting mainly small and major joints. The development for new drugs for the treatment of RAs is constantly underway, while the purposeful synthesis of multi-targeted small molecules can be considered a promising direction for the synthesis of new anti-rheumatic drugs.

The aim

The aim. To evaluate the anti-inflammatory and antiresorptive effects of acyl substituted chromone derivatives in experimental animal model for rheumatoid arthritis.

Materials and methods

Materials and methods. RА was modeled in rats by injection of a suspension of human type II collagen and a complete Freunds adjuvant (in a ratio of 1:1) under plantar aponeurosis of the hind limb of the animal. The analyzed substances under ciphers X3A7 and X3A9 at a dose of 20 mg/kg and the reference drug dexamethasone at a dose of 3 mg/kg were administered intraperitoneally for 28 days from the moment of RA modeling. On the 7th, 14th, 21st and 28th days of the experiment, the severity of the clinical manifestations of RA was determined. After 28 days, changes in the content of cytokines in the rats blood serum were assessed: tumor necrosis factor-α (TNF-α), interleukins (IL-1, IL-6, IL-10 and IL-12). Changes of myeloperoxidase activity and concentrations of matrix metalloproteinases (MMPs) of type 2 and 9 were determined in synovial tissues.

Results

Results. During the study, it was shown that the use of the tested compounds X3A7 and X3A9, as well as the reference, contributed to a decrease in the severity of clinical manifestations of RA, starting from the 14th day of the experiment. Subsequently, it was demonstrated that in animals treated with dexamethasone, the cytokine content in blood serum decreased in relation to untreated animals: TNF-α – by 57.8% (p <0.05), IL-1 – 64.1% (p <0.05), IL-6 – 59.1% (p <0.05) and IL-12 – 72.3% (p <0.05), with an increase in the level of IL-10 – by 75.4% (p <0.05). The cytokine profile of the blood serum changed similarly when the studied compounds were administered to animals. It worth be noting that against the background of the administration of dexamethasone, X3A7 and X3A9 substances, the activity of myeloperoxidase decreased by 41.7 (p <0.05), 61.7 (p <0.05) and 65.0% (p <0.05), respectively, while the concentration of MMP2 decreased by 24.0 (p <0.05), 38.5 (p <0.05) and 34.4% (p <0.05), respectively, and MMP9 – by 13.5 (p <0.05), 37.9 (p <0.05) and 35.6% (p <0.05).

Conclusion

Conclusion. The study showed that the administration of the analyzed chromone derivatives X3A7 and X3A9 suppresses inflammatory reactions and resorptive processes in synovial tissues, which can serve as a basis for their further study as antirheumatic agents.

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The authors declare that there are no conflicts of interest present.