mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IEO-1875mimmun-1875Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИммунотропные эффекты куркумина в составе оригинальных ректальных суппозиториев при экспериментальной болезни КронаImmunotropic effects of Curcuma longa extract as a component of original rectal suppositories in the dynamics of experimental Сrohn’s diseaseОсиковМ. В.OsikovМ. V.

д.м.н., профессор, заведующий кафедрой патофизиологии

г. Челябинск

PhD, MD (Medicine), Professor, Head, Department of Pathophysiology

Chelyabinsk

prof.osikov@yandex.ruСимонянЕ. В.SimonyanЕ. V.

к.фарм.н., доцент, заведующая кафедрой химии и фармации фармацевтического факультета

г. Челябинск

PhD (Pharmacology), Associate Professor, Head, Department of Chemistry and Pharmacy, Pharmaceutical Faculty

Chelyabinsk

elenasimonian@yandex.ruБакееваА. Е.BakeevaA. E.

лаборант кафедры химии и фармации фармацевтического факультета

г. Челябинск

Laboratory Assistant, Department of Chemistry and Pharmacy, Pharmaceutical Faculty

Chelyabinsk

a.kurenkova01@yandex.ruОгневаО. И.OgnevaO. I.

Огнева Ольга Игоревна – к.м.н., доцент кафедры патологической физиологии

454092, г. Челябинск, ул. Воровского, 66Тел.: 8 (351) 262-78-23

Ogneva Olga I., PhD (Medicine), Associate Professor, Department of Pathophysiology

454092, Chelyabinsk, Vorovsky str., 66Phone: 7 (351) 262-78-23

ognevaolga2@mail.ruФГБОУ ВО «Южно-Уральский государственный медицинский университет» Министерства здравоохранения РФРоссияSouth-Ural State Medical UniversityRussian Federation202020052020223483496Copyright © Осиков М.В., Симонян Е.В., Бакеева А.Е., Огнева О.И., 20202020Осиков М.В., Симонян Е.В., Бакеева А.Е., Огнева О.И.Osikov М.V., Simonyan Е.V., Bakeeva A.E., Ogneva O.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1875

Болезнь Крона (БК) является актуальной проблемой современной гастроэнтерологии в связи с увеличением распространенности, тяжестью осложнений и побочными эффектами при базисной терапии, в частности препаратами 5-аминосалициловой кислоты (5-АСК). Поиск, разработка и обоснование применения при БК эффективных лекарственных препаратов с минимальным количеством побочных эффектов является актуальной задачей. Интерес представляет куркума длинная, содержащая куркумин с выраженными антиоксидантными, цитопротекторными, противовоспалительными свойствами, эффективность которой продемонстрирована при БК в единичных работах при системном применении. Цель – провести сравнительный анализ влияния куркумина и 5-АСК в составе ректальных суппозиториев на клиническую картину и показатели иммунного статуса при экспериментальной БК.

Работа выполнена на 70 крысах-самцах линии Wistar. БК моделировали введением 50% спиртового раствора тринитробензосульфоновой кислоты (ТНБС) per rectum, верифицировали клиническими и морфологическими методами. Ректальные суппозитории с 50 мг 5-АСК и оригинальные суппозитории, содержащие 0,075 мг куркумина, применяли через 12 ч в течение 7 суток. Исследования проводили на 3, 5 и 7 сутки БК.

В динамике экспериментальной ТНБС-индуцированной БК у животных зафиксированы увеличение частоты дефекаций, появление крови в каловых массах, снижение массы тела, прогрессирующие от 3 к 7 суткам наблюдения, увеличение в крови количества CD3+ , CD45RA+ лимфоцитов, количества сегментоядерных нейтрофилов, повышение поглотительной и НСТ-редуцирующей активности нейтрофилов крови, увеличение концентрации в сыворотке IL-23, IgM, IgG. Обоснован состав и разработана технология получения и стандартизации новой лекарственной формы – суппозиториев, содержащих куркумин для лечения БК. Применение ректальных суппозиториев с куркумином приводит к снижению выраженности клинических проявлений, снижению и частичному восстановлению в крови количества сегментоядерных нейтрофилов, CD3+ лимфоцитов, поглотительной и НСТ-редуцирующей способности нейтрофилов крови, снижению концентрации IL-23, IgM, IgG в сыворотке. Эффективность применения ректальных суппозиториев с куркумином сопоставима с эффективностью применения ректальных суппозиториев с 5-АСК по индексу клинической активности, количеству в крови нейтрофилов, CD3+ лимфоцитов, концентрации в сыворотке IL-23, IgМ и IgG, в меньшей степени – по показателям поглотительной и НСТ-редуцирующей способности нейтрофилов крови.

Разработан состав и технология получения ректальных суппозиториев с куркумином. Продемонстрирована эффективность применения ректальных суппозиториев с куркумином при экспериментальной БК на основании оценки количественного состава в крови популяций лейкоцитов, CD3+ , CD45RA+ лимфоцитов, поглотительной и НСТ-редуцирующей способности нейтрофилов, концентрации IL-23, IgМ и IgG при экспериментальной БК, сопоставимая с эффективностью применения ректальных суппозиториев с 5-АСК

Crohn’s disease is an urgent problem of modern gastroenterology due to increasing prevalence, severity of complications and side effects of the basic therapy, in particular upon treatment with 5-aminosalicylic acid (5-ASA). Searching, development and trials of new effective drugs with minimal side effects in Crohn’s disease is an urgent task. Curcuma longa is one of the initial substances containing curcumin with antioxidant, cytoprotective, anti-inflammatory properties. Its effectiveness has been demonstrated in few studies with its systemic use in Crohn’s disease treatment. Our aim was to perform a comparative analysis of curcumin and 5-ASA effect applied as a composition of rectal suppositories, studying clinical signs and indices of immune status in experimental Crohn’s disease. The study was performed on 70 Wistar male rats. Crohn’s disease was modeled by introduction of a 50% alcohol solution of trinitrobenzene sulfonic acid (TNBS) per rectum, and verified by clinical and morphological methods. Rectal suppositories, each containing 50 mg of 5-ASA and original suppositories containing 0.075 mg of curcumin were used over 12 hours during 7 days. The studies were performed on the 3rd , 5th and 7th days of Crohn’s disease.

In the course of experimental TNBS-induced Crohn’s disease in animals, an increased frequency of bowel motility, appearance of blood in the stool, decreased body weight progressed from the 3rd to the 7th days of observation, along with increased number in CD3+, CD45RA+ lymphocytes in blood, higher number of segmented neutrophils, lower absorption and NBT-reducing activity of blood neutrophils, increased serum concentrations of IL-23, IgM, IgG. Composition of the new medication form was justified; production technology and standardization of the suppositories containing curcumin for the treatment for Crohn’s disease were developed. Usage of rectal suppositories with curcumin is associated with decreased severity of clinical signs, decrease and partial restoration of segmented neutrophils, CD3+ lymphocyte numbers in blood, recovery of absorption and NBT-reducing ability of blood neutrophils, and decrease of IL-23, IgM, IgG concentrations in serum. The effectiveness of rectal suppositories with curcumin is compared to the effectiveness of the use of rectal suppositories with 5-ASA in terms of disease activity index, the number of neutrophils and CD3+ lymphocytes in the blood, serum concentrations of IL-23, IgM and IgG, in, at lesser extent, in terms of absorption and NBT- reducing ability of blood neutrophils.

The composition and production technology of rectal suppositories with curcuminwas developed; the leukocyte populations, CD3+, CD45RA+ lymphocytesin blood were assesed, neutrophil absorption and NBT-reducing ability, IL-23, IgM and IgG concentrations were determined; the use of rectal suppositories with curcumin in experimental Crohn’s disease is comparable with the effectiveness of rectal suppositories with 5-ASA.

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