phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.37489/2587-7836-2024-1-66-76AQCTAJphkinetica-411Research ArticleПОИСК НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВNEW DRUGS DISCOVERYФармакоинформационные, фундаментальные и клинические исследования 7-гидроксиматаирезинола в контексте поиска эффективных и безопасных терапевтических подходов к лечению мастопатииPharmacoinformational, basic and clinical studies of 7-hydroxymatairesinol in the context of searching for effective and safe therapeutic approaches to the treatment of mastopathyhttps://orcid.org/0000-0002-9639-2525РубашкинаА. Н.RubashkinaА. N.

Рубашкина Анна Николаевна – аспирант

Иваново

Аnna N. Rubashkina – graduate student 

Ivanovo

https://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич – к. ф–м. н., к. х. н., в. н. с.

Москва

Ivan Yu. Torshin – PhD, Cand. Physico-Mathematical Sci., Cand. Chemical Sci., Leading researcher

Moscow

https://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна – д. м. н, профессор, в. н. с. 

Москва

Olga A. Gromova – Dr. Sci. (Med.), Professor, Leading researcher

Moscow

unesco.gromova@gmail.comФГБОУ ВО «Ивановский государственный медицинский университет» Минздрава РоссииРоссияFSBEI HE «Ivanovo State Medical University» of MOH of RussiaRussian FederationФГУ «Федеральный исследовательский центр «Информатика и управление» РАН» (ФИЦ ИУ РАН)РоссияFRC «Computer Science and Control» RASRussian Federation202425062024016676Copyright © Рубашкина А.Н., Торшин И.Ю., Громова О.А., 20242024Рубашкина А.Н., Торшин И.Ю., Громова О.А.Rubashkina А.N., Torshin I.Y., Gromova O.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.pharmacokinetica.ru/jour/article/view/411

7-гидроксиматаирезинол (7(ОН)МР) – основной лигнан экстрактов ели, характеризующийся онкопротективными и противовоспалительными свойствами. Результаты хемореактомного моделирования позволили сформулировать молекулярные механизмы осуществления фармакологических эффектов 7(ОН)МР для противовоспалительных (ингибирование 5-липоксигеназы, матриксной металлопротеиназы ММР2, митоген-активируемой киназы p38-альфа, рецептора лейкотриена b4, рецептора простациклина), онкопротективных (антиоксидантный эффект за счёт ингибирования гемоксигеназы-2, ингибирование циклин-зависимых киназ 3 и 4, фактора роста эпидермиса, белка mTOR). Оценка транскриптомных эффектов 7(ОН)МР в клетках рака молочной железы показала достоверные дозозависимые эффекты на транскрипцию 3468 из 12700 генов. Молекула 7(ОН)МР, снижая экспрессию пролиферативных генов (401 ген) и хроническое воспаление (148 генов), параллельно повышая транкрипцию генов онкопротективного иммунитета (100 генов), тормозит пролиферацию опухолевых клеток. Эксперименты на солидной карциноме Эрлиха показали достоверный онко- протективный эффект 7(ОН)МР в дозах 60, 120 мг/сут, даже на фоне приёма эстрогенов (p = 0,007). Клиническое исследование показало, что 7(ОН)МР (60 мг/сут, 1 мес.) способствует нормализации метаболизма эстрогенов (МЭ) и улучшению клинической симптоматики мастопатии.

7-hydroxymatairesinol (7(OH)MR) is the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties. The results of chemoreactome modeling made it possible to formulate the molecular mechanisms of the pharmacological effects of 7(OH)MR for anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase MMP2, mitogen-activated kinase p38-alpha, leukotriene b4 receptor, prostacyclin receptor), oncoprotective (antioxidant effect due to inhibition heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein). An assessment of the transcriptomic effects of 7(OH)MR in breast cancer cells showed significant dose-dependent effects on the transcription of 3468 of 12700 genes. The 7(OH)MR molecule, reducing the expression of proliferative genes (401 genes) and chronic inflammation (148 genes), while simultaneously increasing the transcription of oncoprotective immunity genes (100 genes), inhibits the proliferation of tumor cells. Experiments on solid Ehrlich carcinoma showed a significant oncoprotective effect of 7(OH)MR at doses of 60, 120 mg/day, even while taking estrogen (p = 0.007). A clinical study showed that 7(OH)MR (60 mg/day, 1 month) helps normalize estrogen metabolism and improve the clinical symptoms of mastopathy.

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