<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pharmjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Разработка и регистрация лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Drug development &amp; registration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2305-2066</issn><issn pub-type="epub">2658-5049</issn><publisher><publisher-name>LLC «CPHA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33380/2305-2066-2020-9-3-143-149</article-id><article-id custom-type="elpub" pub-id-type="custom">pharmjournal-832</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>МЕТОДЫ АНАЛИЗА ЛЕКАРСТВЕННЫХ СРЕДСТВ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ANALYTICAL METHODS</subject></subj-group></article-categories><title-group><article-title>Изучение химического состава и дофаминергической активности плодов Витекса священного (Vitex agnus-castus L.)</article-title><trans-title-group xml:lang="en"><trans-title>Investigation of the Chemical Composition and Dopaminergic Activity of the Vitex Agnus-castus Fruits</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7347-175X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Адамов</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Adamov</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Адамов Григорий Васильевич - научный сотрудник.</p><p>117216, Москва, ул. Грина, д. 7, стр. 1.</p></bio><bio xml:lang="en"><p>Grigorij V. Adamov.</p><p>7/1, Green str., Moscow, 117216.</p></bio><email xlink:type="simple">grig.adamov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8993-4808</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мельников</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Melnikov</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мельников Евгений Сергеевич.</p><p>119991, Москва, ул. Трубецкая, д. 8, стр. 2.</p></bio><bio xml:lang="en"><p>Evgenij S. Melnikov.</p><p>8/2, Trubetskaya str., Mosrow, 119991.</p></bio><email xlink:type="simple">melnik11@list.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8183-2877</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лупанова</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lupanova</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лупанова Ирина Александровна.</p><p>117216, Москва, ул. Грина, д. 7, стр. 1.</p></bio><bio xml:lang="en"><p>Irina A. Lupanova.</p><p>7/1, Green str., Moscow, 117216.</p></bio><email xlink:type="simple">iriss86@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1139-8902</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Радимич</surname><given-names>А. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Radimich</surname><given-names>A. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Радимич Андрей Иванович.</p><p>117216, Москва, ул. Грина, д. 7, стр. 1.</p></bio><bio xml:lang="en"><p>Andrej I. Radimich.</p><p>7/1, Green str., Moscow, 117216.</p></bio><email xlink:type="simple">vilarnii.meshkov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8059-5064</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сайбель</surname><given-names>О. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Saybel</surname><given-names>O. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сайбель Ольга Леонидовна.</p><p>117216, Москва, ул. Грина, д. 7, стр. 1.</p></bio><bio xml:lang="en"><p>Ol'ga L. Saybel.</p><p>7/1, Green str., Moscow, 117216.</p></bio><email xlink:type="simple">olster@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Всероссийский научно-исследовательский институт лекарственных и ароматических растений» (ВИЛАР)</institution></aff><aff xml:lang="en"><institution>All-Russian research Institute of medicinal and aromatic plants</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский Университет)</institution></aff><aff xml:lang="en"><institution>I.M. Sechenov First MSMU of the Ministry of Health of the Russian Federation (Sechenov University)</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>29</day><month>08</month><year>2020</year></pub-date><volume>9</volume><issue>3</issue><fpage>143</fpage><lpage>149</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Адамов Г.В., Мельников Е.С., Лупанова И.А., Радимич А.И., Сайбель О.Л., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Адамов Г.В., Мельников Е.С., Лупанова И.А., Радимич А.И., Сайбель О.Л.</copyright-holder><copyright-holder xml:lang="en">Adamov G.V., Melnikov E.S., Lupanova I.A., Radimich A.I., Saybel O.L.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmjournal.ru/jour/article/view/832">https://www.pharmjournal.ru/jour/article/view/832</self-uri><abstract><sec><title>Введение</title><p>Введение. Плоды Витекса священного являются перспективным источником получения фармацевтической субстанции для создания на её основе отечественного лекарственного средства для коррекции негативных проявлений предменструального синдрома и нарушений менструального цикла.</p></sec><sec><title>Цель</title><p>Цель. Изучить химический состав водно-этанольного экстракта плодов Витекса священного. Установить дофаминергическую активность различных фракций экстракта, разделенных по признаку липофильности для выявления наиболее активной фракции вторичных метаболитов. </p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Исследование качественного состав водно-этанольного извлечения проводили методами ВЭЖХ-УФ и ВЭЖХ-МС/МС. Идентификацию компонентов экстракта проводили путём сопоставления времен удерживания на хроматограммах испытуемого и стандартного образцов. Суммарный экстракт и фракции, полученные обработкой последовательно органическими растворителями различной полярности кубового остатка водно-спиртового извлечения из исследуемого сырья, были проанализированы с применением тирозингидроксилазной биотест-системы in vitro. В качестве препарата сравнения использовали Циклодинон®, капли для приема внутрь, действующим веществом которого является Прутняка обыкновенного плодов экстракт (Vitex agni casti fructuum extract).</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. В исследуемом экстракте подтверждено наличие соединений: протокатеховая кислота, кафтаровая кислота, хлорогеновая кислота, n-гидроксибензойная кислота, агнузид, мизодендрон, 6'-О-п-гидроксибензоилмусаенозидная кислота, лютеолин-7-глюкозид, 3,5-дифеолхинная кислота, витексин, лютеолин, апигенин, кастицин, артеметин, маслиниковая кислота, корозоловая кислота, линоленовая кислота, впервые идентифицированы цикориевая, каафтаровая и изохлорогеновая А кислоты. Полученный в лабораторных условиях жидкий экстракт продемонстрировал сопоставимую активность с коммерческим препаратом, на этом же уровне находились и этилацетатная фракция, и агнузид.</p></sec><sec><title>Заключение</title><p>Заключение. Описаны результаты ВЭЖХ-УФ и ВЭЖХ-МС/МС анализа экстракта плодов Витекса священного. Приведены времена удерживания, максимумы поглощения в УФ области, характерные ионы масс-спектры большинства идентифицированных соединений. После фракционирования по принципу липофильности установлено, что ни одна из фракций экстракта не демонстрирует большую активность, чем суммарный экстракт. Это доказывает синергическое действие компонентов на дофаминовую нейромедиаторную систему и показывает целесообразность использования суммарного экстракта плодов Витекса священного. Агнузид в опытах in vitro демонстрирует высокую дофаминергическую активность, что допускает возможность стандартизации экстракта и лекарственного растительного сырья по содержанию агнузида.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Vitex agnus-castus is an important plant in medicine. Extract from its fruits is used as part of drugs for the treatment of premenstrual syndrome.</p></sec><sec><title>Aim</title><p>Aim. To study the chemical composition of water-ethanol extract from Vitex fruits, to establish the dopaminergic activity of various extract fractions separated by lipophilicity, as that of its dominant iridoid-agnuside</p></sec><sec><title>Materials and methods</title><p>Materials and methods. The composition of water-ethanol extraction was studied using HPLC-UV and HPLC-MS/MS methods. Identification of the extract components was performed by comparing the retention times on the chromatograms of the test and standard samples. The extract and its fractions were analyzed in vitro using the tyrosine hydroxylase biotest system. Cyclodinone® (oral drops, Vitex agni casti fructuum extract) was used as a reference drug.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. Protocatechuic acid, chlorogenic acid, p-hydroxybenzoic acid, agnuside, mizodendron, 6'-O-p-hydroxybenzoylmusaenoside acid, luteolin-7-glucoside, 5-O-caffeoylquinic acid, vitexin, luteolin, apigenin, maslinic acid, corosolic acid and linolenic acid were identified. The liquid extract obtained in the laboratory showed the same activity as Cyclodinone®, ethyl acetate fraction, and agnuside.</p></sec><sec><title>Conclusion</title><p>Conclusion. This work is the most extensive study of the vitex fruit in relation to the nomenclature of identified compounds. The total extract was shown to be more active than any of its fractions proving the synergistic effect of the extract components on the dopamine neurotransmitter system. This observation justifies the feasibility of using the total extract of the vitex fruit. In vitro agnuside demonstrates high dopaminergic activity. This makes it possible to standardize the extract and medicinal plant materials according to the agnuside content.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>Витекс священный</kwd><kwd>агнузид</kwd><kwd>ВЭЖХ-МС/МС</kwd><kwd>дофаминергическое действие</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Vitex agnus-castus</kwd><kwd>agnuside</kwd><kwd>HPLC-MS/MS</kwd><kwd>dopaminergic effect</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Wuttke V., Zaydlova-Wuttke D., Yarri G., Artymuk, N. The role of the Vitex agnus castus in gynecological endocrinology. Zdrov'e zhenshchiny = Health of woman. 2016;10:24-27. (In Ukraine).</mixed-citation><mixed-citation xml:lang="en">Wuttke V., Zaydlova-Wuttke D., Yarri G., Artymuk, N. The role of the Vitex agnus castus in gynecological endocrinology. Zdrov'e zhenshchiny = Health of woman. 2016;10:24-27. (In Ukraine).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Prilepskaya V. N., Ledina A. V., Tagiyeva A. V., Revazova F. S. Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome. Maturitas. 2006;55:55-63. Doi: 10.1016/j.maturitas.2006.06.017.</mixed-citation><mixed-citation xml:lang="en">Prilepskaya V. N., Ledina A. V., Tagiyeva A. V., Revazova F. S. Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome. Maturitas. 2006;55:55-63. Doi: 10.1016/j.maturitas.2006.06.017.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Jarry H., Spengler B., Wuttke W., Christoffel V. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. Maturitas. 2006;55:S26-S36. Doi: 0.1016/j.maturitas.2006.06.014.</mixed-citation><mixed-citation xml:lang="en">Jarry H., Spengler B., Wuttke W., Christoffel V. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. Maturitas. 2006;55:S26-S36. Doi: 0.1016/j.maturitas.2006.06.014.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Jarry H., Spengler B., Wuttke W., Christoffel V. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. Maturitas. 2006;55:S26-S36. Doi: 0.1016/j.maturitas.2006.06.014.</mixed-citation><mixed-citation xml:lang="en">Jarry H., Spengler B., Wuttke W., Christoffel V. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. Maturitas. 2006;55:S26-S36. Doi: 0.1016/j.maturitas.2006.06.014.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Liu J., Burdette J. E., Sun Y., Deng S., Schlecht S. M., Zheng W., Nikolic D., Mahady G., van Breemen R. B., Fong H. S., Pezzuto J. M., Bolton J. L., Farnsworth N. R. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. 2004;11(1):18-23.</mixed-citation><mixed-citation xml:lang="en">Liu J., Burdette J. E., Sun Y., Deng S., Schlecht S. M., Zheng W., Nikolic D., Mahady G., van Breemen R. B., Fong H. S., Pezzuto J. M., Bolton J. L., Farnsworth N. R. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. 2004;11(1):18-23.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Meier B., Berger D., Hoberg E., Sticher O., Schaffner W. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. 2000;7(5):373-381. Doi: 10.1016/S0944-7113(00)80058-6.</mixed-citation><mixed-citation xml:lang="en">Meier B., Berger D., Hoberg E., Sticher O., Schaffner W. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. 2000;7(5):373-381. Doi: 10.1016/S0944-7113(00)80058-6.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Mineeva-Vyalykh M. F. A Direct spectrophotometric method for estimation of the rate of tyrosine hydroxylase reaction (Russian). Voprosy medicinskoj himii = Biomeditsinskaya Khimiya.1976;22(2):274-279. (In Russ.).</mixed-citation><mixed-citation xml:lang="en">Mineeva-Vyalykh M. F. A Direct spectrophotometric method for estimation of the rate of tyrosine hydroxylase reaction (Russian). Voprosy medicinskoj himii = Biomeditsinskaya Khimiya.1976;22(2):274-279. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Choudhary M. I., Jalil S., Nawaz S. A., Khan K. M., Tareen R. B. Antiinflammatory and lipoxygenase inhibitory compounds from vitex agnus-castus. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2009;23(9):336-1339. Doi: 10.1002/ptr.2639.</mixed-citation><mixed-citation xml:lang="en">Choudhary M. I., Jalil S., Nawaz S. A., Khan K. M., Tareen R. B. Antiinflammatory and lipoxygenase inhibitory compounds from vitex agnus-castus. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2009;23(9):336-1339. Doi: 10.1002/ptr.2639.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Jarer E., Gokbulut A. Determination of caffeic and chlorogenic acids in the leaves and fruits of Vitex agnus-castus. Turk J. Pharm. Sci. 2008;5(3):167-174.</mixed-citation><mixed-citation xml:lang="en">Jarer E., Gokbulut A. Determination of caffeic and chlorogenic acids in the leaves and fruits of Vitex agnus-castus. Turk J. Pharm. Sci. 2008;5(3):167-174.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Mari A., Montoro P., D'Urso G., Macchia M., Pizza C., Piacente S. Metabolic profiling of Vitex agnus castus leaves, fruits and sprouts: analysis by LC/ESI/(QqQ) MS and (HR) LC/ESI/(Orbitrap)/MSn. Journal of pharmaceutical and biomedical analysis. 2015;102:215-221. Doi: 10.1016/j.jpba.2014.09.018.</mixed-citation><mixed-citation xml:lang="en">Mari A., Montoro P., D'Urso G., Macchia M., Pizza C., Piacente S. Metabolic profiling of Vitex agnus castus leaves, fruits and sprouts: analysis by LC/ESI/(QqQ) MS and (HR) LC/ESI/(Orbitrap)/MSn. Journal of pharmaceutical and biomedical analysis. 2015;102:215-221. Doi: 10.1016/j.jpba.2014.09.018.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Hoberg E., Meier B., Sticher O. An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructus. Phytochemical Analysis: An International Journal of Plant Chemical and Biochemical Techniques. 2000;11(5):327-329. Doi: 10.1002/1099-1565(200009/10)11:5&lt;327::AID-PCA523&gt;3.0.CO;2-0.</mixed-citation><mixed-citation xml:lang="en">Hoberg E., Meier B., Sticher O. An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructus. Phytochemical Analysis: An International Journal of Plant Chemical and Biochemical Techniques. 2000;11(5):327-329. Doi: 10.1002/1099-1565(200009/10)11:5&lt;327::AID-PCA523&gt;3.0.CO;2-0.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Kuruuzum-Uz A., Stroch K., Demirezer L. O., Zeeck, A. Glucosides from Vitex agnus-castus. Phytochemistry. 2003;63(8):959-964. Doi: 10.1016/S0031-9422(03)00285-1.</mixed-citation><mixed-citation xml:lang="en">Kuruuzum-Uz A., Stroch K., Demirezer L. O., Zeeck, A. Glucosides from Vitex agnus-castus. Phytochemistry. 2003;63(8):959-964. Doi: 10.1016/S0031-9422(03)00285-1.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hajdu Z., Hohmann J., Forgo P., Martinek T., Dervarics M., Zupko I., Falkay G., Cossuta D., Mathe I. Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2007;21(4):391-394. Doi: 10.1002/ptr.2021.</mixed-citation><mixed-citation xml:lang="en">Hajdu Z., Hohmann J., Forgo P., Martinek T., Dervarics M., Zupko I., Falkay G., Cossuta D., Mathe I. Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2007;21(4):391-394. Doi: 10.1002/ptr.2021.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Chen S. N., Friesen J. B., Webster D., Nikoli D., van Breemen R. B., Wang Z. J., Pauli G. F. Phytoconstituents from Vitex agnus-castus fruits. Fitoterapia. 2011;82(4):528-533. Doi: 10.1016/j.fitote.2010.12.003.</mixed-citation><mixed-citation xml:lang="en">Chen S. N., Friesen J. B., Webster D., Nikoli D., van Breemen R. B., Wang Z. J., Pauli G. F. Phytoconstituents from Vitex agnus-castus fruits. Fitoterapia. 2011;82(4):528-533. Doi: 10.1016/j.fitote.2010.12.003.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Liu J., Burdette J. E., Xu H., Gu C., Van Breemen R. B., Bhat K. P, Booth N., Constantinou A. I., Pezzuto J. M., Fong H. S., Farnsworth N. R., Bolton J. L. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Journal of agricultural and food chemistry. 2001;49(5):2472-2479. Doi: 10.1021/jf0014157.</mixed-citation><mixed-citation xml:lang="en">Liu J., Burdette J. E., Xu H., Gu C., Van Breemen R. B., Bhat K. P, Booth N., Constantinou A. I., Pezzuto J. M., Fong H. S., Farnsworth N. R., Bolton J. L. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Journal of agricultural and food chemistry. 2001;49(5):2472-2479. Doi: 10.1021/jf0014157.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Makhmoor T., Choudhary M. I. Radical scavenging potential of compounds isolated from Vitex agnus-castus. Turkish Journal of Chemistry. 2010;34(1):119-126.</mixed-citation><mixed-citation xml:lang="en">Makhmoor T., Choudhary M. I. Radical scavenging potential of compounds isolated from Vitex agnus-castus. Turkish Journal of Chemistry. 2010;34(1):119-126.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Mineeva M. F. Tyrosinehydroxylase of leukocytes from blood. Byulleten' eksperimental'noj biologii i mediciny = Bulletin of Experimental Biology and Medicine. 1987;104(7):99-101. (In Russ.).</mixed-citation><mixed-citation xml:lang="en">Mineeva M. F. Tyrosinehydroxylase of leukocytes from blood. Byulleten' eksperimental'noj biologii i mediciny = Bulletin of Experimental Biology and Medicine. 1987;104(7):99-101. (In Russ.).</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
