<?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="review-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">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/ms2025-557</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-9767</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>ГИНЕКОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>GYNECOLOGY</subject></subj-group></article-categories><title-group><article-title>Индолкарбинол: механизмы действия, эффекты и перспективы клинического применения</article-title><trans-title-group xml:lang="en"><trans-title>Indolecarbinol: Mechanisms of action, effects and prospects for clinical use</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9441-3468</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Карева</surname><given-names>Е. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Kareva</surname><given-names>E. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Карева Елена Николаевна, д.м.н., профессор, профессор кафедры молекулярной фармакологии и радиобиологии имени академика П.В. Сергеева, Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; профессор кафедры фармакологии Института цифрового биодизайна и искусственного интеллекта в медицине, Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)</p><p>117997, Москва, ул. Островитянова, д. ,</p><p>119991, Москва, ул. Трубецкая, д. 8, стр. 2</p></bio><bio xml:lang="en"><p>Elena N. Kareva, Dr. Sci. (Med.), Professor, Professor of the Department of Molecular Pharmacology and Radiobiology named after Acad. P.V. Sergeev, Pirogov Russian National Research Medical University; Professor of the Department of Pharmacology, Institute of Digital Biodesign and Artificial Intelligence in Medicine, Sechenov First Moscow State Medical University (Sechenov University)</p><p>1, Ostrovityanov St., Moscow, 117997,</p><p>8, Bldg. 2, Trubetskaya St., Moscow, 119991</p></bio><email xlink:type="simple">elenakareva@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; &#13;
Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pirogov Russian National Research Medical University;&#13;
Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>22</day><month>01</month><year>2026</year></pub-date><volume>0</volume><issue>23</issue><fpage>151</fpage><lpage>159</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Карева Е.Н., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Карева Е.Н.</copyright-holder><copyright-holder xml:lang="en">Kareva E.N.</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.med-sovet.pro/jour/article/view/9767">https://www.med-sovet.pro/jour/article/view/9767</self-uri><abstract><p>В статье перечислены защитные эффекты индолкарбинола (IC) и его производного – дииндолилметана (DIM) – в отношении функционирования сердечно-сосудистой, нервной, репродуктивной, костно-мышечной и иммунной систем, а также печени. Экспериментальные данные свидетельствуют о том, что IC и DIM обеспечивают защиту органов и тканей благодаря своим антиоксидантным, противовоспалительным, антиапоптотическим, иммуномодулирующим и ксенобиотическим свойствам. До настоящего времени большинство данных о защитных эффектах IC и DIM при лечении различных заболеваний получено только в доклинических исследованиях, что подчеркивает острую необходимость проведения крупномасштабных клинических испытаний этих многообещающих фитохимических веществ. В статье рассматриваются молекулярные механизмы действия IC и DIM, их фармакокинетика и побочные эффекты в эксперименте. Представлены данные о клинической эффективности и безопасности лекарственного препарата на основе IC в клинической практике. Дальнейшее углубленное исследование эффективности и безопасности препаратов IC/DIM позволит значительно расширить арсенал фармакологических средств для борьбы с социально значимыми заболеваниями. Проанализированные нами исследования показали, что DIM и IC имеют общие и несколько различных механизмов противоопухолевого действия, эффективность которых зависит от вида опухоли и/или генотипа линии раковых клеток. Например, оба соединения влияют на развитие клеточного цикла рака молочной железы и подавляют рост и миграцию клеток. Кроме того, эти соединения повышают экспрессию детоксицирующих и антиоксидантных ферментов посредством активации Nrf2-зависимого пути, а также могут влиять на пролиферацию клеток, апоптоз, миграцию, инвазию, ангиогенез и иммунитет. В статье рассмотрены все основные механизмы противоопухолевого действия.</p></abstract><trans-abstract xml:lang="en"><p>This article describes the protective effects of indolecarbinol (IC) and its derivative diindolylmethane (DIM) on the functioning of the cardiovascular, nervous, reproductive, musculoskeletal, and immune systems, as well as the liver. Experimental data indicate that IC and DIM provide organ and tissue protection through their antioxidant, anti-inflammatory, antiapoptotic, immunomodulatory, and xenobiotic properties. To date, most reports of the protective effects of IC and DIM in the treatment of various diseases have been obtained only in preclinical studies; this underscores the urgent need for large-scale clinical trials of these promising phytochemicals. The molecular mechanisms of action of IC and DIM, their pharmacokinetics, and experimental side effects are discussed. Data on the clinical efficacy and safety of an IC-based medicinal product in clinical practice are presented. Further in-depth studies of the efficacy and safety of IC/DIM preparations will significantly expand the arsenal of pharmacological agents for combating socially significant diseases. The studies we analysed have demonstrated that DIM and IC have common and several unique anti-tumour mechanisms, which efficacy depends on the tumour type and/or genotype of the cancer cell line. For example, both compounds influence BC cell cycle progression and inhibit cell growth and migration. In addition, these compounds enhance the expression of detoxifying and antioxidant enzymes by the activation of the Nrf2-dependent pathway and can also influence cell proliferation, apoptosis, migration, invasion, angiogenesis, and immunity. This article examines all the major mechanisms of antitumor action.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>индолкарбинол</kwd><kwd>дииндолилметан</kwd><kwd>молекулярные механизмы действия</kwd><kwd>антиоксидант</kwd><kwd>иммуномодуляция</kwd><kwd>защита органов</kwd><kwd>противоопухолевая активность</kwd></kwd-group><kwd-group xml:lang="en"><kwd>indolecarbinol</kwd><kwd>diindolylmethane</kwd><kwd>molecular mechanisms of action</kwd><kwd>antioxidant</kwd><kwd>immunomodulation</kwd><kwd>organ protection</kwd><kwd>antitumor activity</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">Srikanth Y, Reddy DH, Anusha VL, Dumala N, Viswanadh MK, Chakravarthi G et al. Unveiling the Multifaceted Pharmacological Actions of Indole-3- Carbinol and Diindolylmethane: A Comprehensive Review. Plants. 2025;14(5):827. https://doi.org/10.3390/plants14050827.</mixed-citation><mixed-citation xml:lang="en">Srikanth Y, Reddy DH, Anusha VL, Dumala N, Viswanadh MK, Chakravarthi G et al. Unveiling the Multifaceted Pharmacological Actions of Indole-3- Carbinol and Diindolylmethane: A Comprehensive Review. Plants. 2025;14(5):827. https://doi.org/10.3390/plants14050827.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Hubbard TD, Murray IA, Perdew GH. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation. Drug Metab Dispos. 2015;43(10):1522–1535. https://doi.org/10.1124/dmd.115.064246.</mixed-citation><mixed-citation xml:lang="en">Hubbard TD, Murray IA, Perdew GH. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation. Drug Metab Dispos. 2015;43(10):1522–1535. https://doi.org/10.1124/dmd.115.064246.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett. 2001;120(1-3):1–7. https://doi.org/10.1016/s0378-4274(01)00301-0.</mixed-citation><mixed-citation xml:lang="en">Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett. 2001;120(1-3):1–7. https://doi.org/10.1016/s0378-4274(01)00301-0.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Li Y, Li X, Sarkar FH. Gene expression profiles of I3C- and DIM-treated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr. 2003;133(4):1011–1019. https://doi.org/10.1093/jn/133.4.1011.</mixed-citation><mixed-citation xml:lang="en">Li Y, Li X, Sarkar FH. Gene expression profiles of I3C- and DIM-treated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr. 2003;133(4):1011–1019. https://doi.org/10.1093/jn/133.4.1011.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Saw CL, Cintrón M, Wu TY, Guo Y, Huang Y, Jeong WS, Kong AN. Pharmacodynamics of dietary phytochemical indoles IC and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011;32(5):289–300. https://doi.org/10.1002/bdd.759.</mixed-citation><mixed-citation xml:lang="en">Saw CL, Cintrón M, Wu TY, Guo Y, Huang Y, Jeong WS, Kong AN. Pharmacodynamics of dietary phytochemical indoles IC and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011;32(5):289–300. https://doi.org/10.1002/bdd.759.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Шиловский ГА, Сорокина ЕВ, Орловский ИВ. Транскрипционный фактор NRF2 – мишень активирующих антиоксидантную систему клетки препаратов: перспективные применения при возрастных заболеваниях. Клиническая геронтология. 2021;(11-12):57–62. https://doi.org/10.26347/1607-2499202111-12057-062.</mixed-citation><mixed-citation xml:lang="en">Shilovsky GA, Sorokina EV, Orlovsky IV. Transcription factor NRF2 – a target of potential antioxidant drugs: prospects in treatment of age-related diseases. Clinical Gerontology. 2021;(11-12):57–62. (In Russ.) https://doi.org/10.26347/1607-2499202111-12057-062.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Watson GW, Beaver LM, Williams DE, Dashwood RH, Ho E. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention. AAPS J. 2013;15(4):951–961. https://doi.org/10.1208/s12248-013-9504-4.</mixed-citation><mixed-citation xml:lang="en">Watson GW, Beaver LM, Williams DE, Dashwood RH, Ho E. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention. AAPS J. 2013;15(4):951–961. https://doi.org/10.1208/s12248-013-9504-4.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Wu TY, Khor TO, Su ZY, Saw CL, Shu L, Cheung KL et al. Epigenetic modifications of Nrf2 by 3,3'-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. AAPS J. 2013;15(3):864–874. https://doi.org/10.1208/s12248-013-9493-3.</mixed-citation><mixed-citation xml:lang="en">Wu TY, Khor TO, Su ZY, Saw CL, Shu L, Cheung KL et al. Epigenetic modifications of Nrf2 by 3,3'-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. AAPS J. 2013;15(3):864–874. https://doi.org/10.1208/s12248-013-9493-3.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Licznerska BE, Szaefer H, Murias M, Bartoszek A, Baer-Dubowska W. Modulation of CYP19 expression by cabbage juices and their active components: indole-3- carbinol and 3,3'-diindolylmethene in human breast epithelial cell lines. Eur J Nutr. 2013;52(5):1483–1492. https://doi.org/10.1007/s00394-012-0455-9.</mixed-citation><mixed-citation xml:lang="en">Licznerska BE, Szaefer H, Murias M, Bartoszek A, Baer-Dubowska W. Modulation of CYP19 expression by cabbage juices and their active components: indole-3- carbinol and 3,3'-diindolylmethene in human breast epithelial cell lines. Eur J Nutr. 2013;52(5):1483–1492. https://doi.org/10.1007/s00394-012-0455-9.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Yuan F, Chen DZ, Liu K, Sepkovic DW, Bradlow HL, Auborn K. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res. 1999;19(3A):1673–1680. Available at: https://pubmed.ncbi.nlm.nih.gov/10470100.</mixed-citation><mixed-citation xml:lang="en">Yuan F, Chen DZ, Liu K, Sepkovic DW, Bradlow HL, Auborn K. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res. 1999;19(3A):1673–1680. Available at: https://pubmed.ncbi.nlm.nih.gov/10470100.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the ‘good’ estrogen. J Endocrinol. 1996;150(Suppl.):S259–S265. Available at: https://pubmed.ncbi.nlm.nih.gov/8943806/.</mixed-citation><mixed-citation xml:lang="en">Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the ‘good’ estrogen. J Endocrinol. 1996;150(Suppl.):S259–S265. Available at: https://pubmed.ncbi.nlm.nih.gov/8943806/.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1953–1960. https://doi.org/10.1158/1055-9965.EPI-05-0121.</mixed-citation><mixed-citation xml:lang="en">Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1953–1960. https://doi.org/10.1158/1055-9965.EPI-05-0121.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Marconett CN, Sundar SN, Poindexter KM, Stueve TR, Bjeldanes LF, Firestone GL. Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loop. Mol Biol Cell. 2010;21(7):1166–1177. https://doi.org/10.1091/mbc.e09-08-0689.</mixed-citation><mixed-citation xml:lang="en">Marconett CN, Sundar SN, Poindexter KM, Stueve TR, Bjeldanes LF, Firestone GL. Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loop. Mol Biol Cell. 2010;21(7):1166–1177. https://doi.org/10.1091/mbc.e09-08-0689.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Biersack B. 3,3'-Diindolylmethane and its derivatives: nature-inspired strategies tackling drug resistant tumors by regulation of signal transduction, transcription factors and microRNAs. Cancer Drug Resist. 2020;3(4):867–878. https://doi.org/10.20517/cdr.2020.53.</mixed-citation><mixed-citation xml:lang="en">Biersack B. 3,3'-Diindolylmethane and its derivatives: nature-inspired strategies tackling drug resistant tumors by regulation of signal transduction, transcription factors and microRNAs. Cancer Drug Resist. 2020;3(4):867–878. https://doi.org/10.20517/cdr.2020.53.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Власов АВ, Якушевская ОВ. Химиопрофилактические свойства 3,3'-дииндолилметана: от экспериментального до клинического применения. Гинекология. 2024;26(3):270–274. https://doi.org/10.26442/20795696.2024.3.202953.</mixed-citation><mixed-citation xml:lang="en">Vlasov AV, Yakushevskaya OV. Chemopreventive properties of 3,3'-diindolylmethane: From experimental to clinical studies. A review. Gynecology. 2024;26(3):270–274. (In Russ.) https://doi.org/10.26442/20795696.2024.3.202953</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Ho JN, Jun W, Choue R, Lee J. IC and ICZ inhibit migration by suppressing the EMT process and FAK expression in breast cancer cells. Mol Med Rep. 2013;7(2):384–388. https://doi.org/10.3892/mmr.2012.1198.</mixed-citation><mixed-citation xml:lang="en">Ho JN, Jun W, Choue R, Lee J. IC and ICZ inhibit migration by suppressing the EMT process and FAK expression in breast cancer cells. Mol Med Rep. 2013;7(2):384–388. https://doi.org/10.3892/mmr.2012.1198.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Li WX, Chen LP, Sun MY, Li JT, Liu HZ, Zhu W. 3’3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget. 2015;6(27):23776–23792. https://doi.org/10.18632/oncotarget.4196.</mixed-citation><mixed-citation xml:lang="en">Li WX, Chen LP, Sun MY, Li JT, Liu HZ, Zhu W. 3’3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget. 2015;6(27):23776–23792. https://doi.org/10.18632/oncotarget.4196.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Wong CP, Hsu A, Buchanan A, Palomera-Sanchez Z, Beaver LM, Houseman EA et al. Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells. PLoS ONE. 2014;9(1):e86787. https://doi.org/10.1371/journal.pone.0086787.</mixed-citation><mixed-citation xml:lang="en">Wong CP, Hsu A, Buchanan A, Palomera-Sanchez Z, Beaver LM, Houseman EA et al. Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells. PLoS ONE. 2014;9(1):e86787. https://doi.org/10.1371/journal.pone.0086787.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Wang ML, Shih CK, Chang HP, Chen YH. Antiangiogenic activity of indole-3- carbinol in endothelial cells stimulated with activated macrophages. Food Chem. 2012;134(2):811–820. https://doi.org/10.1016/j.foodchem.2012.02.185.</mixed-citation><mixed-citation xml:lang="en">Wang ML, Shih CK, Chang HP, Chen YH. Antiangiogenic activity of indole-3- carbinol in endothelial cells stimulated with activated macrophages. Food Chem. 2012;134(2):811–820. https://doi.org/10.1016/j.foodchem.2012.02.185.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Wu HT, Lin SH, Chen YH. Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables. J Agric Food Chem. 2005;53(13):5164–5169. https://doi.org/10.1021/jf050034w.</mixed-citation><mixed-citation xml:lang="en">Wu HT, Lin SH, Chen YH. Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables. J Agric Food Chem. 2005;53(13):5164–5169. https://doi.org/10.1021/jf050034w.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Kunimasa K, Kobayashi T, Kaji K, Ohta T. Antiangiogenic effects of indole-3- carbinol and 3,3'-diindolylmethane are associated with their differential regulation of ERK1/2 and Akt in tube-forming HUVEC. J Nutr. 2010;140(1):1–6. https://doi.org/10.3945/jn.109.112359.</mixed-citation><mixed-citation xml:lang="en">Kunimasa K, Kobayashi T, Kaji K, Ohta T. Antiangiogenic effects of indole-3- carbinol and 3,3'-diindolylmethane are associated with their differential regulation of ERK1/2 and Akt in tube-forming HUVEC. J Nutr. 2010;140(1):1–6. https://doi.org/10.3945/jn.109.112359.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Tsai JT, Liu HC, Chen YH. Suppression of Inflammatory Mediators by Cruciferous Vegetable-Derived Indole-3-Carbinol and Phenylethyl Isothiocyanate in Lipopolysaccharide-Activated Macrophages. Mediators Inflamm. 2010;2010:293642. https://doi.org/10.1155/2010/293642.</mixed-citation><mixed-citation xml:lang="en">Tsai JT, Liu HC, Chen YH. Suppression of inflammatory mediators by cruciferous vegetable-derivedindole-3-carbinoland phenylethyl isothiocyanate in lipopolysaccharide-activated macrophages. Mediators Inflamm. 2010;2010:293642. https://doi.org/10.1155/2010/293642.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Jiang J, Kang TB, Shim do W, Oh NH, Kim TJ, Lee KH. Indole-3-carbinol inhibits LPS-induced inflammatory response by blocking TRIF-dependent signaling pathway in macrophages. Food Chem Toxicol. 2013;57:256–261. https://doi.org/10.1016/j.fct.2013.03.040.</mixed-citation><mixed-citation xml:lang="en">Jiang J, Kang TB, Shim do W, Oh NH, Kim TJ, Lee KH. Indole-3- carbinolinhibitsLPS-induced inflammatory response by blocking TRIFdependent signaling pathway in macrophages. Food Chem Toxicol. 2013;57:256–261. https://doi.org/10.1016/j.fct.2013.03.040.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Cho HJ, Seon MR, Lee YM, Kim J, Kim JK, Kim SG, Park JH. 3,3´-Diindolylmethane Suppresses the Inflammatory Response to Lipopolysaccharide in Murine Macrophages. J Nutr. 2008;138(1):17–23. https://doi.org/10.1093/jn/138.1.17.</mixed-citation><mixed-citation xml:lang="en">Cho HJ, Seon MR, Lee YM, Kim J, Kim JK, Kim SG, Park JH. 3,3'-Diindolylmethanesuppressestheinflammatory response to lipopolysaccharide in murine macrophages. J Nutr. 2008;138(1):17–23. https://doi.org/10.1093/jn/138.1.17.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Park SY, Shim JH, Kim JD, Yoon Park JH. The Effect of 12-O-Tetradecanoylphorbol13-acetate-induced COX-2 Expression by 3,3'-Diindolylmethane (DIM) on Human Mammary Epithelial Cells. J Korean Soc Food Sci Nutr. 2012;41(12):1701–1707. Available at: https://www.e-jkfn.org/journal/view.html?uid=5097&amp;vmd=Full.</mixed-citation><mixed-citation xml:lang="en">Park SY, Shim JH, Kim JD, Yoon Park JH. The Effect of 12-O-Tetradecanoylphorbol13-acetate-induced COX-2 Expression by 3,3'-Diindolylmethane (DIM) on Human Mammary Epithelial Cells. J Korean Soc Food Sci Nutr. 2012;41(12):1701–1707. Available at: https://www.e-jkfn.org/journal/view.html?uid=5097&amp;vmd=Full.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Rouse M, Rao R, Nagarkatti M, Nagarkatti PS. 3,3'-diindolylmethane ameliorates experimental autoimmune encephalomyelitis by promoting cell cycle arrest and apoptosis in activated T cells through microRNA signaling pathways. J Pharmacol Exp Ther. 2014;350(2):341–352. https://doi.org/10.1124/jpet.114.214742.</mixed-citation><mixed-citation xml:lang="en">Rouse M, Rao R, Nagarkatti M, Nagarkatti PS. 3,3'-diindolylmethane ameliorates experimental autoimmune encephalomyelitis by promoting cell cycle arrest and apoptosis in activated T cells through microRNA signaling pathways. J Pharmacol Exp Ther. 2014;350(2):341–352. https://doi.org/10.1124/jpet.114.214742.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Elliott DM, Nagarkatti M, Nagarkatti PS. 3,39-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B–Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells. J Pharmacol Exp Ther. 2016;357(1):177–187. https://doi.org/10.1124/jpet.115.226563.</mixed-citation><mixed-citation xml:lang="en">Elliott DM, Nagarkatti M, Nagarkatti PS. 3,39-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B–Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells. J Pharmacol Exp Ther. 2016;357(1):177–187. https://doi.org/10.1124/jpet.115.226563.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Singh NP, Singh UP, Rouse M, Zhang J, Chatterjee S, Nagarkatti PS, Nagarkatti M. Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA. J Immunol. 2016;196(3):1108–1122. https://doi.org/10.4049/jimmunol.1501727.</mixed-citation><mixed-citation xml:lang="en">Singh NP, Singh UP, Rouse M, Zhang J, Chatterjee S, Nagarkatti PS, Nagarkatti M. Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA. J Immunol. 2016;196(3):1108–1122. https://doi.org/10.4049/jimmunol.1501727.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Higdon J, Drake VJ, Delage B, Williams DE. Indole-3-carbinol. Linus Pauling Institute, Micronutrient Information Center, Oregon State University; 2025. Available at: https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/indole-3-carbinol.</mixed-citation><mixed-citation xml:lang="en">Higdon J, Drake VJ, Delage B, Williams DE. Indole-3-carbinol. Linus Pauling Institute, Micronutrient Information Center, Oregon State University; 2025. Available at: https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/indole-3-carbinol.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Choi KM, Yoo HS. Amelioration of Hyperglycemia-Induced Nephropathy by 3,3'-Diindolylmethane in Diabetic Mice. Molecules. 2019;24(24):4474. https://doi.org/10.3390/molecules24244474.</mixed-citation><mixed-citation xml:lang="en">Choi KM, Yoo HS. Amelioration of Hyperglycemia-Induced Nephropathy by 3,3'-Diindolylmethane in Diabetic Mice. Molecules. 2019;24(24):4474. https://doi.org/10.3390/molecules24244474.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Maiyoh GK, Kuh JE, Casaschi A, Theriault AG. Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr. 2007;137(10):2185–2189. https://doi.org/10.1093/jn/137.10.2185.</mixed-citation><mixed-citation xml:lang="en">Maiyoh GK, Kuh JE, Casaschi A, Theriault AG. Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr. 2007;137(10):2185–2189. https://doi.org/10.1093/jn/137.10.2185.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH. Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes. 2011;35(12):1530–1538. https://doi.org/10.1038/ijo.2011.12.</mixed-citation><mixed-citation xml:lang="en">Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH. Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes. 2011;35(12):1530–1538. https://doi.org/10.1038/ijo.2011.12.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Okulicz M, Hertig I, Chichlowska J. Effects of indole-3-carbinol on metabolic parameters and on lipogenesis and lipolysis in adipocytes. Czech J Anim Sci. 2009;54(4):182–189. https://doi.org/10.17221/1745-CJAS.</mixed-citation><mixed-citation xml:lang="en">Okulicz M, Hertig I, Chichlowska J. Effects of indole-3-carbinol on metabolic parameters and on lipogenesis and lipolysis in adipocytes. Czech J Anim Sci. 2009;54(4):182–189. https://doi.org/10.17221/1745-CJAS.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Choi Y, Um SJ, Park T. Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. Int J Obes. 2013;37(6):881–884. https://doi.org/10.1038/ijo.2012.158.</mixed-citation><mixed-citation xml:lang="en">Choi Y, Um SJ, Park T. Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. Int J Obes. 2013;37(6):881–884. https://doi.org/10.1038/ijo.2012.158.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Mao X, Paerhati G, Wu Y, Cheng LF. Modulation of gut microbiota, upregulation of ZO-1, and promotion of metabolism as therapeutic mechanisms of indole-3-carbinol against obesity in mice. Front Pharmacol. 2024;15:1499142. https://doi.org/10.3389/fphar.2024.1499142.</mixed-citation><mixed-citation xml:lang="en">Mao X, Paerhati G, Wu Y, Cheng LF. Modulation of gut microbiota, upregulation of ZO-1, and promotion of metabolism as therapeutic mechanisms of indole-3-carbinol against obesity in mice. Front Pharmacol. 2024;15:1499142. https://doi.org/10.3389/fphar.2024.1499142.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Ezhilarasan D. Oxidative stress is bane in chronic liver diseases: Clinical and experimental perspective. Arab J Gastroenterol. 2018;19(2):56–64. https://doi.org/10.1016/j.ajg.2018.03.002.</mixed-citation><mixed-citation xml:lang="en">Ezhilarasan D. Oxidative stress is bane in chronic liver diseases: Clinical and experimental perspective. Arab J Gastroenterol. 2018;19(2):56–64. https://doi.org/10.1016/j.ajg.2018.03.002.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Munakarmi S, Chand L, Shin HB, Jang KY, Jeong YJ. Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress. Int J Mol Sci. 2020;21(6):2048. https://doi.org/10.3390/ijms21062048.</mixed-citation><mixed-citation xml:lang="en">Munakarmi S, Chand L, Shin HB, Jang KY, Jeong YJ. Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress. Int J Mol Sci. 2020;21(6):2048. https://doi.org/10.3390/ijms21062048.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Ramakrishna K, Sinku S, Majumdar S, Singh N, Gajendra TA, Rani A, Krishnamurthy S. Indole-3-carbinol ameliorated the thioacetamide-induced hepatic encephalopathy in rats. Toxicology. 2023;492:153542. https://doi.org/10.1016/j.tox.2023.153542.</mixed-citation><mixed-citation xml:lang="en">Ramakrishna K, Sinku S, Majumdar S, Singh N, Gajendra TA, Rani A, Krishnamurthy S. Indole-3-carbinol ameliorated the thioacetamide-induced hepatic encephalopathy in rats. Toxicology. 2023;492:153542. https://doi.org/10.1016/j.tox.2023.153542.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Choi Y, Abdelmegeed MA, Song BJ. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis. J Nutr Biochem. 2018;55:12–25. https://doi.org/10.1016/j.jnutbio.2017.11.011.</mixed-citation><mixed-citation xml:lang="en">Choi Y, Abdelmegeed MA, Song BJ. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis. J Nutr Biochem. 2018;55:12–25. https://doi.org/10.1016/j.jnutbio.2017.11.011.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Ping J, Gao AM, Xu D, Li RW, Wang H. Therapeutic effect of indole-3-carbinol on pig serum-induced hepatic fibrosis in rats. Yao Xue Xue Bao. 2011;46(8):915–921. (In Chinese) Available at: https://pubmed.ncbi.nlm.nih.gov/22007515/.</mixed-citation><mixed-citation xml:lang="en">Ping J, Gao AM, Xu D, Li RW, Wang H. Therapeutic effect of indole-3-carbinol on pig serum-induced hepatic fibrosis in rats. Yao Xue Xue Bao. 2011;46(8):915–921. (In Chinese) Available at: https://pubmed.ncbi. nlm.nih.gov/22007515/.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Paliwal P, Chauhan G, Gautam D, Dash D, Patne SCU, Krishnamurthy S. Indole3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model. Naunyn-Schmiedebergs Arch Pharmacol. 2018;391(6):613–625. https://doi.org/10.1007/s00210-018-1488-2.</mixed-citation><mixed-citation xml:lang="en">Paliwal P, Chauhan G, Gautam D, Dash D, Patne SCU, Krishnamurthy S. Indole3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model. Naunyn-Schmiedebergs Arch Pharmacol. 2018;391(6):613–625. https://doi.org/10.1007/s00210-018-1488-2.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Ramakrishna K, Jain SK, Krishnamurthy S. Pharmacokinetic and Pharmacodynamic Properties of Indole-3-carbinol in Experimental Focal Ischemic Injury. Eur J Drug Metab Pharmacokinet. 2022;47(4):593–605. https://doi.org/10.1007/s13318-022-00771-y.</mixed-citation><mixed-citation xml:lang="en">Ramakrishna K, Jain SK, Krishnamurthy S. Pharmacokinetic and Pharmacodynamic Properties of Indole-3-carbinol in Experimental Focal Ischemic Injury. Eur J Drug Metab Pharmacokinet. 2022;47(4):593–605. https://doi.org/10.1007/s13318-022-00771-y.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Rzemieniec J, Wnuk A, Lasoń W, Bilecki W, Kajta M. The neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/ CYP19A1 signaling. Apoptosis. 2019;24(5-6):435–452. https://doi.org/10.1007/s10495-019-01522-2.</mixed-citation><mixed-citation xml:lang="en">Rzemieniec J, Wnuk A, Lasoń W, Bilecki W, Kajta M. The neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/ CYP19A1 signaling. Apoptosis. 2019;24(5-6):435–452. https://doi.org/10.1007/s10495-019-01522-2.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Peng L, Zhu X, Wang C, Jiang Q, Yu S, Song G et al. Indole-3-carbinol (I3C) reduces apoptosis and improves neurological function after cerebral ischemia–reperfusion injury by modulating microglia inflammation. Sci Rep. 2024;14(1):3145. https://doi.org/10.1038/s41598-024-53636-6.</mixed-citation><mixed-citation xml:lang="en">Peng L, Zhu X, Wang C, Jiang Q, Yu S, Song G et al. Indole-3-carbinol (I3C) reduces apoptosis and improves neurological function after cerebral ischemia–reperfusion injury by modulating microglia inflammation. Sci Rep. 2024;14(1):3145. https://doi.org/10.1038/s41598-024-53636-6.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Matsumoto K, Kinoshita K, Yoshimizu A, Kurauchi Y, Hisatsune A, Seki T, Katsuki H. Laquinimod and 3,3'-diindolylemethane alleviate neuropathological events and neurological deficits in a mouse model of intracerebral hemorrhage. J Neuroimmunol. 2020;342:577195. https://doi.org/10.1016/j.jneuroim.2020.577195.</mixed-citation><mixed-citation xml:lang="en">Matsumoto K, Kinoshita K, Yoshimizu A, Kurauchi Y, Hisatsune A, Seki T, Katsuki H. Laquinimod and 3,3'-diindolylemethane alleviate neuropathological events and neurological deficits in a mouse model of intracerebral hemorrhage. J Neuroimmunol. 2020;342:577195. https://doi.org/10.1016/j.jneuroim.2020.577195.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Gehrcke M, Sari MHM, Ferreira LM, Barbieri AV, Giuliani LM, Prado VC et al. Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models. Eur J Pharm Sci. 2018;111:133–141. https://doi.org/10.1016/j.ejps.2017.09.050.</mixed-citation><mixed-citation xml:lang="en">Gehrcke M, Sari MHM, Ferreira LM, Barbieri AV, Giuliani LM, Prado VC et al. Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models. Eur J Pharm Sci. 2018;111:133–141. https://doi.org/10.1016/j.ejps.2017.09.050.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Deng W, Zong J, Bian Z, Zhou H, Yuan Y, Zhang R et al. Indole-3- carbinolprotectsagainst pressure overload induced cardiac remodeling via activating AMPK-α. Mol Nutr Food Res. 2013;57(9):1680–1687. https://doi.org/10.1002/mnfr.201300012.</mixed-citation><mixed-citation xml:lang="en">Deng W, Zong J, Bian Z, Zhou H, Yuan Y, Zhang R et al. Indole-3- carbinolprotectsagainst pressure overload induced cardiac remodeling via activating AMPK-α. Mol Nutr Food Res. 2013;57(9):1680–1687. https://doi.org/10.1002/mnfr.201300012.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Deng W, Wei L, Zong J, Bian Z, Zhou H, Zhang R, Tang Q. Attenuation of cardiac remodeling by indole-3-carbinolinmice is associated with improved energy metabolism. Int J Cardiol. 2014;172(3):e531–e533. https://doi.org/10.1016/j.ijcard.2014.01.066.</mixed-citation><mixed-citation xml:lang="en">Deng W, Wei L, Zong J, Bian Z, Zhou H, Zhang R, Tang Q. Attenuation of cardiac remodeling by indole-3-carbinolinmice is associated with improved energy metabolism. Int J Cardiol. 2014;172(3):e531–e533. https://doi.org/10.1016/j.ijcard.2014.01.066.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Ramakrishna K, Krishnamurthy S. Indole-3-carbinol ameliorated the isoproterenol-induced myocardial infarction via multimodal mechanisms in Wistar rats. Nat Prod Res. 2022;36(23):6044–6049. https://doi.org/10.1080/14786419.2022.2041632.</mixed-citation><mixed-citation xml:lang="en">Ramakrishna K, Krishnamurthy S. Indole-3-carbinol ameliorated the isoproterenol-induced myocardial infarction via multimodal mechanisms in Wistar rats. Nat Prod Res. 2022;36(23):6044–6049. https://doi.org/10.1080/14786419.2022.2041632.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Ampofo E, Lachnitt N, Rudzitis-Auth J, Schmitt BM, Menger MD, Laschke MW. Indole-3-carbinol is a potent inhibitor of ischemia–reperfusion–induced inflammation. J Surg Res. 2017;215:34–46. https://doi.org/10.1016/j.jss.2017.03.019.</mixed-citation><mixed-citation xml:lang="en">Ampofo E, Lachnitt N, Rudzitis-Auth J, Schmitt BM, Menger MD, Laschke MW. Indole-3-carbinol is a potent inhibitor of ischemia–reperfusion–induced inflammation. J Surg Res. 2017;215:34–46. https://doi.org/10.1016/j.jss.2017.03.019.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Zhu Z, Xu W, Liu L. Ovarian aging: Mechanisms and intervention strategies. Med Rev. 2023;2(6):590–610. https://doi.org/10.1515/mr-2022-0031.</mixed-citation><mixed-citation xml:lang="en">Zhu Z, Xu W, Liu L. Ovarian aging: Mechanisms and intervention strategies. Med Rev. 2023;2(6):590–610. https://doi.org/10.1515/mr-2022-0031.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Hu H, Li F, Zhu F, Li J, Wang S, He Z et al. Indole-3-carbinolamelioratesovarian damagein female old mice through Nrf2/HO-1 pathway activation. Biochem Pharmacol. 2024;223:116193. https://doi.org/10.1016/j.bcp.2024.116193.</mixed-citation><mixed-citation xml:lang="en">Hu H, Li F, Zhu F, Li J, Wang S, He Z et al. Indole-3-carbinolamelioratesovarian damagein female old mice through Nrf2/HO-1 pathway activation. Biochem Pharmacol. 2024;223:116193. https://doi.org/10.1016/j.bcp.2024.116193.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Baez-Gonzalez AS, Carrazco-Carrillo JA, Figueroa-Gonzalez G, Quintas-Granados LI, Padilla-Benavides T, Reyes-Hernandez OD. Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells. Biochem Biophys Rep. 2023;35:101492. https://doi.org/10.1016/j.bbrep.2023.101492.</mixed-citation><mixed-citation xml:lang="en">Baez-Gonzalez AS, Carrazco-Carrillo JA, Figueroa-Gonzalez G, QuintasGranados LI, Padilla-Benavides T, Reyes-Hernandez OD. Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells. Biochem Biophys Rep. 2023;35:101492. https://doi.org/10.1016/j.bbrep.2023.101492.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Adwas AA, Elkhoely AA, Kabel AM, Abdel-Rahman MN, Eissa AA. Anti-cancer and cardioprotective effects of indol-3-carbinol in doxorubicin-treated mice. J Infect Chemother. 2016;22(1):36–43. https://doi.org/0.1016/j.jiac.2015.10.001.</mixed-citation><mixed-citation xml:lang="en">Adwas AA, Elkhoely AA, Kabel AM, Abdel-Rahman MN, Eissa AA. Anti-cancer and cardioprotective effects of indol-3-carbinol in doxorubicin-treated mice. J Infect Chemother. 2016;22(1):36–43. https://doi.org/0.1016/j.jiac.2015.10.001.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Hajra S, Patra AR, Basu A, Bhattacharya S. Prevention of doxorubicin (DOX)- induced genotoxicity and cardiotoxicity: Effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation. Biomed Pharmacother. 2018;101:228–243. https://doi.org/10.1016/j.biopha.2018.02.088.</mixed-citation><mixed-citation xml:lang="en">Hajra S, Patra AR, Basu A, Bhattacharya S. Prevention of doxorubicin (DOX)- induced genotoxicity and cardiotoxicity: Effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation. Biomed Pharmacother. 2018;101:228–243. https://doi.org/10.1016/j.biopha.2018.02.088.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Ilias I, Milionis C, Zoumakis E. An Overview of Glucocorticoid-Induced Osteoporosis. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G et al. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK278968/.</mixed-citation><mixed-citation xml:lang="en">Ilias I, Milionis C, Zoumakis E. An Overview of Glucocorticoid-Induced Osteoporosis. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G et al. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK278968/.</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Lin H, Gao X, Chen G, Sun J, Chu J, Jing K et al. Indole-3-carbinolasinhibitorsofg lucocorticoid-induced apoptosis in osteoblastic cells through blocking ROSmediated Nrf2 pathway. Biochem Biophys Res Commun. 2015;460(2):422–427. https://doi.org/10.1016/j.bbrc.2015.03.049.</mixed-citation><mixed-citation xml:lang="en">Lin H, Gao X, Chen G, Sun J, Chu J, Jing K et al. Indole-3-carbinolasinhibitorsofg lucocorticoid-induced apoptosis in osteoblastic cells through blocking ROSmediated Nrf2 pathway. Biochem Biophys Res Commun. 2015;460(2):422–427. https://doi.org/10.1016/j.bbrc.2015.03.049.</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Ma Y, Zhu Y, Wang F, Zhao G, Huang L, Lu R et al. 3,3'-Diindolylmethane promotes bone formation – A assessment in MC3T3-E1 cells and zebrafish. Biochem Pharmacol. 2024;230(Pt 3):116618. https://doi.org/10.1016/j.bcp.2024.116618.</mixed-citation><mixed-citation xml:lang="en">Ma Y, Zhu Y, Wang F, Zhao G, Huang L, Lu R et al. 3,3'-Diindolylmethane promotes bone formation – A assessment in MC3T3-E1 cells and zebrafish. Biochem Pharmacol. 2024;230(Pt 3):116618. https://doi.org/10.1016/j.bcp.2024.116618.</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Beaver LM, Yu TW, Sokolowski EI, Williams DE, Dashwood RH, Ho E. 3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells. Toxicol Appl Pharmacol. 2012;263(3):345–351. https://doi.org/10.1016/j.taap.2012.07.007.</mixed-citation><mixed-citation xml:lang="en">Beaver LM, Yu TW, Sokolowski EI, Williams DE, Dashwood RH, Ho E. 3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells. Toxicol Appl Pharmacol. 2012;263(3):345–351. https://doi.org/10.1016/j.taap.2012.07.007.</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Boyle MC, Crabbs TA, Wyde ME, Painter JT, Hill GD, Malarkey DE et al. Intestinal lymphangiectasis and lipidosis in rats following subchronic exposure to indole-3-carbinol via oral gavage. Toxicol Pathol. 2012;40(4):561–576. https://doi.org/10.1177/0192623311436178.</mixed-citation><mixed-citation xml:lang="en">Boyle MC, Crabbs TA, Wyde ME, Painter JT, Hill GD, Malarkey DE et al. Intestinal lymphangiectasis and lipidosis in rats following subchronic exposure to indole-3-carbinol via oral gavage. Toxicol Pathol. 2012;40(4):561–576. https://doi.org/10.1177/0192623311436178.</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Wyde ME, Boyle MC, Herbert RA, Nyska A, Adams ET, Atkinson B et al . Toxicology studies of indole-3-carbinol in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 2017;(584):NTP-TR-584. https://doi.org/10.22427/NTP-TR-584.</mixed-citation><mixed-citation xml:lang="en">Wyde ME, Boyle MC, Herbert RA, Nyska A, Adams ET, Atkinson B et al . Toxicology studies of indole-3-carbinol in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 2017;(584):NTP-TR-584. https://doi.org/10.22427/NTP-TR-584.</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl. 1997;67(S28-29):111–116. https://doi.org/10.1002/(sici)1097-4644(1997)28/29+3.0.co;2-k.</mixed-citation><mixed-citation xml:lang="en">Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl. 1997;67(S28-29):111–116. https://doi.org/10.1002/(sici)1097-4644(1997)28/29+3.0.co;2-k.</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus. 2001;10(11):779–783. https://doi.org/10.1177/096120330101001104.</mixed-citation><mixed-citation xml:lang="en">McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus. 2001;10(11):779–783. https://doi.org/10.1177/096120330101001104.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810–815. https://doi.org/10.1016/S0194-5998(98)70274-8.</mixed-citation><mixed-citation xml:lang="en">Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810–815. https://doi.org/10.1016/S0194-5998(98)70274-8.</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Reed GA, Arneson DW, Putnam WC, Smith HJ, Gray JC, Sullivan DK et al. Singledose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2477–2481. https://doi.org/10.1158/1055-9965.EPI-06-0396.</mixed-citation><mixed-citation xml:lang="en">Reed GA, Arneson DW, Putnam WC, Smith HJ, Gray JC, Sullivan DK et al. Singledose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2477–2481. https://doi.org/10.1158/1055-9965.EPI-06-0396.</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Киселев ВИ, Сметник ВП, Сутурина ЛВ, Селиванов СП, Рудакова ЕБ, Рахматуллина ИР u др. Индолкарбинол – метод мультитаргетной терапии при циклической мастодинии. Акушерство и гинекология. 2013;(7):56–63. Режим доступа: https://elibrary.ru/rfkyoj.</mixed-citation><mixed-citation xml:lang="en">Kiselev VI, Smetnik VP, Suturina LV, Selivanov SP, Rudakova EB, Rakhmatullina IR et al. Indole carbinol is a multitargeted therapy option for cyclic mastodynia. Akusherstvo i Ginekologiya (Russian Federation). 2013;(7):56–63. (In Russ.) Available at: https://elibrary.ru/rfkyoj.</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Родионов ВВ, Сметник АА. Доброкачественные заболевания молочных желез. Акушерство и гинекология: новости, мнения, обучение. 2018;(1):90–100. Режим доступа: https://acu-gin-journal.ru/ru/jarticles_acu/342.html.</mixed-citation><mixed-citation xml:lang="en">Rodionov VV, Smetnik AA. Benign breast diseases. Akusherstvo i Ginekologiya: Novosti, Mneniya, Obuchenie. 2018;(1):90–100. (In Russ.) Available at: https://acu-gin-journal.ru/ru/jarticles_acu/342.html.</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Su J, Fang H, Lin Y, Yao Y, Liu Y, Zhong Y at et al. 3,3'-Diindolylmethane Ameliorates Metabolism Dysfunction-Associated Fatty Liver Disease via AhR/p38 MAPK Signaling. Nutrients. 2025;15;17(10):1681. https://doi.org/10.3390/nu17101681.</mixed-citation><mixed-citation xml:lang="en">Su J, Fang H, Lin Y, Yao Y, Liu Y, Zhong Y at et al. 3,3'-Diindolylmethane Ameliorates Metabolism Dysfunction-Associated Fatty Liver Disease via AhR/p38 MAPK Signaling. Nutrients. 2025;15;17(10):1681. https://doi.org/10.3390/nu17101681.</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Hendler SS, Rorvik DM. PDR for Nutritional Supplements. 2nd ed. Thomson Reuters; 2008. 788 p.</mixed-citation><mixed-citation xml:lang="en">Hendler SS, Rorvik DM. PDR for Nutritional Supplements. 2nd ed. Thomson Reuters; 2008. 788 p.</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Муйжнек ЕЛ, Киселев ВИ, Рожкова НИ, Ашрафян ЛА. Между мастопатией и раком молочной железы: факторы риска и патогенетическое лечение. М.: ГЭОТАР-Медиа; 2024. 336 c.</mixed-citation><mixed-citation xml:lang="en">Муйжнек ЕЛ, Киселев ВИ, Рожкова НИ, Ашрафян ЛА. Между мастопатией и раком молочной железы: факторы риска и патогенетическое лечение. М.: ГЭОТАР-Медиа; 2024. 336 c.</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Pondugula SR, Flannery PC, Abbott KL, Coleman ES, Mani S, Samuel T, Xie W. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. Toxicol Lett. 2015;232(3):580–589. https://doi.org/10.1016/j.toxlet.2014.12.015.</mixed-citation><mixed-citation xml:lang="en">Pondugula SR, Flannery PC, Abbott KL, Coleman ES, Mani S, Samuel T, Xie W. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. Toxicol Lett. 2015;232(3):580–589. https://doi.org/10.1016/j.toxlet.2014.12.015.</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>
