Молекулярные механизмы осуществления фармакологических эффектов препаратов на основе экстрактов Cimicifuga racemosa

1. Громова О.А, Торшин И.Ю., Лиманова О.А., Лапочкина Н.П. Систематический анализ фармакологии стандартизированных природных экстрактов цимицифуги для поддержки женского здоровья. 2017. / Gromova O.A, Torshin I.Iu., Limanova O.A., Lapochkina N.P. Sistematicheskii analiz farmakologii standartizirovannykh prirodnykh ekstraktov tsimitsifugi dlia podderzhki zhenskogo zdorov'ia. 2017. [in Russian]
2. Lee JH, Cuong TD, Kwack SJ et al. Cycloartane-type Triterpene Glycosides from the Rhizomes of Cimicifuga heracleifolia and Their Anticomplementary Activity. Planta Med 2012; 78 (12): 1391–4.
3. Liu WH, Wang YG, Yang J. Black Cohosh (Cimicifuga Species) for Menopausal Symptoms. Clin Nurse Spec 2013; 27 (6): 289–90.
4. Gai YY, Liu WH, Sha CJ et al. Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats. J Ethnopharmacol 2012; 143 (1): 249–55.
5. Chen JY, Li PL, Tang XL et al. Cycloartane Triterpenoids and Their Glycosides from the Rhizomes of Cimicifuga foetida. J Nat Prod 2014; 77 (9): 1997–2005.
6. Disch L, Forsch K, Siewert B et al. In Vitro and In Situ Characterization of Triterpene Glycosides From Cimicifuga racemosa Extract. J Pharm Sci 2017. pii: S0022-3549(17)3055.
7. Guo Y, Yin T, Wang X et al. Traditional uses, phytochemistry, pharmacology and toxicology of the genus Cimicifuga: A review. J Ethnopharmacol 2017; 209: 264–82.
8. Ruhlen RL, Sun GY, Sauter ER. Black Cohosh: Insights into its Mechanism(s) of Action. Integr Med Insights 2008; 3: 21–32.
9. Жидкова Е.В., Лесиовская Е.Е., Линде В.А. Эффективность фитоэстрогенов в коррекции климактерических расстройств. Проблемы репродукции. 2012; 5: 115–9. / Zhidkova E.V., Lesiovskaia E.E., Linde V.A. Effektivnost' fitoestrogenov v korrektsii klimaktericheskikh rasstroistv. Problemy reproduktsii. 2012; 5: 115–9. [in Russian]
10. Татарчук Т.Ф., Ефименко О.А. Фитотерапия ранних менопаузальных расстройств. Репродуктивная эндокринол. 2012; 3: 41–4. / Tatarchuk T.F., Efimenko O.A. Fitoterapiia rannikh menopauzal'nykh rasstroistv. Reproduktivnaia endokrinol. 2012; 3: 41–4. [in Russian]
11. Балан В.Е. Применение фитоэстрогенов для лечения гипоэстрогенных состояний. Рус. мед. журн. 2000; 8 (3): 56–61. / Balan V.E. Primenenie fitoestrogenov dlia lecheniia gipoestrogennykh sostoianii. Rus. med. zhurn. 2000; 8 (3): 56–61. [in Russian]
12. Никитин А.И. Фитоэстрогены (лекция). Проблемы репродукии. 2000; 3. / Nikitin A.I. Fitoestrogeny (lektsiia). Problemy reprodukii. 2000; 3. [in Russian]
13. Powers CN, Setzer WN. A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements. In Silico Pharmacol 2015; 3: 4.
14. Park J, Shim M, Rhyu MR, Lee Y. Estrogen receptor mediated effects of Cimicifuga extracts on human breast cancer cells. Pharmazie 2012; 67 (11): 947–50.
15. Zierau O, Bodinet C, Kolba S et al. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002; 80 (1): 125–30.
16. Nikolic D, Li J, van Breemen RB. Metabolism of Nomega -methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes. Biomed Chromatogr 2014; 28 (12): 1647–51.
17. Burdette JE, Liu J, Chen SN et al. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J Agric Food Chem 2003; 51 (19): 5661–70.
18. Cicek SS, Khom S, Taferner B et al. Bioactivity-guided isolation of GABA(A) receptor modulating constituents from the rhizomes of Actaea racemosa. J Nat Prod 2010; 73 (12): 2024–8.
19. Strommer B, Khom S, Kastenberger I et al. A cycloartane glycoside derived from Actaea racemosa L. modulates GABAA receptors and induces pronounced sedation in mice. J Pharmacol Exp Ther 2014; 351 (2): 234–42.
20. Oktem M, Eroglu D, Karahan HB et al. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther 2007; 24 (2): 448–61.
21. Woo KC, Park YS, Jun DJ et al. Phytoestrogen cimicifugoside-mediated inhibition of catecholamine secretion by blocking nicotinic acetylcholine receptor in bovine adrenal chromaffin cells. J Pharmacol Exp Ther 2004; 309 (2): 641–9.
22. Reame NE, Lukacs JL, Padmanabhan V et al. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 2008; 15 (5): 832–40.
23. Yang CL, Chik SC, Li JC et al. Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages. J Med Chem 2009; 52 (21): 6707–15.
24. Loser B, Kruse SO, Melzig MF, Nahrstedt A. Inhibition of neutrophil elastase activity by cinnamic acid derivatives from Cimicifuga racemosa. Planta Med 2000; 66 (8): 751–3.
25. Wuttke W, Jarry H, Haunschild J et al. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol 2014; 139: 302–10.
26. Торшин И.Ю., Громова О.А., Лиманова О.А. «Быстрый эффект» бета-аланина при приливах: сравнительное исследование взаимодействий бета-аланина, таурина и глицина с глициновыми рецепторами. Гинекология. 2012; 14 (2): 65–9. / Torshin I.Iu., Gromova O.A., Limanova O.A. “Bystryi effect” beta-alanina pri prilivakh: sravnitel'noe issledovanie vzaimodeistvii beta-alanina, taurina i glitsina s glitsinovymi retseptorami. Gynecology. 2012; 14 (2): 65–9. [in Russian]
27. Suh KS, Choi EM, Jung WW et al. Deoxyactein protects pancreatic beta-cells against methylglyoxal-induced oxidative cell damage by the upregulation of mitochondrial biogenesis. Int J Mol Med 2017; 40 (2): 539–48.
28. Meeprom A, Sompong W, Suantawee T et al. Isoferulic acid prevents methylglyoxal-induced protein glycation and DNA damage by free radical scavenging activity. BMC Complement Altern Med 2015; 15: 346.
29. Gaikwad AB, Viswanad B, Ramarao P. PPAR gamma agonists partially restores hyperglycemia induced aggravation of vascular dysfunction to angiotensin II in thoracic aorta isolated from rats with insulin resistance. Pharmacol Res 2007; 55 (5): 400–7.
30. Kato H, Tanaka G, Masuda S et al. Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes. J Pineal Res 2015; 59 (2): 267–75. DOI: 10.1111/jpi.12259
31. Lee YS, Choi EM. Actein isolated from black cohosh promotes the function of osteoblastic MC3T3-E1 cells. J Med Food 2014; 17 (4): 414–23.
32. Choi EM, Suh KS, Jung WW et al. Actein alleviates 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated cellular dysfunction in osteoblastic MC3T3-E1 cells. Environ Toxicol 2017; 101002/tox22459.
33. Suh KS, Chon S, Choi EM. Actein protects against methylglyoxal-induced oxidative damage in osteoblastic MC3T3-E1 cells. J Sci Food Agric 2017; 97 (1): 207–14.
34. Cui G, Leng H, Wang K et al. Effects of remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis. PLoS One 2013; 8 (12): e82815.
35. Min L, Wang F, Liang S et al. Menopausal status and the risk of lung cancer in women: A PRISMA-compliant meta-analysis. Medicine (Baltimore) 2017; 96 (26): e7065. DOI: 10.1097/MD.0000000000007065.
36. Beral V, Gaitskell K, Hermon C et al; Collaborative Group On Epidemiological Studies Of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 2015; 385 (9980): 1835–42. DOI: 10.1016/S0140-6736(14)61687-1
37. Einbond LS, Shimizu M, Nuntanakorn P et al. Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells. Planta Med 2006; 72 (13): 1200–6.
38. Dai X, Liu J, Nian Y et al. A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells. Oncol Rep 2017; 37 (4): 2079–86.
39. Дубовик Б.В., Кострова Л.Н., Молофей В.П. и др. Влияние меланина на мутагенное действие хронического облучения и адаптивный ответ у мышей. Химико-фармацевтический журн. 2017; 4: 45–7. / Dubovik B.V., Kostrova L.N., Molofei V.P. i dr. Vliianie melanina na mutagennoe deistvie khronicheskogo oblucheniia i adaptivnyi otvet u myshei. Khimiko-farmatsevticheskii zhurn. 2017; 4: 45–7. [in Russian]
40. Дубовик Б.В., Кострова Л.Н., Молофей В.П. и др. Влияние меланина на мутагенное действие хронического облучения и адаптивный ответ у мышей. Радиационная биология. Радиоэкология. 1999; 2: 329–33. / Dubovik B.V., Kostrova L.N., Molofei V.P. i dr. Vliianie melanina na mutagennoe deistvie khronicheskogo oblucheniia i adaptivnyi otvet u myshei. Radiatsionnaia biologiia. Radioekologiia. 1999; 2: 329–33. [in Russian]
41. Skoczyńska A, Budzisz E, Trznadel-Grodzka E, Rotsztejn H. Melanin and lipofuscin as hallmarks of skin aging. Postepy Dermatol Alergol 2017; 34 (2): 97–103. DOI: 10.5114/ada.2017.67070
42. Godowski KC. Antimicrobial action of sanguinarine. J Clin Dent 1989; 1 (4): 96–101.
43. Southard GL, Boulware RT, Walborn DR et al. Sanguinarine, a new antiplaque agent: Retention and plaque specificity. J Am Dent Assoc 1984, 108 (3): 338–41.

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1. Gromova O.A, Torshin I.Iu., Limanova O.A., Lapochkina N.P. Sistematicheskii analiz farmakologii standartizirovannykh prirodnykh ekstraktov tsimitsifugi dlia podderzhki zhenskogo zdorov'ia. 2017. [in Russian]
2. Lee JH, Cuong TD, Kwack SJ et al. Cycloartane-type Triterpene Glycosides from the Rhizomes of Cimicifuga heracleifolia and Their Anticomplementary Activity. Planta Med 2012; 78 (12): 1391–4.
3. Liu WH, Wang YG, Yang J. Black Cohosh (Cimicifuga Species) for Menopausal Symptoms. Clin Nurse Spec 2013; 27 (6): 289–90.
4. Gai YY, Liu WH, Sha CJ et al. Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats. J Ethnopharmacol 2012; 143 (1): 249–55.
5. Chen JY, Li PL, Tang XL et al. Cycloartane Triterpenoids and Their Glycosides from the Rhizomes of Cimicifuga foetida. J Nat Prod 2014; 77 (9): 1997–2005.
6. Disch L, Forsch K, Siewert B et al. In Vitro and In Situ Characterization of Triterpene Glycosides From Cimicifuga racemosa Extract. J Pharm Sci 2017. pii: S0022-3549(17)3055.
7. Guo Y, Yin T, Wang X et al. Traditional uses, phytochemistry, pharmacology and toxicology of the genus Cimicifuga: A review. J Ethnopharmacol 2017; 209: 264–82.
8. Ruhlen RL, Sun GY, Sauter ER. Black Cohosh: Insights into its Mechanism(s) of Action. Integr Med Insights 2008; 3: 21–32.
9.  Zhidkova E.V., Lesiovskaia E.E., Linde V.A. Effektivnost' fitoestrogenov v korrektsii klimaktericheskikh rasstroistv. Problemy reproduktsii. 2012; 5: 115–9. [in Russian]
10.  Tatarchuk T.F., Efimenko O.A. Fitoterapiia rannikh menopauzal'nykh rasstroistv. Reproduktivnaia endokrinol. 2012; 3: 41–4. [in Russian]
11.  Balan V.E. Primenenie fitoestrogenov dlia lecheniia gipoestrogennykh sostoianii. Rus. med. zhurn. 2000; 8 (3): 56–61. [in Russian]
12. Nikitin A.I. Fitoestrogeny (lektsiia). Problemy reprodukii. 2000; 3. [in Russian]
13. Powers CN, Setzer WN. A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements. In Silico Pharmacol 2015; 3: 4.
14. Park J, Shim M, Rhyu MR, Lee Y. Estrogen receptor mediated effects of Cimicifuga extracts on human breast cancer cells. Pharmazie 2012; 67 (11): 947–50.
15. Zierau O, Bodinet C, Kolba S et al. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002; 80 (1): 125–30.
16. Nikolic D, Li J, van Breemen RB. Metabolism of Nomega -methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes. Biomed Chromatogr 2014; 28 (12): 1647–51.
17. Burdette JE, Liu J, Chen SN et al. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J Agric Food Chem 2003; 51 (19): 5661–70.
18. Cicek SS, Khom S, Taferner B et al. Bioactivity-guided isolation of GABA(A) receptor modulating constituents from the rhizomes of Actaea racemosa. J Nat Prod 2010; 73 (12): 2024–8.
19. Strommer B, Khom S, Kastenberger I et al. A cycloartane glycoside derived from Actaea racemosa L. modulates GABAA receptors and induces pronounced sedation in mice. J Pharmacol Exp Ther 2014; 351 (2): 234–42.
20. Oktem M, Eroglu D, Karahan HB et al. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther 2007; 24 (2): 448–61.
21. Woo KC, Park YS, Jun DJ et al. Phytoestrogen cimicifugoside-mediated inhibition of catecholamine secretion by blocking nicotinic acetylcholine receptor in bovine adrenal chromaffin cells. J Pharmacol Exp Ther 2004; 309 (2): 641–9.
22. Reame NE, Lukacs JL, Padmanabhan V et al. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 2008; 15 (5): 832–40.
23. Yang CL, Chik SC, Li JC et al. Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages. J Med Chem 2009; 52 (21): 6707–15.
24. Loser B, Kruse SO, Melzig MF, Nahrstedt A. Inhibition of neutrophil elastase activity by cinnamic acid derivatives from Cimicifuga racemosa. Planta Med 2000; 66 (8): 751–3.
25. Wuttke W, Jarry H, Haunschild J et al. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol 2014; 139: 302–10.
26. Torshin I.Iu., Gromova O.A., Limanova O.A. “Bystryi effect” beta-alanina pri prilivakh: sravnitel'noe issledovanie vzaimodeistvii beta-alanina, taurina i glitsina s glitsinovymi retseptorami. Gynecology. 2012; 14 (2): 65–9. [in Russian]
27. Suh KS, Choi EM, Jung WW et al. Deoxyactein protects pancreatic beta-cells against methylglyoxal-induced oxidative cell damage by the upregulation of mitochondrial biogenesis. Int J Mol Med 2017; 40 (2): 539–48.
28. Meeprom A, Sompong W, Suantawee T et al. Isoferulic acid prevents methylglyoxal-induced protein glycation and DNA damage by free radical scavenging activity. BMC Complement Altern Med 2015; 15: 346.
29. Gaikwad AB, Viswanad B, Ramarao P. PPAR gamma agonists partially restores hyperglycemia induced aggravation of vascular dysfunction to angiotensin II in thoracic aorta isolated from rats with insulin resistance. Pharmacol Res 2007; 55 (5): 400–7.
30. Kato H, Tanaka G, Masuda S et al. Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes. J Pineal Res 2015; 59 (2): 267–75. DOI: 10.1111/jpi.12259
31. Lee YS, Choi EM. Actein isolated from black cohosh promotes the function of osteoblastic MC3T3-E1 cells. J Med Food 2014; 17 (4): 414–23.
32. Choi EM, Suh KS, Jung WW et al. Actein alleviates 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated cellular dysfunction in osteoblastic MC3T3-E1 cells. Environ Toxicol 2017; 101002/tox22459.
33. Suh KS, Chon S, Choi EM. Actein protects against methylglyoxal-induced oxidative damage in osteoblastic MC3T3-E1 cells. J Sci Food Agric 2017; 97 (1): 207–14.
34. Cui G, Leng H, Wang K et al. Effects of remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis. PLoS One 2013; 8 (12): e82815.
35. Min L, Wang F, Liang S et al. Menopausal status and the risk of lung cancer in women: A PRISMA-compliant meta-analysis. Medicine (Baltimore) 2017; 96 (26): e7065. DOI: 10.1097/MD.0000000000007065.
36. Beral V, Gaitskell K, Hermon C et al; Collaborative Group On Epidemiological Studies Of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 2015; 385 (9980): 1835–42. DOI: 10.1016/S0140-6736(14)61687-1
37. Einbond LS, Shimizu M, Nuntanakorn P et al. Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells. Planta Med 2006; 72 (13): 1200–6.
38. Dai X, Liu J, Nian Y et al. A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells. Oncol Rep 2017; 37 (4): 2079–86.
39. Dubovik B.V., Kostrova L.N., Molofei V.P. i dr. Vliianie melanina na mutagennoe deistvie khronicheskogo oblucheniia i adaptivnyi otvet u myshei. Khimiko-farmatsevticheskii zhurn. 2017; 4: 45–7. [in Russian]
40. Dubovik B.V., Kostrova L.N., Molofei V.P. i dr. Vliianie melanina na mutagennoe deistvie khronicheskogo oblucheniia i adaptivnyi otvet u myshei. Radiatsionnaia biologiia. Radioekologiia. 1999; 2: 329–33. [in Russian]
41. Skoczyńska A, Budzisz E, Trznadel-Grodzka E, Rotsztejn H. Melanin and lipofuscin as hallmarks of skin aging. Postepy Dermatol Alergol 2017; 34 (2): 97–103. DOI: 10.5114/ada.2017.67070
42. Godowski KC. Antimicrobial action of sanguinarine. J Clin Dent 1989; 1 (4): 96–101.
43. Southard GL, Boulware RT, Walborn DR et al. Sanguinarine, a new antiplaque agent: Retention and plaque specificity. J Am Dent Assoc 1984, 108 (3): 338–41.

О.А.Громова*1,2, И.Ю.Торшин1, Н.К.Тетруашвили3, Л.Э.Федотова2, Н.П.Лапочкина2

1. ФГБУ «Федеральный исследовательский центр “Информатика и управление”» РАН. 119333, Россия, Москва, ул. Вавилова, д. 44, корп. 2;
2. ФГБОУ ВО «Ивановская государственная медицинская академия» Минздрава России. 153462, Россия, Иваново, пр. Шереметевский, д. 8;
3. ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*unesco.gromova@gmail.com

________________________________________________

O.A.Gromova*1,2, I.Yu.Torshin1, N.K.Tetruashvili3, L.E.Fedotova2, N.P.Lapochkina2

1. Federal Research Centre "Information and Management" of the Russian Academy of Sciences. 119333, Russian Federation, Moscow, ul. Vavilova, d. 44, кorp. 2;
2. Ivanovo State Medical Academy of the Ministry of Health of the Russian Federation. 153462, Russian Federation, Ivanovo, pr. Sheremetevskii, d. 8;
3. V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*unesco.gromova@gmail.com