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Экстракты лекарственных растений в гепатопротекции: антиоксидантные и иммуномодулирующие эффекты
Ших Е.В., Хайтович Е.Д., Цветков Д.Н. Экстракты лекарственных растений в гепатопротекции: антиоксидантные и иммуномодулирующие эффекты. Терапевтический архив. 2024;96(8):836–845.
DOI: 10.26442/00403660.2024.08.202841
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
DOI: 10.26442/00403660.2024.08.202841
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
________________________________________________
Shikh EV, Khaytovich ED, Tsvetkov DN. Herbal extracts in hepatoprotection: antioxidant and immunomodulatory effects. A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2024;96(8):836–845.
DOI: 10.26442/00403660.2024.08.202841
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Глобальный рынок растительных препаратов оценивается в 83 млрд дол. и продолжает стремительно расти. Экстракты лекарственных растений (ЛР), широко используемые благодаря эффективности и минимальным побочным эффектам, играют значительную роль в поддержании функции печени. Лечение заболеваний печени, включая гепатиты различной этиологии, алкогольную и неалкогольную жировую болезнь печени и цирроз, а также профилактика лекарственных поражений печени требуют назначения эффективных гепатопротекторных препаратов. Антиоксидантные и иммуномодулирующие фармакологические эффекты играют значимую роль в механизмах гепатопротекции экстрактов ЛР. Цель исследования – проанализировать механизмы гепатопротекторных эффектов различных экстрактов ЛР, входящих в состав лекарственного препарата (ЛП) ДИПАНА®, их антиоксидантные и иммуномодулирующие эффекты, а также представить результаты клинических исследований (КИ), подтверждающих их эффективность при различных заболеваниях печени. Анализ проводили на основе доступных литературных данных и результатов КИ по применению ЛП ДИПАНА®. Рассмотренные экстракты ЛР и их комплекс (ЛП ДИПАНА®) демонстрируют эффективность на экспериментальных моделях поражения печени и при проведении КИ у пациентов с заболеваниями данного органа, включая алкогольный и неалкогольный стеатогепатит, лекарственные поражения, а также функциональные расстройства желчного пузыря. Препарат оказывает гепатопротекторное, холеретическое, спазмолитическое действие и хорошо переносится больными.
Ключевые слова: гепатопротекторы, антиоксиданты, иммуномодуляторы, экстракты, заболевания печени
Ключевые слова: гепатопротекторы, антиоксиданты, иммуномодуляторы, экстракты, заболевания печени
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The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.
Keywords: hepatoprotectors, antioxidants, immunomodulators, plant extracts, liver diseases
Полный текст
Список литературы
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8. Dhawan BN. Picroliv – A New Hepatoprotective Agent from an Indian Medicinal plant, Picrorhiza Kurroa. Med Chem Res. 1995;5:595-605.
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14. Rajkumar V, Guha G, Kumar RA. Antioxidant and anti-neoplastic activities of Picrorhiza kurroa extracts. Food Chem Toxicol. 2011;49(2):363-9. DOI:10.1016/j.fct.2010.11.009
15. Almeleebia TM, Alsayari A, Wahab S. Pharmacological and Clinical Efficacy of Picrorhiza kurroa and Its Secondary Metabolites: A Comprehensive Review. Molecules. 2022;27(23). DOI:10.3390/molecules27238316
16. Singh H, Sharma Y. Clinical evaluation of the hepatoprotective effect of Katuki (Picrorhiza kurroa Royle ex Benth.) processed in Guduchi (Tinospora cordifolia Wild.) Miers in patients receiving lipid lowering drugs (Statins). Indian Journal of Traditional Knowledge. 2011;10:657-60.
17. Tarapure S, Tubaki BR, Khot S. Elastographic liver evaluation of Katukyadi churna in the management of Non-Alcoholic Steatohepatitis (NASH) – A single arm clinical trial. J Ayurveda Integr Med. 2021;12(1):136-42. DOI:10.1016/j.jaim.2020.12.015
18. Vaidya AB, Antarkar DS, Doshi JC, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent-experimental & clinical studies. J Postgrad Med. 1996;42(4):105-8.
19. Jiang M, Sheng F, Zhang Z, et al. Andrographis paniculata (Burm.f.) Nees and its major constituent andrographolide as potential antiviral agents. J Ethnopharmacol. 2021;272:113954. DOI:10.1016/j.jep.2021.113954
20. Lee JC, Tseng CK, Young KC, et al. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells. Br J Pharmacol. 2014;171(1):237-52. DOI:10.1111/bph.12440
21. Chandrasekaran CV, Gupta A, Agarwal A. Effect of an extract of Andrographis paniculata leaves on inflammatory and allergic mediators in vitro. J Ethnopharmacol.
2010;129(2):203-7. DOI:10.1016/j.jep.2010.03.007
22. Chandrasekaran CV, Thiyagarajan P, Deepak HB, Agarwal A. In vitro modulation of LPS/calcimycin induced inflammatory and allergic mediators by pure compounds of Andrographis paniculata (King of bitters) extract. Int Immunopharmacol. 2011;11(1):79-84. DOI:10.1016/j.intimp.2010.10.009
23. Liu J, Wang ZT, Ge BX. Andrograpanin, isolated from Andrographis paniculata, exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways. Int Immunopharmacol. 2008;8(7):951-8. DOI:10.1016/j.intimp.2007.12.014
24. Singha PK, Roy S, Dey S. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J Ethnopharmacol. 2007;111(1):13-21. DOI:10.1016/j.jep.2006.10.026
25. Liu FP, Ma X, Li MM, et al. Hepatoprotective effects of Solanum nigrum against ethanol-induced injury in primary hepatocytes and mice with analysis of glutathione S-transferase A1. J Chin Med Assoc. 2016;79(2):65-71. DOI:10.1016/j.jcma.2015.08.013
26. Amin ZA, Abdulla MA, Ali HM, et al. Assessment of in vitro antioxidant, antibacterial and immune activation potentials of aqueous and ethanol extracts of Phyllanthus niruri. J Sci Food Agric. 2012;92(9):1874-7. DOI:10.1002/jsfa.5554
27. Colpo E, Vilanova CD, Pereira RP, et al. Antioxidant effects of Phyllanthus niruri tea on healthy subjects. Asian Pac J Trop Med. 2014;7(2):113-8. DOI:10.1016/S1995-7645(14)60005-5
28. Nworu CS, Akah PA, Okoye FB, Esimone CO. Aqueous extract of Phyllanthus niruri (Euphorbiaceae) enhances the phenotypic and functional maturation of bone marrow-derived dendritic cells and their antigen-presentation function. Immunopharmacol Immunotoxicol. 2010;32(3):393-401. DOI:10.3109/08923970903463939
29. Koay YH, Basiri A, Murugaiyah V, Chan KL. Isocorilagin, a cholinesterase inhibitor from Phyllanthus niruri. Nat Prod Commun. 2014;9(4):515-7.
30. Latha P, Chaitanya D, Rukkumani R. Protective effect of Phyllanthus niruri on alcohol and heated sunflower oil induced hyperlipidemia in Wistar rats. Toxicol Mech Methods. 2010;20(8):498-503. DOI:10.3109/15376516.2010.511301
31. Kaur N, Kaur B, Sirhindi G. Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review. Phytother Res. 2017;31(7):980-1004. DOI:10.1002/ptr.5825
32. Thyagarajan SP, Thiruneelakantan K, Subramanian S, Sundaravelu T. In vitro inactivation of HBsAg by Eclipta alba Hassk and Phyllanthus niruri Linn. Indian J Med Res.
1982;(Suppl. 76):124-30.
33. Venkateswaran PS, Millman I, Blumberg BS. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Proc Natl Acad Sci U S A. 1987;84(1):274-8. DOI:10.1073/pnas.84.1.274
34. Thyagarajan SP, Subramanian S, Thirunalasundari T, et al. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet. 1988;2(8614):764-6.
DOI:10.1016/s0140-6736(88)92416-6
35. Wang M, Cheng H, Li Y, et al. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med. 1995;126(4):350-2.
36. Panneer SK, Payyappallimana U, Ravikumar K, Venkatasubramanian P. Can Guduchi (Tinospora cordifolia), a well-known ayurvedic hepato-protectant cause liver damage? J Ayurveda Integr Med. 2023;14(1):100658. DOI:10.1016/j.jaim.2022.100658
37. Arunachalam K, Yang X, San TT. Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases. J Ethnopharmacol. 2022;283:114540. DOI:10.1016/j.jep.2021.114540
38. Goel HC, Prasad J, Singh S, et al. Radioprotective potential of an herbal extract of Tinospora cordifolia. J Radiat Res. 2004;45(1):61-8. DOI:10.1269/jrr.45.61
39. Bishayi B, Roychowdhury S, Ghosh S, Sengupta M. Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. J Toxicol Sci. 2002;27(3):139-46. DOI:10.2131/jts.27.139
40. Singh HK, Rastogi RP, Srimal RC, Dhawan BN. Effect of bacosides A and B on avoidance responses in rats. Phytother Res. 1988;2(2):70-5. DOI:10.1002/ptr.2650020205
41. Russo A, Izzo AA, Borrelli F, et al. Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage. Phytother Res. 2003;17(8):870-5. DOI:10.1002/ptr.1061
42. Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol. 2009;27(1):62-9. DOI:10.1016/j.etap.2008.08.00
43. Anand T, Naika M, Swamy MSL, Khanum F. Antioxidant and DNA Damage Preventive Properties of Bacopa Monniera (L) Wettst. Free Radic Antioxid. 2011;1(1):84-90. DOI:10.5530/ax.2011.1.13
44. Tewtrakul S, Subhadhirasakul S, Tansakul P, et al. Antiinflammatory constituents from Eclipta prostrata using RAW264.7 macrophage cells. Phytother Res. 2011;25(9):1313-6. DOI:10.1002/ptr.3383
45. Lee JS, Ahn JH, Cho YJ, et al. α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells. J Ethnopharmacol. 2015;169:426-34. DOI:10.1016/j.jep.2015.04.029
46. Guenné S, Ouattara N, Ouédraogo N, et al. Phytochemistry and neuroprotective effects of Eclipta alba (L.) Hassk. J Complement Integr Med. 2019;17(1). DOI:10.1515/jcim-2019-0026
47. Dungca NT. Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats. J Ethnopharmacol. 2016;184:18-21. DOI:10.1016/j.jep.2016.03.002
48. Mishra S, Aeri V, Gaur PK, Jachak SM. Phytochemical, therapeutic, and ethnopharmacological overview for a traditionally important herb: Boerhavia diffusa Linn. Biomed Res Int. 2014;2014:808302. DOI:10.1155/2014/808302
49. Borrelli F, Ascione V, Capasso R, et al. Spasmolytic effects of nonprenylated rotenoid constituents of Boerhaavia diffusa roots. J Nat Prod. 2006;69(6):903-6. DOI:10.1021/np060073h
50. Gulati R, Agarwal S, Agarwal SS. Hepatoprotective activity of Boerhaavia diffusa linn. against country made liquor induced hepatotoxicity in albino rats fed on controlled calorie diet. Indian J Pharmacol. 1991;23:264-7.
51. Devaki T, Shivashangari KS, Ravikumar V, Govindaraju P. Effect of Boerhaavia diffusa on tissue anti-oxidant defense system during ethanol-induced hepatotoxicity in rats. Journal of Natural Remedies. 2005;5(2):102-7.
52. Oke GO, Abiodun AA, Imafidon CE, Monsi BF. Zingiber officinale (Roscoe) mitigates CCl(4)-induced liver histopathology and biochemical derangements through antioxidant, membrane-stabilizing and tissue-regenerating potentials. Toxicol Rep. 2019;6:416-25. DOI:10.1016/j.toxrep.2019.05.001
53. Yamahara J, Huang QR, Li YH, et al. Gastrointestinal motility enhancing effect of ginger and its active constituents. Chem Pharm Bull (Tokyo). 1990;38(2):430-1. DOI:10.1248/cpb.38.430
54. Haniadka R, Saldanha E, Sunita V, et al. A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe). Food Funct. 2013;4(6):845-55. DOI:10.1039/c3fo30337c
55. Christina AJ, Saraswathy GR, Robert SJ, et al. Inhibition of CCl4-induced liver fibrosis by Piper longum Linn.? Phytomedicine. 2006;13(3):196-8. DOI:10.1016/j.phymed.2004.01.009
56. Dash M, Singh S, Sahoo BC, et al. Potential role of Indian long pepper (Piper longum L.) volatiles against free radicals and multidrug resistant isolates. Nat Prod Res. 2022;36(16):4271-5. DOI:10.1080/14786419.2021.1975703
57. Fan D, Zhou C, Chen C, et al. Lignans from the genus Piper L. and their pharmacological activities: An updated review. Fitoterapia. 2023;165:105403. DOI:10.1016/j.fitote.2022.105403
________________________________________________
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DOI:10.1016/s0140-6736(88)92416-6
35. Wang M, Cheng H, Li Y, et al. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med. 1995;126(4):350-2.
36. Panneer SK, Payyappallimana U, Ravikumar K, Venkatasubramanian P. Can Guduchi (Tinospora cordifolia), a well-known ayurvedic hepato-protectant cause liver damage? J Ayurveda Integr Med. 2023;14(1):100658. DOI:10.1016/j.jaim.2022.100658
37. Arunachalam K, Yang X, San TT. Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases. J Ethnopharmacol. 2022;283:114540. DOI:10.1016/j.jep.2021.114540
38. Goel HC, Prasad J, Singh S, et al. Radioprotective potential of an herbal extract of Tinospora cordifolia. J Radiat Res. 2004;45(1):61-8. DOI:10.1269/jrr.45.61
39. Bishayi B, Roychowdhury S, Ghosh S, Sengupta M. Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. J Toxicol Sci. 2002;27(3):139-46. DOI:10.2131/jts.27.139
40. Singh HK, Rastogi RP, Srimal RC, Dhawan BN. Effect of bacosides A and B on avoidance responses in rats. Phytother Res. 1988;2(2):70-5. DOI:10.1002/ptr.2650020205
41. Russo A, Izzo AA, Borrelli F, et al. Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage. Phytother Res. 2003;17(8):870-5. DOI:10.1002/ptr.1061
42. Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol. 2009;27(1):62-9. DOI:10.1016/j.etap.2008.08.00
43. Anand T, Naika M, Swamy MSL, Khanum F. Antioxidant and DNA Damage Preventive Properties of Bacopa Monniera (L) Wettst. Free Radic Antioxid. 2011;1(1):84-90. DOI:10.5530/ax.2011.1.13
44. Tewtrakul S, Subhadhirasakul S, Tansakul P, et al. Antiinflammatory constituents from Eclipta prostrata using RAW264.7 macrophage cells. Phytother Res. 2011;25(9):1313-6. DOI:10.1002/ptr.3383
45. Lee JS, Ahn JH, Cho YJ, et al. α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells. J Ethnopharmacol. 2015;169:426-34. DOI:10.1016/j.jep.2015.04.029
46. Guenné S, Ouattara N, Ouédraogo N, et al. Phytochemistry and neuroprotective effects of Eclipta alba (L.) Hassk. J Complement Integr Med. 2019;17(1). DOI:10.1515/jcim-2019-0026
47. Dungca NT. Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats. J Ethnopharmacol. 2016;184:18-21. DOI:10.1016/j.jep.2016.03.002
48. Mishra S, Aeri V, Gaur PK, Jachak SM. Phytochemical, therapeutic, and ethnopharmacological overview for a traditionally important herb: Boerhavia diffusa Linn. Biomed Res Int. 2014;2014:808302. DOI:10.1155/2014/808302
49. Borrelli F, Ascione V, Capasso R, et al. Spasmolytic effects of nonprenylated rotenoid constituents of Boerhaavia diffusa roots. J Nat Prod. 2006;69(6):903-6. DOI:10.1021/np060073h
50. Gulati R, Agarwal S, Agarwal SS. Hepatoprotective activity of Boerhaavia diffusa linn. against country made liquor induced hepatotoxicity in albino rats fed on controlled calorie diet. Indian J Pharmacol. 1991;23:264-7.
51. Devaki T, Shivashangari KS, Ravikumar V, Govindaraju P. Effect of Boerhaavia diffusa on tissue anti-oxidant defense system during ethanol-induced hepatotoxicity in rats. Journal of Natural Remedies. 2005;5(2):102-7.
52. Oke GO, Abiodun AA, Imafidon CE, Monsi BF. Zingiber officinale (Roscoe) mitigates CCl(4)-induced liver histopathology and biochemical derangements through antioxidant, membrane-stabilizing and tissue-regenerating potentials. Toxicol Rep. 2019;6:416-25. DOI:10.1016/j.toxrep.2019.05.001
53. Yamahara J, Huang QR, Li YH, et al. Gastrointestinal motility enhancing effect of ginger and its active constituents. Chem Pharm Bull (Tokyo). 1990;38(2):430-1. DOI:10.1248/cpb.38.430
54. Haniadka R, Saldanha E, Sunita V, et al. A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe). Food Funct. 2013;4(6):845-55. DOI:10.1039/c3fo30337c
55. Christina AJ, Saraswathy GR, Robert SJ, et al. Inhibition of CCl4-induced liver fibrosis by Piper longum Linn.? Phytomedicine. 2006;13(3):196-8. DOI:10.1016/j.phymed.2004.01.009
56. Dash M, Singh S, Sahoo BC, et al. Potential role of Indian long pepper (Piper longum L.) volatiles against free radicals and multidrug resistant isolates. Nat Prod Res. 2022;36(16):4271-5. DOI:10.1080/14786419.2021.1975703
57. Fan D, Zhou C, Chen C, et al. Lignans from the genus Piper L. and their pharmacological activities: An updated review. Fitoterapia. 2023;165:105403. DOI:10.1016/j.fitote.2022.105403
Авторы
Е.В. Ших*, Е.Д. Хайтович, Д.Н. Цветков
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*chih@mail.ru
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*chih@mail.ru
________________________________________________
Evgenia V. Shikh*, Evgeniy D. Khaytovich, Dmitry N. Tsvetkov
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*chih@mail.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.