Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum63484210.26442/20751753.2024.5.202840ArticlesСтатьиReview ArticleMulticomponent phytopharmaceutical Dipana for the treatment of hepatobiliary disorders. A reviewПоликомпонентный растительный препарат Дипана® в лечении заболеваний гепатобилиарной системыhttps://orcid.org/0000-0002-4690-1811PrikhodkoVeronika A.ПриходькоВероника Александровна
Russian Federation

Cand. Sci. (Biol.)

канд. биол. наук, ст. преподаватель каф. фармакологии и клинической фармакологии

veronika.prihodko@pharminnotech.comhttps://orcid.org/0000-0003-4294-5531OkovityySergey V.ОковитыйСергей Владимирович
Russian Federation

D. Sci. (Med.), Prof.

д-р мед. наук, проф., зав. каф. фармакологии и клинической фармакологии; проф. Научно-клинического и образовательного центра гастроэнтерологии и гепатологии

veronika.prihodko@pharminnotech.comSaint Petersburg State Chemical and Pharmaceutical UniversityФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава РоссииSaint Petersburg State UniversityФГБОУ ВО «Санкт-Петербургский государственный университет»05082024265GastroenterologyГастроэнтерология3093160408202404082024Copyright ©; 2024, Consilium MedicumCopyright ©; 2024, ООО "Консилиум Медикум"2024Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/634842

Hepatobiliary disorders contribute significantly to the structure of morbidity, causes of disability and mortality of the world’s population. Therefore, the search for and development of effective and safe hepatoprotective agents for the pharmacotherapy thereof remains a problematic issue. This article presents a pharmacological profile for each of the active ingredients of the composite phytopharmaceutical Dipana, and reviews the evidence for its effectiveness and safety in chronic hepatobiliary disorders.

Заболевания гепатобилиарной системы занимают значительное место в структуре заболеваемости, причин нетрудоспособности и смертности мирового населения. Поэтому вопрос поиска и разработки эффективных и безопасных средств с гепатопротекторной активностью, применимых в рамках фармакотерапии, остается актуальным. Обзор посвящен фармакологической характеристике компонентов, входящих в комплексный фитопрепарат Дипана®, а также доказательной базе его эффективности и безопасности при хронических заболеваниях гепатобилиарной системы.

Dipanahepatoprotectorsphytopharmaceuticalshepatobiliary disordersДипана®гепатопротекторырастительные препаратызаболевания гепатобилиарной системыGBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133-61. DOI:10.1016/S0140-6736(24)00757-8Оковитый С.В., Райхельсон К.Л., Приходько В.А. Комбинированная гепатопротекторная фармакотерапия заболеваний печени. Экспериментальная и клиническая гастроэнтерология. 2022;203(7):5-20 [Okovityi SV, Raikhelson KL, Prikhodko VA. Combined hepatoprotective pharmacotherapy for liver disease. Experimental and Clinical Gastroenterology. 2022;203(7):5-20 (in Russian)]. DOI:10.31146/1682-8658-ecg-203-7-5-20Almeleebia TM, Alsayari A, Wahab S. Pharmacological and Clinical Efficacy of Picrorhiza kurroa and Its Secondary Metabolites: A Comprehensive Review. Molecules. 2022;27(23):8316. DOI:10.3390/molecules27238316Dhami-Shah H, Vaidya R, Talwadekar M, et al. Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells. J Ayurveda Integr Med. 2021;12(3):465-73. DOI:10.1016/j.jaim.2021.04.007Li T, Xu L, Zheng R, et al. Picroside II protects against cholestatic liver injury possibly through activation of farnesoid X receptor. Phytomedicine. 2020;68:153153. DOI:10.1016/j.phymed.2019.153153Dai S, Wu R, Fu K, et al. Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification. J Ethnopharmacol. 2024;322:117584. DOI:10.1016/j.jep.2023.117584Yang L, Ao Q, Zhong Q, et al. SIRT1/IGFBPrP1/TGF β1 axis involved in cucurbitacin B ameliorating concanavalin A-induced mice liver fibrosis. Basic Clin Pharmacol Toxicol. 2020;127(5):371-9. DOI:10.1111/bcpt.13446Rahman MM, Muse AY, Khan DMIO, et al. Apocynin prevented inflammation and oxidative stress in carbon tetra chloride induced hepatic dysfunction in rats. Biomed Pharmacother. 2017;92:421-8. DOI:10.1016/j.biopha.2017.05.101Fayed MR, El-Naga RN, Akool ES, El-Demerdash E. The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4. Drug Discov Ther. 2018;12(2):58-67. DOI:10.5582/ddt.2017.01065Dwivedi Y, Rastogi R, Garg NK, Dhawan BN. Picroliv and its components kutkoside and picroside I protect liver against galactosamine-induced damage in rats. Pharmacol Toxicol. 1992;71(5):383-7. DOI:10.1111/j.1600-0773.1992.tb00566.xRaut A, Dhami-Shah H, Phadke A, et al. Picrorhiza kurroa, Royle ex Benth:Traditional uses, phytopharmacology, and translational potential in therapy of fatty liver disease. J Ayurveda Integr Med. 2023;14(1):100558. DOI:10.1016/j.jaim.2022.100558Chao WW, Lin BF. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med. 2010;5:17. DOI:10.1186/1749-8546-5-17Bi C, Han W, Yu J, et al. Insights into the pharmacological and therapeutic effects of apigenin in liver injuries and diseases. Heliyon. 2023;9(5):e15609. DOI:10.1016/j.heliyon.2023.e15609Randy A, Kim M, Nho CW. Ligularia fischeri and its constituent 3,4-dicaffeoylquinic acid improve obesity-induced nonalcoholic fatty liver disease by regulating lipid metabolism and activating AMPK. J Funct Foods. 2016;27:1-16. DOI:10.1016/j.jff.2016.08.050Jadhav V, Thorat R, Kadam V, Salaskar KP. Chemical composition, pharmacological activities of Eclipta alba. J Pharm Res. 2009;2:1229-31.Gupta A, Kumar A, Kumar D, et al. Ecliptal, a promising natural lead isolated from Eclipta alba modulates adipocyte function and ameliorates metabolic syndrome. Toxicol Appl Pharmacol. 2018;338:134-47. DOI:10.1016/j.taap.2017.11.016Lima RP, Nunes PIG, Viana AFSC, et al. α,β-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism. Braz J Med Biol Res. 2021;54(10):e11391. DOI:10.1590/1414-431X2021e11391Liang Y, Niu QQ, Zhao YH. Pharmacological research progress of ursolic acid for the treatment of liver diseases. Tradit Med Res. 2021;6(4):1-11. DOI:10.12032/TMR20210331227Wang Y, Liu K. Therapeutic potential of oleanolic acid in liver diseases. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(7):4537-54. DOI:10.1007/s00210-024-02959-2Feng S, Dai Z, Liu AB, et al. Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(10):1274-84. DOI:10.1016/j.bbalip.2018.08.004Zhang Y, Gu Y, Jiang J, et al. Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism. NPJ Sci Food. 2022;6(1):38. DOI:10.1038/s41538-022-00156-0Nisar MF, He J, Ahmed A, et al. Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature. Molecules. 2018;23(10):2567. DOI:10.3390/molecules23102567Wan Saidin WA, Jantan I, Abdul Wahab SM, et al. Pharmacological activities and mechanisms of action of hypophyllanthin: A review. Front Pharmacol. 2023;13:1070557. DOI:10.3389/fphar.2022.1070557Jagtap S, Khare P, Mangal P, et al. Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice. RSC Adv. 2016;6(63):58343-53. DOI:10.1039/C6RA10774ELu CC, Yang SH, Hsia SM, et al. Inhibitory effects of Phyllanthus emblica L. on hepatic steatosis and liver fibrosis in vitro. J Funct Foods. 2016;20:20-30. DOI:10.1016/j.jff.2015.10.012Jafaripour L, Sohrabi Zadeh B, Jafaripour E, et al. Gallic acid improves liver cirrhosis by reducing oxidative stress and fibrogenesis in the liver of rats induced by bile duct ligation. Scand J Gastroenterol. 2023;58(12):1474-83. DOI:10.1080/00365521.2023.2229929Zhang R, Chu K, Zhao N, et al. Corilagin Alleviates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced C57BL/6 Mice by Ameliorating Oxidative Stress and Restoring Autophagic Flux. Front Pharmacol. 2020;10:1693. DOI:10.3389/fphar.2019.01693Abu Hassan MR, Hj Md Said R, Zainuddin Z, et al. Effects of one-year supplementation with Phyllanthus niruri on fibrosis score and metabolic markers in patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Heliyon. 2023;9(6):e16652. DOI:10.1016/j.heliyon.2023.e16652Sowjanya K, Girish C, Bammigatti C, Prasanna Lakshmi NC. Efficacy of Phyllanthus niruri on improving liver functions in patients with alcoholic hepatitis: A double-blind randomized controlled trial. Indian J Pharmacol. 2021;53(6):448-56. DOI:10.4103/ijp.IJP_540_20Chen X, Dai X, Liu Y, et al. Solanum nigrum Linn.: An Insight into Current Research on Traditional Uses, Phytochemistry, and Pharmacology. Front Pharmacol. 2022;13:918071. DOI:10.3389/fphar.2022.918071Zhang F, Wang M, Zha Y, et al. Daucosterol Alleviates Alcohol-Induced Hepatic Injury and Inflammation through P38/NF-κB/NLRP3 Inflammasome Pathway. Nutrients. 2023;15(1):223. DOI:10.3390/nu15010223Gao XY, Li XY, Zhang CY, Bai CY. Scopoletin: a review of its pharmacology, pharmacokinetics, and toxicity. Front Pharmacol. 2024;15:1268464. DOI:10.3389/fphar.2024.1268464Tai CJ, Choong CY, Shi YC, et al. Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats. Molecules. 2016;21(3):269. DOI:10.3390/molecules21030269Gupta A, Gupta P, Bajpai G. Tinospora cordifolia (Giloy): An insight on the multifarious pharmacological paradigms of a most promising medicinal ayurvedic herb. Heliyon. 2024;10(4):e26125. DOI:10.1016/j.heliyon.2024.e26125Xu T, Kuang T, Du H, et al. Magnoflorine: A review of its pharmacology, pharmacokinetics and toxicity. Pharmacol Res. 2020;152:104632. DOI:10.1016/j.phrs.2020.104632Nie Q, Li M, Huang C, et al. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. J Transl Med. 2024;22(1):225. DOI:10.1186/s12967-024-05011-2Сыров В.Н., Исламова Ж.И., Эгамова Ф.Р., и др. Стресс-протекторные свойства фитоэкдистероидов. Экспериментальная и клиническая фармакология. 2014;77(7):35-8 [Syrov VN, Islamova ZI, Egamova FR, et al. Stress-protective properties of phytoecdysteroids. Experimental and Clinical Pharmacology. 2014;77(7):35-8 (in Russian)]. DOI:10.30906/0869-2092-2014-77-7-35-38Kang P, Li S. Makisterone A attenuates experimental cholestasis by activating the farnesoid X receptor. Biochem Biophys Res Commun. 2022;623:162-9. DOI:10.1016/j.bbrc.2022.07.030Fatima U, Roy S, Ahmad S, et al. Pharmacological attributes of Bacopa monnieri extract: Current updates and clinical manifestation. Front Nutr. 2022;9:972379. DOI:10.3389/fnut.2022.972379Deivasigamani A, Boopathy U, Durairaj R, Chandrasekar S. Bacoside – A improves Non-Alcoholic Fatty Liver Disease in rats fed on a high fat diet. J Chem Health Risks. 2024;14(1):2109-29.Lee IC, Bae JS. Hepatic Protective Effects of Jujuboside B through the Modulation of Inflammatory Pathways. Biotechnol Bioprocess Eng. 2022;27(3):336-43. DOI:10.1007/s12257-022-0049-1Yi J, Xia W, Wu J, et al. Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice. J Vet Sci. 2014;15(1):141-8. DOI:10.4142/jvs.2014.15.1.141Mu Q, Wang H, Tong L, et al. Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway. FASEB J. 2020;34(9):13033-48. DOI:10.1096/fj.202000546RNayak P, Thirunavoukkarasu M. A review of the plant Boerhaavia diffusa: its chemistry, pharmacology and therapeutical potential. J Phytopharmacol. 2016;5(2):83-92. DOI:10.31254/phyto.2016.5208Manu KA, Kuttan G. Immunomodulatory activities of Punarnavine, an alkaloid from Boerhaavia diffusa. Immunopharmacol Immunotoxicol. 2009;31(3):377-87. DOI:10.1080/08923970802702036Yu ZY, Cheng G. Protective effect of liriodendrin against liver ischaemia/reperfusion injury in mice via modulating oxidative stress, inflammation and nuclear factor kappa B/toll-like receptor 4 pathway. Folia Morphol (Warsz). 2023;82(3):668-76. DOI:10.5603/FM.a2022.0049Olaleye MT, Akinmoladun AC, Ogunboye AA, Akindahunsi AA. Antioxidant activity and hepatoprotective property of leaf extracts of Boerhaavia diffusa Linn against acetaminophen-induced liver damage in rats. Food Chem Toxicol. 2010;48(8-9):2200-5. DOI:10.1016/j.fct.2010.05.047Mao QQ, Xu XY, Cao SY, et al. Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale Roscoe). Foods. 2019;8(6):185. DOI:10.3390/foods8060185Akbari A, Nasiri K, Heydari M, et al. Ameliorating Potential of Ginger (Zingiber officinale Roscoe) Extract on Liver Function and Oxidative Stress Induced by Ethanol in Male Rats. Zahedan J Res Med Sci. 2019;21(2):e86464. DOI:10.5812/zjrms.86464Mahluji S, Attari VE, Mobasseri M, et al. Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr. 2013;64(6):682-6. DOI:10.3109/09637486.2013.775223Ebrahimzadeh Attari V, Ostadrahimi A, Asghari Jafarabadi M, et al. Changes of serum adipocytokines and body weight following Zingiber officinale supplementation in obese women: a RCT. Eur J Nutr. 2016;55(6):2129-36. DOI:10.1007/s00394-015-1027-6Zaveri M, Khandhar A, Patel SG, et al. Chemistry and pharmacology of Piper Longum L. Int J Pharm Sci Rev Res. 2010;5(1):67-76.Nouri-Vaskeh M, Hashemi P, Hataminia N, et al. The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: a randomized double-blind controlled trial. Sci Rep. 2024;14(1):1053. DOI:10.1038/s41598-024-51726-zZhang R, Yu Y, Hu S, et al. Sesamin ameliorates hepatic steatosis and inflammation in rats on a high-fat diet via LXRα and PPARα. Nutr Res. 2016;36(9):1022-30. DOI:10.1016/j.nutres.2016.06.015Scandiffio R, Bonzano S, Cottone E, et al. Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors. Int J Mol Sci. 2023;24(7):6060. DOI:10.3390/ijms24076060Rage N, Dhanukar S, Karandukar SM. Hepatoprotective effects of P. longum against carbon tetrachloride induced liver damage. Indian Drugs. 1984;21:569-70.Ищенко Н.В., Малюков Д.А., Мордасова В.И. Возможности применения многокомпонентных растительных препаратов у больных алкогольным стеатогепатитом. Гастроэнтерология Санкт-Петербурга. 2011;(2-3):М37-М37а [Ishchenko NV, Malyukov DA, Mordasova VI. Vozmozhnosti primeneniya mnogokomponentnykh rastitel'nykh preparatov u bol'nykh alkogol'nym steatogepatitom. Gastroenterologiya Sankt-Peterburga. 2011;(2-3):М37-М37а (in Russian)].Мордасова В.И., Свиридова Т.Н. Использование препарата Дипана в лечении больных с алкогольным жировым гепатитом. Документ внутреннего пользования. ООО «Сентисс Рус». Воронеж. 2008 [Mordasova VI, Sviridova TN. Ispol'zovanie preparata Dipana v lechenii bol'nykh s alkogol'nym zhirovym gepatitom. Internal document. Sentiss Rus. Voronezh. 2008 (in Russian)].Радченко В.Г., Мигунов В.А. Качество жизни больных неалкогольным стеатогепатитом на фоне терапии препаратом ДИПАНА. Поликлиника. 2008;(5):8-11 [Radchenko VG, Migunov VA. Kachestvo zhizni bol'nykh nealkogol'nym steatogepatitom na fone terapii preparatom DIPANA. Poliklinika. 2008;(5):8-11 (in Russian)].Михалёва Е.Н., Вологжанина Л.Г. Современный гепатопротектор растительного происхождения Дипана в лечении больных стеатогепатозом. Документ внутреннего пользования. ООО «Сентисс Рус». Москва. 2008 [Mikhaleva EN, Vologzhanina LG. Sovremennyy gepatoprotektor rastitel'nogo proiskhozhdeniya Dipana v lechenii bol'nykh steatogepatozom. Internal document. Sentiss Rus. Moscow. 2008 (in Russian)].Скрипачева М.В. Оценка клинической эффективности препаратов Дипана и Карсил у больных ХГС. Дальневосточный журнал инфекционной патологии. 2008;12(12):206-7 [Skripacheva MV. Otsenka klinicheskoy effektivnosti preparatov Dipana i Karsil u bol'nykh KhGS. Dal'nevostochnyy Zhurnal Infektsionnoy Patologii. 2008;12(12):206-7 (in Russian)].Непомнящих Д.Л., Нохрина Ж.В., Мигуськина Е.И., Виноградова Е.В. Опыт применения нового гепатопротектора Дипаны в лечении пациентов с хроническим описторхозом и в комплексной терапии хронического гепатита С. РМЖ. 2008;16(29):1936-9 [Nepomnyashchikh DL, Nokhrina ZV, Migus'kina EI, Vinogradova EV. Opyt primeneniya novogo gepatoprotektora Dipany v lechenii patsientov s khronicheskim opistorkhozom i v kompleksnoy terapii khronicheskogo gepatita S. RMJ. 2008;16(29):1936-9 (in Russian)].Соколова Г.Б. Применение препарата Дипана у больных туберкулезом с носительством гепатита С и В и с лекарственным поражением печени. Документ внутреннего пользования. ООО «Сентисс Рус». Москва. 2008 [Sokolova GB. Primenenie preparata Dipana u bol'nykh tuberkulezom s nositel'stvom gepatita S i V i s lekarstvennym porazheniem pecheni. Internal document. Sentiss Rus. Moscow. 2008 (in Russian)].Слогоцкая Л.В., Филиппов А.В., Сельцовский П.П. Отчет по результатам исследования «Открытое сравнительное исследование эффективности и безопасности Дипаны – лекарственного препарата, включающего в себя комплекс биологически активных веществ растительного происхождения производства «Промед» (Индия) – в качестве гепатопротектора у больных туберкулезом, принимающих противотуберкулезные препараты». Документ внутреннего пользования. ООО «Сентисс Рус». Москва. 2008 [Slogotskaya LV, Filippov AV, Sel'tsovskiy PP. Otchet po rezul'tatam issledovaniya Otkrytoe sravnitel'noe issledovanie effektivnosti i bezopasnosti Dipany – lekarstvennogo preparata, vklyuchayushchego v sebya kompleks biologicheski aktivnykh veshchestv rastitel'nogo proiskhozhdeniya proizvodstva Promed (Indiya) – v kachestve gepatoprotektora u bol'nykh tuberkulezom, prinimayushchikh protivotuberkuleznye preparaty. Internal document. Sentiss Rus. Moscow. 2008 (in Russian)].Мордасова В.И., Свиридова Т.Н., Сыч Л.Ф., и др. Применение препарата Дипана у больных с лекарственными поражениями печени. Материалы II Национального конгресса терапевтов «Новый курс: консолидация усилий по охране здоровья нации». Москва. 2007:156 [Mordasova VI, Sviridova TN, Sych LF, et al. Primenenie preparata Dipana u bol'nykh s lekarstvennymi porazheniyami pecheni. Materialy II Natsional'nogo kongressa terapevtov Novyy kurs: konsolidatsiya usiliy po okhrane zdorov'ya natsii. Moscow. 2007:156 (in Russian)].Яковенко Э.П., Агафонова Н.А., Прянишникова А.С., и др. Эффективность препарата Дипана при функциональных заболеваниях билиарной системы. Фарматека. 2009;2(176):76-9 [Yakovenko EP, Agafonova NA, Pryanishnikova AS, et al. Efficacy of the drug dipana in functional diseases of biliary system. Farmateka. 2009;2(176):76-9 (in Russian)].