Hepatoprotective effect of chicory (Cichorium intybus L.) in rat intoxication with mercury (II) chloride
Keywords:
Cichorium intуbus L., dry extract, rat acute intoxication model, mercury (II) chloride
Abstract
Chemical pollution of the environment poses a serious threat to public health, leads to an increase in morbidity, including an increase in diseases of the hepatobiliary system. Liver diseases and the severity of their course require a comprehensive solution to this problem and the creation of new effective medicines. Special attention is paid to herbal medicines with comprehensive preventive and therapeutic potential.
The aim of the study was to evaluate the hepatoprotective effect of the dry extract of aerial part of chicory on a model of acute intoxication in rats with mercury (II) chloride.
Methods. The study was performed on male Wistar rats. A model of acute toxic liver damage was caused by a single subcutaneous injection of mercury (II) chloride at a dose of 3 mg / kg. The dry extract of chicory were administered into the stomach of rats 1 hour before injection of mercury (II) chloride and in the following 20 days at doses of 100 and 500 mg / kg. The hepatoprotector Silimar ® was administered according to the same scheme at a therapeutic dose of 100 mg /kg. On the 21st day of the experiment, integral health indicators of experimental animals were recorded, peripheral blood samples were taken to determine biochemical parameters. At the end of the experiment, pathohistological studies of the rat liver were performed. Statistical processing of the obtained results was carried out using the licensed program Statistica version 13 (TIBCO Software Inc, USA).
Results. A study on rats with an experimental model of acute liver intoxication with mercury (II) chloride showed that the studied extract showed hepatoprotective effect at doses of 100 and 500 mg/kg, reducing their death and toxic effect on the liver, normalizing biochemical and morphological parameters.
According to the degree of severity of the hepatoprotective effect on the specified model of liver pathology, the dry extract of chicory in these doses corresponded to Silimar®, a hepatoprotector currently widely used in medical practice.
Conclusion. The study revealed for the first time new aspects of the pharmacological activity of the dry extract of chicory, which were manifested in its antitoxic effect. The results of the study served as the basis for the creation of a new medicine based on the studied extract for the treatment of liver diseases of various etiologies, including those caused by intoxication with heavy metal salts.
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References
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17. Domitrović R., Potočnjak I. A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. Archives of toxicology. 2016; 90 (1): 39-79.
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19. Aisa Н.А., Xin X-l., Tang D. Chemical constituents and their pharmacological activities of plants from Cichorium genus. Chinese Herbal Medicines. 2020 Jul; 12(3): 224–236. doi: 10.1016/j.chmed.2020.05.001
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21. Janda K., Gutowska I., Geszke-Moritz M., Jakubczyk K. The Common Cichory (Cichorium intybus L.) as a Source of Extracts with Health-Promoting Properties—A Review. Molecules. 2021; 26(6): 1814.https://doi.org/10.3390/ molecules26061814
22. Upadhayay V.K., Gohar Taj. D, Samantaray S.D., Singh S.P. Contemporary Insights on Antibacterial and Pharmacological Importance of Cichorium intybus: A Compendious Review. Biomed J Sci & Tech Res. 2021; 35(2): 27409-27418. BJSTR. MS.ID.005662.
23. Qadir I., Bazaz M. R., Dar R.M., Ovais S., Mir S. R., Zargar M. I., Rehman M. U. Cichorium intybus: A Comprehensive Review on Its Pharmacological Activity and Phytochemistry. In book: Edible Plants in Health and Diseases 15 March 2022; II:373–398. DOI:10.1007/978-981-16-4959-2_12 .
24. Sajbel' O.L., Radimich A.I., Dargaeva T.D. i dr. Fenol'nye soedineniya i farmakologicheskij skrining ekstrakta travy cikoriya obyknovennogo. Razrabotka i registraciya lekarstvennyh sredstv. 2021;10(4):36–45. https://doi.org/10.33380/2305-2066-2021-10-4-36-45 . (In Russian)
25. Saibel O.L., Radimich A.I., Dargaeva T.D., Babenko A.N., Borovkova M.V., Kurmanova E.N., Krepkova L.V., Ferubko E.V., Lupanova I.A., Mizina P.G. Method of obtaining a drug with hepatoprotective and antihepatotoxic effects. Patent 2771028, RF; 2022. (In Russian)
26. Bortnikova V.V, Krepkova L.V., Babenko A.N., Saybel’ O.L., Borovkova M.V., Kuzina O.S., Mizina P.G., Job K.M., Sherwin C.M., Enioutina E.Y. A Perspective Botanical Drug: Hepatoprotective Activity оf Dry Extract Prepared From the Aerial Part of Chicory Plant (Cichorium intybus L.). Clinical pharmacology in drug development. Аbstracts:2021, Тhe American College of Clinical Pharmacology®, September 15, 2021; 10(S1): 100-101. DOI: 10. 1002/срdd.1004
27. Lemyaseva S.V., Krepkova L.V., Babenko A.N. Study of the lipid-lowering activity of common chicory (Cichorium intybus L.) on a twin model. Sovremennye tendencii razvitiya tekhnologij zdorov'esberezheniya. Sbornik trudov 10 mezhdunarodnoj nauchno-prakticheskoj konferencii molodyh uchenyh. Моscow; 2022: 417-420. doi:10.52101/9785870191058. (In Russian)
28. Krasnopeeva I.Y. Mercury intoxication. Sibirskij medicinskij zhurnal (Irkutsk). 2005; 57 (7): 104-108. . (In Russian)
29. Vergilio C.S., Carvalho C.E.V., Melo E.J.T. Mercury-induced dysfunctions in multiple organelles leading to cell death. Toxicolоgy In Vitro. 2015; 29(1): 63-71. doi: 10.1016/j.tiv.2014.09.006.
30. Tsai K. L., Kao C. L., Hung C. H., Cheng Y. H., Lin H. C., Chu P. M. Chicoric acid is a potent anti-atherosclerotic ingredient by antioxidantaction and anti-inflammation capacity. Oncotarget. 2017;8(18):29600–29612. DOI: 10.18632/oncotarget.16768.
31. Sun W., Hesam Shahrajabian M. Therapeutic Potential of Phenolic Compounds in Medicinal Plants-Natural Health Products for Human Health
Molecules. 2023 Feb 15;28(4):1845. doi: 10.3390/molecules28041845.
32.Garg S.S., Gupta J., Sharm S., Sahu D. An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur J Pharm Sci. 2020 Sep 1:152:105424. https://doi.org/10.1016/j.ejps.2020.105424.
33. Garg S. S., Gupta J., Sahu D., Liu C-J. Pharmacological and Therapeutic Applications of Esculetin. Int J Mol Sci. 2022 Oct 20;23(20):12643. doi: 10.3390/ijms232012643.
34. Lupanova I.A. Mizina P.G., Ionov N.S., Poroikov V.V., Khlebnikov A.I., Martynchik I.A. The effect of chicory and chlorogenic acids from Cichorium intybus L. on the activity of cytochrome P450 and glutathione transferase Biofarmacevticheskij zhurnal. 2022. – Т. 14 (5). – С. 8-18 (In Russian)._
35. Choi R.Y. , Ham J. R., Lee M. K. Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet. Chem Biol Interact. 2016 Dec 25:260:13-21. doi: 10.1016/j.cbi.2016.10.013. Epub 2016 Oct 18.
36.Pandey A. , Raj P., Goru S. К., Kadakol A., Malek V., Sharma N., Gaikwad A.B. Esculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway. Pharmacol Rep. 2017Aug;69(4):666-672.
doi: 10.1016/j.pharep.2017.02.005. Epub 2017 Feb 4
37. Xia M., Wu Z., Wang J., Buist-Homan M., Moshage Han. The Coumarin-Derivative Esculetin Protects against Lipotoxicity in Primary Rat Hepatocytes via Attenuating JNK-Mediated Oxidative Stress and Attenuates Free Fatty Acid-Induced Lipid Accumulation. Antioxidants (Basel). 2023 Oct 27;12(11):1922. doi: 10.3390/antiox12111922.
38. Costea L., Chițescu C.L., Boscencu R., Ghica М. , Lupuliasa D., Mihai D.Р., Deculescu-Ioniță Т., Duțu L.E., Popescu М.L., Luță E-A., Nițulescu G.M., Olaru О.T., Gîrd С.E. The Polyphenolic Profile and Antioxidant Activity of Five Vegetal Extracts with Hepatoprotective Potential. Plants (Basel). 2022 Jun 24;11(13):1680. doi: 10.3390/plants11131680
2. Daukaev R.A., Larionova T.K., Afonkina S.R., Allayarova G.R., Adieva G.F., Pecherskaya V.L., Zelenkovskaya E.E., Fazlyeva A.S., Usmanova E.N. Study of heavy metal pollution of plant products grown in the industrial region. Medicina truda i ekologiya cheloveka. 2018; 3: 22-27. (In Russian)
3. Loginov A.F., Butorova L.I., Loginov V.A. Medicinal liver lesions: diagnosis, treatment. RMZh. Gastroenterologiya. 2016; 11: 721–727. (In Russian)
4. Lazebnik L. B., Golovanova E. V., Hlynova O. V., Alekseenko S. A., Aryamkina O. L., Bakulin I. G., Bakulina N. V., Baranovsky A. Yu., Bondarenko O. A.,
Varganova A. N., Volkova T. V., Vologzhanina L. G., Volchegorsky I. A., Demicheva T. P., Dolgushina A. I., Mayev I. V., Minushkin O. N., Raykhelson K. L., Smirnova
E. N., Tarasova L. V., Tsyganova Yu. V. Medicinal liver damage in adults. Experimental and Clinical Gastroenterology. 2020;174(2): 29–54. (In Russian) DOI: 10.31146/1682-8658-ecg-174-2-29-54 (In Russian)
5. Pavithra K. G., Rajan Р. S., Kumar P. S., Rangasamy G. Mercury sources, contaminations, mercury cycle, detection and treatment techniques: A review. Chemosphere. 2023 Jan;312(Pt 1):137314. doi: 10.1016/j.chemosphere.2022.137314.
6. Raj D., Maiti S. K. Sources, toxicity, and remediation of mercury: an essence review. Environ Monit Assess. 2019 Aug 15;191(9):566. doi: 10.1007/s10661-019-7743-2
7. Antonenko O. M. Toxic liver lesions: ways of pharmacological correction. Medicinskij Sovet. 2013;(6):45-51. https://doi.org/10.21518/2079-701X-2013-6-45-51 (In Russian)
8. Sakiev K. Z., Batyrbekova L. S. The influence of environmental factors on the state of the hepatobiliary system of the population living in ecologically unfavorable regions. Medicina i ekologiya. 2015. 4 (77): 8-15. In Russian)
9. Nyeem M. A. B., Alam M. K., Hossain M. A. Islam M. M., Akramuzzaman M., Das S. K. A review of evidence based hepatoprotective selected medicinal plants used in Bangladeshi traditional medicine. International Journal of Veterinary Sciences and Animal Husbandry. 2017; 2(5): 13-17.
10. Krepkova L.V., Shkarenkov A.A., Sokolskaya T.A. Experimental and clinical study of phytopreparations from milk thistle. Voprosy biologicheskoj, medicinskoj i farmacevticheskoj himii. 2008; 4: 3-6. (In Russian)
11. Lupanova I.A., Krepkova L.V., Ferubko E.V., Trumpe T.E., Bortnikova V.V., Babenko A.N., Kurmanova E.N., Fateeva T.V., Mizina P.G., Sidelnikov N.I. New herbal medicines VILAR. M.: FGBNU VILAR; 2021. 160 с. (In Russian)
12. Shulpekova Yu.O. Herbal preparations in the treatment of liver diseases. RMZh. 2006; 4:337. (In Russian)
13. Bortnikova V.V., Krepkova L.V., Javakhyan M.A., Mizina P.G. Investigation of the hepatoprotective effect of volodushka extract of dry. Eksperimental'naya i klinicheskaya farmakologiya.2017; 5: 27-32. https://doi.org/10.30906/0869-2092-2017-80-5-27-32 . (In Russian)
14. Bortnikova V.V., Karabaeva V.V., Krepkova L.V., Sidelnikova G.F., Mizina P.G., Karabaeva O.N. Flacoside is a medicinal product from the leaves of Amur velvet, in the treatment of diseases of the hepatobiliary system. Voprosy biologicheskoj, medicinskoj i farmacevticheskoj himii. 2020; 23(2): 18-23. https://doi.org/10.29296/25877313-2020-02-03. (In Russian)
15. Bortnikova V.V., Karabaeva V.V., Krepkova L.V., Mizina P.G., Babenko A.N., Mikheeva N.S., Karabaeva O.N. A retrospective analysis of the clinical study of the drug Flacoside in the treatment of diseases of the hepatobiliary system.Razrabotka i registraciya lekarstvennyh sredstv. 2021; 10(3): 100-104. https://doi.org/10.33380/2305-2066-2021-10-3-100-104 . (In Russian)
16. Krepkova L.V., Babenko A.N., Saybel’ O.L., Lupanova I.A., Kuzina O.S., Job K.M., Sherwin C.M., Enioutina E.Y. Valuable Hepatoprotective Plants - How Can We Optimize Waste Free Uses of Such Highly Versatile Resources? Front. Pharmacol. 2021; 12: 738504. doi: 10.3389/fphar.2021.738504
17. Domitrović R., Potočnjak I. A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. Archives of toxicology. 2016; 90 (1): 39-79.
18. Street R. A., Sidana J., Prinsloo G. Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology. Evid Based Complement Alternat Med. 2013;2013:579319. doi: 10.1155/2013/579319. Epub 2013 Nov 26.
19. Aisa Н.А., Xin X-l., Tang D. Chemical constituents and their pharmacological activities of plants from Cichorium genus. Chinese Herbal Medicines. 2020 Jul; 12(3): 224–236. doi: 10.1016/j.chmed.2020.05.001
20. Boghrati Z., Zibaee E. , Ayati Z., Amiri M.S., Ramezani M., Jamialahmadi T., Emami S. А., Sahebkar A. Ethnomedicinal Uses, Phytochemistry and Pharmacology of Different Cichorium Species (Asteraceae): A Review. Adv Exp Med Biol. 2021; 1308: 501-546. doi: 10.1007/978-3-030-64872-5_26.
21. Janda K., Gutowska I., Geszke-Moritz M., Jakubczyk K. The Common Cichory (Cichorium intybus L.) as a Source of Extracts with Health-Promoting Properties—A Review. Molecules. 2021; 26(6): 1814.https://doi.org/10.3390/ molecules26061814
22. Upadhayay V.K., Gohar Taj. D, Samantaray S.D., Singh S.P. Contemporary Insights on Antibacterial and Pharmacological Importance of Cichorium intybus: A Compendious Review. Biomed J Sci & Tech Res. 2021; 35(2): 27409-27418. BJSTR. MS.ID.005662.
23. Qadir I., Bazaz M. R., Dar R.M., Ovais S., Mir S. R., Zargar M. I., Rehman M. U. Cichorium intybus: A Comprehensive Review on Its Pharmacological Activity and Phytochemistry. In book: Edible Plants in Health and Diseases 15 March 2022; II:373–398. DOI:10.1007/978-981-16-4959-2_12 .
24. Sajbel' O.L., Radimich A.I., Dargaeva T.D. i dr. Fenol'nye soedineniya i farmakologicheskij skrining ekstrakta travy cikoriya obyknovennogo. Razrabotka i registraciya lekarstvennyh sredstv. 2021;10(4):36–45. https://doi.org/10.33380/2305-2066-2021-10-4-36-45 . (In Russian)
25. Saibel O.L., Radimich A.I., Dargaeva T.D., Babenko A.N., Borovkova M.V., Kurmanova E.N., Krepkova L.V., Ferubko E.V., Lupanova I.A., Mizina P.G. Method of obtaining a drug with hepatoprotective and antihepatotoxic effects. Patent 2771028, RF; 2022. (In Russian)
26. Bortnikova V.V, Krepkova L.V., Babenko A.N., Saybel’ O.L., Borovkova M.V., Kuzina O.S., Mizina P.G., Job K.M., Sherwin C.M., Enioutina E.Y. A Perspective Botanical Drug: Hepatoprotective Activity оf Dry Extract Prepared From the Aerial Part of Chicory Plant (Cichorium intybus L.). Clinical pharmacology in drug development. Аbstracts:2021, Тhe American College of Clinical Pharmacology®, September 15, 2021; 10(S1): 100-101. DOI: 10. 1002/срdd.1004
27. Lemyaseva S.V., Krepkova L.V., Babenko A.N. Study of the lipid-lowering activity of common chicory (Cichorium intybus L.) on a twin model. Sovremennye tendencii razvitiya tekhnologij zdorov'esberezheniya. Sbornik trudov 10 mezhdunarodnoj nauchno-prakticheskoj konferencii molodyh uchenyh. Моscow; 2022: 417-420. doi:10.52101/9785870191058. (In Russian)
28. Krasnopeeva I.Y. Mercury intoxication. Sibirskij medicinskij zhurnal (Irkutsk). 2005; 57 (7): 104-108. . (In Russian)
29. Vergilio C.S., Carvalho C.E.V., Melo E.J.T. Mercury-induced dysfunctions in multiple organelles leading to cell death. Toxicolоgy In Vitro. 2015; 29(1): 63-71. doi: 10.1016/j.tiv.2014.09.006.
30. Tsai K. L., Kao C. L., Hung C. H., Cheng Y. H., Lin H. C., Chu P. M. Chicoric acid is a potent anti-atherosclerotic ingredient by antioxidantaction and anti-inflammation capacity. Oncotarget. 2017;8(18):29600–29612. DOI: 10.18632/oncotarget.16768.
31. Sun W., Hesam Shahrajabian M. Therapeutic Potential of Phenolic Compounds in Medicinal Plants-Natural Health Products for Human Health
Molecules. 2023 Feb 15;28(4):1845. doi: 10.3390/molecules28041845.
32.Garg S.S., Gupta J., Sharm S., Sahu D. An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur J Pharm Sci. 2020 Sep 1:152:105424. https://doi.org/10.1016/j.ejps.2020.105424.
33. Garg S. S., Gupta J., Sahu D., Liu C-J. Pharmacological and Therapeutic Applications of Esculetin. Int J Mol Sci. 2022 Oct 20;23(20):12643. doi: 10.3390/ijms232012643.
34. Lupanova I.A. Mizina P.G., Ionov N.S., Poroikov V.V., Khlebnikov A.I., Martynchik I.A. The effect of chicory and chlorogenic acids from Cichorium intybus L. on the activity of cytochrome P450 and glutathione transferase Biofarmacevticheskij zhurnal. 2022. – Т. 14 (5). – С. 8-18 (In Russian)._
35. Choi R.Y. , Ham J. R., Lee M. K. Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet. Chem Biol Interact. 2016 Dec 25:260:13-21. doi: 10.1016/j.cbi.2016.10.013. Epub 2016 Oct 18.
36.Pandey A. , Raj P., Goru S. К., Kadakol A., Malek V., Sharma N., Gaikwad A.B. Esculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway. Pharmacol Rep. 2017Aug;69(4):666-672.
doi: 10.1016/j.pharep.2017.02.005. Epub 2017 Feb 4
37. Xia M., Wu Z., Wang J., Buist-Homan M., Moshage Han. The Coumarin-Derivative Esculetin Protects against Lipotoxicity in Primary Rat Hepatocytes via Attenuating JNK-Mediated Oxidative Stress and Attenuates Free Fatty Acid-Induced Lipid Accumulation. Antioxidants (Basel). 2023 Oct 27;12(11):1922. doi: 10.3390/antiox12111922.
38. Costea L., Chițescu C.L., Boscencu R., Ghica М. , Lupuliasa D., Mihai D.Р., Deculescu-Ioniță Т., Duțu L.E., Popescu М.L., Luță E-A., Nițulescu G.M., Olaru О.T., Gîrd С.E. The Polyphenolic Profile and Antioxidant Activity of Five Vegetal Extracts with Hepatoprotective Potential. Plants (Basel). 2022 Jun 24;11(13):1680. doi: 10.3390/plants11131680
Published
2024-10-09
How to Cite
Krepkova L. V., Babenko A. N., Lemyaseva S. V., Kuzina O. S., Вorovkova M. V. Hepatoprotective effect of chicory (Cichorium intybus L.) in rat intoxication with mercury (II) chloride // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2024. VOL. 68. № 3. PP. 75–84.
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