IN VITRO ANTIOXIDANT ACTIVITY OF LEAF AND STEM EXTRACTS OF GREATER CELANDINE (CHELIDONIUM MAJUS L.) USING A HUMAN BLOOD MODEL

H.  Tkaczenko; T. Tiupova; A. Litovka; O.  Lukash; N. Kurhaluk

doi:10.32999/ksu2524-0838/2023-35-6

H. Tkaczenko
T. Tiupova
A. Litovka
O. Lukash
N. Kurhaluk

DOI: https://doi.org/10.32999/ksu2524-0838/2023-35-6

Abstract

Greater celandine (Chelidoniummajus L., CM) is an important plant in phytotherapy and traditional medicine.CM has been used extensively in folk medicine throughout Europe and in some Asian countries, particularly for the treatment of various ailments such as stomach cancer, stomach ulcers, liver and skin diseases. It also has potential anti-inflammatory, anticancer, antiviral, antimicrobial and antifungal properties.The present study was conducted to evaluate the oxidative stress biomarkers [2-thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC)] in blood samples collected from healthy volunteers after in vitro incubation with extracts derived from stems and roots of greater celandine were used. The aim of this study was to evaluate the dose-dependent changes in biomarkers of oxidative stress in blood samples from healthy volunteers exposed in vitro to extracts of CM roots and stems collected from natural habitats in the area of the South Park in Słupsk (Pomeranian Province, northern part of Poland). Freshly washed plant samples were weighed, crushed and homogenised in 0.1 M phosphate buffer (pH 7.4) (1:19, w/w) at room temperature.The extracts were then filtered and used for analysis. Blood samples from healthy volunteers were preincubated with 4 mM phosphate buffer (pH 7.4) (control) and with CM stem and root extracts (at final concentrations of 5 and 2.5 mg/mL) at 37°C for 60 min.The results of our study showed a statistically significant decrease in TBARS levels in blood samples for root extracts at the final dose of CM extracts at both 5 and 2.5 mg/mL. We observed similar trends after in vitro incubation of blood samples with stem extracts of CM (at a final concentration of 2.5 mg/mL), where there was a statistically significant reduction in the concentration of TBARS compared to the untreated control samples. We also observed a statistically non-significant increase in TAC levels after in vitro incubation of blood samples with stem extracts of CM (at a final dose of 5 and 2.5 mg/mL) compared to control samples, while there was a statistically non-significant reduction in TAC levels after in vitro incubation of blood samples with root extracts of CM (at a final dose of 2.5 mg/mL) compared to untreated control samples. This study provides new insights into the understanding of the antioxidant properties of CM extracts.

References

1. Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG. Acute hepatitis induced by greater celandine (Chelidoniummajus). Gastroenterology. 1999;117(5):1234-1237. doi:10.1016/s0016-5085(99)70410-5.
2. Colombo ML, Bosisio E. Pharmacological activities of Chelidoniummajus L. (Papaveraceae). Pharmacol Res. 1996;33(2):127-134. doi:10.1006/phrs.1996.0019.
3. Galaktionova LP, Molchanov AV, El'chaninova SA, VarshavskiĭBIa. Sostoianieperekisnogookisleniia u bol'nykh s iazvennoĭbolezn'iuzheludkaidvenadtsatiperstnoĭkishki [Lipid peroxidation in patients with gastric and duodenal peptic ulcers]. Klin Lab Diagn. 1998;(6):10-14.
4. Gilca M, Gaman L, Panait E, Stoian I, Atanasiu V. Chelidoniummajus – an integrative review: traditional knowledge versus modern findings. ForschKomplementmed. 2010;17(5):241-248. doi:10.1159/000321397.
5. Hazafa A, Rehman KU, Jahan N, Jabeen Z. The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells. NutrCancer. 2020;72(3):386-397. doi:10.1080/01635581.2019.1637006.
6. Isolani ME, Pietra D, Balestrini L, Borghini A, Deri P, Imbriani M, Bianucci AM, Batistoni R. The in vivo effect of chelidonine on the stem cell system of planarians. Eur J Pharmacol. 2012;686(1-3):1-7. doi:10.1016/j.ejphar.2012.03.036.
7. Jagiełło-Wójtowicz E, Jusiak L, Szponar J, Kleinrok Z. Preliminary pharmacological evaluation of chelidonine in rodents. Pol J Pharmacol Pharm. 1989;41(2):125-131.
8. Jang HJ, Yang JH, Hong E, Jo E, Lee S, Lee S, Choi JS, Yoo HS, Kang H. Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells. Integr Cancer Ther. 2021;20:15347354211006191. doi:10.1177/15347354211006191.
9. Jelic MD, Mandic AD, Maricic SM, Srdjenovic BU. Oxidative stress and its role in cancer. J Cancer Res Ther. 2021;17(1):22-28. doi:10.4103/jcrt.JCRT_862_16.
10. Kamyshnikov VS. A reference work for clinical and biochemical research and laboratory diagnostics. MEDpress-inform, Moscow, 2004.
11. Kedzia B, Łozykowska K, Gryszczynska A. Chemical composition and contents of biological active substances in Chelidoniummajus L. Post Fitoter. 2013;3:174-181.
12. Khan H, Saeedi M, Nabavi SM, Mubarak MS, Bishayee A. Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends Towards Future Drugs. Curr Med Chem. 2019;26(13):2389-2406. doi:10.2174/0929867325666180403145137.
13. Kim SH, Hong JH, Lee YC. Chelidonine, a principal isoquinoline alkaloid of Chelidoniummajus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice. Pharmacol Rep. 2015;67(6):1168-1177. doi:10.1016/j.pharep.2015.04.013.
14. Lenfeld J, Kroutil M, Marsálek E, Slavík J, Preininger V, Simánek V. Antiinflammatory activity of quaternary benzophenanthridine alkaloids from Chelidoniummajus. Planta Med. 1981;43(2):161-5. doi: 10.1055/s-2007-971493. PMID: 7312984.
15. Liao W, He X, Yi Z, Xiang W, Ding Y. Chelidonine suppresses LPS-Induced production of inflammatory mediators through the inhibitory of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages. Biomed Pharmacother. 2018;107:1151-1159. doi:10.1016/j.biopha.2018.08.094.
16. Lorenzon Dos Santos J, Quadros AS, Weschenfelder C, Garofallo SB, Marcadenti A. Oxidative Stress Biomarkers, Nut-Related Antioxidants, and Cardiovascular Disease. Nutrients. 2020;12(3):682. doi:10.3390/nu12030682.
17. Mamedov N, Gardner Z, Craker LE. Medicinal plants used in Russia and Central Asia for the treatment of selected skin conditions. J Herbs Spices Med Plants. 2004;11:191–222. 10.1300/J044v11n01_07.
18. Miao F, Yang XJ, Zhou L, Hu HJ, Zheng F, Ding XD, Sun DM, Zhou CD, Sun W. Structural modification of sanguinarine and chelerythrine and their antibacterial activity. Nat Prod Res. 2011;25(9):863-875. doi:10.1080/14786419.2010.482055.
19. Mikołajczak PŁ, Kędzia B, Ożarowski M, Kujawski R, Bogacz A, Bartkowiak-Wieczorek J, Białas W, Gryszczyńska A, Buchwald W, Szulc M, Wasiak N, Górska-Paukszta M, Baraniak J, Czerny B, Seremak-Mrozikiewicz A. Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidoniummajus L. Cent Eur J Immunol. 2015;40(4):400-410. doi:10.5114/ceji.2015.54607.
20. Nile SH, Wang H, Nile A, Lin X, Dong H, Venkidasamy B, Sieniawska E, Enkhtaivan G, Kai G. Comparative analysis of metabolic variations, antioxidant potential and cytotoxic effects in different parts of Chelidoniummajus L. Food ChemToxicol. 2021;156:112483. doi:10.1016/j.fct.2021.112483.
21. Nowicky JW, Staniszewski A, Zbroja-Sontag W, Slesak B, Nowicky W, Hiesmayr W. Evaluation of thiophosphoric acid alkaloid derivatives from Chelidoniummajus L. («Ukrain») as an immunostimulant in patients with various carcinomas. Drugs ExpClin Res. 1991;17(2):139-143.
22. Och A, Zalewski D, Komsta Ł, Kołodziej P, Kocki J, Bogucka-Kocka A. Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of Chelidoniummajus L. and Berberisthunbergii DC. toward Hematopoietic Cancer Cell Lines. Toxins (Basel). 2019;11(9):485. doi:10.3390/toxins11090485.
23. Perez Gultierrez RM. Spasmolytic effect of constituents from ethnomedicinal plants on smooth muscle. In: Rai, M., Acharya, D., Rios, J.L., editors. Ethnomedicinal Plants: Revitalizing of Traditional Knowledge of Herbs. Tylor and Francis Group; Boca Raton, FL, USA,2011.
24. Petruczynik A, Tuzimski T, Plech T, Misiurek J, Szalast K, Szymczak G. Comparison of Anticancer Activity and HPLC-DAD Determination of Selected Isoquinoline Alkaloids from Thalictrumfoetidum, Berberis sp. and Chelidoniummajus Extracts. Molecules. 2019;24(19):3417. doi:10.3390/molecules24193417.
25. Sārközi Ā, Janicsāk G, Kursinszki L, Kery A. Alkaloid composition of Chelidoniummajus L. studied by different chromatographic techniques. Chromatographia. 2006;S63:81–86. doi:10.1365/s10337-006-0728-7.
26. Senoner T, Dichtl W. Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target?. Nutrients. 2019;11(9):2090. doi:10.3390/nu11092090.
27. Stavely R, Ott LC, Sahakian L, Rashidi N, Sakkal S, Nurgali K. Oxidative Stress and Neural Dysfunction in Gastrointestinal Diseases: Can Stem Cells Offer a Solution?. Stem Cells Transl Med. 2023;12(12):801-810. doi:10.1093/stcltm/szad063.
28. Stickel F, Pöschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Acute hepatitis induced by Greater Celandine (Chelidoniummajus). Scand J Gastroenterol. 2003;38(5):565-568. doi:10.1080/00365520310000942.
29. Táborská E, Bochoráková H, Dostál J, Paulová H. Vlastovicníkvĕtsí (Chelidoniummajus L.) – prehledsoucasnĕhostavupoznatků [The greater celandine (Chelidoniummajus L.) – review of present knowledge]. CeskaSlov Farm. 1995;44(2):71-75.
30. Teodor ED, Ungureanu O, Gatea F, Radu GL. The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents. Anticancer Agents Med Chem. 2020;20(18):2216-2227. doi:10.2174/1871520620666200516150829.
31. Tuzimski T, Petruczynik A, Plech T, Kaproń B, Makuch-Kocka A, Szultka-Młyńska M, Misiurek J, Buszewski B, Waksmundzka-Hajnos M. Determination of Selected Isoquinoline Alkaloids from Chelidoniummajus, Mahoniaaquifolium and Sanguinariacanadensis Extracts by Liquid Chromatography and Their In Vitro and In Vivo Cytotoxic Activity against Human Cancer Cells. Int J Mol Sci. 2023;24(7):6360. doi:10.3390/ijms24076360.
32. Wang H, Yin G, Yu CH, Wang Y, Sun ZL. Inhibitory effect of sanguinarine on PKC-CPI-17 pathway mediating by muscarinic receptors in dispersed intestinal smooth muscle cells. Res Vet Sci. 2013;95(3):1125-1133. doi:10.1016/j.rvsc.2013.07.022.
33. Warowicka A, Popenda Ł, Bartkowiak G, Musidlak O, Litowczenko-Cybulska J, Kuźma D, Nawrot R, Jurga S, Goździcka-Józefiak A. Protoberberine compounds extracted from Chelidoniummajus L. as novel natural photosensitizers for cancer therapy. Phytomedicine. 2019;64:152919. doi:10.1016/j.phymed.2019.152919.
34. Zar J.H. Biostatistical Analysis. 4th ed., Prentice-Hall Inc., Englewood Cliffs, New Jersey, 1999.
35. Zielińska S, Czerwińska ME, Dziągwa-Becker M, Dryś A, Kucharski M, Jezierska-Domaradzka A, Płachno BJ, Matkowski A. Modulatory Effect of Chelidoniummajus Extract and Its Alkaloids on LPS-Stimulated Cytokine Secretion in Human Neutrophils. Molecules. 2020;25(4):842. doi:10.3390/molecules25040842.
36. Zielińska S, Jezierska-Domaradzka A, Wójciak-Kosior M, Sowa I, Junka A, Matkowski AM. Greater Celandine's Ups and Downs-21 Centuries of Medicinal Uses of Chelidoniummajus From the Viewpoint of Today's Pharmacology. Front Pharmacol. 2018;9:299. doi:10.3389/fphar.2018.00299.
37. Zygmuntowicz A, Burmańczuk A, Markiewicz W. Selected Biological Medicinal Products and Their Veterinary Use. Animals (Basel). 2020;10(12):2343. doi:10.3390/ani10122343.