Experimental study of the influence of a neogalenical phytocomplex from the shoots of Ledum palustre on the course of acute bronchitis disease in rats

Keywords: acute bronchitis, formalin, rats, sprouts of Ledum palustre, effervescent tablets Prospan, bronchoalveolar lavage

Abstract

The aim of the experiment was to study the anti-inflammatory effect of the novogalene agent Ledum 50, obtained from Ledum palustre shoots, in a rat model of acute bronchitis.

Materials and methods. Acute bronchitis was initiated by endotracheal administration of 1 % formalin solution. The effectiveness of Ledum 50 was investigated by the number of leukocytes and cell composition in isotonic BAL solution after 24 hours and after 8 days of the experiment. Serum levels of C-reactive protein (CRP), alkaline phosphatase (AP) and CIC were determined. Histological examination of the lungs was carried out.

Results. Endotracheal injection of formalin caused irritation of the trachea and bronchi, excessive formation of bronchial secretions (heavy breathing, wheezing) in all the studied groups. The lethality of animals in the OB group on the 3rd day of the experiment (1 rat) was recorded, in the studied groups there was no death. The level of leukocytes in BAL after 24 hours exceeded the index of the IC group by 9.63 times (p<0.05), after 8 days – by 3.0 times (p<0.05). In the cellular composition of BAL, there was a significant increase in granulocytes (rod- ​​and segmented neutrophils, eosinophils), monocytes and a decrease in the lymphocyte population against the IC group. Such changes were verified in the long term (8 days of the experiment), which indicates an inflammatory process.

In the group of rats that received Ledum 50, leukocytes in the BAL significantly decreased, the number of monocytes and lymphocytes in the BAL decreased, the amount of CIC in the blood serum, CRP and AP normalized. In terms of effectiveness, Ledum 50 significantly exceeded the BAL values ​​of the reference drug. The effectiveness of experimental therapy for acute bronchitis was also verified by studying the histostructure of the airways and the respiratory part of the lungs.

Conclusions. Studies confirm the favorable course of acute bronchitis with Ledum 50 monotherapy. This fact is confirmed by the results of normalization of hematological parameters, leukocytes and BAL cell composition after 7 days of treatment with the claimed agent. This is the basis for further preclinical and clinical studies with the aim of creating an oral drug for the treatment of acute bronchitis.

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Author Biographies

Karyna Tolmachova, National University of Pharmacy

Department of Pharmacology and Pharmacotherapy

Igor Kireiev, National University of Pharmacy

Department of Pharmacology and Pharmacotherapy

Oleg Koshoviy, National University of Pharmacy

Department of Pharmacognosy

Svetlana Grashchenkova, Educational and Scientific Institute of Applied Pharmacy of National University of Pharmacy

Educational and Scientific Training Laboratory of Medical and Biological Research

Taras Upyr, National University of Pharmacy

Department of Pharmacognosy

References

Graham, W. (2018). Acute bronchitis. Can Fam Physician, 54, 238–239.

Sanjay, S. (2020). Acute Bronchitis. Available at: https://www.msdmanuals.com/professional/pulmonary-disorders/acute-bronchitis/acute-bronchitis

Unyfykovanyi klinichnyi protokol pervynnoi medychnoi dopomohy. «Kashel u doroslykh». Available at: https://kiai.com.ua/ua/archive/2016/3%2892%29/pages-38-45/unifikovaniy-klinichniy-protokol-pervinnoyi-medichnoyi-dopomogi-kashel-u-doroslih-

Nastanovy na zasadakh dokazovoi medytsyny. Nastanova 00129. Available at: https://guidelines.moz.gov.ua/documents/3030

Kemmerich, B., Eberhardt, R., Stammer, H. (2011). Efficacy and Tolerability of a Fluid Extract Combination of Thyme Herb and Ivy Leaves and Matched Placebo in Adults Suffering from Acute Bronchitis with Productive Cough. Arzneimittelforschung, 56 (9), 652–660. doi: http://doi.org/10.1055/s-0031-1296767

Wagner, L., Cramer, H., Klose, P., Lauche, R., Gass, F., Dobos, G., Langhorst, J. (2015). Herbal Medicine for Cough: a Systematic Review and Meta-Analysis. Complementary Medicine Research, 22 (6), 359–368. doi: http://doi.org/10.1159/000442111

Yershovа, I. B., Osypova, T. F. (2016). General Requirements to the Preparation of Tinctures, Decoctions. Dosage of Phytopreparations. Actual Infectology, 3 (12), 123–127. doi: http://doi.org/10.22141/2312-413x.3.12.2016.81727

Harnik, T. P., Andriichuk, L. V., Harnik, K. V., Matsko, V. O., Petrysheva, V. O. (2018). Fitozasoby pry hostrykh respiratornykh zakhvoriuvanniakh ta nespetsyfichnykh zakhvoriuvanniakh orhaniv dykhannia. Fitoterapiia. Chasopys, 1, 19–25.

Schaefer, A., Ludwig, F., Giannetti, B. M., Bulitta, M., Wacker, A. (2019). Efficacy of two dosing schemes of a liquid containing ivy leaves dry extract EA 575 versus placebo in the treatment of acute bronchitis in adults. ERJ Open Research, 5 (4), 00019–2019. doi: http://doi.org/10.1183/23120541.00019-2019

Holzinger, F., Chenot, J.-F. (2011). Systematic Review of Clinical Trials Assessing the Effectiveness of Ivy Leaf (Hedera Helix) for Acute Upper Respiratory Tract Infections. Evidence-Based Complementary and Alternative Medicine, 2011, 1–9. doi: http://doi.org/10.1155/2011/382789

Cwientzek, U., Ottillinger, B., Arenberger, P. (2011). Acute bronchitis therapy with ivy leaves extracts in a two-arm study. A double-blind, randomised study vs. an other ivy leaves extract. Phytomedicine, 18 (13), 1105–1109. doi: http://doi.org/10.1016/j.phymed.2011.06.014

Hecker, M., Runkel, F., Voelp, A. (2002). Treatment of chronic bronchitis with ivy leaf special extract--multicenter post-marketing surveillance study in 1,350 patients. Forsch Komplementarmed Klass Naturheilkd, 9 (2), 77–84. doi: http://doi.org/10.1159/000057269

Chebrets. Farmatsevtychna entsyklopediia. Available at: https://www.pharmencyclopedia.com.ua/article/75/chebrec

Tolmachova, K., Kireyev, I., Tsemenko, K., Koshovoyi, O. (2019). Preclinical Study of Acute Toxicity of the Neogalenical phytocomplex from Ledum palustre shoots. Recipe, 22 (5), 688–694.

Tolmachova, K. S., Kireyev, I. V., Koshoviy, O. M., Tsemenko, K. V., Botsula, I. V. (2019). The study of the emotional and behavioral response in rats after introduction of the neogalenical phytocomplex from Ledum palustre shoots. Clinical pharmacy, 23 (3), 48–51. doi: http://doi.org/10.24959/cphj.19.1499

Minarchenko, V. M. (2013). The resources of medicinal plants of the Western Polissya: state, use and trends of dynamics. Naukovyi visnyk NLTU Ukrainy, 23 (13), 20–23.

Gluschenko, L. A. (2014). The influence of some ecological factors on the crop value of Ledumpalustre L. coenopopulations. Chornomorskyi botanichnyi zhurnal, 10 (1), 6–14.

Koshovyi, O., Upyr, T., Komissarenko, A. (2016). Phytochemical and pharmacological study of the dry extract of Labrador tea shoots. History, Problems and Prospects of Development of Modern Civilization. Tokyo: Tokyo University Press, 382–385.

Tolmachova, K. S., Kireiev, I. V., Koshovyi, O. M., Upyr, T. V., Tolmachova, K. S. (2019). Pat. No. 139206 UA. Novohalenovyi fitokompleks z protykashlovoiu diieiu. MPK: A61K 36/45, A61K 47/10, A61K 11/14. No. u 2019 06433; declareted: 10.06.2019; published: 26.12.2019, Bul. No. 24, 3.

Tolmachova, K. S., Kireiev, I. V., Koshovyi, O. M., Upyr, T. V., Tsemenko, K. V. (2019). Pat. No. 142410 UA. Zastosuvannia novohalenovoho fitokompleksu pahoniv Bahna zvychainoho yak bronkholitychnoho zasobu dlia likuvannia hostroho bronkhitu. MPK: A61K 36/45, A61R 11/08, A61R 11/06 No. u 2019 09844; declareted: 16.09.2019; published: 10.06.2020, Bul. No. 11, 3.

Katelnikova, A. E., Kryshen, K. L., Makarov, V. G., Vorobeva, V. V., Pozharitskaia, O. N., Shikov, A. N. (2014). Poisk novykh protvovospalitelnykh sredstv na osnove kompleksa glikolizirovannykh peptidov, vydelennykh iz morskikh ezhei vida strongilocentrotus droebachiensis. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii, 14 (4), 9–15.

Kozhemiakin, Yu. M., Hromov, O. S., Filonenko, M. A., Sayfetdinova, H. A. (2002). Naukovo praktychni rekomendatsii z utrymannia laboratornykh tvaryn ta roboti z nymy. Kyiv: Avitsena, 156.

Yevropeiska konventsiia pro zakhyst khrebetnykh tvaryn, shcho vykorystovuiutsia dlia doslidnykh ta inshykh naukovykh tsilei (1986). Strasburh. Available at: https://zakon.rada.gov.ua/laws/show/994_137#Text

Ulanova, I. P., Sidorov, K. K., Khalepo, A. I.; Letavet, A. A.; Sanotskii, I. V. (Eds.) (1968). K voprosu ob uchete poverkhnosti tela eksperimentalnykh zhivotnykh pri toksikologicheskom issledovanii. Kyiv- Leningrad: Meditsina, 10, 18–25.

Menshikov, V. V., Delektorskaia, L. N., Zolotnitskaia, R. P. (1987). Laboratornye metody issledovaniia v klinike. Moscow: Meditsina, 367.

Zinovev, S. V., Semenova, G. V., Tseluiko, S. S., Chzhou, S. D., Li, Ts. (2014). Tsitokhimicheskaia kharakeristika lokalizatsii kationov kaltsiia natriia v kletkakh indutsirovannoi mokroty i bronkhoalveoliarnoi lavazhnoi zhidkosti u bolnykh bronkhialnoi astmoi. Biulleten fiziologii i patologii dykhaniia, 52, 52–56.

Meyer, K. C., Raghu, G., Baughman, R. P., Brown, K. K., Costabel, U., du Bois, R. M. et. al. (2012). An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular Analysis in Interstitial Lung Disease. American Journal of Respiratory and Critical Care Medicine, 185 (9), 1004–1014. doi: http://doi.org/10.1164/rccm.201202-0320st

Merkulov, G. A. (1969). Kurs patologogistologicheskoi tekhniki. Moscow: Meditsina, Leningr. otd-nie, 424.

Lapach, S. N., Chubenko, A. V., Babich, P. N. (2001). Statisticheskie metody v mediko-biologicheskikh issledovaniiakh s ispolzovaniem Excel. Kyiv, 320.

Osnovnye metody statisticheskoi obrabotki rezultatov farmakologicheskikh eksperimentov (2000). Rukovodstvo po eksperimentalnomu (doklinicheskomu) izucheniiu novykh farmakologicheskikh veschestv. Moscow: Remedium, 349–354.

Rebrova, O. Iu. (2006). Statisticheskii analiz meditsinskikh dannykh. Primenenie paketa programm Statistica. Moscow: MediaSfera, 312.

Standartnie tsitopreparati bronkhoalveoliarnogo lavazha v issledovanii i patologii legkikh. Available at: http://www.clinlab.ru/win/LIBRARY/JOURNLAB/lab6/j6ct2.htm

Feschenko, Iu. І., Golubovska, O. A., Goncharov, K. A. (2012). Negospіtalna pnevmonіia u doroslikh osіb: etіologіia, patogenez, klasifіkatsіia, dіagnostika, antibakterіalna terapіia (proekt klіnіchnіi nastanov). Ch. І. Ukrainskii pulmonologіchnii zhurnal, 4, 5–13.

Cazzola, M., Rogliani, P., Aliberti, S., Blasi, F., Matera, M. G. (2017). An update on the pharmacotherapeutic management of lower respiratory tract infections. Expert Opinion on Pharmacotherapy, 18 (10), 973–988. doi: http://doi.org/10.1080/14656566.2017.1328497

Nazar, O. V., Andrianova, I. V., Titomir, A. I., Kuznetsov, L. V. (2008). Immunologicheskie aspekty vnegospitalnoi pnevmonii. Klіnіchna іmunologіia, alergologіia, іnfektologіia, 5-2. Available at: https://kiai.com.ua/ru/archive/2008/5-2/article-230/immunologicheskie-aspekty-vnegospitalnoy-pnevmonii

Reheda-Furdychko, M. M., Reheda, S. M., Furdychko, L. O. (2016). Derangement of some immune values in blood at late period of experimen-tal pneumonia and thiotriazolin correctio. Odeskyi medychnyi zhurnal, 3, 9–11.

Izotov, D. V., Tagiltsev, Iu. G., Kolesnikova, R. D. (2005). Tekhnologiia polucheniia i fiziko-khimicheskie kharakteristiki bagulnikovoi kondensatsionnoi vody. Tr. DalNIILKH, 38, 6–14.


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Published
2021-03-31
How to Cite
Tolmachova, K., Kireiev, I., Koshoviy, O., Grashchenkova, S., & Upyr, T. (2021). Experimental study of the influence of a neogalenical phytocomplex from the shoots of Ledum palustre on the course of acute bronchitis disease in rats. EUREKA: Health Sciences, (2), 64-72. https://doi.org/10.21303/2504-5679.2021.001712
Section
Pharmacology, Toxicology and Pharmaceutical Science