The current state and prospects for the creation of drugs based on chlorophylls (review)

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Abstract

According to their chemical structure, chlorophylls are magnesium complexes of various tetrapyrroles, the main plant sources of which are dioecious nettle, alfalfa, mulberry, eucalyptus, various types of algae and common spruce. Chlorophylls A, B, C, and D have been studied, but as a percentage, species A and B. Chlorophylls have high biological activity, which is why they are of interest for the development of medicines. Currently, chlorophyll derivatives are actively used for photodynamic therapy of cancer diseases. Proven pharmaceutical effects include hematopoietic, wound healing, bactericidal, antiviral, and immunostimulating.

The purpose of the review is to systematize information sources on the chemical structure, properties, biological activity, technology and standardization of chlorophylls isolated from plant raw materials.

Information about chlorophylls is summarized, their chemical structure, plant sources, properties and biological activity are studied. Special attention is paid to extraction methods and quantitative determination of chlorophylls in plant raw materials. It has been established that the main methods of chlorophyll extraction from plant raw materials are maceration with ethyl alcohol. To intensify the release of chlorophylls, an ultrasonic bath and a microwave oven are used, as well as methods of extraction with a supercritical liquid, deep eutectic solvents, using an accelerated dissolution extractor. Methods of spectrophotometry, photometry, inductively coupled plasma with optical emission spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and high performance liquid chromatography (HPLC) are used to quantify chlorophylls in the obtained extracts. Currently, chlorophylls are mainly used as natural pigments. In this review, they are considered from the point of view of their use in medicine as an active pharmaceutical substance (APS). The state register of medicines and the pharmaceutical market have been studied. It has been established that in Russia, mainly medicinal products for external and topical use are registered with chlorophylls. Preparations with chlorophylls from eucalyptus and dietary supplements have been registered for internal use.

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About the authors

Е. I. Molokhova

Perm State Pharmaceutical Academy of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: profmol17@gmail.com
ORCID iD: 0000-0003-0334-8590
SPIN-code: 4730-4736

Dr.Sc. (Pharm.), Professor of the Department of Industrial Technology of Medicines with a course in Biotechnology

Russian Federation, Polevaya str., 2, Perm, 614990

N. S. Rusaeva

Perm State Pharmaceutical Academy of the Ministry of Health of the Russian Federation

Email: rusaeva.00@mail.ru
ORCID iD: 0009-0004-2950-5501
SPIN-code: 7415-4144

Post-graduate Student of the Department of Industrial Technology of Medicines with a course in Biotechnology

Russian Federation, Polevaya str., 2, Perm, 614990

Е. S. Berezina

Perm State Pharmaceutical Academy of the Ministry of Health of the Russian Federation

Email: berezina.e.s@yandex.ru
ORCID iD: 0000-0002-4122-2414
SPIN-code: 6068-0598

Ph.D. (Pharm.), Associate Professor of the Department of Pharmaceutical Chemistry

Russian Federation, Polevaya str., 2, Perm, 614990

References

  1. The Great Medical Encyclopedia (In Russ.); https://бмэ.орг/index.php.
  2. Lezhneva L.P. Theoretical and experimental substantiation of the prospects of using dioecious nettle in practical medicine. Pjatigorsk. 2022. 120 s. (In Russ.).
  3. Vlasov A.S., Belonogova V.D., Kuricyn A.V. et al. Stocks of raw materials of wild medicinal plants in some areas of the Perm region. Materialy nauchno-prakticheskoj konferencii s mezhdunarodnym uchastiem, posvjashhennoj 75-letiju Permskoj gosudarstvennoj farmacevticheskoj akademii (7-9 dekabrja 2011 goda). g. Perm'. S. 196-197. (In Russ.).
  4. The State Register of Medicines. (In Russ.); https://grls.minzdrav.gov.ru/Default.aspx.
  5. The Great Russian Encyclopedia. (In Russ.); https://bigenc.ru/.
  6. Chlorophyll A and B – what is the difference? (In Russ.); https://vchemraznica.ru/xlorofill-a-i-b-chem-oni-otlichayutsya/.
  7. Hyrije Koraqi, Bujar Qazimi, Waseem Khalid et al. Optimized conditions for extraction, quantification and detection of bioactive compound from Nettle (Urtica dioica L.) using the deep eutectic solvents, ultra-sonication and liquid chromatography-mass spectrometry (LC-DAD-ESI-MS/MS). International Journal of Food Properties. 2023: 2171-2185. doi: 10.1080/10942912.2023.2244194.
  8. Patent No. RU2611409C1 Russian Federation, IPC A61K36/00 (2006.01), A61K33/34 (2006.01). Method for obtaining a copper chlorophyll complex: No. 2016109418: application 15.03.2016: published 21.02.2017 / Mukhortova L.I., Nikiforova N.S., Lukin P.M.; applicant Federal State Budgetary Educational Institution of Higher Professional Education education "I.N. Ulyanov Chuvash State University" – 7 p. (In Russ.).
  9. Zilfikarov I.N., Dajronas Zh.V., Bochkarjova I.I. et al. The main aspects of end-to-end standardization of raw materials and medicines of eucalyptus rod. Vedomosti Nauchnogo centra jekspertizy sredstv medicinskogo primenenija. 2022; 12(2): 183-192. (In Russ.).
  10. Sanarova Е.V., Lancova A.V., Dmitrieva M.V. et al. Photodynamic therapy is a way to increase the selectivity and effectiveness of tumor treatment. Rossijskij bioterapevticheskij zhurnal. 2014; 13(3): 109-118. (In Russ.).
  11. Ahmadi A., Shahidi S.A., Safari R. et al. Evaluation of stability and antibacterial properties of extracted chlorophyll from alfalfa (Medicago sativa L.).
  12. Food Chem Toxicol. 2022 May; 163: 112980. doi: 10.1016/j.fct.2022.112980.
  13. Huihui Z., Yue W., Xin L. et al. Chlorophyll synthesis and the photoprotective mechanism in leaves of mulberry (Morus alba L.) seedlings under NaCl and NaHCO3 stress revealed by TMT-based proteomics analyses. Ecotoxicol Environ Saf. 2020 Mar 1; 190: 110164. doi: 10.1016/j.eco-env.2020.110164.
  14. Balaev T.A., Moldaver B.L., Badjugina I.B. et al. Medicinal preparations from the leaves of eucalyptus rod-shaped, containing copper analogues of chlorophyll. Zdorov'e – osnova chelovecheskogo potenciala: problemy i puti ih reshenija. 2008; 1: 12-16. (In Russ.).
  15. Gorohova O.G. Algae biomass and chlorophyll "a" content in the plankton of rivers in the basin of the Kuibyshev, Saratov and Volgograd reservoirs. Izvestija Samarskogo nauchnogo centra Rossijskoj akademii nauk. 2018; 20(5(3)): 358-363. (In Russ.).
  16. Skrebec T.Je., Ivahnov A.D., Repina V.I. Extraction of chlorophylls and carotenoids from spruce needles with supercritical carbon dioxide. Himija rastitel'nogo syr'ja. 2023; 2: 253-259. (In Russ.). doi: 10.14258/jcprm.20230211878.
  17. Karimov D.R., Makarov V.V., Kruchinin S.O. et al. Optimization of chlorophyll extraction conditions from dioecious nettle (Urtica dioica L.) and spirulina (Spirulina Platenesis). Himija rastitel'nogo syr'ja. 2014; 4: 189-196. (in Russ.).
  18. Allan Morcelli, Eduardo Cassel, Rubem Vargas et al. Supercritical fluid (CO + ethanol) extraction of chlorophylls and carotenoids from Chlorella sorokiniana: COSMO-SAC assisted prediction of properties and experimental approach. Journal of CO2 Utilization. Brasil. 2021. doi: 10.1016/j.jcou.2021.101649.
  19. Maja Repajić, Ena Cegledi, Zoran Zorić et al. Bioactive Compounds in Wild Nettle (Urtica dioica L.) Leaves and Stalks: Polyphenols and Pigments upon Seasonal and Habitat Variations. Foods. 2021; 66(2): 245-251. doi: 10.3390/foods10010190.
  20. Patent No. RU2531940C1 Russian Federation, IPC G01N33/15 (2006.01), G01N33/15 (2006.01). Method of spectrophotometric quantitative determination in the leaves of dioecious nettle with the combined presence of chlorophyll, carotenoids and hydroxycinnamic acids : No. 2013117181 : application 04/15/2013 : published 10/27/2014 / Trineeva O.V., Safonova E.F., Slivkin A.I., Voropaeva S.V.; applicant Federal State Budgetary Educational Institution of Higher Professional Education "Voronezh State University" (VSU). 8 p. (in Russ.).
  21. Patent No. RU172362U1 Russian Federation, IPC B01D 11/02 (2006.01). Liquid extractor for accelerated extraction of water-soluble substances from vegetable raw materials: No. 2017101586: application No. 18.01.2017: published 05.07.2017 / Kilyusheva N.V., Aisenstadt A.M., Danilov V.E.; applicant Federal State Autonomous Educational Institution of Higher Education "Severny M.V. Lomonosov (Arctic) Federal University (NARFU). 6 p. (In Russ.).
  22. Dawson R., Elliott W., Jones K. Handbook of Biochemistry. Moscow. 1991. Р. 344.
  23. Belyh D.V., Zajnullina E.N., Starceva O.M. 1H NMR Quantitative Determination of Chlorophyll a in the Spirulina Biomass. Makrogeterocikly. 2020; 3: 260-268. (In Russ.). doi: 10.6060/mhc200607b.
  24. Glaz N.V., Kazakova N.I., Ufimceva L.V. Methodological approaches to the selection of sampling conditions and assessment of the chlorophyll content in the leaves of a corn plant. Vestnik KrasGAU. 2015; 3: 73-77. (In Russ.).
  25. Bondarev A.V., Bojko N.N., Zalivskaja A.V. et al. Development of technology for obtaining extract of dioecious nettle (Urtica dioica L.). Fundamental'naja nauka v sovremennoj medicine. 2019: 93-96. (In Russ.).
  26. Saša Popov, Suzana Skeledžija, Saša Šorgic´ et al. Application of Contemporary Extraction Techniques for Elements and Minerals Recovery from Stinging Nettle Leaves. Applied sciences. 2020; 10(3): 793. doi: 10.3390/app10030793.
  27. Plyaskina T.V. Complex connections. Hemoglobin and chlorophyll. 2022 (In Russ.); https://multiurok.ru.
  28. Zubov L. A. The use of seaweed preparations for the prevention and treatment of pathological conditions. Jekologija cheloveka. 1998; 3: 27. (In Russ.).
  29. Patent No. RU2322251C2 Russian Federation, IPC A61K35/74 (2006.01), A61P1/00 (2006.01). Method of complex correction of intestinal dysbiosis using liquid probiotic "Narine Forte" and prebiotic syrup "Phytolone" with chlorophyll: No. 2005139433: application 09.12.2005: published 20.04.2008 / Nekrasova V.B., Alexandrovich N.Zh.; the applicant Nekrasova Valeria Borisovna, Alexandrovich Natalia Zhoresovna – 12 p. (In Russ.).
  30. Oleshko L.N., Blinova O.A., Plaksina A.N. et al. Research on the promising use of the product of processing wood greens – sodium chlorophyllin. Materialy nauchno-prakt. konf., posv. 75-letiju Ukr. Farm. akademii. Har'kov. 1996. S. 186-187. (In Russ.).
  31. Information Portal of the Eurasian Economic Union (In Russ.); https://portal.ea-eunion.org/.
  32. GEOTAR Medical Reference Book (In Russ.); https://www.lsgeotar.ru/.
  33. Pogarceva Ju.A., Kauhova I.E. Preparation and standardization of experimental batches of "photoran e6, lyophilizate for the preparation of solution for infusions", a drug for photodynamic therapy using hogweed leaves as raw materials. Voprosy biologicheskoj, medicinskoj i farmacevticheskoj himii. 2024; 7(27): 11-16. (In Russ.). doi: 10.29296/25877313-2024-07-02.

Supplementary files

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2. Fig. 1. Chlorophyll formula [6]

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3. Fig. 2. Reaction of chlorophyll conversion to sodium salt [5]

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4. Fig. 3. Reaction of conversion of magnesium pheophytinate to copper pheophytinate (II) [9]

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5. Fig. 4. Chemical structure of chlorine [10]

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6. Fig. 5. The structure of hemoglobin and chlorophyll A [26]

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