ACTUAL PROBLEMS OF RAW MATERIALS CHEMICAL STANDARDIZATION OF MEDICINAL PLANTS OF THE GENUS HAWTHORN ΈCRATAEGUS L.Ή

The plants of the genus Hawthorn (Crataegus L.) are shrubs or small trees that have been used in medicine since ancient times. Nowadays, on the basis of raw hawthorn, the preparations are available for treatment and prevention of heart failure. The aim of the work is to analyze and systematize research results in the fi eld of chemical standardization of hawthorn raw materials in pharmacopoeias of various countries. Materials and methods. The study was conducted with the use of the State Pharmacopoeia of the USSR, XI-th edition, the State Pharmacopoeia of the Russian Federation, XIII-th edition, the European Pharmacopoeia, 6-th edition, the United States Pharmacopeia, 32-nd editions, the State Pharmacopoeia of the Republic of Belarus and the Republic of Kazakhstan, as well as the information and search (PubMed) and library databases (eLibrary). Results and discussion. In this review, the results of research in the fi eld of chemical standardization of hawthorn raw materials in pharmacopoeias of various countries are systematized. It is determined that in the methods of analysis of raw materials of the species of the genus Hawthorn (Crataegus L.), included in domestic and foreign Pharmacopoeias, various methodological and methodological approaches to the standardization of fruits, fl owers and leaves are used. Besides, it has been found out that the raw materials of the same name are analyzed using different techniques. In our opinion, the use of various extractants in the methods is not always justifi ed from the point of view of the physical-chemical and spectral characteristics of the substances being analyzed. It is also shown that in the methods of qualitative and quantitative analysis of active substances (fl avonoids, procyanidins), the orientation to diagnostically signifi cant standard substances is not always conducted. Conclusion. The analysis of existing methods of qualitative analysis (the section of authenticity) and quantitative determination of the target substances indicates the necessity to unify the methods of raw materials analysis and preparations of hawthorn species on the basis of scientifi cally based approaches to standardization.

1. Martins Ekor. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology [Internet]. 2013;4:177 [cited 2018 Jan 24]. Available from: https://www. ncbi.nlm.nih.gov/pmc/articles/PMC3887317/ DOI: 10.3389/fphar.2013.00177

2. Pal SK, Shukla Y. Herbal medicine: current status and the future. Asian Pacifi c Journal of Cancer Prevention [Internet]. 2003 Aug-Dec;4(4):281-8 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/14728584

3. Sambukova TV, Ovchinnikov BV, Ganapolskii VP, Yatmanov AN, Shabanov PD. Perspektivy ispol’zovaniya fito-preparatov v sovremennoj farmakologii [Prospects for phytopreparations (Botanicals) use in modern pharmacology]. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(2):56-63. DOI: 10.17816/RCF15256-63. Russian.

4. World Health Organization. Cardiovascular diseases (CVDs). [Internet]. [cited 2018 Jan 24]. Available from: http://www.who.int/mediacentre/factsheets/fs317/en/

5. Basyrova IR, Libis RA. Rasprostranennost’ osnovnyh faktorov riska serdechno-sosudistyh zabolevanij i ih kombinacij u zhitelej goroda Orenburga [The prevalence of major cardiovascular risk factors and their combinations in residents of Orenburg city]. Aspirantskiy Vestnik Povolzhiya. 2017;1-2:48-53. Russian.

6. Samylina IA, Sorokina AA, Pyatigorskaya NV. Boyaryshnik (Crataegus): vozmozhnosti medicinskogo prime-neniya [Hawthorn (Crataegus): the possibilities of medical use]. Pharmateca. 2010;8:83-5. Russian.

7. Rastogi S, Pandey MM, Rawat AK. Traditional herbs: a remedy for cardiovascular disorders. Phytomedicine. [Internet]. 2016 Oct 15;23(11):1082-9 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/26656228. DOI: 10.1016/j.phymed.2015.10.012

8. Zorniak M, Szydlo B, Krzeminski TF. Crataegus special extract WS 1442: up-to-date review of experimental and clinical experiences. Journal of physiology and pharmacology. [Internet]. 2017 Aug;68(4):521-6 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29151068

9. JieWang, Xingjiang Xiong, Bo Feng. Effect of Crataegus Usage in Cardiovascular Disease Prevention: An Evidence-Based Approach. Evidence-Based Complementary and Alternative Medicine. [Internet]. 2013 [cited 2018 Jan 24]. Available from: https://www.hindawi.com/journals/ecam/2013/149363/. DOI: 10.1155/2013/149363

10. Liu XY, Zhou L, Liang RY. Study on lipid regulation mechanism of total flavonoids from folium Crataegi by 3T3-L1 cells. Chin. Arch. Tradit. Chin. Med. 2009;27:1066–8.

11. Yang RM, Chen HM, Gao NN, Song X, Li JL, Cai DY. Mechanism of early atherosclerosis in guinea pig: abnormal metabolism of LDL-C. Acta Lab. Anim. Sci. Sin. 2011;23:237–41.

12. Yang XP. Medicinal value of Crataegus pinnatifida. Jilin Med. J. 1998;19:41.

13. Yuan Y, Zhao J, Gao HJ, Wang JH. Experimental study on effect of hawthorn on compounding hypertension and hyperlipoidemia rats. J. Xinjiang Med. Univ. 2013;35:52–27.

14. Li CQ, Wu W, Tong Y. Study on germicidal efficacy of extract of hawthorn fruit pit and its influencing factors. Chin. J. Disinfect. 2007;24:50–2.

15. Lin L, Chen YJ, Li L, Cao Y, Sun QX. Experimental observation on germicidal efficacy of hawthorn liquid and its influencing factors. Chin. J. Disinfect. 2000;17:85–8.

16. Li L, Lv H, Pang H. Anti-aging effect of total flavone of hawthorn leaf. Lishizhen Med. Mater. Med. Res. 2007;9:2143–4.

17. Ji YS, Li H, Yang SJ. Protective effect and its molecular mechanism of FMCL on PC 12 cells apoptosis induced by H2O2. Chin. Pharmacol. Bull. 2006;22:760–2.

18. Chen ZY, Yan MX, He BH. The Change and the immpact of IFHL on oxidative stress in the formation of NASH in rats. J. Med. Res. 2007;36:33–6.

19. Wang CL, Lu BZ, Hou GL. Chemical constituent, pharmacological effects and clinical application of Crataegus pinnatifida. Strait Pharm. J. 2010;3:75–8.

20. Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. American Journal of Medicine. [Internet]. 2003 Jun 1;114(8):665-74 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12798455

21. Hu M, Zeng W, Tomlinson B. Evaluation of a crataegus-based multiherb formula for dyslipidemia: a randomized, double-blind, placebo-controlled clinical trial. Evidence-Based Complementary and Alternative Medicine. [Inter-net]. 2014 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009229/. DOI: 10.1155/2014/365742

22. Jalaly L, Sharifi G, Faramarzi M, Nematollahi A, Rafi eian-kopaei M, Amiri M, Moattar F. Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris. DARU Journal of Pharmaceutical Sciences. [Internet]. 2015;23:54 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684934/. DOI: 10.1186/s40199-015-0137-2

23. Mustapha N, Pinon A, Limami Y, Simon A, Ghedira K, Hennebelle T, Chekir-Ghedira L. Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Col-orectal Cancer Cells. Journal of Cellular Biochemistry. [Internet]. 2016 May;117(5):1262-72. [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26495895. DOI: 10.1002/jcb.25416

24. Gosudarstvennaya farmakopeya SSSR [State Pharmacopoeia of the USSR]. 11th edition. Is. 2. Mockva: Medicina; 1990. 400 p. Russian.

25. Kurkin VA, Morozova TV, Pravdivtseva OE. Issledovanie po razrabotke metodiki standartizacii list’ev boyaryshnika krovavo-krasnogo [Studies on the development of the methodic of standardization of leaves of Crataegus sanguinea Pall.]. Chemistry of plant raw materials. 2017;3:169-79. Russian.

26. European Pharmacopoeia. 8 ed. Strasbourg: Directorate for the Quality of Medicines & HealthCare of the Council of Europe, 2013.

27. 32 United States Pharmacopeia. URL: http://www.uspbpep.com/usp32/pub/data/v32270/usp32nf27s0_m36580. html

28. Gosudarstvennaya farmakopeya Respubliki Belarus’ [State Pharmacopoeia of the Republic of Belarus]. 1st edition. Vol. 2. Ministerstvo zdravoohraneniya Respubliki Belarus’: Minsk; 2007. 471 p. Russian.

29. Atlas arealov i resursov lekarstvennyh rastenij SSSR [Atlas of areals and resources of medicinal plants of the USSR]. Mockva: GUGK; 1980:242-3. Russian.

30. Silaeva TB, Ageeva AM, Kiryuhin IV, Matvienko II. O boyaryshnikah (Crataegus L.) v Respublike Mordoviya [About hawthorn (Crataegus L.) in the Republic of Mordovia]. Phytodiversity of Eastern Europe. 2007;4:216-8. Russian.

31. Gosudarstvennaya Farmakopeya Rossijskoj Federacii [State Pharmacopoeia of the Russian Federation]. 13th edition. Vol. 1. Mockva; 2015. 1470 p. Russian.

32. Gosudarstvennaya Farmakopeya Rossijskoj Federacii [State Pharmacopoeia of the Russian Federation]. 13th edition. Vol. 2. Mockva; 2015. 1004 p. Russian.

33. Gosudarstvennaya Farmakopeya Rossijskoj Federacii [State Pharmacopoeia of the Russian Federation]. 13th edition. Vol. 3. Mockva; 2015. 1294 p. Russian.

34. Gosudarstvennaya farmakopeya Respubliki Kazahstan [State Pharmacopoeia of the Republic of Kazakhstan]. 1st edition. Vol. 2. Ministerstvo zdravoohraneniya Respubliki Kazahstan: Astana; 2009. 803 p. Russian.

35. Kurkin VA, Kurkina AV, Pravdivceva OE, Morozova TV. Izuchenie himicheskogo sostava preparatov na osnove syr’ya boyaryshnika [The study of the chemical composition of preparations based on the raw material of hawthorn]. Materialy IX mezhdunarodnogo simpoziuma «Fenol’nye soedineniya: fundamental’nye i prikladnye aspekty», Moskva. 2015:578-81. Russian.

36. Dinesh Kumar, Vikrant Arya, Zulfi qar Ali Bhat, Nisar Ahmad Khan, Deo Nandan Prasad. The genus Crataegus: chemical and pharmacological perspectives. Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy. [Internet]. 2012;22(5):1187-200 [cited 2018 Jan 24]. Available from: http://www.scielo.br/pdf/rbfar/ v22n5/aop05712.pdf

37. Jiaqi Wu, Wei Peng, Rongxin Qin, Hong Zhou. Crataegus pinnatifi da: Chemical Constituents, Pharmacology, and Potential Applications. Molecules. [Internet]. 2014;19(2):1685-712 [cited 2018 Jan 24]. Available from: http:// www.mdpi.com/1420-3049/19/2/1685. DOI: 10.3390/molecules19021685

38. Seyed Fazel Nabavi, Solomon Habtemariam, Touqeer Ahmed, Antoni Sureda, Maria Daglia, Eduardo Sobarzo-Sánchez, Seyed Mohammad Nabavi. Polyphenolic Composition of Crataegus monogyna Jacq.: From Chemistry to Medical Applications. Nutrients. [Internet]. 2015 Sep 11;7(9):7708-28 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26378574. DOI: 10.3390/nu7095361

39. Wu SJ, Li QJ, Xiao XF, Li M, Yang XR, Lv T. The research of chemical constituent and pharmacological effects of Crataegus pinnatifi da. Drug Eval. Res. 2010;4:316–9.

40. Kurkina AV, Pravdivtseva OE, Kurkin VA, Dubishchev AV. Pharmacological activity of fl avonoid-containing plants. Internationaler medizinischer Kongress. Hannover. 2006:37-38.

41. Khishova OM, Buzuk GN. Kolichestvennoe opredelenie procianidinov plodov boyaryshnika [Quantitative determination of procyanidins in hawthorn fruits]. Pharmaceutical Chemistry Journal. 2006;40(2):20-1. Russian.

42. Kurkina AV. Opredelenie soderzhaniya summy fl avonoidov v plodah boyaryshnika [Determination of total fl avonoids in hawthorn fruits]. Pharmaceutical Chemistry Journal. 2014;48(12):27-30. Russian.

43. Kurkina AV. Novye podhody k standartizacii cvetkov boyaryshnika [The new approaches to the standardization of Crataegus fl owers]. Chemistry of plant raw materials. 2013;2:171-6. DOI: 10.14258/jcprm.1302171. Russian.

44. Sagaradze VA, Babaeva EYu, Kalenikova EI. Ustanovlenie podlinnosti perspektivnogo vida lekarstvennogo syr’ya – cvetkov s list’yami boyaryshnika [Establishment of the authenticity of the perspective species of medicinal raw materials - flowers with hawthorn leaves]. Problems of biological, medical and pharmaceutical chemistry. 2017;2:26-31. Russian.

45. Sagaradze VA, Babaeva EYu, Kalenikova EI. Opredelenie flavonoidov v cvetkah s list’yami boyaryshnika met-odom VEZHKH so spektrofotometricheskim detektirovaniem [Determination of fl avonoids in flowers with hawthorn leaves by HPLC method with spectrophotometric detection]. Pharmaceutical Chemistry Journal. 2017;4:30-4. Russian.

46. Hellenbrand N, Sendker J, Lechtenberg M, Petereit F, Hensel A. Isolation and quantifi cation of oligomeric and polymeric procyanidins in leaves and fl owers of Hawthorn (Crataegus spp.). Fitoterapia. [Internet]. 2015 Jul;104:14-22 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25917901. DOI: 10.1016/j.fi tote.2015.04.010

47. Kurkin VA, Morozova TV, Pravdivceva OE. Issledovanie po razrabotke standartizacii list’ev boyaryshnika krovavo-krasnogo [The study on the development of the standardization of hawthorn leaves blood-red]. Chemistry of plant raw materials. 2017;3:169-73. Russian.

48. Mudge EM, Liu Y, Lund JA, Brown PN. Single-laboratory validation for the determination of fl avonoids in hawthorn leaves and fi nished products by LC-UV // Planta Med. [Internet]. 2016 Nov;82(17):1487-1492 [cited 2018 Jan 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27776376

49. Cheng S, Qiu F, Huang J, He J. Simultaneous determination of vitexin-2”-O-glucoside, vitexin-2”-O-rhamnoside, rutin, and hyperoside in the extract of hawthorn (Crataegus pinnatifi da Bge.) leaves by RP-HPLC with ultraviolet photodiode array detection. Journal of Separation Science. 2007;30(5):717-21.

50. Zhe Gao, Ya-Nan Jia, Tian-Yuan Cui, Zhe Han, Ai-Xia Qin, Xiao-Hu Kang, Yu-Lei Pan, Tong Cui. Quantifi cation of ten polyphenols in the leaves of Chinese hawthorn (Crataegus pinnatifi da Bge. var. major N.E. Br.) by HPLC. Asian Journal of Chemistry. 2013;25(18):10344-8.