Development of Methods for Obtaining of New Medicines Based on Crataegus submollis Sarg. Fruits
VA Kurkin1*, NA Volkova1, IKh Shaikhutdinov2, OE Pravdivtseva1, AV Kurkina1
1Department of Pharmacognosy, Botany and Pytotherapy, Samara State Medical University,
Ulitsa Chapaevskaya 89, Samara, 443099, Russian Federation.
2Institute for Experimental Medicine and Biotechnology, Samara State Medical University,
Ulitsa Gagarina 20, Samara, 443079, Russian Federation.
*Corresponding Author E-mail: kurkinvladimir@yandex.ru
ABSTRACT:
In the medical practice the raw materials of various species of the genus Hawthorn (Crataegus sp., Rosaceae family) are widely used. One of the promising species for the use in medicine is Crataegus submollis Sarg. fruits of Crataegus submollis Sarg. which is expediently to process in fresh form for the obtaining of the juice and extraction preparations based on fruit pulp. The hawthorn fruits are characterized on flavonoid composition, both the oxidized ones, flavones and flavonols, such as hyperoside, vitexin, and the reduced forms of flavonoids. i.e. derivatives of catechin (procyanidins), moreover, the last group of flavonoids is the dominant one. It was determined that the contents of the total flavonoids in the fresh, dried fruits of Crataegus submollis Sarg. and dried fruit pulp are 0,38±0,02%, 3,15±0,16% and 3,95±0,20% (calculated on catechin), respectively. The contents of the total flavonoids in the juice, tincture of Crataegus submollis Sarg., tincture based on dried fruit bagasse, as well as in the industrial sample of the tincture of hawthorn fruits are 0,15±0,01%, 0,15±0,01% and 0,12±0,01% (calculated on catechin), respectively.
KEYWORDS: Crataegus submollis Sarg., fruits, bagasse of fruits, juice, tincture, flavonoids, catechin, spectrophotometry.
INTRODUCTION:
In the medical practice the raw materials of various species of the genus Crataegus L., Rosaceae family) are widely used.1 The raw materials of hawthorn are fruits, flowers, and leaves with flowers.1,2 Hawthorn fruits are most often used to obtain medicines. Hawthorn preparations are used as cardiotonic and antisclerotic agents.2-6
Also, the diuretic and antidepressant effects are characteristic for preparations based on hawthorn fruits.6,7 It was determined, that Crataegus oxyacantha L. demonstrated significant analgesic activity and provided a basis for supporting of the folkloric use of this plant as a diuretic agent.8
The hawthorn fruits contain many biologically active compounds, including flavonoids, saponins, tannins and other substances.6 Of particular importance in the manifestation of the biological activity of preparations from hawthorn fruits are flavonoids, among which the reduced forms of these polyphenols based on catechin as a monomer dominate.6 Along with catechin derivatives, hawthorn fruits also contain oxidized forms of flavonoids in small quantities, in particular hyperoside, for which neurotropic activity was previously detected.6
The unique structural diversity of the chemical nature of biologically active compounds of hawthorn fruits is taken into account by scientists working in the fields of creation and standardization of medicinal herbal preparations based on medicinal plant raw materials.6,9
So, there are different approaches to the issue of quantitative analysis of hawthorn fruits. In accordance with the State Pharmacopoeia of the Russian Federation of the XIV edition, the total flavonoids calculated on hyperoside is determined by spectrophotometry in hawthorn fruits.1 The Pharmacopoeias of the Republic of Belarus and the Republic of Kazakhstan, as well as the European Pharmacopoeia for this type of raw material regulate the determination of the total of procyanidins calculated on cyanidine chloride.2,10,11 In addition to the above, the Pharmacopoeia of the Republic of Belarus also includes a method for determination of the of flavonoid content calculated on hyperoside.9
Thus, the presented regulatory documents describe various approaches to quantifying the content of flavonoids in hawthorn fruits, and there is also a difference in the choice of quality indicator (the total flavonoids calculated on hyperoside or the total procyanidins). Previously, we developed a method for analysis of the total flavonoids in hawthorn fruits by direct spectrophotometry at a wavelength of 282nm calculated on catechin.6
Among the wild hawthorn species in Europe, the most common are Crataegus sanguinea Pall., Crataegus monogina Jacq. and Crataegus oxyacantha Pojark.6 The industrial collection of raw materials from wild plants is limited by natural resources.6,12 At the same time, a North American species, Crataegus submollis Sarg, is widely cultivated.13 This type of hawthorn is characterized by rapid growth and stable yield. Its decorative properties are widely used to produce hedges. The fruits of Crataegus submollis Sarg. are widely are used as food. Previously, we found diuretic and antidepressant effects for Crataegus submollis Sarg. fruit preparations.6,7
Previously, we isolated flavonoids hyperoside, vitexin, isoquercitrin. 3’’-O-p-coumaroyl-isoquercitrin, avicularin from the fruits of Crataegus submollis Sarg. along with the substance of a mixture of procyanidins. Some of them are characteristic of the fruits of other species of the genus Crataegus.6,13,14 The fruits of Crataegus submollis Sarg. are much larger than the fruits of wild hawthorn species, so they are the promising raw materials for obtaining medicines. In medical practice, the hawthorn fruits are used dried. The high moisture content in the fruits of Crataegus submollis Sarg. makes the stage of the drying as the difficult process. Currently, there are methods of the effective extraction of the biologically active compounds (flavonoids, etc.) from the raw materials of various plants, including hawthorn seeds, with the using of Emerging Ultrasound Assisted Extraction Techniques (Innovative Green Technologies) for the effective extraction of the active phytopharmaceuticals.15 There is also a method of processing of juicy fruits of various species of the genus Crataegus L. associated with obtaining of the juice.16 On the example of the hawthorn and other plants there was shown, that the phytosome technology is one such novel approach that enabled in making polyphenolic phytoconstituents (flavonoids, etc.) more skin permeable and absorbable from gastrointestinal tract.
The purpose of this work is the scientific substantiation of development of the rational method of fruit processing of Crataegus submollis Sarg. for the obtaining of phytopharmaceuticals.
MATERIALS AND METHODS:
The fruits of Crataegus submollis Sarg. collected in the Botanical Garden of Samara University in 2020. One part of the fruit was dried in the air, the other part was used to obtain the juice of hawthorn fruits. The juice from fresh hawthorn fruits was obtained by direct pressing. The fruit pulp remaining after pressing was dried in air. The fruit tinctures were obtained on the basis of dried fruits and dried pulp using 70% ethyl alcohol in the ratio “raw material-extractant” - 1:10. The studied raw materials and the obtained preparations were examined for the content of the total flavonoids calculated on catechin by direct spectrophotometry at a wavelength of 282nm (Fig. 1). For comparison, we used an industrial sample of hawthorn fruit tincture. The spectrophotometer “Specord 40” (Analytik Jena) was used for the registration of the electronic UV spectra of test solutions.
RESULTS AND DISCUSSION:
The studies have shown that the juice yield from fresh fruits of Crataegus submollis Sarg. it is about 20-25% of the weight of the fruits. The chemical composition studies by spectrophotometry have shown the similarity of the chemical composition of fresh fruits, juice and dried fruits of Crataegus submollis Sarg. (Fig. 2-5). It was determined, that in all the presented electronic spectra (Fig. 2-5), the absorption maximum is at wavelength of 282nm, which is characteristic for the flavonoid catechin (Fig. 1).
The fruit pulp obtained after juicing is much easier to air dry than the juicy fruits of Crataegus submollis Sarg. Tincture obtained on the basis of the dried fruit pulp Crataegus submollis Sarg. it is not inferior in content to the tincture obtained on the basis of the fruits that have not been pressed (Table 1).
Figure 1. Electronic spectrum of catechin solution.
Figure 2. Electronic spectrum of fresh fruit extraction of Crataegus submollis Sarg.
Figure 3: Electronic spectrum of dried fruit extraction of Crataegus submollis Sarg.
Figure 4. Electronic spectrum of fresh fruit juice of Crataegus submollis Sarg.
Figure 5. Electronic spectrum of tincture from fruits of Crataegus submollis Sarg.
Table 1 - The content of the total flavonoids in raw materials and fruit preparations of Crataegus submollis Sarg.
|
No. |
The studied plant raw material or preparation |
The content of the total of flavonoids (calculated on catechin, %) |
|
1. |
The fresh fruits |
0,38±0,02% |
|
2. |
The dried fruits |
3,15±0,16% |
|
3. |
The juice of fresh fruits |
0,20±0,01% |
|
4. |
The dried bagasse of fruits |
3,95±0,20% |
|
5. |
The tincture based on dried fruits |
0,15±0,01% |
|
6. |
The tincture based on dried bagasse of fruits |
0,15±0,01% |
|
7. |
The industrial sample of the tincture based on fruits |
0,12±0,01% |
Both tincture samples exceed the flavonoid level of the industrial sample of the drug by 25%. The juice of Crataegus submollis Sarg. also contains more flavonoids than an industrial sample of hawthorn fruit tincture. Therefore, the juice can be used for the use in the medical practice as the phytopharmaceuticals. Besides, Crataegus submollis Sarg. fruit pulp can be as a raw material for the obtaining of tinctures.
CONCLUSION:
The fresh fruits of Crataegus submollis Sarg. should be processed immediately after harvesting to obtain the juice from the fresh fruits. Crataegus submollis Sarg. fruit pulp it is advisable to use it to obtain the extraction preparations. The fruits of Crataegus submollis Sarg. are promising medicinal raw materials. The quantitative analysis of the raw materials and preparations of Crataegus submollis Sarg. fruits should be carried out with the determination of the total flavonoids calculated on catechin.
CONFLICTS OF INTEREST:
The authors declare no conflicts of interest.
REFERENCES:
1. Gosudarstvennaya Farmakopeya Rossijskoj Federacii. - Chetyrnadcatoe izdanie. M.: Ministerstvo zdravoohraneniya RF. [The State Pharmacopoeia of the Russian Federation. XIV edition. Ministry of Health of the Russian Federation], 2018. /URL: http://femb.ru/femb/pharmacopea.php
2. European Pharmacopoeia (Ph. Eur.) 10th Edition. EDQM - European Directorate for the Quality of Medicines. Accessed October 13, 2021. Available from: https://www.edqm.eu/en/european-pharmacopoeia-ph-eur-10th-edition.
3. Kurkina AV. Flavonoidy farmakopejnykh rastenij: monografiya [Flavonoids of pharmacopoeia plants: monograph]. Samara: OOO «Ofort», GBOU VPO SamGMU Minzdravsocrazvitiya Rossii 2012.
4. Schüssler M, Hölzl J, Fricke U. Myocardial effects of flavonoids from Crataegus species. Arzneimittel-Forschung. 1995; 45: 8. 842-845.
5. Chang WT, Dao J, Shao ZH. Hawthorn: potential roles in cardiovascular disease. The American Journal of Chinese Medicine. 2005; 33: 01. 1-10.
6. Kurkin VA, Pravdivtseva OE, Shajkhutdinov IH, Kurkina AV, Zajtseva EN, Volkova NA Vidy roda boyaryshnik (Crataegus L.): standartizaciya i sozdanie lekarstvennykh preparatov [Species of the genus hawthorn (Crataegus L.): standardization and creation of medicines]. Samara: OOO «Ofort»; 2020.
7. Morozova TV, Kurkin VA, Zaitceva EN, Pravdivtseva OE, Dubishchev AV, Afanasyeva PV, Kretova AA, Gamirova GF Study of antidepressant properties of the liquid extacts based on raw materials of Crataegus submollis Sarg. Vestnik Bashkirskogo gosudarstvennogo medicinskogo universiteta, 2018; 4. 150-155.
8. Alsayari A, Ghazwani M, Almaghaslah D, Alhamhoom Y, Louis J, Altohami J, Al-Assiri GM, Alaboghobar GS, Alshahrani N, Alfaifi HH. Potential analgesic and diuretic activity of Crataegus oxyacantha Linn. Research Journal of Pharmacy and Technology. 2018; 11: 6. 2476-2482.
9. Khishova OM, Buzuk GN Quantitative determination of procyanidins in hawthorn fruits. Кhimiko-farmacevticheskij zhurnal. 2006; 2: 20-22.
10. Gosudarstvennaya farmakopeya Respubliki Belarus'. – Minsk: Ministerstva zdravoohraneniya Respubliki Belarus'. [The State Pharmacopoeia of the Republic of Belarus. Minsk: Ministry of Health of the Republic of Belarus], 2007.
11. Gosudarstvennaya farmakopeya Respubliki Kazahstan. Astana: Ministerstva zdravoohraneniya Respubliki Kazakhstan. [State Pharmacopoeia of the Republic of Kazakhstan. Astana: Ministry of Health of the Republic of Kazakhstan], 2009.
12. Derev'ya i kustarniki SSSR [Trees and shrubs of the USSR]. Edition of the USSR Academy of Sciences. Moscow-Leningrad, 1954. Vol. 3. 872 p.
13. Morozova TV, Kurkin VA, Pravdivtseva OE, Rozno SA, Zhavkina TM. Comparative phytochemical study of fruits, shoots and flowers of some species of the genus hawthorn. Aspirantskij vestnik Povolzh'ya. 2018: 1-2. 22-4.
14. Kurkin VA, Shajkhutdinov IH, Pravdivtseva OE, Kurkina AV, Daeva EV, Kadentsev VI. Constituents of Crataegus submollis Fruit. Chemistry of Natural Compounds. 2021; 57: 2. 350-352.
15. Kalita B, Das MK, Sharma AK. Novel phytosome formulations in making herbal extracts more effective. Research Journal of Pharmacy and Technology. 2013; 6: 11. 1295-1301.
16. Russian patent for invention No. 2698325. Juice from fresh fruits of hawthorn soft, with diuretic activity from 26.08.2019.
Received on 14.07.2022 Modified on 22.10.2022
Accepted on 28.12.2022 © RJPT All right reserved
Research J. Pharm. and Tech 2023; 16(4):2025-2028.
DOI: 10.52711/0974-360X.2023.00333