CALTHA PALUSTRIS . ANALYTICAL OVERVIEW

Мета. Аналіз та узагальнення даних щодо ареалу, вмісту біологічно активних сполук та спектру використання у фармації та медицині Caltha palustris. Матеріали та методи. Літературні та електронні джерела інформації, що стосуються поширення, хімічного складу та фармакологічної активності Caltha palustris. Результати. Caltha palustris – багаторічна трав'яниста рослина з родини Жовтецевих (Ranunculaceae).. Рослина неофіцинальна, широко застосовується народною медициною як протизапальний, спазмолітичний, бактерицидний, протимікробний, болезаспокійливий, діуретичний засіб. Основними біологічно активними речовинами Caltha palustris є: дубильні речовини, глікозиди (γ-лактони протоанемонін та анемонін ) сапоніни, берберин, гіркоти, вітамін С, холін, каротин, флавоноїди та алкалоїди. Caltha palustris відносять до регіонально рідкісних рослин адміністративних територій України . З огляду на актуальність розширення асортименту лікарської рослинної сировини для створення сучасних лікувальних засобів та хімічний склад, фармакологічну дію Caltha palustris, доцільним є проведення подальших ресурсознавчих, фітохімічних та інших досліджень рослини. Висновки. Враховуючи значний досвід застосування в народній медицині, широкий спектр фармакологічної активності, вміст цінних біологічно активних сполук Caltha palustris є перспективною та цінною сировиною для одержання та виробництва фітохімічних препаратів та впровадження їх у практичне застосування Ключові слова: Ranunculaceae, Caltha palustris, протоанемонін, анемонін, біологічно активні речовини, фармакологічна дія


Introduction
Today, the world pharmaceutical industry is making extensive use of herbal raw materials, which are the basis for the creation of medicines. A large number of drugs that are manufactured worldwide have natural ingredients of plant origin. Therefore, the search for new species of plants that could be a source of biologically active compounds, such as flavonoids, coumarins, hydroxycoric acids, alkaloids, saponins, amino acids and so on. There is some evidence to support the efficacy of herbal medicines in the treatment of a number of serious diseases. One of these is representatives of the Ranunculaceae family, since they are a source of biologically active compounds that have long been used in traditional medicine as a medicine with various pharmacological effects. One such representative is Caltha palustris. The plant is used for a long period in folk medicine of different countries and exhibits a wide range of medicinal properties.
Phytochemical and pharmacological studies of Caltha palustris have been partially conducted by separate groups of scientists in different fields.
Scientists from the University of British Columbia and Indian scientists from the Central Research Institute of Medicines conducted research on the content of triterpene [1][2][3]. In addition, German scientists from Bayreuth University [4] conducted the content of biologically active compounds in some representatives of the Ranun-culaceae family. Researchers from the Wroclaw University of Natural Sciences (Poland) conducted studies on the separation of polysaccharide fraction from Caltha palustris raw material [5]. Italian scientists from Ferraris University [6] carried out the identification of protoanemonin in the plant.
A group of Indian scientists from Kashmir University [7] carried out pharmacological action, including the determination of anthelmintic, antimicrobial, antioxidant and cytotoxic activity.
Polish scientists study the effect of polysaccharide fractions isolated from Caltha palustris on phagocytic cell activity and humoral immune responses in mice with induced arthritis [5,8].
Caltha palustris has not been sufficiently studied at the present stage of the development of pharmaceutical science, so comprehensive studies of its raw materials are relevant.
The purpose of the research is to analyse and summarize the literature on the distribution, chemical composition of Caltha palustris and the features of its use for further pharmacognostic, phytochemical and pharmacological studies.

Planning (methodology) of research
For this purpose, the following problems must be solved: -Analyse current literary sources for data on the distribution of Caltha palustris in Ukraine; -Summarize the literature on the content of biologically active compounds of Caltha palustris; -To analyse and establish the possibilities and peculiarities of the use of Caltha palustris in pharmacy and medicine.

Materials and methods
Literary and electronic sources of information regarding the distribution, chemical composition and pharmacological activity of Caltha palustris were selected.

Results of the research
Caltha palustris (Fig. 1, 2) is a plant belonging to the family Ranunculaceae, a subclass of Ranunculidae. The Latin name of the genus Ranunculaceae is derived from the ancient Roman language. The species name in Latin means swamp [9]. It is herbaceous plant with erect, simple or top branching stems, up to 20-50 cm in height. Leaves petiolate, entire, kidney-or heart-shaped, serrated toothed, dark green, shiny. Root leaves much larger than the stem ones. The flowers are 2-3 cm in diameter. Perianth simple, corolla of five, rarely -many petals. Petals oval or ovoid, golden yellow colour [10].
The plant blooms in April and May. The first flowering of the plant begins only at the 10th year of its life. Leaf fruits containing up to 10 black shiny seeds that fall out after ripening in May and July.

Distribution and harvesting.
Caltha palustris is common in the Ukrainian Carpathians in all highlands.
It grows on the banks of ponds, wet meadows, lakes, wetlands, swamps, along rivers in slow flowing and stagnant waters, near wet channels [14,15]. The distribution map in Ukraine is presented in Fig. 3 [16]. In Ukraine, it has long been used for medicinal purposes. They used all the aboveground part of the plant, which is harvested in the spring during flowering. They are dried in dark and well-ventilated areas, often turning over raw materials. It can be dried in ovens at 50-60 °C.
The roots are harvested in the autumn, washed, crushed, decayed and dried in a dryer.
The seeds have alkaloids, oils and vitamin C. Due to the presence of a toxic substance protoanemonin the plant is poisonous, but after drying the toxic properties are lost because protoanemonin is converted into anemonin [15,23].
The content of protoanemonin in the plant is relatively low compared to other members of the Ranunculaceae family -0.26p.g/g fro wt. Protoanemonin is a metabolite of stress and serves to protect members of the Ranunculaceae family from external stimuli, so its number may vary [24]. Protoanemonin (Fig. 4) is a volatile, viscous, colourless oily substance with a pungent odour and a burning taste.

Fig. 4. Protoanemonin
By chemical nature belongs to the group of lactones. With long-term storage of aqueous solutions, the protoanemonic polymerizes and precipitates as crystalline anemonin. The beneficial effect of protoanemonin is manifested in a stimulating effect on the body: it tones the nervous system, improves haematopoiesis is of great importance In the treatment of purulent wounds and ulcers, as it exhibits antibiotic properties. Actively acts against gram-positive and acid-resistant bacteria [25]. Anemonin (Fig. 5) is found in many members of the Ranunculaceae family, from which it is obtained by distillation of the herbaceous parts. In the processing of chloroform distillation and evaporation of the chloroform solution, there are two crystalline substances: anemone camphor, which has very poisonous properties, quickly turns into amorphous anemonic acid, and anemonin. The latter is a rhombic crystals, melts at 156 ° C, difficult to dissolve in hot water and ethers, easily -in hot alcohol and chloroform. Anemonin is poisonous; its ethereal solution in contact with the eyes leads to dilation of the pupils. However, it has analgesic and antispasmodic properties and is used in asthma, whooping cough, rickets and others [26].

Pharmacological action and use in medicine.
Caltha palustris is an unofficial plant. Caltha palustris is used in folk medicine and homeopathy.
In folk medicine of Ukraine, Caltha palustris is most commonly used externally as an anti-inflammatory and analgesic agent for burns, wounds, bruises, rheumatism, neurodermatitis, eczema, etc. [27].
In small doses decoction or infusion of Caltha palustris grass is used internally for feverish conditions, whooping cough, bronchitis, asthma, metabolic disorders, diathesis, anemia, scurvy, painful menstruation and uterine carcinoma [28].
In Tibetan medicine they used infusion of flowers for the treatment of ascites.
In homeopathy, a plant is used to treat bronchitis and cough, menstrual disorders, and others. Homeopathic anti-cough drug is made from fresh flowering plants [9,28].

Dosage forms.
On the domestic pharmaceutical market there are preparations containing Caltha palustris. These list include the complex homeotic drug Helium-Hel, which is made in the form of drops for oral use by the German company Biologische Heilmittel Heel Gmb H.
The drug has immunomodulatory, antiinflammatory, detoxification and drainage action, which is based on the activation of the body's defences and normalization of impaired functions due to substances of plant, mineral and animal origin, which are part of the drug.
The tool is used for chronic diseases that are often exacerbated; infections that require stimulation of nonspecific immunity; after the consequences of the toxic effects of drug therapy (antibiotics, chemotherapy, radiotherapy) [29].
The American company WHP (Washington Homeopatic Products), founded in 1873 under the name Washington Homeopathic Pharmacy, offers onecomponent homeopathic remedies from Caltha palustris. This company manufactures and markets its own homeopathic remedies and products manufactured by other companies in the world. Caltha palustris preparations are available in the form of tablets, granules and pills [30]. External: • Decoction from the whole plant of the Caltha palustris. ½ teaspoon of crushed dried raw material is poured into a glass of boiling water, simmered for 5 minutes on low heat and cooled for 1 hour, then filtered. Burned areas of the skin are washed with this decoction.
• Juice from fresh leaves and flower buds are used as wound healing agents. Heals wounds, burns, abrasions, rheumatism and removes warts.
• Poultices for the treatment of skin diseases, removal of warts, treatment of neurodermatitis, eczema, burns, wounds and abrasions, treatment of rheumatism. To prepare them, fresh leaves are crushed and boiled, wrapped in cheesecloth and applied to inflamed areas. Internal: • Decoction from the Caltha palustris. Pour 1 teaspoon of crushed roots with 1 cup of boiling water, then bring to low heat and bring to a boil. Simmer on low heat for 10 minutes, cool and strain. Take the decoction 3 times a day for 1 tablespoon after meals in violation of metabolism, anemia and colds. 1 teaspoon taken with bronchitis, whooping cough, painful menstruation. Decoction has weak antitumor properties.
• Decoction from leaves. 1 teaspoon of the leaves is poured with a glass of boiling water, boiled for 15 minutes in a water bath, cooled for 45 minutes, filtered and boiled with water and brought to initial volume.
• Infusion. Take 1 teaspoon of crushed herbs and pour a glass of boiling water, wrap and infuse for 40 minutes. Take 1/3 cup 3 times a day while eating. Treats whooping cough, bronchial catarrh, painful menstruation.
• Decoction from the whole plant of the Caltha palustris. Pour half a teaspoon of shredded raw material with a glass of boiling water; simmer for 5 minutes over low heat. After that, cool and strain. It is necessary to take 50 ml 3 times a day 30 minutes before meals in case of metabolic disorders, anemia, diathesis, colds, fever and as an anti-cingulate agent [23].
Patents Quite often, Caltha palustris is used in oriental medicines. It is used in complex drugs of different spectrum of action. The data are presented in Table 1 [31]. Effectively relieves pain in burns, accelerates the healing of the affected areas, has a bactericidal effect. Promotes blood circulation, softening and resorption of solid mass, improvement of immunity, equilibration of the endocrine system for the treatment of various types of lobular hyperplasia of the breast.

Toxicity and contraindications.
The toxicity of Caltha palustris is caused by the presence of a protoaneminin in a fresh plant. However, according to the literature, they are destroyed in heat treatment [9].
Fresh juice of the aerial part of the plant, collected in the period before flowering, can cause damage to the skin, namely blisters. Excessive intake of infusions or Caltha palustris teas causes pain in the stomach, nausea, vomiting, diarrhoea and allergic reactions [32].

Conclusions
Based on the results of the study and analysing the literature on the distribution, content of biologically active substances in the aerial part of Caltha palustris, the main aspects of its use in medicine and pharmacy, we can conclude that Caltha palustris is a promising medicinal plant of the Ranunculaceae family. The results of the work testify to the prospects of using Caltha palustris as a medicinal raw material for further thorough research, since the plant has long experience in ethnomedicine use and contains valuable biologically active compounds.