Pharmaceutical Sciences, 2020, 26(4), 344-362 doi:10.34172/PS.2020.54 https://ps.tbzmed.ac.ir/ Review Article Vaccinium vitis-idaea L.: Chemical Contents, Pharmacological Activities Arnold Alexeevich Shamilov1* , Valentina Nikolaevna Bubenchikova2 , Maxim Valentinovich Chernikov3, Dmitryi Igorevich Pozdnyakov4 , Ekaterina Robertovna Garsiya1 1Department of Pharmacognosy, Botany and Technology of Phytopreparations, Pyatigorsk Medical-Pharmaceutical Institute (PMPI), Branch of Volgograd State Medical University, Ministry of Health of Russia, 11, Kalinina Prospect, Pyatigorsk, Russian Federation, 357532. 2Department of Pharmacognosy and Botany, Kursk State Medical University (KSMU), Ministry of Health of Russia, 3, K. Marx Street, Kursk, Russian Federation, 305041. 3Department of Biology and Physiology, Pyatigorsk Medical-Pharmaceutical Institute (PMPI), Branch of Volgograd State Medical University, Ministry of Health of Russia, 11, Kalinina prospect, Pyatigorsk, Russian Federation, 357532. 4Department of Pharmacology with course of clinical Pharmacology, Pyatigorsk Medical-Pharmaceutical Institute (PMPI), Branch of Volgograd State Medical University, Ministry of Health of Russia, 11, Kalinina prospect, Pyatigorsk, Russian Federation, 357532. Article Info Abstract One of the most known species of the genus Vaccinium (Ericaceae) is Vaccinium vitis-idaea L. or Article History: lingonberry. Leaves are included in the State Pharmacopoeia of the Russian Federation (XIV-th Received: 15 February 2020 Accepted: 9 July 2020 edition) and the State Pharmacopoeia of the Republic of Belarus (II-nd edition). The aim of this ePublished: 25 December 2020 review is an analysis of data about a chemical content and types of pharmacological activities of Vaccinium vitis-idaea L. to discuss the tendency of future investigations on this plant. The Keywords: main parts of works describe researches of chemical contents of fruits as medicinal and edible -Phytochemistry -Phytotherapy plant material. The majority of researches describe results of in vitro experiments. A significant -Vaccinium interest is the study of the neuroprotective activity of the Vaccinium vitis-idaea extracts as well -Vaccinium vitis-idaea L as their anti-cytokine and antiapoptotic properties and metabolic effects. The main biologically active compounds are phenologlycosides, tannins, proanthocyanes, saponins etc. These results will be of great significance for the development of new drugs from this plant and use along with the fruits of other parts of the plant. Introduction Some well-known medicinal plants can be interesting plants, worked out by A. L. Takhtajan, the genus for a detailed investigation. These plants are included in Vaccinium has the following systematic positions:3 the State Pharmacopeias of different countries and have phylum - Magnoliophyta, class - Magnoliopsida, subclass a broad medical application, but a study of qualitative - Dilleniidae, superorder - Dillenianae, order - Ericales; and quantitative chemical compositions of the groups family - Ericaceae, subfamily - Vaccinioideae (tribe: of substances other than those responsible for the main Oxydendreae, Vaccinieae, Gaultherieae), tribe Vaccinieae pharmacological effect, as well as the study of new and [genus: Gaylussacia, Vaccinium (including Oxycoccus), not well-known therapeutic effects, is promising and Symphysia, Thibaudia, Satyria, Agapetes (including relevant. Many species of genus Vaccinium L. are known as Pentapterigium), Didonica, Lateropora, Notopora, Utleya, medicinal and edible plants. Gonocalyx, Dimorphanthera, Paphia, Cavendishia, The genus Vaccinium comprises more than 100 species, Orthaea, Macleania, Psammisia, Mycerinus, Polyclita, 11 of them grow among the flora of Russia.1 In a lot of Anthopteropsis, Ceratostema, Semiramisia, Oreanthes, countries, a pharmacopoeia species is Vaccinium vitis- Siphonandra, Pellegrinia, Disterigma, Sphyrospermum, idaea L. According to the data of The Plant List (2019), the Diogenesia, Rusbya, Themistoclesia, Plutarchia, synonyms of Vaccinium vitis-idaea L. are: Myrtillus exigua Demosthenesia, Anthopterus, Costera].3 Bubani., Rhodococcum vitis-idaea Avrorin., Vaccinium The latest version of the Angiosperm Phylogeny Group jesoense Miq., Vitis-idaea punctate Moench., Vitis-idaea (APG) is APG IV (2016). APG uses the clades which punctifolia Gray.2 In different countries, this plant is also include all taxa in the hierarchic sequence and they have named as lingonberry (English), preiselbeere (German), only one match. The family Ericaceae matches the clade airelles (French). Asterids, the order Ericales.4 Vaccinium vitis-idaea L. According to the taxonomy and phylogeny of flowering matches the clade Vaccinium.5 *Corresponding Author: Arnold Alexeevich Shamilov, E-mail: [email protected] ©2020 The Author(s). This is an open access article and applies the Creative Commons Attribution License (http://creativecommons.org/licenses/by- nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. Shamilov et al. According to S. K.Cherepanov’s data1,11 species occur homeopathic remedy.12 Fruits are used to treat diabetes, in the Russian flora, among them 4 species grow in the gastric and intesinal ulcers, liver diseases, periodontosis, Caucasus, 4 – in the European part of Russia, 4 – in West hypertension, eczema, dermatophytosis, diathesis, Siberia, 10 – in the Russian Fast East. respiratory infections, gastric and skin cancers, eye V. vitis-idaea L. is an evergreen subshrub with a height diseases, rheumatism, neurasthenia.12,13 of 2.5-25 cm. It has round whitish hairy stems and coriaceus, obovate to elliptic leaves. Their tops are flat or Chemical Composition daedalous, finely toothed or smooth-margin. The leaves In different aerial parts of Vaccinium vitis-idaea L., are induplicate, 5-27 mm long and 3-12 mm wide, on a phenologlycosides, phenylpropanoids, anthocyanes, short pubescent petiole 0.5-3 mm long. The leave upper saponins have been found out by researches from different surface is dark green; the lower surface is pale green, waxy countries; and in fruits, the content of anthocyanes has with deep-brown scattered glandular dots. Flowers have been established. short reddish pubescent peduncles; at the ends of last- year’s branches there are inflorescences in racemes, in Phenols, phenologlycosides, coumarins short, but thick drooping clusters of 2-8 with a faint but Munich scientists Friedrich and Schoenert14 collected pleasant smell. Calyxes are quadridentate with four short Vaccinium vitis-idaea L. fruits and leaves from April to rounded reddish notches, 0.75-1.25 mm long and 0.75-1 August. Aqueous and methanol extracts were prepared mm wide. Corolla is bell-shaped, pale pink, 4-6.5 mm long. from fruits and leaves and then analyzed by thin-layer It has four petals. There are 8 stamens with pilose anther chromatography (TLC) and column chromatography filaments. Fruits are globose berries carmine incolor when (CC). It turned out impossible to isolate hydroquinone- ripe. Fruits are edible. V. vitis-idaea L.’s main bloom time is β-D-glucopyranoside (arbutin) and hydroquinone using early summer and late spring (June-July). Its ripening time either polyamide or silica gel. The presence of these is September.6 compounds was established by TLC after post processing Plants with larger leaves (10-30 mm long) occur in Europe of the chromatogram with diazotized sulfanilic acid and and Asia. This variety is namedV. vitis-idaea var. vitis- saturated sodium carbonate solution. The investigation idaea L., V. vitis-idaea subsp. vitis-idaea or cowberry. In the resulted in the conclusion that Vaccinium vitis-idaea L. North America, lingonberry or V. vitis-idaea var. minus leaves contain arbutin and hydroquinone. The optimal Lodd. (V. vitis-idaea subsp. minus (Lodd.) Hultén), has period of harvesting is August. The authors also claim that leaves 5–18 mm long.7 Vaccinium vitis-idaea L. can hybridize with other species of the Vaccinium genus and form intermediate hybrid forms. Use in Traditional Medicine In 1979 Swiss scientists Sticher et al.15 developed methods Fruits of lingonberry are used as medicinal and edible of phenolic analysis using high-performance liquid plant materials. Fruits are used in jams, juices, vines, pies.8 chromatography (HPLC). In Vaccinium vitis-idaea L. Other plant parts are also used in medicine. leaves they detected 3-5% of arbutin and 0.14-0.20% of Vaccinium vitis-idaeae L. was included in the first Russian hydroquinone. It was established that if the amount of Pharmacopoeia.9 Leaves are included in the Russian State hydroquinone increased, the amount of arbutin decreased. Pharmacopoeia (XIVth edition). At the pharmaceutical Neither methylarbutin nor hydroquinonemonomethyl marker there is “Brusniver”, a polyherbal drug. It includes were detected in the leaves. Vaccinium vitis-idaea L. leaves (50%), herbs of Hypericum In 2005-2006 Pyka et al.16 collected Vaccinium vitis-idaea perforatum L. and Bidens tripartita L. (20% and 10%, L. leaves which are a pharmacopoeia plant material in respectively), fruits of Rosa spp. L. (10%). The data on Poland. The leaves were air-dried. A spectrodensitometric clinical trials of this complex drug are insufficient. Usually, method for the determination of arbutin was worked out it is used as infusion for treatment of diseases of the by the scientists. The aqueous-methanol extract (1:1, v/v) genitourinary system, cystitis, genitourinary