Ethnobotanical Study and Phytochemical Profiling of Traditionally Used Medicinal Plants of Armenia and Georgia: Symphytum caucasicum M. Bieb. (Boraginaceae) and Cyclamen coum Mill. (Primulaceae)
DOI:
https://doi.org/10.56580/GEOMEDI71Keywords:
Symphytum caucasicum M. Bieb., Cyclamen coum Mill., Armenia, Georgia, medicinal plants, alkaloids, saponins and phenolic compoundsAbstract
A variety of climate zones and unique relief make the Caucasus a hotspot, characterized by the highest biological diversity of any area with temperate forests worldwide. The Caucasus hotspot shelters 6350 species of vascular plants, at least 25% of which are unique to the region. For centuries, many Caucasian plants have been used in traditional medicine. Interestingly, in different countries, the same plant could have different applications in traditional medicine. In this study, we considered botanical characteristics, distribution, biochemical composition and use in traditional medicine of Symphytum caucasicum M. Bieb. and Cyclamen coum Mill., medicinal plants used in the traditional medicine of Armenia and Georgia. The review demonstrates that Caucasian medicinal plants Symphytum caucasicum M. Bieb. and Cyclamen coum Mill. are an important source of alkaloids, saponins and phenolic compounds. The review demonstrates the benefits of using Symphytum caucasicum M. Bieb. and Cyclamen coum Mill. for the treatment of different disorders, indicates different applications of these plants in traditional Armenian and Georgian medicine and offers information to produce safe plant-based medications.
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Abdaladze O, Batsatsashvili K, Körner C, Nakhutsrishvili G, Spehn E, eds. Plant Diversity in the Central Great Caucasus: A quantitative assessment. 1st ed. Springer International Publishing: Imprint: Springer; 2017: 170. doi:10.1007/978-3-319-55777-9
Pirtskhalava M, Mittova V, Tsetskhladze ZR, Palumbo R, Pastore R, Roviello GN. Georgian medicinal plants as rich natural sources of antioxidant derivatives: a review on the current knowledge and future perspectives. CMC. 2024; 31. doi: 10.2174/0109298673262575231127034952
Ayvazyan A, Zidorn C. Traditionally used medicinal plants of Armenia. Plants. 2024;13(23):3411. doi:10.3390/plants13233411
Fayvush G, Aleksanyan A, Bussmann RW. Ethnobotany of the Caucasus – Armenia. In: Bussmann RW, ed. Ethnobotany of the Caucasus. European Ethnobotany. Springer International Publishing; 2017:21-36. doi:10.1007/978-3-319-49412-8_18
Manukyan A, Lumlerdkij N, Heinrich M. Caucasian endemic medicinal and nutraceutical plants: in-vitro antioxidant and cytotoxic activities and bioactive compounds. Journal of Pharmacy and Pharmacology. 2019;71(7):1152-1161. doi:10.1111/jphp.13093
Davlianidze M, Gviniashvili T, Mukbaniani M, Jinjolia-Imnadze L, Jugheli T. Nomenclatural checklist of flora of Georgia. Universali; 2018.
Miller JS, McCue K, Consiglio T, Stone J, Eristavi M, Sikharulidze S, Mikatadze-Pantsulaia T, Khutsishvili M. Endemic medicinal plants of Georgia (Caucasus). Missouri Botanical Garden Press; 2005:452.
Roviello GN, Mittova V, Tsetskhladze ZR, Bidzinashvili R, Berdzenishvili M, Vakhania M, Mindiashvili T, Kobiashvili M. Antioxidant properties of some Caucasian medicinal plants. MIMM. 2024;27(1):1-13. doi:10.56580/GEOMEDI44
Fik-Jaskółka M, Mittova V, Motsonelidze C, Vakhania M, Vicidomini C, Roviello GN. Antimicrobial metabolites of Caucasian medicinal plants as alternatives to antibiotics. Antibiotics. 2024; 13 (6): 487. doi: 10.3390/antibiotics13060487
Flora of Georgia. Vol X. Second edition. Metsniereba; 1985: 388 p.
Bokov DO, Krasikova MK, Sergunova ES, Bobkova NV, Kovaleva TYu, Bondar AA, Marakhova AI, Morokhina SL and Moiseev DV. Pharmacognostic, Phytochemical and ethnopharmacological potential of Cyclamen coum Mill. PJ. 2020;12(1):204-212. doi:10.5530/pj.2020.12.31
https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:120758-1.
Bussmann RW, ed. Ethnobotany of the Caucasus. Springer International Publishing; 2017: 6564 p. doi:10.1007/978-3-319-49412-8
https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:700707-1.
Curuk P, Sogut Z, Bozdogan E, Izgu I, Sevindik B, Tagipur EM, Teixeira da Silva JA, Serce S, Solmaz I, Kacar YA, Mendi NYY. Morphological characterization of Cyclamen sp. grown naturally in Turkey: Part I. South African Journal of Botany. 2015; 100:7-15. doi:10.1016/j.sajb.2015.03.199
Kolakovsky AA. Flora of Abkhazia. Vol 3. Metsniereba:292 p.
Trifan A, Wolfram E, Skalicka-Woźniak K, Luca SV. Symphytum genus—from traditional medicine to modern uses: an update on phytochemistry, pharmacological activity, and safety. Phytochem Rev. 2025;24(3):2329-2386. doi:10.1007/s11101-024-09977-1
Grube B, Grünwald J, Krug L, Staiger C. Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial. Phytomedicine. 2007; 14 (1): 2-10. doi: 10.1016/j.phymed.2006.11.006
Veitch NC, Smith M. Herbal Medicines. 4th ed. Pharmaceutical press; 2013: 912 p.
Shengelia Z. The culture of medicinal plants in Georgia. Sabchota Sakartvelo; 1983: 308 p.
Rainer WB, Narel Y PZ, Shalva S, Zaal K, David K. Medicinal and food plants of Svaneti and Lechkhumi, Sakartvelo (Republic of Georgia), Caucasus. Med Aromat Plants. 2016;5(5). doi:10.4172/2167-0412.1000266
Mohammed GJ, Hameed IH, Kamal SA. Anti-inflammatory effects and other uses of Cyclamen species: a review. Ind Jour of Publ Health Rese & Develop. 2018;9(3):206. doi:10.5958/0976-5506.2018.00210.3
Speroni E, Cervellati R, Costa S, Dall'Acqua S, Guerra MC, Panizzolo C, Utan A, Innocenti G. Analgesic and antiinflammatory activity of Cyclamen repandum S. et S. Phytotherapy Research. 2007;21(7):684-689. doi:10.1002/ptr.2145
R. Bidzinashvili, N. Tskhadadze, Kh. Khaikashvil. Medicinal plants of the Tbilisi region. Basiani; 2010: 228 p.
Luca SV, Zengin G, Kulinowski Ł, Sinan KI, Skalicka‐Woźniak K, Trifan A. Phytochemical profiling and bioactivity assessment of underutilized Symphytum species in comparison with Symphytum officinale. J Sci Food Agric. 2024;104(7):3971-3981. doi:10.1002/jsfa.13279
Sharara A, Badran A, Hijazi A, Albahri G, Bechelany M, Mesmar JE, Baydoun E. Comprehensive review of Cyclamen: development, bioactive properties, and therapeutic applications. Pharmaceuticals. 2024;17(7):848. doi:10.3390/ph17070848
Pereira AG, Cassani L, Garcia-Oliveira P, et al. Plant alkaloids: production, extraction, and potential therapeutic properties. In: Carocho M, Heleno SA, Barros L, eds. Natural Secondary Metabolites. Springer International Publishing; 2023: 157-200. doi:10.1007/978-3-031-18587-8_6
Mirifar A, Hemati A, Asgari Lajayer B, Pandey J, Astatkie T. Impact of various environmental factors on the biosynthesis of alkaloids in medicinal plants. In: Aftab T, ed. Environmental challenges and medicinal plants. environmental challenges and solutions. Springer International Publishing; 2022:229-248. doi:10.1007/978-3-030-92050-0_9
Roeder E. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie. 1995; 50(2): 83-98.
Manko I, Melkumova ZV, Malysheva VF. Accumulation of alkaloids in various organs of Symphytum caucasicum. Plant resources. 1972; 4:538-541.
Salehi B, Sharopov F, Boyunegmez Tumer T, Ozleyen A, Rodríguez-Pérez C, Ezzat SM, Azzini E, Hosseinabadi T, Butnariu M, Sarac I, Bostan C, Acharya K, Sen S, Nur Kasapoglu K, Daşkaya-Dikmen C, Özçelik B, Baghalpour N, Sharifi-Rad J, Valere Tsouh Fokou P, Cho WC, Martins N. Symphytum species: a comprehensive review on chemical composition, food applications and phytopharmacology. Molecules. 2019; 24 (12): 2272. doi: 10.3390/molecules24122272
Benamar H, Tomassini L, Venditti A, Marouf A, Bennaceur M, Serafini M, Nicoletti M. Acetylcholinesterase inhibitory activity of pyrrolizidine alkaloids from Echium confusum Coincy. Natural Product Research. 2017; 31 (11): 1277-1285. doi: 10.1080/14786419.2016.1242000
Wang Z, Han H, Wang C, Zheng Q, Chen H, Zhang X, Hou R. Hepatotoxicity of pyrrolizidine alkaloid compound intermedine: comparison with other pyrrolizidine alkaloids and its toxicological mechanism. Toxins. 2021; 13(12): 849. doi: 10.3390/toxins13120849
Schmeller T, El-Shazly A, Wink M. Allelochemical activities of pyrrolizidine alkaloids: interactions with neuroreceptors and acetylcholine-related enzymes. J Chem Ecol. 1997; 23(2): 399-416. doi: 10.1023/B:JOEC.0000006367.51215.88
Reddy J, Harris C, Svoboda D. Inhibition by lasiocarpine of RNA synthesis, RNA polymerase and induction of tryptophan pyrrolase activity. Nature. 1968; 217 (5129): 659-661. doi: 10.1038/217659a0
Yayli N, Baltaci C. A novel glycosidicly linked piperidine alkaloid from Cyclamen coum. Turkish Journal of Chemistry. 1997; 21 (2): 139-143.
Kumar K, Debnath P, Singh S, Kumar N. An overview of plant phenolics and their involvement in abiotic stress tolerance. Stresses. 2023; 3(3): 570-585. doi: 10.3390/stresses3030040
Birková A. Caffeic acid: a brief overview of its presence, metabolism, and bioactivity. Bioactive Compounds in Health and Disease. 2020;3(4):74. doi:10.31989/bchd.v3i4.692
López-Herrador S, Corral-Sarasa J, González-García P, Morillas-Morota Y, Olivieri E, Jiménez-Sánchez L, Díaz-Casado ME. Natural hydroxybenzoic and hydroxycinnamic acids derivatives: mechanisms of action and therapeutic applications. Antioxidants. 2025;14(6):711. doi:10.3390/antiox14060711
Razavi SM, Zahri S, Zarrini G, Nazemiyeh H, Mohammadi S. Biological activity of quercetin-3-O-glucoside, a known plant flavonoid. Russ J Bioorg Chem. 2009;35(3):376-378. doi:10.1134/S1068162009030133
Barbakadze V, Gogilashvili L, Amiranashvili L, Merlani M, Mulkijanyan K. Novel biologically active phenolic polymers from different species of genera Symphytum and Anchusa (Boraginaceae). J Chem Eng Chem Res. 2014;1:47-53.
Barbakadze V, Kemertelidze E, Targamadze I, Mulkijanyan K, Shashkov A, Usov A. Poly[3-(3,4-dihydroxyphenyl)glyceric acid], a new biologically active polymer from Symphytum asperum Lepech. and S. caucasicum Bieb. (Boraginaceae). Molecules. 2005;10(9):1135-1144. doi:10.3390/10091135
Barbakadze VV, Kemertelidze EP, Mulkijanyan KG, van der Berg AJJ, Beukelman CJ, van den Worm E, Quarles van Ufford HC, Usov AI. Antioxidant and anticomplement activity of poly[3-(3,4-dihydroxyphenyl)glyceric acid] from Symphytum asperum and Symphytum caucasicum plants. Pharm Chem J. 2007;41(1):14-16. doi:10.1007/s11094-007-0004-7
Merlani M, Barbakadze V, Amiranashvili L, Gogilashvili L, Yannakopoulou E, Papadopoulos K, Chankvetadze B. Enantioselective synthesis and antioxidant activity of 3‐(3,4‐dihydroxyphenyl)‐glyceric acid—basic monomeric moiety of a biologically active polyether from Symphytum asperum and S. caucasicum. Chirality. 2010;22(8):717-725. doi:10.1002/chir.20823
Barbakadze V, Merlani M, Gogilashvili L, Amiranashvili L, Petrou A, Geronikaki A, Ćirić A, Glamočlija J, Soković M. Antimicrobial activity of catechol-containing biopolymer poly[3-(3,4-dihydroxyphenyl)glyceric acid] from different medicinal plants of Boraginaceae family. Antibiotics. 2023;12(2):285. doi:10.3390/antibiotics12020285
Aydin C, Mammadov R, Davidov M. Biological activities, phenolic constituents and of various extracts of Cyclamen coum tubers and leaves from Turkey. JCPRM. 2023; (1): 255-263. doi: 10.14258/jcprm.20230111262
Roychoudhury S, Sinha B, Choudhury BP, Jha NK, Palit P, Kundu S, Mandal SC, Kolesarova A, Yousef MI, Ruokolainen J, Slama P, Kesari KK. Scavenging properties of plant-derived natural biomolecule para-coumaric acid in the prevention of oxidative stress-induced diseases. Antioxidants. 2021; 10(8): 1205. doi: 10.3390/antiox10081205
Mahomoodally MF, Picot-Allain MCN, Zengin G, Llorent-Martínez EJ, Stefanucci A, Ak G, Senkardes I, Tomczyk M, Mollica A. Chemical profiles and biological potential of tuber extracts from Cyclamen coum Mill. Biocatalysis and Agricultural Biotechnology. 2021; 33: 102008. doi: 10.1016/j.bcab.2021.102008
Zhao YY, Fan Y, Wang M, Cheng JX, Zou Jb, Zhang Xf, Shi Yaj, Guo Dy. Studies on pharmacokinetic properties and absorption mechanism of phloretin: in vivo and in vitro. Biomedicine & Pharmacotherapy. 2020; 132: 110809. doi: 10.1016/j.biopha.2020.110809
Chen L, Li J, Luo C, Liu H, Xu W, Chen G, Liew OW, Zhu W, Puah CM, Shen X, Jiang H. Binding interaction of quercetin-3-β-galactoside and its synthetic derivatives with SARS-CoV 3CLpro: Structure–activity relationship studies reveal salient pharmacophore features. Bioorganic & Medicinal Chemistry. 2006;14(24):8295-8306. doi:10.1016/j.bmc.2006.09.014
Shakeel A, Noor JJ, Jan U, Gul A, Handoo Z, Ashraf N. Saponins, the unexplored secondary metabolites in plant defense: opportunities in integrated pest management. Plants. 2025; 14(6): 861. doi: 10.3390/plants14060861
Iovinella I, Barbieri F, Biazzi E, Sciandra C, Tava A, Mazza G, Marianelli L, Cini A, Roversi PF, Torrini G. Antifeedant and insecticidal effects of alfalfa saponins in the management of the Japanese beetle Popillia japonica. J Applied Entomology. 2023;147(8):651-660. doi:10.1111/jen.13153
Aftab K, Shaheen F, Mohammad FV, Noorwala M, Ahmad VU. Phyto-pharmacology of saponins from Symphytum officinale L. In: Waller GR, Yamasaki K, eds. Saponins used in traditional and modern medicine. Vol 404. Advances in Experimental Medicine and Biology. Springer US; 1996:429-442. doi:10.1007/978-1-4899-1367-8_34
Çaliş İ, Yürüker A, Tanker N, Wright A, Sticher O. Triterpenesaponins from Cyclamen coum var. coum. Planta Med. 1997;63(02):166-170. doi:10.1055/s-2006-957637
Yayli N, Baltaci C, Zengin A, Kuçukislamoglu M, Genc H. A triterpenoid saponin from Cyclamen coum. Phytochemistry. 1998;48(5):881-884. doi:10.1016/S0031-9422(97)00978-3
Yayli N, Baltaci C, Zengin A, Küçükislamoglu M, Genç H, Küçük M. Pentacyclic triterpenoid saponin from Cyclamen coum. Planta Med. 1998;64(04):382-384. doi:10.1055/s-2006-957459
Reznicek G, Jurenitsch J, Robien W, Kubelka W. Saponins in Cyclamen species: configuration of cyclamiretin C and structure of isocyclamin. Phytochemistry. 1989; 28(3): 825-828. doi: 10.1016/0031-9422(89)80123-2
Voutquenne L, Lavaud C, Massiot G, Men-Olivier LL. Structure-activity relationships of haemolytic saponins. Pharmaceutical Biology. 2002; 40 (4): 253-262. doi: 10.1076/phbi.40.4.253.8470
Schwarz PF, Perhal AF, Preglej T, et al. Primulagenin A is a potent inverse agonist of the nuclear receptor RAR-related orphan receptor gamma (RORγ). Preprint posted online April 4, 2025. doi: 10.1101/2025.04.01.646598