Document Type : Original Article


Dipartimento di Chimica: Università di Roma “La Sapienza”, Piazzale Aldo Moro, 5 - 00185 Rome (Italy)


The results of the phytochemical analysis of a Hypericum richeri Vill. accession collected from a population living in Appennines, Central Italy, are reported in this paper. The secondary metabolites pattern resulted mainly composed of flavonoids as both aglycones and in glycosidic form, such as quercetin (2), quercetin-3-O-methyl ether (3), 5,7,3′,5′-tetrahydroxyflavanone (8), isorhamnetin glucoside (7), isoquercitrin (9), hyperoside (10), quercitrin (11) and myricetin-3-O-rutinoside (12). It was also observed the presence of the naphtodianthrones hypericin (5) and pseudohypericin (6) together with organic acids (benzoic acid (4)), a glycolipid (2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-β-D-galactopyranosyl glycerol (1) and the saccharides glucose (13), galactose (14) and sucrose (15). Among these constituents, compounds (1) and (3) have been identified in H. richeri Vill. for the first time during this study. The other difference in composition observed in the present study in respect to population from different regions is the absence of hyperforin and caffeoylquinic derivatives. The observed chemovariability, already reported in H. perforatum L., might be derived from the environmental characteristic of the collection site. The chemotaxonomic aspects, together with the pharmacologic relevance in traditional medicine of the isolated compounds were also discussed.

Graphical Abstract

Secondary metabolites of Hypericum richeri Vill. collected in Central Italy: chemotaxonomy and ethnomedicinal relevance


Aeschimann, D., Lauber, K., Moser, D.M., Theurillat, J.P., 2004. Flora Alpina: ein Atlas sämtlicher 4500 Gefässpflanzen der Alpen, Vol. 1, p. 400.
Ahmed, F.A., Ela, I.M.A., Khamis, W., Desoukey, S.Y., 2011. Flavonoids of Neotorularia aculeolata plant. J. Pharm. Nutr. Sci. 1(2), 134-139.
Allen, D.A., Hatfield, G., 2004. Medicinal Plants in Folk Tradition. An Ethnobotany of Britain and Ireland. Portland, OR: Timber Press, Inc.
Atzei, A.D., 2003. Le piante nella tradizione popolare della Sardegna, First ed. Delfino C. Sassari.
Bartolucci, F., Peruzzi, L., Galasso, G., Albano, A., Alessandrini, A., Ardenghi, N.M.G., Astuti, G., Bacchetta, G., Ballelli, S., Banfi, E., Barberis, G., Bernardo, L., Bouvet, D., Bovio, M., Cecchi, L., Di Pietro, R., Domina, G., Fascetti, S., Fenu, G., Festi, F., Foggi, B., Gallo, L., Gottschlich, G., Gubellini, L., Iamonico, D., Iberite, M., Jiménez-Mejías, P., Lattanzi, E., Marchetti, D., Martinetto, E., Masin, R.R., Medagli, P., Passalacqua, N.G., Peccenini, S., Pennesi, R., Pierini, B., Poldini, L., Prosser, F., Raimondo, F.M., Roma-Marzio, F., Rosati, L., Santangelo, A., Scoppola, A., Scortegagna, S., Selvaggi, A., Selvi, F., Soldano, A., Stinca, A., Wagensommer, R.P., Wilhalm, T., Conti, F., 2018. An updated checklist of the vascular flora native to Italy. Plant Biosyst. 152(2), 179-303.
Bianco, A., Serrilli, A. M., Venditti, A., Petitto, V., Serafini, M., 2016. Endemic plants of Italy and their peculiar molecular pattern. In Studies in Natural Products Chemistry (Vol. 50, pp. 215-247). Elsevier.
Camilo, C.J., Alves Nonato, C.d.F., Galvão-Rodrigues, F.F., Costa, W.D., Clemente, G.G., Sobreira Macedo, M.A.C., Galvão Rodrigues, F.F., da Costa, J.G.M., 2017. Acaricidal activity of essential oils: a review. Trends Phytochem. Res. 1(4), 183-198.
Caprioli, G., Alunno, A., Beghelli, D., Bianco, A., Bramucci, M., Frezza, C., Iannarelli, R., Papa, F., Quassinti, L., Sagratini, G., Tirillini, B., Venditti, A., Vittori, S., Maggi, F., 2016. Polar constituents and biological activity of the berry-like fruits from Hypericum androsaemum L. Front. Plant Sci. 7(232), 1-12.
Douros, A., Hadjipavlou-Litina, D., Nikolaou, K., Skaltsa, H., 2017. The occurrence of flavonoids and related compounds in Cedrus brevifolia A. Henry ex Elwes & A. Henry needles. Inhibitory potencies on lipoxygenase, linoleic acid lipid peroxidation and antioxidant activity. Plants 7(1), 1.
Esposito, F., Sanna, C., Del Vecchio, C., Cannas, V., Venditti, A., Corona, A., Bianco, A., Serrilli, A.M., Guarcini, L., Parolin, C., Ballero, M., 2013. Hypericum hircinum L. components as new single-molecule inhibitors of both HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities. Pathog. Dis. 68(3), 116-124.
Estork, D.M., Gusmão, D.F., Paciencia, M.L., Díaz, I.E., Varella, A.D., Younes, R.N., Reis, L.F., Montero, E.F., Bernardi, M.M., Suffredini, I.B., 2014. First chemical evaluation and toxicity of Casinga-cheirosa to Balb-c male mice. Molecules 19(4), 3973-3987.
Ferretti, G., Maggi, F., Tirillini, B., 2005. Essential oil composition of Hypericum richeri Vill. from Italy. Flav. Fragr. J.20(3), 295-298.
Fleming, T., 2000. PDR for Herbal Medicines, New Jersey: Medical Economics Company.
Flores-Bocanegra, L., Pérez-Vásquez, A., Torres-Piedra, M., Bye, R., Linares, E., Mata, R., 2015. α-Glucosidase inhibitors from Vauquelinia corymbosa. Molecules 20(8), 15330-15342.
Franklin, G., Beerhues, L., Čellárová, E., 2016. Molecular and biotechnological advancements in Hypericum species. Front. Plant Sci. 7, 1687.
Frezza, C., Venditti, A., Sciubba, F., Tomai, P., Antonetti, M., Franceschin, M., Di Cocco, M.E., Gentili, A., Delfini, M., Serafini, M., Bianco, A., 2018. Phytochemical profile of Euphorbia peplus L. collected in Central Italy and NMR semi-quantitative analysis of the diterpenoid fraction. J. Pharm. Biomed. Anal. 160, 152-159.
Kitanov, G.M., 2001. Hypericin and pseudohypericin in some Hypericum species. Biochem. Syst. Ecol. 29, 171-178.
Krenn, L., Miron, A., Pemp, E., Petr, U., Kopp, B., 2003. Flavonoids from Achillea nobilis L. Zeitschrift für Naturforschung C 58(1-2), 11-16.
Maffi, L., Benvenuti, S., Fornasiero, R.B., Bianchi, A., Melegari, M., 2001. Inter‐population variability of secondary metabolites in Hypericum spp. (Hypericaceae) of the Northern Apennines, Italy. Nord. J. Bot. 21(6), 585-593.
Maggi, F., Cecchini, C., Cresci, A., Coman, M.M., Tirillini, B., Sagratini, G., Papa, F., Vittori, S., 2010. Chemical composition and antimicrobial activity of the essential oils from several Hypericum taxa (Guttiferae) growing in central Italy (Appennino Umbro‐Marchigiano). Chem. Biodivers. 7(2), 447-466.
Maggi, F., Papa, F., Giuliani, C., Maleci Bini, L., Venditti, A., Bianco, A., Nicoletti, M., Iannarelli, R., Caprioli, G., Sagratini, G., Cortese, M., 2015. Essential oil chemotypification and secretory structures of the neglected vegetable Smyrnium olusatrum L. (Apiaceae) growing in central Italy. Flav. Fragr. J. 30(2), 139-159.
Mandrone, M., Lorenzi, B., Venditti, A., Guarcini, L., Bianco, A., Sanna, C., Ballero, M., Poli, F., Antognoni, F., 2015. Antioxidant and anti-collagenase activity of Hypericum hircinum L. Ind. Crops Prod. 76, 402-408.
Martorati A. 2005. "Hypericum richeri Vill. {ID 4138} - Erba di San Giovanni di Belleval". In Acta Plantarum, Forum. Available on line:
Medina, J.H., Pena, C., Levi M., Wolftnan, C., Paladini, A.C., 1989. Benzodiazepine-like molecules as well as other ligands for the brain benzodiazepine receptor are relatively common constituents of plantas. Biochem. Biophys. Res. Comm. 165, 547-553.
Medina, J.H., Viola, H., Wolfman, C., Marder, M., Wasowski, C., Calvo, D., Paladini, A.C., 1997. Overview-flavonoids: a new family of benzodiazepine receptor ligands. Neurochem. Res. 22(4), 419-425.
Mohammadhosseini, M., 2017. The ethnobotanical, phytochemical and pharmacological properties and medicinal applications of essential oils and extracts of different Ziziphora species. Ind. Crops Prod. 105, 164-192.
Mohammadhosseini, M., Sarker, S.D., Akbarzadeh, A., 2017. Chemical composition of the essential oils and extracts of Achillea species and their biological activities: A review. J. Ethnopharmacol. 199, 257-315.
Olennikov, D.N., Kashchenko, N.I., Chirikova, N.K., Akobirshoeva, A., Zilfikarov, I.N., Vennos, C., 2017. Isorhamnetin and quercetin derivatives as anti-acetylcholinesterase principles of marigold (Calendula officinalis) flowers and preparations. Int. J. Mol. Sci. 18(8), 1685, 1-17.
Ornano, L., Feroci, M., Guarcini, L., Venditti, A., Bianco, A., 2018. Anti-HIV agents from nature: Natural compounds from Hypericum hircinum and carbocyclic nucleosides from iridoids. Stud. Nat. Prod. Chem. 56, 173-228.
Pieroni, A., Quave, C.L., Santoro, R.F., 2004. Folk pharmaceutical knowledge in the territory of the Dolomiti Lucane, inland southern Italy. J. Ethnopharmacol. 95, 373-384.
Pignatti S, 1982. Flora d’Italia. Edagricole, Bologna, Vol. 1, p. 348.
Phillips, R. 1977. Wild Flowers of Britain. London, UK: Pan Books.
Prasain, J.K., Rajbhandari, R., Keeton, A.B., Piazza, G.A., Barnes, S., 2016. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells. Food Funct. 7(9), 4012-4019.
Radanovic, D., Nastovski, T., Menkovic, N., 2006. Kantarion (Hypericum perforatum L.) i druge vrste roda Hypericum. Belgrade: Institute for Medicinal Plant Research ‘Dr. Josif Pancic’.
Ragab, E.A., 2015. Highly methoxylated flavonoids and the anti-eczematous activity of Rhamnus disperma roots. J. Pharmacogn. Phytochem. 4(3), 1-8.
Robson, N.K.B., Strid, A., 1986. Hypericum L. In: Strid, A. (Ed.), Mountain Flora of Greece, Vol. 1 Cambridge University Press, Cambridge, pp. 594e608.
Sciubba, F., Di Cocco, M.E., Gianferri, R., Impellizzeri, D., Mannina, L., De Salvador, F.R., Venditti, A., Delfini. M., 2014. Metabolic profile of different Italian cultivars of hazelnut (Corylus avellana) by nuclear magnetic resonance spectroscopy. Nat. Prod. Res. 28(14), 1075-1081.
Smelcerovic, A., Spiteller, M., 2006. Phytochemical analysis of nine Hypericum L. species from Serbia and the F.Y.R. Macedonia. Pharmazie 61, 251-252.
Smelcerovic, A., Spiteller, M., Ligon, A.P., Smelcerovic, Z., Raabe, N., 2007. Essential oil composition of Hypericum L. species from Southeastern Serbia and their chemotaxonomy. Biochem. Syst. Ecol. 35(2), 99-113.
Stojanovic, G., Dordevic, A., Smelcerovic, A., 2013. Do other Hypericum species have medical potential as st. john's wort (Hypericum perforatum)? Curr. Med. Chem. 20(18), 2273-2295.
Toniolo, C., Nicoletti, M., Maggi, F., Venditti, A., 2013. HPTLC determination of chemical composition variability in raw materials used in botanicals. Nat. Prod. Res. 28(2), 119-126.
Valentão, P., Fernandes, E., Carvalho, F., Andrade, P.B., Seabra, R.M., Bastos, M.D.L. 2002. Antioxidant activity of Hypericum androsaemum infusion: scavenging activity against superoxide radical, hydroxyl radical and hypochlorous acid. Biol. Pharm. Bull. 25, 1320-1323. doi:10.1248/bpb.25.1320
Venditti, A., Bianco, A., Nicoletti, M., Quassinti, L., Bramucci, M., Lupidi, G., Vitali, L.A., Papa, F., Vittori, S., Petrelli, D., Maleci Bini L., Giuliani, C., Maggi, F., 2014. Characterization of secondary metabolites, biological activity and glandular trichomes of Stachys tymphaea Hausskn. from the Monti Sibillini National Park (Central Apennines, Italy). Chem Biodivers. 11(2), 245-261.
Venditti, A., Ballero, M., Serafini, M., Bianco, A., 2015a. Polar compounds from Parentucellia viscosa (L.) Caruel from Sardinia. Nat. Prod. Res. 29(7), 602-606.
Venditti, A., Bianco, A., Quassinti, L., Bramucci, M., Lupidi, G., Damiano, S., Papa, F., Vittori, S., Maleci Bini, L., Giuliani, C., Lucarini, D., 2015b. Phytochemical analysis, biological activity, and secretory structures of Stachys annua (L.) L. subsp. annua (Lamiaceae) from Central Italy. Chem. Biodiv. 12(8), 1172-1183.
Venditti, A., Frezza, C., Gatto Agostinelli, V., Di Cecco, M., Ciaschetti, G., Serafini, M., Bianco, A. 2016a. Study on the molecular composition of an indigenous Italian species: Coristospermum cuneifolium (Guss.) Bertol. Int. J. Indig. Med. Pl. 48(2), 1930-1938.
Venditti, A., Frezza, C., Maggi, F., Lupidi, G., Bramucci, M., Quassinti, L., Giuliani, C., Cianfaglione, K., Papa, F., Serafini, M., Bianco, A., 2016b. Phytochemistry, micromorphology and bioactivities of Ajuga chamaepitys (L.) Schreb. (Lamiaceae: Ajugoideae): two new harpagide derivatives and an unusual iridoid glycosides pattern. Fitoterapia 113, 35-43.
Venditti, A., Lattanzi, C., Ornano, L., Maggi, F., Sanna, C., Ballero, M., Alvino, A., Serafini, M., Bianco, A., 2016c. A new glucosidic phthalide from Helichrysum microphyllum subsp. tyrrhenicum from La Maddalena Island (Sardinia, Italy). Nat. Prod. Res. 30(7), 789-795.
Venditti, A., Frezza, C., Rossi, G., Di Cecco, M., Ciaschetti, G., Serafini, M., Bianco, A., 2016d. Secondary metabolites with ecologic and medicinal implications in Anthemis cretica subsp. petraea from Majella National Park. AIMS Mol. Sci. 3(4), 648-660.
Venditti, A., Frezza, C., Sciubba, F., Foddai, S., Serafini, M., Bianco, A., 2017a. Terpenoids and more polar compounds from the male cones of Wollemia nobilis. Chem. Biodiv. 14(3), e1600332.
Venditti, A., Frezza, C., Trancanella, E., Zadeh, S. M. M., Foddai, S., Sciubba, F., Delfini, M., Serafini, M., Bianco, A., 2017b. A new natural neo-clerodane from Teucrium polium L. collected in Northern Iran. Ind. Crops Prod. 97, 632-638. DOI: 10.1016/j.indcrop.2017.01.010
Venditti, A., Frezza, C., Foddai, S., Serafini, M., Nicoletti, M., Bianco, A., 2017c. Chemical traits of hemiparasitism in Odontites luteus. Chem Biodiv. 14(4), e1600416.
Venditti, A., Frezza, C., Campanelli, C., Foddai, S., Bianco, A., Serafini, M., 2017d. Phytochemical analysis of the ethanolic extract of Agathis robusta (C. Moore ex F. Muell.) FM Bailey. Nat. Prod. Res. 31(14), 1604-1611.
Venditti, A., Frezza, C., Rai, R., Sciubba, F., Di Cecco, M., Ciaschetti, G., Serafini, M., Bianco, A., 2017e. Isoflavones and other compounds from the roots of Iris marsica I. Ricci E Colas. collected from Majella National Park, Italy. Med. Chem. (Los Angeles), 7, 787-794.
Venditti, A., Frezza, C., Celona, D., Sciubba, F., Foddai, S., Delfini, M., Serafini, M., Bianco, A., 2017f. Phytochemical comparison with quantitative analysis between two flower phenotypes of Mentha aquatica L.: pink-violet and white. AIM S Mol. Sci. 4(3), 288-300.
Venditti, A., Frezza, C., Sciubba, F., Serafini, M., Bianco, A., 2017g. Primary and secondary metabolites of an European edible mushroom and its nutraceutical value: Suillus bellinii (Inzenga) Kuntze. Nat. Prod. Res. 31(16), 1910-1919.
Venditti, A., Ukwueze, S.E., 2017h. A possible glycosidic benzophenone with full substitution on B-ring from Psidium guajava leaves. Nat. Prod. Res. 31(7), 739-741.
Venditti, A., Frezza, C., Bianco, A., Serafini, M., Cianfaglione, K., Nagy, D.U., Iannarelli, R., Caprioli, G., Maggi, F., 2017j. Polar constituents, essential oil and antioxidant activity of Marsh Woundwort (Stachys palustris L.). Chem. Biodiv. 14, 1-8.
Venditti, A., Frezza, C., Serafini, I., Pulone, S., Scardelletti, G., Sciubba, F., Bianco, A., Serafini, M., 2018a. Chemical profiling of the fruits of Styrax officinalis L. from Monti Lucretili (Latium region, Central Italy): Chemotaxonomy and nutraceutical potential. Trends Phytochem. Res. 2(1), 1-12.
Wolfender, J.L., Verotta, L., Belvisi, L., Fuzzati, N., Hostettmann, K., 2003. Structural investigations of isomeric oxidised forms of hyperforin by HPLC‐NMR and HPLC‐MSn. Phytochem. Anal. Int. J. Plant Chem. Biochem. Tech. 14(5), 290-297.
Yazaki, K., Okada, T., 1994. Medicinal and Aromatic Plants VI. In: Bajaj, Y.P.S. (Ed.), Biotechnology in Agriculture and Forestry, Vol. 26. Springer-Verlag, Berlin, pp. 167-178.
Zdunić, G., Godevac, D., Milenković, M., Savikin, K., Menković, N., Petrović, S., 2010. Anti-inflammatory and gastroprotective properties of Hypericum richeri oil extracts. Nat. Prod. Res. 5(8), 1215-1218.
Zdunić, G., Gođevac, D., Šavikin, K., Novaković, M., Milosavljević, S., Petrović, S., 2011. Isolation and identification of phenolic compounds from Hypericum richeri Vill. and their antioxidant capacity. Nat. Prod. Res. 25(3), 175-187.
Zdunic, G., Godjevac, D., Savikin, K., Petrovic, S. 2017. Comparative analysis of phenolic compounds in seven Hypericum species and their antioxidant properties. Nat. Prod. Commun. 12(11), 1805-1811.
Zou, L., Chen, S., Li, L., Wu, T., 2017. The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. Exp. Toxicol. Pathol. 69(7), 451-460.