Skip to main content
SpringerLink
Log in

Secondary Metabolites of Teucrium Species with Toxic Effects

  • Chapter
  • First Online:
Teucrium Species: Biology and Applications

Abstract

The genus Teucrium L. has a long-term use in folk medicine, however there are some implications for human health related to the consumption of germander-containing products. Numerous cases of hepatotoxicity have been reported, mostly in Europe, where the plants were used as herbal products for weight loss and still are used in folklore medicine to treat hypercholesteraemia and diabetes. During the last decades several cases of germander toxicity including chronic hepatitis as well as acute cytolytic hepatitis and a case of death have been reported. The most well known toxic Teucrium species are Teucrium chamaedrys, T. polium and T. capitatum, the use of which as herbal medicines and dietary supplements should be strictly controlled. The neo-clerodane diterpenoids occurring in Teucrium species have been the subject of intensive studies, since they have been correlated to the toxic effects of the genus. Studies in mice showed that the hepatotoxicicity of the genus is being induced by this type of diterpenes, which are transformed into their reactive metabolites by P450. Teucrin A and teuchamaedrin A have been subjected to numerous studies in order to reveal the mechanism of action. This chapter aims to summarize the diterpenes isolated from Teucrium spp., as well as the hepatotoxicity of some of them.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CEFS:

Council of Europe Committee of Experts on Flavouring Substances

FDA:

Food and Drug Administration

NFG:

Nerve growth factor

PP:

Pyrophosphate

UV:

Ultraviolet

References

  • Ahmad S, Ulllah Abd Elsalam RM, Fouad H, Bibi A, Tariq Jan M, Shad AA, Arfan M (2014) One new royleanumoate from Teucrium royleanum Wall. Ex Benth. Sci World J 2014:581629. https://doi.org/10.1155/2014/581629

    Article  CAS  Google Scholar 

  • Alcazar R, de la Torre MC, Rodríguez B, Bruno M, Piozzi F, Savona G, Arnold NA (1992) Neo-clerodane diterpenoids from three species of Teucrium. Phytochemistry 31:3957–39661

    Article  CAS  Google Scholar 

  • Al-Kubaisy K (2013) Hepatoprotective activity of Teucrium polium against CCl4 induced hepatoxicity in male albino rats. Int J Indig Med Plant 46:1206–1210

    Google Scholar 

  • Al-Yahya MA, El-Feraly FS, Chuck Dunbar D, Muhammad I (2002) Neo-clerodane diterpenoids from Teucrium oliverianum and structure revision of teucrolin E. Phytochemistry 59:409–414

    Article  CAS  PubMed  Google Scholar 

  • Antognoni F, Iannello C, Mandrone M, Scognamiglio M, Fiorentino A, Giovannini PP, Poli F (2012) Elicited Teucrium chamaedrys cell cultures produce high amounts of teucrioside, but not the hepatotoxic neo-clerodane diterpenoids. Phytochemistry 81:50–59

    Article  CAS  PubMed  Google Scholar 

  • Anulika NP, Ignatius EO, Raymond ES, Osasere O, Hilda A (2016) The chemistry of natural product: plant secondary metabolites. Int J Technol Enhanc Emerg Eng Res 4:1–7

    Google Scholar 

  • Aravind S, Balachandran J, Ramanujam Ganesh M, Krishna Kumari GN (2010) Further anti-feedant neo-clerodanes from Teucrium tomentosum. Nat Prod Res 24:7–12

    Article  CAS  PubMed  Google Scholar 

  • Baali N, Belloum Z, Baali S, Chabi B, Pessemesse L, Fouret G, Ameddah S, Benayache F, Benayache S, Feillet-Coudray C, Cabello G, Wrutniak-Cabello C (2016) Protective activity of total polyphenols from Genista quadriflora munby and Teucrium polium geyrii maire in acetaminophen-induced hepatotoxicity in rats. Nutrients 8:193. https://doi.org/10.3390/nu8040193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bedir E, Tasdemira D, Calis I, Zerbeb O, Sticherb O (1999) Neo-clerodane diterpenoids from Teucrium polium. Phytochemistry 51:921–925

    Article  CAS  Google Scholar 

  • Bedir E, Manyam R, Khan IA (2003) Neo-clerodane diterpenoids and phenylethanoid glycosides from Teucrium chamaedrys L. Phytochemistry 63:977–983

    Article  CAS  PubMed  Google Scholar 

  • Berendes J (1902) Des Pedianos Dioskurides aus Anazarbos Arzneimittellehre. In: Sandig M (ed) Ãœbersetzt und Mit Erklärungen Versehen. Enke Verlag (reprint 1970) Wiesbaden

    Google Scholar 

  • Bianco A, Ramunno A, Serrilli AM, Lo Castro M, Ballero M, Serafini M (2004) Phytochemical characters of Teucrium marum from Sardinia: an endemic plant. Nat Prod Res 18:557–564

    Article  CAS  PubMed  Google Scholar 

  • Boneva IM, Malakov PY, Papanov GY (1988) 12-Epiteupolin II, a neo-clerodane diterpenoid from Teucrium lamiifolium. Phytochemistry 27:295–297

    Article  CAS  Google Scholar 

  • Bruno M, Dominguez G, Lourenffo A, Piozzi F, Rodríguez B, Savona G, de la Torre MC, Arnold NA (1991) Neo-clerodane diterpenoids from Teucrium gracile. Phytochemistry 30:3693–3697

    Article  CAS  Google Scholar 

  • Bruno M, Alcázar R, de la Torre MC, Piozzi F, Rodríguez B, Savona G, Perales A, Arnold NA (1992a) Neo- and seco-neo-clerodane diterpenoids from Teucrium gracile and T. Fruticans. Phytochemistry 31(10):3531–3534

    Article  CAS  Google Scholar 

  • Bruno M, Piozzi F, Rodríguez B, Savona G, de la Torre MC, Servettaz O (1992b) Neo-clerodane diterpenes from Teucrium species. Phytochemistry 31(12):4366–4367

    Article  CAS  Google Scholar 

  • Bruneton J (1993) Pharmacognosie, phytochimie, plantes medicinales, 2nd edn. Technique et Documentation-Lavoisier, Paris

    Google Scholar 

  • Bruno M, Piozzi F, Rodríguez B, Savona G, Servettaz O (1985) Ent-clerodane diterpenoids from six further species of Teucrium. Phytochemistry 24:2597–2599

    Article  CAS  Google Scholar 

  • Bruno M, Piozzi F, Savona G, Maria C, Rodríguez B, de la Torre MC, Servettaz O (1987) 2-Deoxychamaedroxide, A neo-clerodane diterpenoid from Teucrium divaricatum. Phytochemistry 26:2859–2861

    Article  CAS  Google Scholar 

  • Bruno M, Piozzi F, Savona G, Maria C, Rodríguez B (1989) Neo-clerodane diterpenoids from Teucrium canadense. Phytochemistry 28:3539–3541

    Article  CAS  Google Scholar 

  • Bruno M, Dominguez G, Lourenffo A, Piozzi F, Rodríguez B, Savona G, de la Torre MC, Arnold NA (1991) Neo-clerodane diterpenoids from Teucrium gracile. Phytochemistry 30:3693–3697

    Article  CAS  Google Scholar 

  • Bruno M, Bondı ML, Rosselli S, Piozzi F, Al-Hillo MRY, Lamara K, Ladjel S (2000) Neoclerodane diterpenoids from Teucrium maghrebinum. J Nat Prod 63:1029–1031

    Article  CAS  PubMed  Google Scholar 

  • Bruno M, Bondì ML, Rosselli S, Maggio A, Piozzi F, Arnold NA (2002) Neoclerodane diterpenoids from Teucrium montbretii subsp. libanoticum and their absolute configuration. J Nat Prod 65:142–146

    Article  CAS  PubMed  Google Scholar 

  • Bruno M, Maggio AM, Piozzi F, Puech S, Rosselli S, Simmonds MSJ (2003) Neoclerodane diterpenoids from Teucrium polium subsp. polium and their antifeedant activity. Biochem Syst Ecol 31:1051–1056

    Article  CAS  Google Scholar 

  • Bruno M, Rosselli S, Maggio A, Piozzi F, Scaglioni L, Arnold NA, Simmonds MSJ (2004) Neoclerodanes from Teucrium orientale. Phytochemisty 31:4366–4367

    Article  Google Scholar 

  • Camps F, Coll J, Dargallo O, Rius J, Miravitlles C (1987) Clerodane diterpenoids from Teucrium and Ajuga plants. Phytochemistry 26:1475–1479

    Article  CAS  Google Scholar 

  • Carnoy A (1959) Dictionnaire étymologique des noms grecs de plantes. In: Bibliothèque du Muséon, vol 46. Publications Universitaires, Louvain

    Google Scholar 

  • Carratù B, Federici E, Gallo FR, Geraci A, Guidotti M, Multari G, Palazzino G, Sanzini E (2010) Plants and parts of plants used in food supplements: an approach to their safety assessment. Ann Ist Super Sanita 46:370–388

    PubMed  Google Scholar 

  • Carreiras MC, Rodríguez B, de la Terre MC, Perales A, Torres MR, Savona G, Piozzi F (1990) Rearranged abietane diterpenoids from the root of Teucrium polium subsp. vincetinum. Tetrahedron 46:847–860

    Article  CAS  Google Scholar 

  • Castro A, Moco S, Coll J, Vervoort J (2010) LC-MS-SPE-NMR for the isolation and characterization of neo-clerodane diterpenoids from Teucrium luteum subsp. flavovirens. J Nat Prod 73:962–965

    Article  CAS  PubMed  Google Scholar 

  • Chitturi S, Farrell GC (2008) Hepatotoxic slimming aids and other herbal hepatotoxins. J Gastroenterol Hepatol 23:366–373

    Article  CAS  PubMed  Google Scholar 

  • Coll J, Tandrón Y (2004) Neo-clerodane diterpenes from Teucrium fruticans. Phytochemistry 65:387–392

    Article  CAS  PubMed  Google Scholar 

  • Coll J, Tandrón Y (2005) Isolation and structure elucidation of three neo-clerodane diterpenes from Teucrium fruticans L. (Labiatae). Phytochemistry 66:2298–2303

    Article  CAS  PubMed  Google Scholar 

  • De Berardinis V, Moulis C, Maurice M, Beaune P, Pessayre D, Pompon D, Loeper J (2000) Human microsomal epoxide hydrolase is the target of germander-induced autoantibodies on the surface of human hepatocytes. Mol Pharmacol 58:542–551

    Article  PubMed  Google Scholar 

  • De Smet PAGM (2002) Herbal Remedies. N Engl J Med 347:2046–2056

    Article  PubMed  Google Scholar 

  • de Torre L, Rodríguez B, Plozzi F, Savona G, Brunot M, Carreiras MC (1990) Neo-clerodane from diterpenoids Teucrium abutiloides. Phytochemistry 29:579–584

    Article  Google Scholar 

  • De Vincenzi M, Maialetti F, Silano M (2003) Constituents of aromatic plants: Teucrin A. Fitoterapia 74:746–749

    Article  PubMed  CAS  Google Scholar 

  • Dewick PM (1999) The biosynthesis of C5–C25 terpenoid compounds. Nat Prod Rep 16:97–130

    Article  CAS  Google Scholar 

  • Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Meta 2:303–336

    CAS  Google Scholar 

  • Djabou N, Lorenzi V, Guinoiseau E, Andreani S, Giuliani MC, Dominguez XA, Merijania NA, Gonzalez BI (1974) Terpenoids from Teucrium cubense. Phytochemistry 13:754–755

    Article  Google Scholar 

  • Dourakis SP, Papanikolaou IS, Tzemanakis EN, Hadziyannis SJ (2002) Acute hepatitis associated with herb (Teucrium capitatum L.) administration. Eur J Gastroenterol Hepatol 14:693–695

    Article  PubMed  Google Scholar 

  • Druckova A, Mernaugh RL, Ham AJL, Marnett LJ (2007) Identification of the protein targets of the reactive metabolite of teucrin A in vivo in the rat. Chem Res Toxicol 20:1393–1408

    Article  CAS  PubMed  Google Scholar 

  • Dominguez XA, Merijanian A, Gonzalez B (1974) Terpenoids of Teucrium cubense. Phytochemistry 13:754–755

    Article  CAS  Google Scholar 

  • Elmastas M, Erenler R, Isnac B, Aksit H, Sen O, Genc N, Demirtas I (2016) Isolation and identification of a new neo-clerodane diterpenoid from Teucrium chamaedrys L. Nat Prod Res 30:299–304

    Article  CAS  PubMed  Google Scholar 

  • Fatima N (2016) A review on Teucrium oliveranum, a plant found abundantly in Saudi Arabia. Sci Int (Lahore) 28:1229–1231

    CAS  Google Scholar 

  • Fau D, Lekehal M, Farrell G, Moreau A, Moulis C, Feldmann G, Haouzi D, Pessayre D (1997) Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes. Gastroenterology 113:1334–1346

    Article  CAS  PubMed  Google Scholar 

  • Fernández P, Rodríguez B, Savona G, Piozz F (1986a) Neo-clerodane diterpenoids from Teucrium polium subsp. capitatum. Phytochemistry 25:181–181

    Article  Google Scholar 

  • Fernández P, Rodríguez B, Villegast JA, Perales A, Savona G, Piozzi F, Bruno M (1986b) Neo-clerodane diterpenoids from Teucrium pyrenaicum and T. subspinosum. Phytochemistry 25:1405–1409

    Article  Google Scholar 

  • Fernandez-Gadea F, Rodríguez B, Savona G, Piozzi F (1984) Isoeriocephalin and 20-deacetyleriocephalin, neoclerodane diterpenoids from Teucrium lanigerum. Phytochemistry 23:1113–1181

    Article  CAS  Google Scholar 

  • Fiorentino A, D’Abrosca B, Ricci A, Pacifico S, Piccolella S, Monaco P (2009) Structure determination of chamaedryosides A-C, threenovel nor-neo-clerodane glucosides from Teucrium chamaedrys, by NMR spectroscopy. Magn Reson Chem 47:1007–1012

    Article  CAS  PubMed  Google Scholar 

  • Fiorentino A, D’Abrosca B, Pacifico S, Scognamiglio M, D’Angelo G, Monaco P (2010) Abeo-Abietanes from Teucrium polium roots as protective factors against oxidative stress. Bioorg Med Chem 18:8530–8536

    Article  CAS  PubMed  Google Scholar 

  • Fiorentino A, D’Abrosca B, Pacifico S, Scognamiglio M, D’Angelo G, Gallicchio M, Chambery A, Monaco P (2011) Structure elucidation and hepatotoxicity evaluation against HepG2 human cells of neo-clerodane diterpenes from Teucrium polium L. Phytochemistry 72:2037–2044

    Article  CAS  PubMed  Google Scholar 

  • Fontana G, Paternostro MP, Savona G, Rodríguez B, de la Torre MC (1998) Neoclerodane diterpenoids from Teucrium massiliense. J Nat Prod 61:1242–1247

    Article  CAS  PubMed  Google Scholar 

  • Forouzandeh H, Azemi ME, Rashidi I, Goudarzi M Kalantari H (2013) Study of the protective effect of Teucrium polium L. extract on acetaminophen-induced hepatotoxicity in mice. Iran J Pharm Res 12:123–129

    PubMed  PubMed Central  Google Scholar 

  • Gács-Baitz E, Radics L, Oganessian GB, Mnatsakanian VA (1978) Teucrins H1-H4, novel clerodane-type diterpenes from Teucrium hyrcanicum. Phytochemistry 17:1967–1973

    Article  Google Scholar 

  • Gao C, Han L, Zheng D, Jin H, Gai C, Wang J, Zhang H, Zhang L, Fu H (2015) Dimeric abietane diterpenoids and sesquiterpenoid lactones from Teucrium viscidum. J Nat Prod 78:630–638

    Article  CAS  PubMed  Google Scholar 

  • Gaspar H, Palma F, De la Torre M, Rodríguez B, Perales A (1995) A rearranged homo-neo-clerodane diterpenoid from Teucrium betonicum. Tetrahedron 51:2363–2368

    Article  CAS  Google Scholar 

  • Gori L, Galluzzi P, Mascherini V, Gallo E, Lapi F, Menniti-Ippolito F, Raschetti R, Mugelli A, Vannacci A, Firenzuoli F (2011) Two contemporary cases of hepatitis associated with Teucrium chamaedrys L. decoction use. Case reports and review of literature. Basic Clin Pharmacol Toxicol 109:521–526

    Article  CAS  PubMed  Google Scholar 

  • Greuter W, Burdet HM, Long G (1986) Med-Checklist Conservatoire et Jardin Botanique de la Ville de Genève. Genéve 3:366–380

    Google Scholar 

  • Hao X, Zhang Z, Zhan G, Xue Y, Luo Z, Yao G, Zhang Y (2013) Chemical constituents from Teucrium viscidum. Biochem Syst Ecol 51:78–82

    Article  CAS  Google Scholar 

  • Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M (2010) A systematic review of the efficacy and safety of Teucrium species; from anti-oxidant to anti-diabetic effects. Int J Pharmacol 6:315–325

    Article  Google Scholar 

  • Jakupovic J, Baruah RN, Bohlmann F, Quack W (1985) New clerodane derivatives from Teucrium scordium. Planta Med 51:341–342

    Article  CAS  PubMed  Google Scholar 

  • Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4:27–30

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kisiel W, Piozzi F, Grzybek J (1995) Terpenoids from Teucrium montanus subsp. pannonicum. Planta Med 61:191–192

    Article  CAS  PubMed  Google Scholar 

  • Kouzi SA, McMurtry RJ, Nelson SD (1994) Hepatotoxicity of germander (Teucrium chamaedrys L.) and one of its constituent neoclerodane diterpenes Teucrin A in the mouse. Chem Res Toxicol 7:850–856

    Article  CAS  PubMed  Google Scholar 

  • Kumari GNK, Aravind S, Balachandran J, Ganesh MR, Soundarya Devi S, Rajan SS, Malathi R, Ravikumar K (2003) Antifeedant neo-clerodanes from Teucrium tomentosum Heyne. (Labiatae). Phytochemistry 64:1119–1123

    Article  CAS  Google Scholar 

  • Labbe C, Polanco MI, Castillo M (1989) 12-Epi-Teuscordonin and other neoclerodanes from Teucrium bicolor. J Nat Prod 52:871–874

    Article  CAS  PubMed  Google Scholar 

  • Ladjel S, Laamara K, Al-Hillo MRY, Pays M (1994) Neo-clerodane diterpenoids from Teucrium polium ssp. aurasianum. Phytochemistry 37:1663–1666

    Article  CAS  Google Scholar 

  • Laliberté L, Villeneuve JP (1996) Hepatitis after the use of germander, a herbal remedy. Can Med Assoc J 154:1689–1692

    Google Scholar 

  • Larrey D, Faure S (2011) Herbal medicine hepatotoxicity: a new step with development of specific biomarkers. J Hepatol 54:599–601

    Article  PubMed  Google Scholar 

  • Larrey D, Vial T, Pauwels A, Castot A, Biour M, David M, Michel H (1992) Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann Intern Med 117:129–132

    Article  CAS  PubMed  Google Scholar 

  • Lekehal M, Pessayre D, Lereau JM, Moulis C, Fourasté I, Fau D (1996) Hepatotoxicity of the herbal medicine germander: metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton- associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology 24:212–218

    Article  CAS  PubMed  Google Scholar 

  • Li R, Morris-Natschkeb SK, Lee KH (2016) Clerodane diterpenes: sources, structures, and biological activities. Nat Prod Rep 33:1166–1226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loeper J, Descatoire V, Letteron P, Moulis C, Degott C, Dansette P, Fau D, Pessayre D (1994) Hepatotoxicity of germander in mice. Gastroenterology 106:464–472

    Article  CAS  PubMed  Google Scholar 

  • Lv H, Luo J, Zhu M, Shan S, Kong L (2014) Teucrisins A–E, five new neo-Clerodane diterpenes from Teucrium viscidum. Chem Pharm Bull 62:472–476

    Article  CAS  Google Scholar 

  • Lv HW, Luo JG, Zhu MD, Zhao HJ, Kong LY (2015) Neo-Clerodane diterpenoids from the aerial parts of Teucrium fruticans cultivated in China. Phytochemistry 119:26–31

    Article  CAS  PubMed  Google Scholar 

  • Mac Milan J, Beale ME (1999) Diterpene biosynthesis. In: Barton SD, Nakanishi K, Meth-Cohn (eds) Isoprenoids including cartenoids and steroids. Comprehensive natural products chemistry, vol 2. Elsevier, Amsterdam, pp 217–243

    Chapter  Google Scholar 

  • Malakov PY, Papanov GY (1983) Furanoid diterpenes from Teucrium polium. Phytochemistry 22:2791–2793

    Article  CAS  Google Scholar 

  • Malakov PY, Papanov GY, Ziesche J (1982) Teupolin III, a furanoid diterpene from Teucrium polium. Phytochemistry 21:2597–2598

    Article  CAS  Google Scholar 

  • Malakov PY, Papanov GY, Boneva IM (1992) Neo-clerodane diterpenoids from Teucrium montanum. Phytochemistry 31:4029–4030

    Article  CAS  Google Scholar 

  • Malakov PY, Papanov GY, Boneva IM, de la Torre MC, Rodríguez B (1993) Teulamioside, a neo-clerodane glucoside from Teucrium lamiifolium. Phytochemistry 34:1095–1098

    Article  CAS  Google Scholar 

  • Marquez C, Rabanal RM, Valverde S, Eguren L, Perales A, Fayos J (1981) Diterpenes from Teucrium capitatum L. x-ray crystal and molecular structure of lolin. Tetrahedron Lett 22:2823–2826

    Article  CAS  Google Scholar 

  • Mattéi A, Rucay P, Samuel D, Feray C, Reynes M, Bismuth H (1995) Liver transplantation for severe acute liver failure after herbal medicine (Teucrium polium) administration. J Hepatol 22:597. https://doi.org/10.1016/0168-8278(95)80458-7

    Article  PubMed  Google Scholar 

  • Mazokopakis E, Lazaridou S, Tzardi M, Mixaki J, Diamantis I, Ganotakis E (2004) Acute cholestatic hepatitis caused by Teucrium polium L. Phytomedicine 11:83–84

    Article  CAS  PubMed  Google Scholar 

  • Mehdinia Z, Eftekhar-Vaghefi R, Mehrabani M, Nabipoor F, Mehdinia N, nematolahi Mahani N (2013) The effect of petroleum ether fraction of Teucrium polium extract on laboratory mouse liver. J Kerman Univ Med Sci 20:279–291

    Google Scholar 

  • Merritt AT, Ley SV (1992) Clerodane diterpenoids. Nat Prod Rep 9:243–287

    Article  CAS  PubMed  Google Scholar 

  • Mostefa-Kara N, Pauwels A, Pines A, Biour M, Levy VG (1992) Fatal hepatitis after herbal tea. Lancet 340:674. https://doi.org/10.1016/0140-6736(92)92209-X

    Article  CAS  PubMed  Google Scholar 

  • Nasri Hamid Shirzad H (2013) Toxicity and safety of medicinal plants. J HerbMed Pharmacol 2:21–22

    Google Scholar 

  • Nencini C, Galluzzi P, Pippi F, Menchiari A, Micheli L (2014) Hepatotoxicity of Teucrium chamaedrys L. decoction: role of difference in the harvesting area and preparation method. Indian J Pharm 46:181–184

    Article  Google Scholar 

  • Node M, Sai M, Fujita E (1981) Isolation of the diterpenoid teuflin (6-epiteucvin) from Teucrium viscidum var. miquelianum. Phytochemistry 20:757–760

    Article  CAS  Google Scholar 

  • Nur-e-Alam M, Kanthasamy G, Yousaf M, Alqahtani AS, Ghabbour HA, Al-Rehaily AJ (2017a) Spectroscopy and crystal structures of natural stereoisomers of neoclerodane diterpenoids from Teucrium yemense of Saudi medicinal plant. J Mol Struct 1147:616–621

    Article  CAS  Google Scholar 

  • Nur-E-Alam M, Yousaf M, Ahmed S, Al-Sheddi ES, Parveen I, Fazakerley DM, Bari A, Ghabbour HA, Threadgill MD, Whatley KCL, Hoffmann KF, Al-Rehaily AJ (2017b) Neoclerodane diterpenoids from Reehal Fatima, Teucrium yemense. J Nat Prod 80:1900–1908

    Article  CAS  PubMed  Google Scholar 

  • Pacifico S, D’Abrosca B, Scognamiglio M, D’Angelo G, Gallicchio M, Galasso S, Monaco P, Fiorentino A (2012) NMR-based metabolic profiling and in vitro antioxidant and hepatotoxic assessment of partially purified fractions from Golden germander (Teucrium polium L.) methanolic extract. Food Chem 135:1957–1967

    Article  CAS  PubMed  Google Scholar 

  • Panovska TK, Kulevanova S, Gjorgoski I, Bogdanova M, Petrushevska G (2007) Hepatoprotective effect of the ethyl acetate extract of Teucrium polium L. against carbontetrachloride-induced hepatic injury in rats. Acta Pharma 57:241–248

    Article  CAS  Google Scholar 

  • Papanov GY, Malakov PY (1985) 2-keto-19-hydroxyteuscordin, a neo-clerodane diterpene from Teucrium scordium. Phytochemistry 24:297–299

    Article  CAS  Google Scholar 

  • Papanov GY, Malalov P, Bohlmann F (1981) Teuscordinon, a furanoid diterpene from Teucrium scordium. Phytochemistry 20:170–171

    Article  CAS  Google Scholar 

  • Pérez Alvarez J, Sáez-Royuela F, Gento Peña E, López Morante A, Velasco Osés A, Martín Lorente J (2001) Acute hepatitis due to ingestion of Teucrium chamaedrys infusions. Gastroenterol Hepatol 24:240–243

    Article  PubMed  Google Scholar 

  • Pichersky E, Gang DR (2000) Genetics and biochemistry of secondary metabolites in plants: an evolutionary perspective. Trends Plant Sci 5:439–445

    Article  CAS  PubMed  Google Scholar 

  • Piozzi F, Bruno M, Ciriminna R, Fazio C, Vassallo N, Arnold NA, De La Torre MC, Rodríguez B (1997) Putative hepatotoxic neoclerodane diterpenoids from Teucrium species. Planta Med 63:483–484

    Article  CAS  PubMed  Google Scholar 

  • Piozzi F, Bruno M, Rosselli S (1998) Further furoclerodanes from Teucrium species. Heterocycles 48:2185–2203

    Article  CAS  Google Scholar 

  • Piozzi F, Bruno M, Rosselli S, Maggio A (2005) Advances on the chemistry of furano-diterpenoids from Teucrium genus. Heterocycles 65:1221–1234

    Article  CAS  Google Scholar 

  • Polymeros D, Kamberoglou D, Tzias V (2002) Acute cholestatic hepatitis caused by Teucrium polium (Golden Germander) with transient appearance of antimitochondrial antibody. J Clin Gastroenterol 34:100–101

    Article  PubMed  Google Scholar 

  • Poon WT, Chau TL, Lai CK, Tse KY, Chan YC, Leung KS, Chan YW (2008) Hepatitis induced by Teucrium viscidum. Clin Toxicol 46:819–822

    Article  CAS  Google Scholar 

  • Rahmouni F, Daoud S, Rebai T (2019) Teucrium polium attenuates carbon tetrachloride-induced toxicity in the male reproductive system of rats. Andrologia 51:1–8

    Article  CAS  Google Scholar 

  • Rodríguez B, de la Torre M, Bruno M, Fazio C, Piozzi F, Savona G, Perales A, Arnold NA (1994) Rearranged neo-Clerodane diterpenoids from Teucrium brevifolium. Tetrahedron 50:2289–2296

    Article  Google Scholar 

  • Rodríguez B, de la Torre MC, Jimeno ML, Bruno M, Fazio C, Piozzi F, Savona G, Perales A (1995) Rearranged neo-clerodane diterpenoids from Teucrium brevifolium and their biogenetic pathway. Tetrahedron 51:837–848

    Article  Google Scholar 

  • Rodríguez B, de la Torre MC, Bruno M, Piozzi F, Vassallo N, Ciriminna R, Servettaz O (1996) Neo-clerodane diterpenoids from three species of Teucrium. Phytochemistry 43:435–438

    Article  Google Scholar 

  • Rodríguez B, de la Torre MC, Bruno M, Piozzi F, Vassallo N, Ciriminna R, Servettaz O (1997) A neo-clerodane diterpenoid from Teucrium asiaticum. Phytochemistry 45:383–385

    Article  Google Scholar 

  • Rodríguez B, Robledo A, Pascual-Villalobos MJ (2009) Rearranged abietane diterpenoids from the root of Teucrium lanigerum. Biochem Syst Ecol 37:76–79

    Article  CAS  Google Scholar 

  • Sattar EA, Mossa JS, Muhammad I, El-Feraly FS (1995) Neo-clerodane diterpenoids from Teucrium yemense. Phytochemistry 40:1737–1741

    Article  CAS  Google Scholar 

  • Savona G, Paternostro M, Piozzi F (1979) New furanoid diterpenes from Teucrium gnaphalodes L’hep. Tetrahedron Lett 4:379–582

    Article  Google Scholar 

  • Savona G, Piozzi F, Servettaz O, Maria C, Rodríguez B, Gadea FF, Martin-Loma M (1984) A neo-clerodane glucoside and neo-clerodane diterpenoids from Teucrium flavum subsp. glaucum. Phytochemistry 23:843–848

    Article  CAS  Google Scholar 

  • Savona G, Piozzi F, Servettaz O, Rodríguez B, Hueso-Rodriguez JA, De La Torre MC (1986) Neo-clerodane diterpenoids from Teucrium lepicephalum and Teucrium buxifolium. Phytochemistry 25:2569–2572

    Article  CAS  Google Scholar 

  • Savvidou S, Goulis J, Giavazis I, Patsiaoura K, Hytiroglou P, Arvanitakis C (2007) Herb-induced hepatitis by Teucrium polium L.: report of two cases and review of the literature. Eur J Gastroenterol Hepatol 19:507–511

    Article  PubMed  Google Scholar 

  • Sexmero Cuadrado MJ, de la Torre MC, Rodríguez B, Bruno M, Piozzi F, Savona G (1991) Neo-clerodane diterpenoids from Teucrium oxylepls subsp. marianum. Phytochemistry 30:4079–4082

    Article  CAS  Google Scholar 

  • Sexmero Cuadrado MJ, Bruno M, de la Torre MC, Piozzin F, Savona G, Rodríguez B (1992) Rearranged abietane diterpenoids from the root of two Teucrium species. Phytochemistry 31:1697–1701

    Article  CAS  Google Scholar 

  • Shahraki MR, Arab MR, Mirimokaddam E, Palan MJ (2007) The effect of Teucrium polium (Calpoureh) on liver function, serum lipids and glucose in diabetic male rats. Iran Biomed J 11:65–68

    PubMed  Google Scholar 

  • Stanković SM, Zlatić N (2019) Ethnobotany of Teucrium species. In: Martinez LJ, Muñoz-Acevedo A, Rai M (eds) Ethnobotany: local knowledge and traditions. CRC Press, Boca Raton, pp 214–231

    Chapter  Google Scholar 

  • Stanković MS, Curcic MG, Zizic JB, Topuzovic MD, Solujic SR, Markovic SD (2011) Teucrium plant species as natural sources of novel anticancer compounds: Antiproliferative, proapoptotic and antioxidant properties. Int J Mol Sci 12:4190–4205

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Starakis I, Siagris D, Leonidou L, Mazokopakis E, Tsamandas A, Karatza C (2006) Hepatitis caused by the herbal remedy Teucrium polium L. Eur J Gastroenterol Hepatol 18:681–683

    Article  PubMed  Google Scholar 

  • Stickel F, Shouval D (2015) Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol 89:851–865

    Article  CAS  PubMed  Google Scholar 

  • Stickel F, Egerer G, Seitz HK (2000) Hepatotoxicity of botanicals. Public Health Nutr 3:113–124

    Article  CAS  PubMed  Google Scholar 

  • Tanira MOM, Wasfi IA, Al Homsi M, Bashir AK (1996) Toxicological effects of Teucrium stocksianum after acute and chronic administration in rats. J Pharm Pharmacol 48:1098–1102

    Article  CAS  PubMed  Google Scholar 

  • Theis N, Lerdau M (2003) The evolution of function in plant secondary metabolites. Int J Plant Sci 164(S3):S93–S102. https://doi.org/10.1086/374190

    Article  CAS  Google Scholar 

  • Topcu G, EriÅŸ C, Che CT, Ulubelen A (1996) C-10 oxygenated neo-clerodane diterpenes from Teucrium sandrasicum. Phytochemistry 42:775–778

    Article  CAS  Google Scholar 

  • Torre de la M, Fernandez-Gadea F, Michavila A, Rodríguez B, Piozzi F, Savona G (1986) Neo-clerodane diterpenoids from Teucrium botrys. Phytochemistry 25:2385–2387

    Article  Google Scholar 

  • Torre de la M, Rodríguez B, Bruno M, Savona G, Piozzi F, Servettaz O (1988) Neo-clerodane diterpenoids from Teucrium micropodioldes. Phytochemistry 27:213–216

    Article  Google Scholar 

  • Tutin TG, Heywood VH, Burges NA, Moore DM, Valentine DH, Walters SM, Webb DA (1972) Flora Europaea III. Cambridge University Press, Cambridge

    Google Scholar 

  • Ulubelen A, Topcu G, Olcal S (1994) Rearranged abietane diterpenes from Teucrium divaricatum subsp. villosum. Phytochemistry 37:1371–1375

    Article  CAS  Google Scholar 

  • Ulubelen A, Topcu G, Sönmez U (2000) Chemical and biological evaluation of genus Teucrium. Stud Nat Prod Chem 23:591–648

    Article  CAS  Google Scholar 

  • Venditti A, Frezza C, Trancanella E, Zadeh SMM, Foddai S, Sciubba F, Delfini M, Serafini M, Bianco A (2017) A new natural neo-clerodane from Teucrium polium L. collected in Northern Iran. Ind Crop Prod 97:632–638

    Article  CAS  Google Scholar 

  • Wellmann M (1958) Pedanii Dioscuridis Anazarbei De Materia Medica. Berlin Libri III, 97

    Google Scholar 

  • Wink M (2009) Mode of action and toxicology of plant toxins and poisonous plants. Julius-Kuhn-Archiv 421:93–112

    Google Scholar 

  • Zal F, Vasei M, Rasti M, Vessal M (2001) Hepatotoxicity associated with hypoglycemic effects of Teucrium polium in diabetic rats. Arch Iran Med 4:188–192

    Google Scholar 

  • Zhi-da MIN, Ning XIE, Pei Z, Shou-xun Z, Chong-shu W, Qi-tai Z (1991) A neo-clerodane diterpene from Teucrium japonicum. Phytochemistry 30:4175–4177

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Maria-Eleni Grafakou, Christina Barda & Helen Skaltsa

Authors
  1. Maria-Eleni Grafakou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Barda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helen Skaltsa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helen Skaltsa .

Editor information

Editors and Affiliations

  1. Department of Biology and Ecology, Faculty of Science, University of Kragujevac, Kragujevac, Serbia

    Milan Stanković

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Grafakou, ME., Barda, C., Skaltsa, H. (2020). Secondary Metabolites of Teucrium Species with Toxic Effects. In: Stanković, M. (eds) Teucrium Species: Biology and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-52159-2_8

Download citation

Publish with us

Policies and ethics

Search

Navigation