ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 8 (2010), No 1, p 11-18
DOI 10.2478/v10136-009-0002-z

Biomedically relevant chemical constituents of Valeriana officinalis

Jiri Patocka, Jiri Jakl

Address: Jiri Patocka, Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice, Czech Republic
prof.patocka@gmail.com

Received 24th July 2009.
Revised 15th October 2009.
Published online 1st December 2009.

Full text article (pdf)
Full text article (html)
Abstract in xml format

SUMMARY
Valerian is used to treat sleeping disorders, restlessness and anxiety, but it seemsonly to work when taken over long periods (several weeks). Some studies have demonstrated that valerian extracts interact with the GABA and benzodiazepine receptors. Valerian is also used traditionally to treat gastrointestinal pain and spastic colitis. There are no long term safety studies. Valerian contains over 150 chemical constituents and many of them are physiologically active, mainly pyridine alkaloids, some organic acids and terpenes, especially the so called valepotriates, esterified iridoid-monoterpenes. As valepotriates may be potential mutagens, valerian should only be used after consultation with a physician. Valerian medication is sometimes recommended as first line treatment when the benefit-risk relation requires it and is often indicated as transition medication during the discontinuation processes involving bromazepam, clonazepam and diazepam, among others.

KEY WORDS
Valeriana officinalis; valerian; chemical constituents; alkaloids; terpenes; valepotriates


REFERENCES
Al-Majed AA, Al-Yahya AA, Al-Bekairi AM, Al-Shabanah OA, Qureshi S: Studies on the cytological and biochemical effects of valerian in somatic and germ cells of Swiss albino mice. Food Chem Toxicol 44:1830-1837, 2006.

Andreatini R, Leite JR: Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Eur J Pharmacol 260:233-235, 1994.

Auda H, Waller GR, Eisenbraun EJ: Biosynthesis of methylcyclopentane monoterpenoids. 3. Actinidine. J Biol Chem 242:4157-4160, 1967.

Baby R, Cabezas M, Castro E, Filip R, Walsoe de Reca NE: Quality control of medicinal plants with an electronic nose. Sensors Actuators B Chemical 106:24-28, 2005.

Bellas TE, Brown WV, Moore BP: The alkaloid actinidine and plausible precursors in defensive secretions of rove beetles. J Insect Physiol 20:277-280, 1974.

Benke D, Barberis A, Kopp S, Altmann KH, Schubiger M, Vogt KE, Rudolph U, Mohler H: GABA(A) receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology 56:174-181, 2009.

Braun R, Dieckmann H, Machut M, Echarti C, Maurer HR: Studies on the effects of baldrinal on hemopoietic cells in vivo, on the metabolic activity of the liver in vivo, and on the content in proprietry drugs. [Article in German] Planta Med 52:446-450, 1986.

Cavadas C, Araujo I, Cotrim MD, Amaral T, Cunha AP, Macedo T, Ribeiro CF: In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABAA receptor in rat brain. Arzneimittelforschung 45:753-755, 1995.

Clark J, Davis J, Favor DA, Fay L, Franklyn L, Heneger K, Johnson D, Zhijian Z: [1,8]Naphthyridin-2-ones and related compounds for the treatment of schizophrenia. US Patent WO2005019215, March 3, 2005.

Cohen DL, Del Torro Y: A case of valerian-associated hepatotoxicity. J Clin Gastroenterol 42:961-962, 2008.

Dennehy CE, Tsourounis C, Horn AJ: Dietary supplement-related adverse events reported to the California Poison Control System. Am J Health Syst Pharm 62:1476-1482, 2005.

Dietz BM, Mahady GB, Pauli GF, Farnsworth NR: Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res Mol Brain Res 138:191-197, 2005.

Duke JA: CRC Handbook of Medicinal Herbs. CRC Press, Boca Raton 1985.

Favor DA, Johnson DS, Repine JT, White AD: Isoquinoline [1,8]naphthyridin-2-ones and related compounds for treatment os schizophrenia. US Patent WO2006090272, August 31, 2006.

Franck B, Petersen U, Huper F: Valerianine, a tertiary monoterpene alkaloid from valerian. Angew Chem Int Ed Engl 9:891, 1970.

Fugh-Berman A, Cott JM: Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 61:712-728, 1999.

Funke ED, Friedrich H: Valepotriates in the aerial parts of some more valerianaceae species. [Article in German] Planta Med 28:215-224, 1975.

Garges HP, Varia I, Doraiswamy PM: Cardiac complications and delirium associated with valerian root withdrawal. JAMA 280:1566-1567, 1998.

Grunwald J: The European Phytomedicines Market-Figures, Trends Analyses. Herbal Gram, Austin 1995.

Gupta PD, Virmani V: Clinical trial of jatamansone (syn: Valeranone) in hyperkinetic behaviour disorders. Neurol India. 16:168-173, 1968.

Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP: Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 78:57-64, 2004.

Hazelhoff B: Phytochemical and pharmacological aspects of valerian compounds. With special reference to valepotriates. Dissertation, Thesis, University of Groningen, Groningen 1984.

Hazelhoff B, Malingre TM, Meijer DK: Antispasmodic effects of valeriana compounds: an in-vivo and in-vitro study on the guinea-pig ileum. Arch Int Pharmacodyn Ther 257:274-287, 1982.

Hendriks H, Geertsma HJ, Th. M. Malingre TM: The occurence of valeranone and crypto-fauronol in the essential oil of Valeriana offcinalis L. s.l. collected in the northern part of The Netherlands. Pharm Worls Sci 3:1316-1320, 1981.

Hikino H, Hikino Y, Kato H, Takeshita Y, Takemoto T: Constituents of wild Japanese valerian root. 1. Yakugaku Zasshi 91:766-769, 1971.

Hikino H, Ono M, Takemoto T: Constituents of wild Japanese valerian root. 2. Yakugaku Zasshi 92:479-481, 1972a.

Hikino H, Hikino Y, Nakamara R, Ono M, Takemoto T: Constituents of wild Japanese valerian root. 3. Yakugaku Zasshi 92:498-502, 1972b.

Hikino H, Takeshita Y, Hikino Y, Takemoto T: Structure of fauronyl acetate and cryptofauronol. Chem Pharm Bull (Tokyo) 13:631-632, 1965.

Holzl J: The pharmacology and therapeutics of valeriana. In: Houghton PJ (ed.): Valerian. The Genus Valeriana. Harwood Acad Publ Amsterdam 1997. pp. 55-74.

Huang KC: The Pharmacology of Chinese Herbs. Boca Raton: CRC Press, 1999.

Hude von der W, Scheutwinkel-Reich M, Braun R: Bacterial mutagenicity of the tranquilizing constituents of Valerianaceae roots. Mutat Res 169:23-27, 1986.

Hui-lian W, Dong-fang Z, Zhao-feng L, Yang L, Qian-rong L, Yu-zhen W: In vitro study on the genotoxicity of dichloromethane extracts of valerian (DEV) in human endothelial ECV304 cells and the effect of vitamins E and C in attenuating the DEV-induced DNA damages. Toxicol Appl Pharmacol 188:36-41, 2003.

Iwu MM: Handbook of African Medicinal Plants. Boca Raton: CRC Press, 1993.

Jacobo-Herrera NJ, Vartiainen N, Bremner P, Gibbons S, Koistinaho J, Heinrich M: NF-kappaB modulators from Valeriana officinalis. Phytother Res 20:917-919, 2006.

Janot MM, Guilhem J, Contz O, Venera G, Cionga E: Contribution to the study of valerian alcaloids (Valeriana officinalis L.): actinidine and naphthyridylmethylketone, a new alkaloid. Ann Pharm Fr 37:413-420, 1979.

Jarema M: Herbal drug treatment. Neuro Endocrinol Lett 29, Suppl 1:93-104, 2008.

Jiang X, Zhang JC, Liu YW, Fang Y: Studies on chemical constituents of Valeriana officinalis. [Article in Chinese]. Zhong Yao Cai. 30:1391-1393, 2007.

Johnson DS, Singer JM, White AD: [1,8]Naphthyridin-2-ones and related compounds with keto or hydroxyl linkers for the treatment of schizophrenia. US Patent WO2006090273, August 31, 2006.

Johnson RD, Waller GR: Isolation of actinidine from Valeriana officinalis. Phytochemistry 10:3334-3335, 1971.

Judd WS, Campbell CS, Kellogg EA, Stevens PF, Donoghue MJ: Plant Systematics, a Phylogenetic Approach. Sinauer Associates, Sunderland, 2002.

Klich R: Behavior disorders in childhood and their therapy. Med Welt 26:1251-1254, 1975.

Miyasaka LS, Atallah AN, Soares BG: Valerian for anxiety disorders. Cochrane Database Syst Rev 18:CD004515, 2006.

Mowrey DB: The Scientific Validation of Herbal Medicine. Keats Pub., New Cannan 1986, p. 316.

Muller SF, Klement S: A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 13:383-387, 2006.

Neuhaus W, Trauner G, Gruber D, Oelzant S, Klepal W, Kopp B, Noe CR: Transport of a GABAA receptor modulator and its derivatives from Valeriana officinalis L. s. l. Across an in Vitro Cell Culture Model of the Blood-Brain Barrier. Planta Med 74:1338-1344, 2008.

Ribeiro CA, Balestro F, Grando V, Wajner M: Isovaleric acid reduces Na+, K+-ATPase activity in synaptic membranes from cerebral cortex of young rats. Cell Mol Neurobiol 27:529-540, 2007.

Rucker G, Tautges J, Sieck A, Wenzl H, Graf E: Isolation and pharmacodynamic activity of the sesquiterpene valeranone from Nardostachys jatamansi DC. [Article in German] Arzneimittelforschung. 28:7-13, 1978.

Sakan T: Matatabi (Actinidia polygama Miq.)-isolation and structure of its biologically active components [Article in Japanese] Tanpakushitsu Kakusan Koso 12:2-9, 1967.

Sandor P, Kovach AG, Horvath KB, Szentpetery GB, Clauder O: Pharmacological studies on the effect of synthetic alpha-methyl-pyrryl-ketone on the central nervous system and blood circulation. [Article in German] Arzneimittelforschung 20:29-32, 1970.

Simpson MG: Plant Systematics. Elsevier, Amsterdam, 2006.

Schulz V, Hansel R, Tyler VE: Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. Berlin. Springer, p. 306, 1997.

Spinella M: Herbal medicines and epilepsy: The potential for benefit and adverse effects. Epilepsy Behav 2:524-532, 2001.

Tariq SH, Pulisetty S: Pharmacotherapy for insomnia. Clin Geriatr Med 24:93-105, 2008.

Thies PW: On the chromomgenic behavior of valepotriate. 5. Report on the active substances of Valerian. [Article in German] Arzneimittelforschung. 19:319-322, 1969.

Torssell K, Wahlberg K: Isolation, structure and synthesis of alkaloids from Valeriana officinalis L. Acta Chem Scand 21:53-62, 1967.

Trauner G, Khom S, Baburin I, Benedek B, Hering S, Kopp B: Modulation of GABAA receptors by valerian extracts is related to the content of valerenic acid. Planta Med 74:19-24, 2008.

Veith J, Schneider G, Lemmer B, Willems M: The influence of some degradation products of valepotriates on the motor activity of light-dark synchronized mice. [Article in German] Planta Med 52:179-183, 1986.

Violon C, Dekegel D, Vercruysse A: Relation between valepotriate content and differentiation level in various tissues from Valerianeae. J Nat Prod 47:934-940, 1984.

Wagner H, Schaette R, Horhammer L, Holzl J: Dependence of the valepotriate and essential oil content in Valeriana officinalis L. on various exogenous and endogenous factors. Arzneimittelforschung 22:1204-1209, 1972.

Wheatley D: Medicinal plants for insomnia: a review of their pharmacology, efficacy and tolerability. J Psychopharmacol 19:414-421, 2005.

Wheeler JW, Olagbemiro T, Nash A, Blum MS: Actinidine from defensive secretions of dolichoderine ants. J Chem Ecol 3:241-244, 1977.

Willey LB, Mady SP, Cobaugh DJ, Wax PM: Valerian overdose: a case report. Vet Hum Toxicol 37:364-365, 1995.

Yao M, Ritchie HE, Brown-Woodman PD: A developmental toxicity-screening test of valerian. J Ethnopharmacol 113:204-209, 2007.

Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK: The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 98:353-358, 2004.
CITED

Abdualmjid RJ, Sergi C. Hepatotoxic botanicals - An evidence-based systematic review. J Pharm Pharmaceut Sci. 16: 376-404, 2013.

Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, part 2: A review of clinical studies with supporting preclinical evidence. CNS Drugs. 27: 301-319, 2013.

Hidalgo O, Valles J. First record of a natural hexaploid population for Valeriana officinalis: genome size is confirmed to be a suitable indicator of ploidy level in the species. Caryologia. 65: 243-245, 2012.

Abramson CI, Lay A, Bowser TJ, Varnon CA. The use of silver vine (Actinidia polygama maxim, family actinidiaceae) as an enrichment aide for felines: Issues and prospects. Am J Anim Veter Sci. 7: 21-27, 2012.

Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. Eur Neuropsychopharm. 21: 841-860, 2011.

Berger J. The age of biomedicine: current trends in traditional subjects. J Appl Biomed. 9: 57-61, 2011.

Mohamed MEF, Frye RF. Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, and In Vitro Studies. Planta Med. 7: 311-321, 2011.

BACK