Valeriana L., is an important genus of the family Caprifoliaceae whose members are frequently used as medicinal plants. The underground parts (roots and rhizomes) have been used as a plant-based medicine to encourage sleep, improve sleep quality, and reduce blood pressure. Sedative, hypnotic, anti-spasmodic, antiepileptic, anxiolytic and antidepressive actions have been described [1-4]. Despite intensive research effort, the pharmacological actions accounting for the CNS suppressant effect of valerian remain unclear . Rezvani et al. concluded that part of the anticonvulsant effect of valerian is probably mediated through the activation of the adenosine system . Other experiments have established that anxiolytic activity can be mediated through GABA and the serotonergic system and that valerenic acid produced barbiturate-like effects on performance tests with mice [2, 6]. Further studies clearly showed that Valerian extracts, with valerenic acid, as a compound with determined pharmacological activity, allosterically modulates GABAA receptors, while derivatives of valerenic acid, i.e. acetoxyvalerenic acid or hydroxyvalerenic acid, do not allosterically modulate GABAA receptors, but they bind to identical binding sites . Valerenic acid and its esters can also serve as prodrugs that become non-sedative anxiolytic and anticonvulsant agents . According to the requirements of the European Pharmacopoeia (monograph 04/2017:0453) the dried, whole, or fragmented underground parts of Valeriana officinalis L., including the rhizome surrounded by the roots and stolons, should contain a minimum 0.17% w/w of sesquiterpenic acids, expressed as valerenic acid . Well over one hundred products which are marketed in Europe contain various extracts based on V. officinalis.
Numerous studies have concentrated on the composition of the essential oil from different species of Valeriana, and valeric and isovaleric acid, hydrocarbon monoterpenes (α-pinene, α-fenchene, and camphene), monoterpenic esters (bornyl acetate, myrtenyl acetate, and myrtenyl isovalerate), oxygenated sesquiterpenes, and valerenane sesquiterpenoids, such as valerenal, valerenone, valerenol, valerenyl acetate, valerenic acid, and valerenyl isovalerate have been described as the main constituents [1, 4].
The flora of Kazakhstan has about 6,000 species of vascular plants, 1,067 genera and 159 families [10, 11]. The valerian-related plants in the Kazakhstani flora have six representatives: Patrinia intermedia (Hornem.) Roem. & Schult. - patrinia average; Patrinia sibirica (L.) Juss. - patrinia Siberian; Valeriana capitata Pall. ex Link - valerian capitatum; Valeriana chionophila M. Pop. & Kult. - valerian snow-loving; Valeriana dubia Bunge- valerian dubious, and Valeriana rossica P.A. Smirn. . Two plants are used as substitutes for V. officinalis: Valeriana turkestanica Sumnev., (syn. Valeriana dubia Bunge) and Valeriana rossica [12, 13, http://www.theplantlist.org/tpl/record/tro-33500633].
Valeriana turkestanica (VT) is a perennial plant that stands 40-50 cm tall. The roots are 1-2 mm thick. The bottom stem is short, ascending or straight, up to 2 m tall, with slight foliage (but occasionally with dense foliage). Bottom leaves are lyre-pinnate, with 3-5 pairs of lateral, integrally edged, ovate-lanceolate segments, 25-30 mm long and 4-11 mm wide. Inflorescence is initially capitate, with purple flowers, up to 7 mm in length. Fruits are 4 mm long and 1.5 mm wide, elongated and brown. VT blooms in June, and the fruits ripen from July through to September. It grows in subalpine and alpine meadows, and spruce forests, in the forest and water meadows and grassy slopes of the ravines at an altitude of up to 2000- 4000 m. The plant is characterized by a Central Asian growth area. In Kazakhstan it is a ubiquitous plant, found in the Jungar, Zailiyskiy and Kungei Alatau, Ketmen, Terskey Alatau, the Chu-Ili mountains, and the Kyrgyz Alatau, Karatau [14, 15].
No information concerning the identity of the constituents of VT is available. Phytochemical screening indicated that it contains iridoids, flavonoids, terpenoids, and an essential oil . In view of the increasing demand of Valeriana preparations, as well as considering the high level of production of VT in Kazakhstan, the aim of this study was to compare the chemical constituents of the underground parts of the well-known VO and the poorly investigated VT, for consideration as an alternative, sustainable resource.
2 Materials and methods
2.1 Plant material
The underground parts of Valeriana officinalis L. and Valeriana turkestanica Sumnev. were investigated. Three samples of V. officinalis were analysed: 1) cultivated in the garden of the Research and Science Innovation Centre (RSIC) in Wola Zdybska near Lublin (Poland) (51°44’49”N 21°50’38”E) (VO RSIC); 2) cultivated in the Botanical Garden of Marie Curie University in Lublin, Poland (VO UMCS); and 3) a commercially available sample (Flos Lek, Poland; VO FL). Results were compared to those obtained after analysis of the composition of the underground part of Valeriana turkestanica (VT) collected in the Zailiyskiy Alatau mountains (Kazachstan), at an altitude of 2215 m (43°07’459”N, 077°04’972”E). All samples were harvested during the second year of vegetation in August / September 2016.
Plant identities were confirmed by a specialist in botany from the RSCI, Botanical Garden of Marie Curie University in Lublin and the Ministry of Education and Sciences of the Republic of Kazakhstan Science Committee, Institute of Botany and Phytointroduction, respectively. The representative voucher specimens (VOR/2016; VOU/2016; VOF/2016 and VTK/2016, respectively) have been placed in the Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, Poland.
Plants were dried at room temperature, ground to a powder and subjected to extraction. A sample of each plant material (1 g) was extracted three times with n-hexane in an ultrasonic bath for 30 min each time. The combined extracts were concentrated under vacuum and dissolved with the same solvent (5 mL).
2.3 GC-MS analysis
Identification of the constituents was determined by gas chromatography-mass spectrometry (GC-MS). The GC analysis was performed on a Shimadzu GC-2010 Plus instrument coupled to a Shimadzu QP2010 Ultra mass spectrometer. A fused-silica capillary column ZB-5 MS (Phenomenex) (30 m × 0.25 mm), was used. The initial column temperature was 50 °C with a 3 min holding time, then the temperature was programmed to increase at 5 °C /min to 250 °C, and held for 15 min in 250 °C. The injector temperature was set at 280 °C. Split injection was conducted with a ratio split of 1:20. Helium was used as the carrier gas at 1 mL/min flow rate. Mass spectra were recorded at 70 eV. Mass range was from m/z 40-500. The ion source temperature was maintained at 230 °C.
Constituents were identified based on their retention indices (determined with reference to a homologous series of C8–C24 n-alkanes). Compounds were identified using a computer-supported spectral library [16, 17] of the mass spectra of reference compounds, as well as MS data from the literature [18-23].
3 Results and discussion
The volatile components detected in the examined n-hexane extracts of the valerian samples are listed in Table 1 in the order of their elution from the HP-5MS column. The most characteristic components present in all of the analysed samples were sesquiterpenoids (Fig. 1). The three investigated samples of V. officinalis (VO) produce mainly valerenane and kessane sesquiterpenoids. Among the valerenanes, the presence of valerenal (1) (9.6-9.96%), and valerenic acid (2) (11.15-15.00%) and its acetoxy derivative (3) (7.33-9.39%) are of note. Furthermore, the presence of valerenol esters with acetic (4, 6) and isovaleric (5) acids were confirmed. Kessanes, which belong to the guaiane-type sesquiterpenoids, are the second most characteristic group of compounds detected in the valerian roots. Kessane (7) (0.53%), α-kessyl acetate (8) (1.05-1.82%) and kessyl glycol (9) (0.76-9.11%) were identified. Other characteristic volatile sesquiterpenoids identified were elemol (0.77-10.73%), guaia-6,9-dien-4β-ol (0.9-2.48%) and guaia-6,10(14)-dien-4β-ol (1.40-3.98). Among the volatile components present in the V. officinalis root extracts were the polyunsaturated fatty acids, linoleic and α-linolenic acid, together with hexadecanoic acid (or palmitic acid) and valeric acid esters, e.g. valeric acid 2,6-dimethylnon-1-en-3-yn-5-yl ester. There is little available information concerning the presence of fatty acids in valerian extracts, however, linoleic acid  and hydroxylated derivatives of conjugated linoleic acid were previously isolated from the rhizomes and roots of V. fauriei Briq. .
There are small differences between the composition of the extracts between the samples obtained by cultivation (VO RSIC and VO UMCS) and the commercially available sample (VO FLOS). Elemol (6.20-10.73%) and valeric acid 2,6-dimethylnon-1-en-3-yn-5-yl ester (1.70-1.87%) were detected in quite high amount in the cultivated samples, while only 0.77% of elemol and traces of valeric acid 2,6-dimethylnon-1-en-3-yn-5-yl ester were observed in the VO FLOS extract.
Acetoxyvalerenic acid (33.94%), valerenic acid (15.05%), valerenal (11.93%), valeric acid 2,6-dimethylnon-1-en-3-yn-5-yl ester (5.24%), valerenol (3.31%), elemol (3.19%) and (E)-valerenyl isovalerate (2.53%) were the most characteristic components identified in the n-hexane extract from the roots of V. turkestanica (VT). Unlike VO, this species does not produce the kessane sesquiterpenoids and polyunsaturated fatty acids. Among the components detected only in the VT were (Z)- and (E)-α-bisabolene, and valerenol.
The GC-MS chromatogram of the VO RSIC and VT n-hexane extracts are presented in Fig. 2.
Previous studies of VO from the Lublin region (collected in the first year of vegetation) revealed that bornyl acetate (15.42%), followed by elemol (8.01%), β-gurjunene (6.20%) and camphene (5.43%), were the dominant compounds in the essential oil . Bornyl acetate was also predominant in the genotypes from Estonia, France, Latvia, Lithuania, Moldavia, and Russia . The content and the composition of valerian essential oil undergoes genetic and environmental variability. In addition, cultivation variables, such as a later sowing time and a lower valerian plant density in the plantation, enhances the accumulation of camphene, bornyl acetate, and valerenal in the resultant essential oil [3, 26]. The content of valerenic acid and its derivatives depends on the plant age, the harvest phase, and the growing conditions, but it is not genotypically differentiated [3, 27]. The level of valerenic acids can be highly variable based on the age of the plants. With ageing, the concentrations of valerenic acid, valerenal and α-humulene increase in valerian roots . This observation was confirmed by Seidler-Łożykowska et al. who indicated that higher levels of valerenic acids could be obtained in the second year of cultivation, particularly during the full bloom to fall rosette phase of plant growth .
According to Houghton et al. , there are three phenotypes of VO, identified as types A, B, and C. Plants classified as type A contain no kessane derivatives, but high amounts of valerenal, and moderate amounts of elemol and valeranone. No kessane derivatives or valeranone, but high amounts of elemol and valerenal can be detected in VO plants from type B, while the type C VO plants have moderate amounts of kessane derivatives, elemol, and valerenal, together with high amounts of valeranone . In all of the VO samples analysed in this study, kessane derivatives were detected (e.g. α-kessyl acetate, kessyl glycol or kessane itself in VO RSIC and VO FLOS). The concentration of elemol was high in the cultivated samples (6.2% and 10.73% in VO RSIC and VO UMCS, respectively) while only 0.77% was detected in the commercially available VO FLOS. Only this sample contained valeranone (0.37%). No kessane derivatives were identified in VT, however, the investigated sample was quite rich in elemol (3.19%) and valeranone (1.87%).
The use of plant-based supplements to treat anxiety and insomnia has been increasing, and Valeriana officinalis is one of the most important. The present study is the first to evaluate the chemical composition of V. turkestanica. This study suggests that VT, with the high content of valerenic acid and its derivatives, which are considered to be compounds responsible for the CNS activity, can be considered for use as a substitute of the European VO for the preparation of pharmacologically important medicines. Further studies are necessary to conclude whether VT fully meets the requirements of European Pharmacopoeia for valerian.
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About the article
Published Online: 2017-04-21
Citation Information: Open Chemistry, Volume 15, Issue 1, Pages 75–81, ISSN (Online) 2391-5420, DOI: https://doi.org/10.1515/chem-2017-0010.
© 2017 Olga Sermukhamedova et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0