Abstract
Context: Essential oils (EOs) have been reported to possess pharmacological properties, of which those related to the central nervous system have been especially attributed to mono- and sesquiterpenes. Baccharis uncinella DC. (Asteraceae) is used by the Laklaño Indians (Santa Catarina, Brazil) for sedative purposes. Interestingly, the species does not seem to be used medicinally elsewhere in Brazil.
Objective: This study was designed to compare the composition and sedative properties of B. uncinella EOs obtained closer (BU-SC) and farther (BU-PR) to the Laklaño Indian Reserve.
Materials and methods: BU-SC and BU-PR obtained by hydrodistillation were analyzed by CG-MS. Mice treated with BU-SC and BU-PR (50 and 100 mg/kg) were evaluated regarding pentobarbital-induced sleeping time, body temperature, and locomotion.
Results: BU-SC presents a higher monoterpene/sesquitherpene ratio (0.31); α-pinene (6.42%), limonene (7.21%), caryophyllene (26.13%), spathulenol (13.39%) and caryophyllene oxide (13.26%) were identified as major components. BU-PR presents a low monoterpene/sesquitepene ratio (0.004); spathulenol (32.93%), caryophyllene oxide (27.78%), viridiflorol (5.29%) and α-cadinol (2.42%) were identified as the main components. Both samples significantly (p < 0.05, ANOVA) decreased locomotion and body temperature, as well as increased sleeping time. The hypnotic activity was sensitive to the differences in monoterpene composition.
Conclusions: In comparison with a sample collected in Paraná State, B. uncinella EO collected closer to the Laklaño Indians possess a composition that better justifies the claimed sedative properties. The study confirms the value of traditional information to guide bioactivity assessment in medicinal plants, and gives notice to the ecological factors that can interfere with the conclusions of such assessments.
Introduction
Medicinal plants present a variety of chemical constituents accumulated as byproducts of the plants secondary metabolism. Among these chemicals, a distinct class is composed by essential oils (EOs), of which some are used in indigenous medical systems to treat various conditions including mental illnesses (CitationUmezu et al., 2001, Citation2006). From the dozens of components usually found in EOs, the monoterpenes and sesquiterpenes seem to be the main responsible for central nervous system (CNS) effects (CitationHeuberger et al., 2010). For instance, the monoterpene (R)-(-)-linalool is recognized as the sedative/calming component of numerous traditional and commercial plant preparations and/or their EOs (CitationElisabetsky et al., 1995; CitationSugawara et al., 1998; CitationKuroda et al., 2005; CitationShaw et al., 2007; CitationLinck et al., 2009, Citation2010; CitationHeuberger et al., 2010). α-Terpineol is another monoterpenoid derivative identified as the active component of traditional sedatives (Citationde Sousa et al., 2007).
The phytochemical analysis of many Baccharis species indicates the presence of flavonoids, diterpenes and triterpenes, which have been associated with antimicrobial, antinflammatory, antioxidant and gastroprotector properties (Heral et al., 1998; CitationBaggio et al., 2003; CitationAbad et al., 2006; CitationMorales et al., 2008). EOs obtained from B. notosergila Griseb. (CitationCobos et al., 2001), B. latifolia Pers. and B. prunifolia Kunth (CitationRojas et al., 2007), B. elaeoides J. Rémy and B. magellanica Pers. (CitationSimonsen et al., 2009) showed antimicrobial properties. B. salicifolia (Ruiz & Pav.) Pers. produces volatile compounds with insect repellent properties (CitationGarcia et al., 2005). The EO obtained from B. dracunculifolia DC. possesses antiulcerogenic properties associated with a high content of E-nerolidol (CitationKloppel et al., 2007). Additionally, caffeic acid and pectolinaringenin isolated from the ethanol extract of B. uncinella showed anti-leishmanial effects (CitationPassero et al., 2011).
Baccharis uncinella is used by the Laklaño Indians (Santa Catarina, Brazil) as a sedative as well as to “regulate blood pressure”. The Shokleng Indians, who now designate themselves as Laklaño, are recognized as a group since the XVIII century. Living in the valleys and plateau borders in the South of Brazil since 1914, the contacted group (approximately 800 individuals) was more intensively exposed to the dominant society at the State of Santa Catarina (Ibirama Indian Reserve). The intercultural exchange introduced the use of salt and alcohol beverages (CitationUrban, 1985), as well as diseases unknown to the Indians; moreover, medicinal plants from several sources and cultural backgrounds were introduced by local authorities and health providers (CitationSantos, 1973).
Mr. Congo Patté, recognized up to this day as a medicinal plant expert at the Laklaño Reserve, was yet to be born when a 1932 census listed 106 Laklaño individuals living in the area (CitationHenry, 1941). He speaks at easy of “heaviness in the head”, nape pain, nausea and discouragement as the symptoms indicative of high blood pressure; moreover, he is ready to recognize the “cooking salt” as dangerous to older people’s health and recommends the use of B. uncinella (known as vassourinha) tea to be used daily for various days. He remembers that during the tense period marked by land dispute with loggers, he used to recommend that men avoid cachaça (Brazilian distilled alcohol from sugar cane) and frequently used the same B. uncinella tea in order to calm down.
CNS relevant components were identified in EOs obtained from B. uncinella leaves collected in the South of Brazil plateau above 1000 m of altitude (CitationAscari et al., 2009). Noteworthy, significant differences in the EOs composition were observed with different collections: while the sample from the Paraná State (altitude 1050 m) presents low levels of monoterpenes (~2%) and a high proportion of caryophyllene oxide (~16%) and α-eudesmol (7.5%), the sample from Santa Catarina State (locality of Vacas Gordas, altitude 1360 m) contains over 36% of monoterpenes (12.9% α-pinene and 9.9% limonene) but a low proportion of caryophyllene oxide (2.9%) and α-eudesmol (1.9%) (CitationAscari et al., 2009).
Given the traditional uses and relevance attributed by the Laklaños to B. uncinella, the aim of this study was to compare EOs obtained from two different areas of Southern Brazil in terms of EO composition and sedative effects.
Materials and methods
Ethnopharmacological survey
Ethnopharmacological data obtained for “vassourinha”, Baccharis uncinella are part of a broader study carried out at the Laklaño Indians land reserves known as Terra Indígena Ibirama (State of Santa Catarina, Brazil), between August 1999 and September 2001. The survey was mainly conducted with three elderly native plant specialists, Mr. Congó Patté, and the ladies Iocô Uvanhecu and Ngãvene Patté. “Vassourinha” tea is prepared with a handful of leaves in a litter of cold water to be slowly heated until boiling (decoction). The tea is to be drunk for various days, by adults and the elderly, with the purpose of regulating blood pressure and as a calming tea.
Plant material
The leaves of B. uncinella were initially collected in the district of Ponta Grossa, State of Paraná, Brazil (sample BU-PR, altitude of 1050 m, 25°06′23′′ South and 50°00′39′′ West) in July of 2005. A second collection was done close to the Laklaño Reserve, at the locality of Pouso Redondo, State of Santa Catarina, Brazil (sample BU-SC, altitude of 440 m, 27°16′19′′ South and 49°49′60′′ West) in July of 2006. Voucher specimens were deposited at the Herbarium of the Universidade Estadual de Ponta Grossa (HUPG-13105). Both collections were treated as follows: plant material was dried for 7 days at room temperature, the leaves separated and conserved at −18°C until the oil extraction procedure.
Steam distillation and analyses of the EOs
The EO samples were obtained by hydrodistillation with the use of aluminum and glass equipment. Close to 1.2 kg of each milled leaves sample was submitted to 4 h distillation, and the EO collected in ethyl ether. The organic solutions were dried with anhydrous Na2SO4, with repeated filtrations and evaporations to yield 9.60 g of BU-PR and 10.32 g BU-SC.
The oil samples were analyzed in a Varian® CP-3800 Gas Chromatograph coupled to a Saturn® 2000 Mass Spectrometer using the software Saturn® GC-MS Workstation 5.51, operating in the EI mode at 70 eV with a mass range of 40–650 m/z and at a sample rate of 1.0 scan s−1. An apolar capillary column CP-Sil-8 CB Low Bleed/MS (30 × 0.25 mm i.d., 0.25 µm) film was used with the following conditions: split ratio of 1/50, 250°C for the injector and 240°C for the interface. The oven temperature was programmed for 60°C for the first 3 min, raising at a rate of 5°C/min to reach 220°C, remaining as such for slightly over 15 min. The retention indices (RI) were calculated by using the data from a series of n-alkane (C10-C26) injections in the same chromatographic conditions as those used for the oil samples (CitationVan den Dool & Kratz, 1963). The components were firstly identified by comparing the obtained mass spectra with those of the equipment data bank, following by comparison of retention indices with published data (CitationAdams, 1995; CitationPherobase, 2010). Isolated standards of heptanal, α-pinene, β-pinene, limonene, linalool, caryophyllene, spathulenol, viridiflorol, guaiacol, camphor, trans-anetol, safrol, thymol, eugenol and tert-butil-hydroxytoluene were used to validate the system and guarantee the reliability of the calculated indices.
The relative composition of each oil sample was determined by using a Shimadzu Gas Chromatograph 14 B with a Flame Ionization Detector (GC-FID), an OV-5 column (30 m × 0.25 mm d.i. × 0.25 µm) under the following conditions: N2 used as the carrier gas at a constant pressure 80 kPa, a split ratio of 1/150, and an injection volume of 1 µL of the oil diluted in ethyl ether, with detector at 300°C, and injector at 250°C. The initial column temperature was set to 50°C for 3 min, programmed for heating up at a rate of 5°C/min to reach final temperature of 270°C, completing with an isotherm of 8 min.
Pharmacological assessment
Animals
Experiments were performed with 2 month old (35–45 g) male (CF1) albino mice, purchased from Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS). Animals were maintained in our own animal facility, under controlled environmental conditions (22 ± 1°C, 12 h light/dark cycle), with free access to food [Nuvilab CR1] and water, for at least 2 weeks before the experiments. All procedures were carried out in accordance with institutional policies on experimental animals handling, which follows de NIH guidelines (NIH Guide for Care and Use of Laboratory Animals, NIH publication No. 85–23, 1985).
Drugs
Diazepam and pentobarbital were acquired from Sigma. B. uncinella EOs (BU-PR and BU-SC) were diluted in 1% Tween 80. Drugs and vehicles were administered intraperitoneally, always as 10 mL/kg of body weight.
Hypnotic activity
Mice (n = 8–10) were treated i.p. with saline, 1% Tween 80, diazepam (2 mg/kg, positive control), or 50 or 100 mg/kg of BU-PR or BU-SC. Thirty minutes later mice received sodium pentobarbital (35 mg/kg, i.p.). The sleeping time (time elapsed between loss and recovery of righting reflex) was recorded; a cut-off time of 180 min was adopted. Results were analyzed by means of ANOVA/SNK (CitationLinck et al., 2009).
Hypothermic effects
Groups of mice (n = 6) were treated i.p. with 50 or 100 mg/kg of BU-PR, BU-SC or controls (saline and 1% Tween 80). The body temperature measured with a sensor probe of a digital thermometer (inserted at 1 cm into the rectum) was recorded before treatments (time 0) and 15, 30, 60 and 120 min after drug administration. Pentobarbital (50 mg/kg, i.p.) was used as the reference drug. Results were analyzed by repeated measures ANOVA followed by SNK (CitationDallmeier & Carlini, 1981).
Locomotion
The method was adapted from CitationLinck et al. (2009). Activity cages (45 × 25 × 20 cm, Albarsch Electronic Equipments), equipped with three parallel photocells, automatically record the number of crossings. Animals (n = 8–10) were individually habituated to an activity cage for 10 min before receiving the following treatments (i.p.): saline, 1% Tween 80, BU-PR and BU-SC 50 or 100 mg/kg. The animals returned to the activity cages 30 min after treatments and the number of crossings were recorded for 15 min. Diazepam 1 mg/kg was used as positive control. Results were analyzed by means of ANOVA/SNK.
Results
Chemical composition of the EOs
resumes the chemical analysis of BU-PR (over 1000 m altitude) and BU-SC (approximately 400 m altitude). As can be seen, BU-PR presents a lower monoterpene content; the only monoterpene identified was the oxygenated terpinen-4-ol (0.31%), resulting in a low monoterpene/sesquitepene ratio (0.004). The main components identified in this oil sample were sesquiterpenes: spathulenol (32.93%), caryophyllene oxide (27.78%), viridiflorol (5.29%) and α-cadinol (2.42%). These oxygenated compounds respond, therefore, for the majority (68.42%) of the sample.
Table 1. Relative compositions of volatile components of the two essential oils samples of Baccharis uncinella collected near (BU-SC) or far (BU-PR) from the Laklaño reservation.
In a clearly distinct manner, the BU-SC sample presents a sizable monoterpene content as well as non-oxygenated sesquiterpenes, resulting in a monoterpene/sesquitherpene ratio of 0.31. Only non-oxygenated monoterpenes were identified (20.22%), of which α-pinene (6.42%) and limonene (7.21%) are the major components. The non-oxygenated sesquiterpenes identified comprise 38.63% of the sample, with caryophyllene (26.13%) as the most abundant component. The two oxygenated sesquiterpenes identified in BU-SC are spathulenol (13.39%) and caryophyllene oxide (13.26%), which are often the major components of EOs obtained from Baccharis spp. (CitationAgostini et al., 2005; CitationLago et al., 2008; CitationRetta et al., 2009).
CNS activity of the EOs
A significant increase (F4.51 = 16.2; p < 0.01) in sleeping time was induced by BU-PR at 100 mg/kg (but not 50 mg/kg); the effect of BU-PR 100 mg/kg was comparable to diazepam. BU-SC likewise produced a significant increase (F4.50 = 39.7; p < 0.01) in sleeping time, at both 50 and 100 mg/kg; these doses had equal activity. At 100 mg/kg, BU-SC was significantly (p < 0.05) more active than BU-PR ().
Figure 1. Effects of Baccharis uncinella essential oils (BU-PR and BU-SC, 50 and 100 mg/kg, i.p.) on pentobarbital-induced sleep in mice. Diazepam 2 mg/kg was used as positive control. Each column represent the mean ± S.E.M. (n = 8–10). * = p < 0.05; ** = p < 0.01 vs. control ANOVA/SNK.
Repeated measures ANOVA confirmed that the body temperature was significantly decreased (F6.51 = 6.73; p < 0.01) by all treatments in comparison to controls (). The post hoc analyses showed that BU-PR and BU-SC significantly and comparably decreased body temperature at 15 and 30 min post treatment, while at 60 min post treatment only the hypothermic effect of pentobarbital was still at place. There was no significant difference between the two doses of BU-PR and/or BU-SC.
Figure 2. Hypothermic effects of Baccharis uncinella essential oils (BU-PR and BU-SC, 50 and 100 mg/kg i.p.). Pentobarbital 50 mg/kg was used as positive control. * = p < 0.05; ** = p < 0.01 vs. control. ANOVA/SNK.
shows the results of treatments on locomotion. A significant decrease (F6.56 = 17.5; p < 0.01) in locomotion was induced by BU-PR and BU-SC at both doses; the differences between samples or doses of the same sample did not reach statistical significance.
Figure 3. Effects of Baccharis uncinella essential oils (BU-PR and BU-SC, 50 and 100 mg/kg, i.p.) on spontaneous locomotor activity. Each column represents the mean ± S.E.M. (n = 8–10). ** = p < 0.01 vs. control. ANOVA/SNK.
Discussion
In agreement with the claims from the Laklaño Indians, we provide evidence that EOs obtained from Bacharis uncinella possess sedative properties given that diminished locomotion, hypothermia and hypnosis is a classic triad indicative of hypno-sedative effects. Differences in the composition of the samples BU-PR and BU-SC were reflected in differences in hypnotic activities. Though the effects of EOs in blood pressure was not studied, considering the relationship between blood pressure and stress, it is arguable that the perception of the usefulness of B. uncinella in regulating blood pressure can be in part associated with its sedative effects. Nonetheless, for a clear and comprehensive pharmacological profile of these EOs further studies, including additional animal models and dose ranges, would be necessary. Though the activity cannot be related to components of EOs, sedative effects were also seen with B. serraefolia DC. methanol extract, which was effective against strychnine- and cardiazol-induced seizures, and increased sleeping time (CitationTortoriello & Santamaria, 1996).
The major components of the samples here studied are monoterpenes and sesquiterpenes. As mentioned earlier, among volatile terpenes of natural origin several are known to be centrally active (CitationHeuberger et al., 2010). Some of these can be found in EOs from Bacharis species, such as α-pinene, limonene, linalool, myrcene, α-terpineol, and the sesquiterpenes eudesmene, α- and β-eudesmol, and caryophyllene oxide (CitationAgostini et al., 2005; CitationLago et al., 2008; CitationAscari et al., 2009; CitationRetta et al., 2009; CitationSimonsen et al., 2009). Monoterpenes identified in the EO samples here evaluated that can be related to hypno-sedative properties include α-pinene (CitationSayyah et al., 2004) and limonene (CitationVale et al., 1999; Citation2002).
In contrast, only a few volatile sesquiterpenes presenting CNS activity are currently known. The sesquiterpenes caryophyllene oxide and β-selinene (= β-eudesmene) isolated from the hexane extract from Psidium guayava var. minor (Myrtaceae) Mattos leaves potentiated pentobarbital-induced sleep and increased the latency for PTZ-induced convulsions in mice; additionally, blockade of extracellular Ca2+ was observed in isolated guinea-pig ileum with the hexane extract and its fractions containing both sesquiterpenes (CitationMeckes et al., 1997). β-Eudesmol was found to be one of the volatile active principles of the Chinese medicinal herb Atractylodes lancea DC. (Asteraceae) with antagonist properties useful against organophosphorous anticholinesterase agents intoxication (CitationChiou et al., 1997). Experimental data show that β-eudesmol prevents convulsions and lethality induced by electroshock, but not those induced by PTZ or picrotoxin (CitationChiou et al., 1995). With a very similar chemical structure, α-eudesmol protects the development of post-ischemic brain injury in rats by blocking ω-Aga-IVA-sensitive Ca2+ channels (CitationAsakura et al., 2000). The structure resemblance of β-eudesmol and β-selinene is likely to indicate relevant characteristic patterns common to these two compounds that are relevant for central nervous system activity.
It has been documented that EOs from aerial parts of B. uncinella obtained from Santa Catarina highlands (CitationAscari et al., 2009) and the state of Rio Grande do Sul, Brazil (CitationAgostini et al., 2005; CitationFrizzo et al., 2001, Citation2008) contain 3–60% of monoterpenes. The volatile metabolites in Baccharis are likely to be influenced by ecological and geographical factors as luminosity (CitationSilva et al., 2006), rainfall regime (CitationFerracini et al., 1995), ground mineral content (CitationSilva et al., 2007) and/or interaction with insects and predators (CitationDamasceno et al., 2010), and the occurrence of chemotypes based on sesquiterpenes has been also reported (CitationFrizzo et al., 2008). It is therefore arguable that the distinct composition of BU-SC and BU-PR are related to ecological or genetics factors; it is to be expected that the differences observed in these samples CNS activities are consequent to these differences in composition. The sedative effect is likely to be related to sesquiterpenes (e.g., carophyllene oxide) present in both samples, while the more marked hypnotic activity of BU-SC can be attributed to its higher monoterpene content (e.g., α-pinene, limonene, α-thujene). Given that the traditional preparation may include compounds other than those found in the EO, the contribution from other compounds to the pharmacological properties alleged by Mr. Patté cannot be excluded before different extracts from B. uncinella are properly evaluated.
Conclusions
Clear differences exist in the phytochemical profile of EOs obtained from the two collections, consistent with the extensively documented effects of geographical/ecological circumstances in EOs composition. The B. uncinella EO sample collected closer to the Laklaño Indians possesses a composition that better justifies the claimed sedative properties. The differences in composition likewise may be associated with the lack of use of the same species in the State of Paraná. It is arguable that this is yet another study that confirms the value of traditional information to guide bioactivity assessment in medicinal plants. Moreover, the data give notice to the ecological factors that can interfere with such assessments if plant samples are collected without considering geographical factors that can ultimately result in failure to correlate experimental data with traditional claims.
Declaration of interest
Authors are grateful to CAPES for MSc fellowship (J A), and CNPq for fellowships (EE and VML). Financial support was received from CNPq (478229/2006-2) and the Fundação Araucária (047/2007-1573).
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