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Sacred Maya incense, copal (Protium copal - Burseraceae), has antianxiety effects in animal models
Abstract
Ethnopharmacological relevance:
The Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavior in animal models using rats. A second objective was to characterize active constituents and discern potential mechanism(s) of action, specifically the involvement of the GABAergic and endocannabinoid (eCB) systems. Despite the extensive Central American use of this resin, there are currently no known scientific behavioral or pharmacological studies done with the incense.
Materials and methods:
Quantification of the triterpenes in the copal resin and cold trapped incense was achieved by HPLC MS. Behavioral effects in rats were assessed using the elevated plus maze (EPM), social interaction (SI) test, conditioned emotion response (CER) and Novel object recognition (NOR) paradigms. Rats were exposed to burning copal (200 mg) over 5 min in a smoking chamber apparatus and then immediately tested in each behavioral paradigm. Follow-up SI tests were done using two antagonists flumazenil (1 mg/kg) and AM251 (1 mg/kg) administered systemically. Inhibition of MAGL (monoacylglycerol lipase) was measured by microplate assay with recombinant human enzyme and probe substrate.
Results:
Phytochemical analysis revealed that copal resin and incense had high α- and β-amyrins and low lupeol triterpene content. Exposure to Protium copal incense significantly reduced anxiety-like behavior in the SI and CER tests. In contrast, no anxiolytic effects were observed in the EPM. The CER effect was time dependent. Both flumazenil and AM251 blocked the anxiolytic activity of copal revealing the involvement of GABAergic and endocannabinoid systems. Copal, as well as the identified triterpenes, potently inhibited monoacylglycerol lipase (MAGL) activity in vitro (IC50 ≤ 811 ng/mL).
Conclusions:
This is the first study to show that copal incense from Protium copal elicits anxiolytic-like effects in fear and social interaction models as evidenced by a reduced learned fear behavior and an increase in active social interaction. It's high α and β-amyrin content suggests behavioral effects may be mediated, in part, by the known action of these terpenes at the benzodiazepine receptor. Furthermore, P. copal's observed activity through the eCB system via MAGL offers a new potential mechanism underlying the anxiolytic activity.
... Valerian is another medicinal plant typically used as a sleep aid (Zanoli & Zavatti, 2008), with valerenic acid and valepotriates, among other compounds responsible for its sedative effects (Houghton, 1999). Copal (Protium copal) has been used for ceremonial purposes to heal community members and has also been shown to have anxiolytic properties due to the presence of α-and ß-amyrins (Merali et al., 2018). Echinacea angustifolia and E. purpurea have been used by the North American First Nations to treat sore throat and upper-respiratory infections and promote wound healing, and both species produce secondary metabolites with anti-inflammatory, antibiotic, and cannabimimetic activity (Barrett, 2003;R. ...
... In addition, Cistanche phelypaea, a desert plant, contains a phenylethanoid glycoside that exhibits MAGL inhibition activity greater than other phytochemicals tested in the study (Beladjila et al., 2018). Studies have also demonstrated MAGL inhibition by triterpenoids such as pristimerin (King et al., 2009) and ß-amyrin (Chicca et al., 2012;Merali et al., 2018). ...
... Jewenol A found in Salvia pseudorosmarinus aerial parts had a MAGL IC50 of 46.8 µM (De Leo et al., 2018); therefore, the present study still has twice the IC50 from xanthohumol (Table 4- 4). Other phytochemicals with reported MAGL inhibiting activity include phenylethanoid glycoside and triterpenes beta-amyrin and pristimerin (Beladjila et al., 2018;Chicca et al., 2012;King et al., 2009;Merali et al., 2018). ...
This thesis used biochemometrics, metabolomics, and bioassay-guided fractionation to quantify, group, and identify active chemical constituents in hop (Humulus lupulus L. Cannabaceae) extracts, a phytochemically unique plant of cultural and economic significance around the world. Hops produce infructescence (cones) from the female plant that contain < 30% (dry weight) secondary metabolites such as the polyketides humulones (α-acids), lupulones (ß-acids), and prenylated chalcones (e.g., xanthohumol), that were quantified via high-performance liquid chromatography with diode array detection (HPLC-DAD). Hops have anti-bacterial, anti-inflammatory, and sedative properties, though most are destined for the brewing industry. However, the traditional uses, unique metabolites, and reported bioactivity of hops have led to increasing interest in hops as a natural health product.
Hop breeders select hops for their unique chemical properties (aroma or bittering) that differ between varieties. Previously, it was found that the alpha acids were positively correlated to xanthohumol, though the relationship between alpha acids and beta acids remained unclear. Alpha acids (co- and ad-humulone) correlated with one another, beta acids (lupulone, colupulone, and adlupulone) correlated with one another, and the individual alpha acids correlated more strongly with xanthohumol than the individual beta acids did with xanthohumol. Indigenous North American hops usually have greater alpha acid content than European hops. Bittering hops and North American hop samples contained significantly more alpha acids (humulone, cohumulone, and adhumulone). They had a higher alpha-to-beta ratio than the aroma and European hop samples.
The biochemometric approach uses a chemically diverse set of plants and modelled bioactivity to chemistry from these HPLC data, along with testing isolated constituents of hops, metabolomic analysis on the hop extracts using ultra-performance liquid chromatography with high resonance mass spectroscopy, and bioassay-guided fractionation to identify other compounds or confirm the identity of targeted compounds.
Free radicals are sometimes a natural byproduct of cellular respiration; enzymes typically scavenge these free radicals. However, oxidative stress occurs when free-radical production outpaces free-radical scavenging activity (RSA). Continued oxidative stress leads to an inflammatory response and activation of oxidase enzymes, such as cyclooxygenase-2 (COX-2). The endocannabinoid system consists of receptors, ligands, and enzymes that metabolize endocannabinoids (e.g., FAAH and MAGL). FAAH and MAGL inhibition increases endocannabinoids levels, reducing the quantity of arachidonic acid used by some inflammatory pathways (e.g., COX-2 and LOX).
Hop extract chemistry modelled RSA and FAAH inhibitory activity based on marker compounds. In contrast, extract chemistry did not model COX-2 and MAGL inhibitions as there was a narrow activity range among extracts. Isolated n-adlupulone demonstrated the strongest RSA, comparable to ascorbic acid. Xanthohumol potently inhibited COX-2, FAAH, and MAGL. Colupulone potently inhibited COX-2 and MAGL. Mass features were tentatively identified from the metabolomics dataset and modelled bioactivity, while bioassay-guided fractionation confirmed xanthohumol as a strong FAAH and MAGL inhibitor. This is the first study to use biochemometrics, metabolomics, and bioassay-guided fractionation to identify bioactive components in hops and that assessed isolated compounds in a concentration-dependent manner. These results will further support the development of hop-based natural health products.
... Medicinal smokes are warranted as promising options for bioprospecting purposes (Mohagheghzadeh et al., 2006;Pennacchio et al., 2010;Antonio et al., 2011;Vishnuprasad et al., 2013;Naidoo et al., 2019). Although the use of Burseraceae resin smokes has been extensively reported in ethnobotanical surveys throughout the decades, they have received little attention regarding their pharmacological potential (Basar, 2005;Al-Harrasi et al., 2014;Grbić et al., 2018;Merali et al., 2018). This study presents, for the first time, the composition of the smokes produced by the incomplete combustion of Brazilian pitch oleoresins, discussing their anti-headache potential on the basis of their traditional quilombola indication. ...
... The main pitfall when analysing medicinal smokes is capturing them. Most studies use self-developed assemblies to produce/concentrate smokes, and the usual strategy chosen for their collection is continuous trapping (e.g., Braithwaite et al., 2008;Mohagheghzadeh et al., 2010;Faridi et al., 2013;Al-Harrasi et al., 2014;Nongmaithem et al., 2017;Grbić et al., 2018;Merali et al., 2018;Serabele et al., 2021). In the present study, this collection method was tested, but intermittent sampling gave the best results, with the advantage of allowing the assessment of how time affects the composition of the smoke. ...
... Five of these 32 were detected in both black and white pitch oleoresin smoke headspaces and were tentatively identified as the triterpenoids α-amyrin, β-amyrin, α-amyrone, and β-amyrone, and the monoterpenoid α-terpineol (Tables 1 and 2; Fig. 4C). The presence of α-amyrin and β-amyrin in pitch oleoresin smoke could be anticipated based on the study of Merali et al. (2018) on Protium copal (Schltdl. & Cham.) ...
Ethnopharmacological relevance
In Latin American Traditional Medicine, the use of Burseraceae oleoresins for headache relief is widespread. In the quilombola (maroon) communities of the municipality of Oriximiná, Pará State, Brazil, Burseraceae oleoresins are burned as incenses to treat headache; an effect attained by inhaling the smokes.
Aim of the study
This study was designed to investigate the scientific rationale behind the use of Burseraceae pitch oleoresin smokes on headache by identifying its chemical constituents and discussing whether they could be beneficial for headache treatment.
Materials and Methods
Two samples of pitch oleoresins were purchased from Amazonian public markets; one of them marketed as “breu preto” (black pitch), and the other as “breu branco” (white pitch). The smoke headspaces produced upon burning these oleoresins were collected and analysed by GC-MS. For comparative purposes, the triterpenoid fingerprints of the oleoresins’ dichloromethane extracts and profiles of the essential oils were also obtained by GC-MS — and GC-FID, in the case of the essential oils.
Results
A total of 32 compounds were detected in black and white pitch oleoresin smokes. All smoke headspaces of the pitch oleoresins shared the presence of volatile terpenoids (e.g., α-terpineol) and triterpenoids (e.g., α-amyrin, β-amyrin, α-amyrone, and β-amyrone). These compounds were also present in the crude resins and could potentially be responsible for anti-inflammatory, antinociceptive and analgesic effects on headache.
Conclusions
The pharmacological data on the terpenoids detected in the Burseraceae pitch smokes strongly support their traditional use for headache, but their actual effects upon inhalation have yet to be determined.
... For this reason, over the past years, the analysis of resins has attracted interest in the characterization of archaeological objects [7][8][9]. Different approaches have been described for the chemical analysis of resins in archeological items using gas chromatography (GC) coupled to mass spectrometry (MS) [7,9,10], liquid chromatography (LC) coupled to MS [10] or UV detection [9,11,12] and thin layer chromatography (TLC) [11]. Most of those studies were aimed at differentiating the samples according to their botanical origin through the comparison of the chromatographic profiles of the extracts obtained from the samples (chemical fingerprinting), often in combination with chemometric tools [8,10]. ...
... The amount of sample in those studies was not limited, and therefore, the required sensitivity for quantification could be achieved after exhaustive sample treatments of large amounts of the samples, including multiple extractions, purification, solvent evaporation, and redissolution. Very recently, the quantification of the triterpenes lupeol, α-amyrin and β-amyrin in copal resins used in folk ceremonies was described using LC and UV detection, although the analytical performance of the method applied was not reported [12]; moreover, due to the large amount of resin needed (0.5 g), the method might be unsuitable for the analysis of microsamples. ...
... Moreover, because of the high sensitivity attainable with capillary LC, the method is compatible with the analysis of a low amount of the samples. As only a few mg of the samples is necessary, the sample treatment is very simple and avoids heating, multiple extractions or evaporation operations that could modify the content of volatile compound limonene [7,12]. ...
A method has been developed for the separation and quantification of terpenic compounds typically used as markers in the chemical characterization of resins based on capillary liquid chromatography coupled to UV detection. The sample treatment, separation and detection conditions have been optimized in order to analyze compounds of different polarities and volatilities in a single chromatographic run. The monoterpene limonene and the triterpenes lupeol, lupenone, β-amyrin, and α-amyrin have been selected as model compounds. The proposed method provides linear responses and precision (expressed as relative standard deviations) of 0.6% to 17%, within the 0.5–10.0 µg mL⁻¹ concentration interval; the limits of detection (LODs) and quantification (LOQs) were 0.1–0.25 µg mL⁻¹ and 0.4–0.8 µg mL⁻¹, respectively. The method has been applied to the quantification of the target compounds in microsamples. The reliability of the proposed conditions has been tested by analyzing three resins, white copal, copal in tears, and ocote tree resin. Percentages of the triterpenes in the range 0.010% to 0.16% were measured using sample amounts of 10–15 mg, whereas the most abundant compound limonene (≥0.93%) could be determined using 1 mg portions of the resins. The proposed method can be considered complementary to existing protocols aimed at establishing the chemical fingerprint of these kinds of samples.
... and Protium spp. (Burseraceae) (Mexico) [41][42][43] x ...
... contain also lupane compounds (e.g. lupeol) [41][42][43]. Moreover, several studies report that betulin, lupeol and lupenone are typical constituents of birch bark and its related exudate [52][53][54][55]. ...
This paper reports a pioneering study of an unknown historical drug formulation preserved in the Spezieria of Santa Maria della Scala in Rome, founded at the end of the seventeenth century by the Discalced Carmelites. Due to limited literature related to pharmaceutical remedies and drugs of the Early Modern Era (between the XV and XVIII centuries) and the complexity in their formulations, the study of these drugs represents a great challenge. The untargeted nature of the selected drug required a multi-analytical approach with complementary techniques to formulate a compositional hypothesis: FT-IR spectroscopy, gas chromatography-associated/mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) were successfully employed to identify different organic compounds. Systematic archaeobotanical research was performed as well, allowing us to acquire data related to the possible genus of plants from which these natural compounds derive and their geographical origin. The unknown drug formulation turned out to be a complex mixture used as an ointment with an anti-inflammatory purpose. It mainly contains a mixture of Venetian turpentine; a Pine resin (colophony) from the Pinaceae family; an exudate of a plant from South America, whose identified components are triterpenic compounds such as alpha- and beta-amyrins, betulin and lupeol; and saturated fatty acids which act as carriers and/or to reduce the viscosity of abovementioned exudates and resins. The study of historical drugs is important not only in order to know the practices handed down by the speziali in the past but also to reconstruct historical recipes, which can inspire new dermatological, cosmetic, hygienic and current healing products.Graphical abstract.
... 99 Protium copal, commonly used as incense by the Maya, displayed significant MAGL inhibitory activity, alleviating anxiety-like behaviors in rats, and this effect was blocked by a CB2R blocker. 100 The compound 8-prenylnaringenin in Humulus lupulus L. reversibly inhibited MAGL and reduces neuroinflammation, promising for Alzheimer's disease. 101 Extracts from Myristica fragrans exhibited anxiolytic and antidepressant effects, with significant MAGL inhibitory activity. ...
Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
... como incenso durante as cerimônias por acreditarem em seus possíveis efeitos calmantes. Merali et al. 45 estudaram que esse tipo de incenso provocaria um comportamento ansiolítico, isso utilizando ratos como modelos animais. O estudo demonstrou que o este incenso realmente provoca efeitos ansiolíticos por um comportamento de medo reduzido e um aumento na interação social. ...
... For example, copal from Protium copal calms rats, probably through the effects of amyrin on the GABA and endocannabinoid systems. This effect is undoubtedly desired in rituals (Merali et al. 2018). Anti-inflammatory properties also have scientific support, e.g., Bursera copallifera (Zúñiga et al. 2005, Romero-Estrada et al. 2016. ...
This work examines the development of ethnobotany, focusing on Mexico in this millennium. How has the discipline grown? What is the relative importance of Spanish? Are there inflection points? How did some select areas develop, and why? Numerical growth was analyzed mainly through Google Scholar queries. Other subjects were treated based on literature and experience of the authors. Spanish continues to be relevant, especially in Mexico. The discipline gained momentum from 2000 onwards because of the social context of the 1990s, the publication of several foundational works, methodological advances, and particularities of Mexican science. The trajectory of ethnobotany is congruent with a model derived from Kuhn’s proposal of cyclical advancement of science: an initial defining stage was followed by a first synthesis, then fast growth of descriptive studies, with a notable recent turn to theory and framework construction. The causes for advances are discussed for three areas (medicinal plants, agriculture, and wild-growing resources). General interest, financing, the consolidation of research groups and the internal organization of institutions have played a role. We highlight important open questions. Ethnobotany is maturing from a descriptive to an analytical stage. However, careful descriptive studies continue to be valuable because the sources of information are in decline, and theory needs an empirical basis. Also, ethnobotany encourages the transmission of knowledge and biocultural memory. It is a key element for integrated sustainability science.
... The gum copal is a natural resin-type substance obtained from the plant of Bursera bipinnata, which belongs to the family Burseraceae. Copal resin contains agathic acid along with cis-communic acid, trans-communic acid, polycommunic acid, sandaracopimaric acid, agathalic acid, monomethyl ester of agathalic acid, agatholic acid, and acetoxy agatholic acid (Milind et al. 2008;Merali et al. 2018). Copal is enactment against fever, headache, burns and stomach. ...
Nowadays, natural polysaccharide-based drug delivery systems have increasingly drawn attention as intelligent and active
biomedical devices. Polysaccharides of natural AQ3 gums are abundant in plants and extensively used for biomedical applications
due to their multi-functionality, biodegradability, biocompatibility, hydrophilicity, non-toxicity, more flexibility to modify on surface
and safetiness for human consumption. The main focus of the current book chapter is to summarize the recent technological
advancements in developing multi-structured drug delivery systems from polysaccharides of natural gums. In additionally, we also
emphasize the usage of various dimensions of natural gum polysaccharide-based polymeric matrices such as hydrogels, beads,
microparticles, nanoparticles, complexes and metal nanocomposites.
... Rats were exposed to BL following the method described by Merali et al. [28]. Before behavioral tests, rats were individually placed within the exposure chamber for 5 min. ...
Bay leaf (Laurus nobilis L.) has been shown to possesses various biological activities such as wound healing activity, antioxidant activity, antibacterial activity, antiviral activity, immunostimulant activity, anticholinergic activity, antifungal activity, insect repellant activity, anticonvulsant activity, antimutagenic activity, and analgesic and anti-inflammatory activity. The present study aimed to investigate whether the bay leaf incense (BL) elicits the memory formation via the action on the cholinergic system using a scopolamine (Sco)-induced rat model. Rats were exposed to BL over 5 min in a smoking chamber apparatus once daily for 22 days, whereas memory impairment was induced by Sco (0.7 mg/kg), a muscarinic receptor antagonist, delivered 30 min before each behavioral test. The phytochemical composition of BL was achieved by gas chromatograph–mass spectrometry (GCMS). Behavioral effects in rats were assessed by Y-maze, radial arm maze (RAM), and novel object recognition (NOR) paradigms. Additionally, the acetylcholinesterase (AChE) activity and the oxidative stress markers in the rat hippocampus were also evaluated. Exposure to BL significantly ameliorated Sco-induced cognitive impairment and oxidative stress in the rat hippocampus. The obtained results suggested that BL-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic system and antioxidant activities.
... Furthermore, pentacyclic triterpenes were detected as well, namely alpha /beta-amyrin (peaks 11 and 9 respectively) and lupeol acetate (peak 10 of Fig. 6). Moreover, the experimental evidence combined with historical research and the botanical composition has allowed us to formulate a hypothesis regarding the co-presence of these triterpene compounds: It could be the exudate of a plant from South America, most likely a copal (Merali et al. 2018). This hypothesis can be sustained by the fact that friars controlled the trade route with the West Indies (da Cruz Albino et al. 2020). ...
The present paper reports one of the first studies on the identification of natural resins and balsams in modern era drug formulations. Gas chromatography coupled with mass spectrometry (GC-MS) was applied to investigate the composition of ancient remedies and pharmaceutical formulations coming from the Spezieria di Santa Maria della Scala in Rome, founded at the end of the seventeenth century by the Discalced Carmelites. The obtained results highlight the presence of complex mixtures containing resinaceous and lipidic-based compounds. Thanks to the detection of characteristic markers, it was possible to identify several natural resins, such as guaiacum resin, ladano resin and scammony resin. Balsamic and aromatic compounds characteristic of essential oils were identified as well. In addition, an anti-inflammatory ointment, composed by mixing Venetian turpentine, a Pinaceae resin and a triterpene resin exudate of a plant from South America, was found among the analysed formulations. Combining the analytical results, the historical research and the botanical composition, it was possible to formulate compositional hypotheses of this historical medicine and provided some indications about their use in health. The study of historical drugs is not only important to know the practices handed down by apothecaries in the past, but also fundamental to reconstruct historical recipes that can inspire new dermatological, cosmetic, hygienic and current curative products.
Graphical abstract
... Another example is copal incense, obtained by burning the triterpenoid rich resin of Protium copal (Burseraceae), used both in classic and modern Maya spiritual ceremonies. Our pharmacological studies [20] showed that the incense also has remarkable activity as a potent anxiolytic activity, which may explain its long historical use. ...
The Maya employed the k’an |K’AN| glyph in Late Classic (~750 CE) hieroglyphs on murals and polychrome pottery as an adjective meaning precious, yellow. On cacao drinking vessels, the k’an glyph was suggested as a descriptor for a flavoring ingredient, allspice, Pimenta dioica (L.) Merr. (Myrtaceae). However, our previous consensus ethnobotanical fieldwork with Q’eqchi’ Maya healers of Belize revealed another candidate among antidiabetic plants, Tynanthus guatemalensis Donn. Sm. (Bignoniaceae), which was the healers’ top selection for treatment of diabetes and an exceptionally active extract in an antidiabetic assay for inhibition of protein glycation. Traits of T. guatemalensis observed after cross sectioning the liana were: (1) a cross-shaped xylem organization similar to the k’an glyph; (2) an allspice-like aroma; and (3) yellow color. Based on taxonomy and ethnobotany, confirmation of the allspice-like aromatic compound eugenol, and antidiabetic activity, we determined the plant described by the k’an glyph to be T. guatemalensis (chib’ayal in Q’eqchi’), not P. dioica (allspice). In contemporary Q’eqchi’ tradition, the section of the chib’ayal vine with its cross is associated with the eighth day of their Tzolk’in calendar, which is called the “nawal” (energy) of “q’anil” (ripe, full yellow). This day is represented with a different glyph from the k’an glyph, but notably has a cross representing the four cardinal points. The identification of a potent medicinal plant used in the late classic as well as contemporary times may suggest the long-term preservation of traditional medicinal knowledge in Maya culture for pharmacologically significant plants.
... Religious uses of aromatic plants are often justified by the value of these plants due to their appreciable perfumes and by the benefits that people claimed to gain from their combustion. Indeed, a common characteristic of medicinal, religious, and magic practices was the healthy use of the smoke of aromatic plants as incense (Brandon 1991;Merali et al. 2018;Mulas 2006). This generalization may be exemplified by González et al. (2014), who noted that the most documented curative rituals (in western Spain) are based on the smoke produced by the combustion of certain aromatic or non-aromatic plants. ...
This study surveys the history, origin, and ethnobotanical evidence of why Myrtus communis L., Ocimum basilicum L., Rosmarinus officinalis L., and Salvia fruticosa Mill. are used as ritual plants in the main monotheistic religions (Judaism, Islam, and Christianity, but also Druze, Mandaeism, and Zoroastrianism). All these aromatic plants are odoriferous, medicinal, and apotropaic. By reviewing about 180 selected references, mainly from the Mediterranean basin, we compiled five tables with 313 citations on these ritual uses in different territories and according to diverse religions. The use of these species in rites of passage is found in all the main monotheistic religions and, in critical stages of the human life cycle, is related to warding off the evil eye/bad spirits/Satan, demons, or witches. These ritual customs have deep roots in ancient pagan cultures. The use of these plants in official religious ceremonies shows that different religious ritual uses of myrtle in Judaism (as a compulsory part of the Sukkoth festival), basil in the Greek Orthodox Church (mainly as a component of the Exaltation of the Cross), and rosemary mainly in the Catholic Church (especially as a decoration in the church). The uses of the three-lobed sage for a ritual by Muslims in the Holy Land are local and are not part of established religious ceremonies. While these plants have many similar ritual aspects in different regions/religions, it seems that they can be used interchangeably, probably as a result of syncretism and cultural migration of customs.
... To support the memory enhancement and anti-AChE activities of STF in the scopolamine-treated rats, the brain antioxidant status was assessed secondly. Antioxidant enzymes including SOD, CAT, and GPX play a decisive role in the reduction of oxidative stress [54]. ...
Schinus terebinthifolius is a plant well recognized for its therapeutic profile such as anti-inflammatory and antitumor activities, promoting antibacterial activity and antioxidant and antidiabetic properties. .is study aimed at examining whether Schinus terebinthifolius memory-enhancing activities are mediated by cholinergic and brain antioxidant systems in a scopolamine zebrafish model. Schinus terebinthifolius essential oil (10, 25, and 50 μL/L) was delivered to zebrafish by immersion in water for 8 days. Memory deficits were induced by scopolamine (100 μM) administration. Zebrafish were divided into seven groups (n � 15/ group): vehicle group, scopolamine (100 μM) group, Schinus terebinthifolius essential oil groups (STF; 10, 25, and 50 μL/L), the imipramine group (IMP; 20 mg/L, as the positive control in the NTT test), and the donepezil group (DP; 10 mg/L, as the positive control in the Y-maze test). Memory status was estimated by the novel tank diving test (NTT) and the Y-maze test and finally was validated by comparison with imipramine (20 mg/L) and donepezil (10 mg/L). Gas chromatography-mass spectrometry (GC-MS) was used to detect oil compounds. Brain levels of acetylcholinesterase (AChE) and antioxidant enzymes were measured. After being exposed to Schinus terebinthifolius essential oil, the scopolamine zebrafish exhibited an improvement of memory processes in the NTT and Y-maze tests. .e essential oil attenuated the elevated level of AChE and brain oxidative stress. Schinus ter-ebinthifolius essential oil was found to support memory formation through the inhibition of the AChE activity and decreasing oxidative stress in the scopolamine-treated zebrafish brains.
Ethnopharmacological relevance:
Amid all the Brazilian phytodiversity, in all its shades and shapes, black and white amorphous masses glued to the barks of Burseraceae species stand out as some of the nation's most appreciated plant medicinal resources. Burseraceae resins have been used in all macroregions of Brazil, wherever they occur, for a variety of medicinal purposes. However, despite ongoing interest in them, their cultural and health relevance in the country has been underexamined.
Aim of the study:
This review aimed to illuminate the therapeutic importance and potential of Brazilian Burseraceae by assembling the ethnomedicinal, chemical, and pharmacological data available on its resins used in Brazil.
Materials and methods:
A search for journal articles documenting local ethnomedicinal uses of Burseraceae resins and reporting chemical and pharmacological data associated with their botanical sources was conducted in ScienceDirect, Google Scholar, and PubMed databases. Books and theses were also appraised for such information.
Results:
At least 21 Burseraceae taxa, belonging to Protium, Trattinnickia, and Commiphora, are recorded as sources of medicinal resins in Brazil. Protium and Trattinickia yield oleoresins typically rich in mono- and triterpenoids, especially the pentacyclic triterpenoids α- and β-amyrin. Although Commiphora oleo-gum-resins are expected to differ significantly from Protium and Trattinickia oleoresins by the presence of gum fractions, they often exhibit distinct terpenoid compositional patterns, characterized by a high proportion of sesquiterpenoids and tetracyclic triterpenoids. Burseraceae resins are more frequently cited in the Brazilian ethnomedicinal literature for relieving headaches and healing wounds. Pharmacological evidence corroborates the potential of Burseraceae resins against these and some other conditions and diseases, however, further studies are needed to confirm their efficacy and safety when used topically and through inhalation—the two primary routes of administration explored for them in Brazil.
Conclusions:
The present review unearths a consistent, persistent, and cross-cultural pattern of using Burseraceae resins against pain conditions. But to really tap into the Burseraceae's therapeutic potential in Brazil, we first need to address the following gaps: (a) conduct more thorough pharmacological studies, including clinical trials; (b) give more attention to the triterpenoid fraction of Burseraceae oleoresins, not only to essential oils and α- and β-amyrin; and (c) deepen our understanding of the impact of resin aging on chemical composition.
Protium ovatum é uma espécie vegetal presente nos mais variados tipos de Cerrado do Brasil, sendo esta espécie reconhecida como planta fitoterápica. O objetivo do estudo, foi caracterizar química e biologicamente os óleos essenciais de pecíolos de Protium ovatum coletados em três áreas do Cerrado no estado de Goiás, Brasil. Pecíolos foram coletados em três áreas do Cerrado. O óleo essencial foi extraído em Clevenger, sendo o rendimento determinado em porcentagem. As análises físico-químicas foram realizadas quanto à composição química por cromatografia gasosa com espectrometria de massas, densidade relativa, solubilidade, índice de refração e rotação óptica. Para determinar a atividade antioxidante biológica, foi utilizado o DPPH, determinado no CI50, e a atividade antifúngica foi realizada pela diluição do óleo essencial pelo método de difusão em disco. Os óleos essenciais apresentaram rendimento de 0,35; 0,44 e 0,29%, densidade 0,905; 0,907 e 0,912 g mL-1, solubilidade positiva, índice de refração de 1,3881; 1,3853 e 1,3799, rotação óptica de +40,6; +40,9 e +39,8 αD e CI50 de 1,67; 1,57 e 2,19 µL mL-1, para Cerradão, Cerrado rupestre e Campo sujo, respectivamente. Foram obtidos cerca de 12 compostos majoritários, e excepcional atividade antifúngica sobre as cepas de Candida. Os óleos essenciais apresentam-se como uma nova fonte antioxidante e antifúngica contra às cepas de Candidas. As características físico-químicas são semelhantes às de outros óleos essenciais da literatura. As características fitofisionômicas devem ser avaliadas futuramente por análise genética entre os grupos de indivíduos nas três áreas de estudo.
This review describes an Indigenous-led project run by Q’eqchi’ Maya Healers of Belize meant to strengthen and improve traditional botanical healing. The goals of this project were to conserve medicinal plant knowledge by way of ethnobotanical studies, and to conserve the plants themselves by creating a community ethnobotanical garden. A total of 169 medicinal species were collected in the ethnobotanical survey, which provided unique knowledge on many rainforest species of the wet lowland forest of southern Belize, not found in neighbouring Indigenous cultures. Consensus on plant uses by the Healers was high, indicating a well-conserved, codified oral history. After horticultural experimentation by the Healers, the Indigenous botanical garden provided a habitat for and conservation of 102 medicinal species including many epiphytes that were rescued from forested areas. Ethnopharmacological studies by the university partners showed a pharmacological basis for, and active principles of, plants used for epilepsy and anxiety, for inflammatory conditions such as arthritis, for dermatological mycoses, and for type 2 diabetes complications. Overall, the project has provided a model for Indigenous empowerment and First Nation’s science, as well as establishing traditional medicine as an important, unified healing practice that can safely and effectively provide primary health care in its cultural context.
The 4,4-dimethyl phytosterols possess two methyl groups at the carbon-4 atom of the aliphatic A-ring. The methyl groups are crucial for the molecular recognition of endogenous and exogenous bioactive compounds. Phytosterols have received worldwide attention owing to the recognized health benefits. However, 4,4-dimethyl phytosterols are less appreciated. Recent researches revealed that 4,4-dimethyl phytosterols exert numerous beneficial effects on disease prevention, and are particularly involved in the endogenous cannabinoid system (ECS). The purpose of this review is to summarize and highlight the current available information regarding the structures and sources of 4,4-dimethyl phytosterols, and to provide detailed preclinical studies performed to evaluate their potential for treating various diseases. Future research on 4,4-dimethyl phytosterols is warranted to confirm the relationship with ECS, and to elucidate the mechanism directly toward clinical trials.
Natural amber, copal resin and colophony are have investigated by UV-VIS, infrared and Raman spectrum. In order to distinguish the natural amber, copal resin and colophony, we have successfully used the nondestructive examination (NDE) technology. The results show that UV-VIS could not distinguish these compositions. The infrared spectra can distinguish them, but the technology may destroy the specimen. The Raman spectra show three characteristic peaks of vibration near position 932 cm−1 and position 1179 cm−1 of copal resin, which confirm the existence of terpenes compounds in it. In the Raman spectra of colophony, the vibration characteristic peak at position 1589 cm−1, caused by the conjugate double bond of internal unsaturated resin acid, is the basis of the characteristic difference between colophony and natural amber. The advantages of the distinguished technology by Raman spectroscopy are convenient and nondestructive examination for natural amber, copal resin and colophony.
A simple, fast and efficient method was developed for the isolation of phytochemicals with bioactive properties from valuable resins and medicinal plants. The method involves rapid qualitative detection of triterpenes by thin-layer chromatography (TLC), efficient extraction with n-hexane, quantitative analysis by HPLC and preparative separation (preparative TLC and crystallization) to obtain high-purity α-amyrin (98.5%), 3-epi-lupeol (98.0%) and β-amyrin (82.0%). The presence of α- and β-amyrin, or a mixture of both, was detected by TLC on silica gel in all the sources investigated, while 3-epi-lupeol was only found in the Mexican Copal resins. The results demonstrated that HPLC is a selective method for the analysis of α- and β-amyrin and 3-epi-lupeol, and that the best source of α-amyrin was Mexican Copal Tepoztlan, that of β-amyrin was Nance wastes and that of 3-epi-lupeol was Mexican Copal Sonora.
This study aims to examine the antidepressant-like action of Ghrelin (Ghr), a hormone synthesized predominantly by gastrointestinal endocrine cells and released during periods of negative energy balance, in two behavioral models: tail suspension test (TST), a predictive model of antidepressant activity, and the olfactory bulbectomy (OB), an established animal model of depression. The reduction in the immobility time in the TST was the parameter used to assess antidepressant-like effect of Ghr. The depressive-like behavior in olfactory bulbectomized mice was inferred through the increase in the immobility time in the TST and the hyperlocomotor activity in the open-field test. Ghr produced antidepressant-like effect in TST (0.3 nmol/μl, i.c.v.), and reversed OB-induced depressive-like behavior. In conclusion, these results provide clear evidence that an acute administration of ghrelin produce antidepressant-like effect in the TST and OB.
Monoacylglycerol lipase (MGL) is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Previous efforts to design MGL inhibitors have focused on chemical scaffolds that irreversibly block the activity of this enzyme. Here, we describe two naturally occurring terpenoids, pristimerin and euphol, which inhibit MGL activity with high potency (median effective concentration, IC(50) = 93 nM and 315 nM, respectively) through a reversible mechanism. Mutational and modeling studies suggest that the two agents occupy a common hydrophobic pocket located within the putative lid domain of MGL, and each reversibly interacts with one of two adjacent cysteine residues (Cys(201) and Cys(208)) flanking such pocket. This previously unrecognized regulatory region might offer a molecular target for potent and reversible inhibitors of MGL.
The current studies further investigated the effects, in animal models of anxiety, of novel putative anxiolytic and anxiogenic compounds believed to induce their effects by actions at the GABA-benzodiazepine receptor complex. It was expected that the results would also provide further validation for a novel test of anxiety based on the ratio of open to closed arm entries in an elevated plus maze in the rat. The novel putative anxiolytics CL 218,872 (10-20 mg/kg) and tracazolate (5 mg/kg) significantly elevated the percentage of time spent on the open arms of an elevated plus-maze, consistent with their anxiolytic activity in several other animal tests. Also consistent with results from other animal tests, no anxiolytic activity was observed for the phenylquinoline PK 8165 (10-25 mg/kg), the 3,4-benzodiazepine tofisopam (25-50 mg/kg), or buspirone (0.5-20 mg/kg). The benzodiazepine receptor inverse agonists FG 7142 (1-5 mg/kg) and CGS 8216 (3-10 mg/kg) had anxiogenic activity in this test, as did the atypical benzodiazepine Ro 5-4864 (1-5 mg/kg). Interestingly, however, the benzodiazepine receptor antagonists Ro 15-1788 (10-20 mg/kg) and ZK 93426 (5-10 mg/kg) had no anxiogenic activity in this test.
Social interaction (play fighting) was studied in socially housed and individually housed juvenile rats (18–30 days of age). Pinning (an animal on its back, with the other on top) proved to be a simple measure of play which correlated highly with other measures of playful behavior (solicitive behaviors, following, rough-and-tumble play, and together-time measures). Play behaviors were markedly increased by social deprivation and reduced by social satiation. The results suggest that social play is a regulated process which can be easily quantified by the simple and objective measure of pinning behavior.
Behavioral categories were measured in rats left on an elevated plus-maze for 5 min, in addition to the traditional measures. Four independent factors emerged from a factor analysis. The variables that loaded highly and positively on Factor 1, seemingly related with anxiety, were: number of entries onto open arms, time spent on open arms, percentage of open/total arm entries, percentage of time on open arms, scanning over the edge of an open arm, and open arm end-exploring. The time spent on enclosed arms loaded highly, but negatively on the same factor. Risk-assessment from an enclosed arm also loaded negatively on Factor 1. Number of enclosed arm entries, total number of arm entries and rearing loaded highly on Factor 2, probably related to motor activity. However, the total number of entries also loaded on Factor 1, being thus a mixed index. Similarly, the number of open arm entries loaded on both Factors 1 and 2. As expected, the variables having high loads on Factor 1 were changed to one direction by administration of two anxiolytics (nitrazepam and midazolam) and to the opposite direction by two anxiogenic drugs (pentylenetetrazol and FG 7142). Such pattern of drug effects was not observed with the remaining variables.
This chapter reviews the role of the amygdala in emotional learning. The amygdala is an almond-shaped area of the brain lying between the external capsule and the hypothalamus. A brief overview of amygdaloid morphology and electrophysiology is presented. Anatomical targets of the central nucleus of the amygdala that appear important for various signs of fear are enumerated, along with studies looking at the effects of lesions and electrical or chemical stimulation of the amygdala. The chapter shows the possible role of the amygdala in attention as well as the data showing that an intact amygdala is necessary for fear conditioning is mentioned. Finally, the role of excitatory amino acid transmitters in the amygdala in the acquisition and expression of conditioned fear is reviewed. Many of the amygdala projection areas are critically involved in specific signs that are used to measure fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviors that mimics natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear, as well as various measures of attention, and local infusion of drugs into the amygdala has anxiolytic effects in several behavioral tests.
The fear-potentiated startle paradigm has proven to be a useful system with which to analyze neural systems involved in fear and anxiety. This test measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with a shock. Fear-potentiated startle is sensitive to a variety of drugs such as diazepam, morphine, and buspirone that reduce anxiety in people and can be measured reliably in humans when the eyeblink component of startle is elicited at a time when they are anticipating a shock. Electrical stimulation techniques suggest that a visual conditioned stimulus ultimately alters acoustic startle at a specific point along the acoustic startle pathway. The lateral, basolateral and central amygdaloid nuclei and the caudal branch of the ventral amygdalofugal pathway projecting to the brainstem are necessary for potentiated startle to occur. The central nucleus of the amygdala projects directly to one of the brainstem nuclei critical for startle and electrical stimulation of this nucleus increases startle amplitude. Chemical or electrolytic lesions of either the central nucleus or the lateral and basolateral nuclei of the amygdala block the expression of fear-potentiated startle. The perirhinal cortex, which projects directly to the lateral and basolateral amygdaloid nuclei, plays a critical role in the expression of fear-potentiated startle using either visual or auditory conditioned stimuli. These latter amygdaloid nuclei may actually be the site of plasticity for fear conditioning, because local infusion of the NMDA antagonist AP5 into these nuclei blocks the acquisition of fear-potentiated startle. On the other hand, the expression of fear-potentiated startle is blocked by local infusion of the non-NMDA ionotropic antagonist CNQX or the G-protein inactivating toxin, pertussis toxin, but not by AP5. Finally, we have begun to investigate brain systems that might be involved in the inhibition of fear. Local infusion of AP5 into the amygdala was found to block the acquisition of experimental extinction, a prototypical method for reducing fear. We have also established a reliable procedure for producing both external and conditioned inhibition of fear-potentiated startle and hope to eventually understand the neural systems involved in these phenomena.
The social interaction test of anxiety was developed 25 years ago to provide an ethologically based test that was sensitive to both anxiolytic and anxiogenic effects. It is sensitive to a number of environmental and physiological factors that can affect anxiety. It has detected anxiogenic effects of peptides such as corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and anxiolytic effects of neuropeptide Y and substance P receptor antagonists. It has successfully identified neuropharmacological sites of action of anxiogenic compounds and drug withdrawal. Effects of compounds acting on the gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) systems have been extensively investigated after both systemic administration and microinjection into specific brain regions. The use of this test has, thus, played a crucial role in unravelling the neural basis of anxiety. It is hoped that in the next 25 years, the test will play a crucial role in determining the genetic basis of anxiety disorders.
In the present study, we examined the anxiolytic and antidepressant effects of the mixture of alpha- and beta-amyrin (AMY), pentacyclic triterpenes isolated from the stem bark resin of Protium heptaphyllum. These effects of AMY were demonstrated by the open-field, elevated-plus-maze, rota rod, forced swimming, and pentobarbital-induced sleeping time tests, in mice. In the open-field test, AMY at the doses of 10, 25 and 50 mg/kg, after intraperitoneal or oral administrations, significantly decreased the number of crossings, grooming, and rearing. All these effects were reversed by the pre-treatment with flumazenil (2.5 mg/kg, i.p.), similarly to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, AMY increased the time of permanence and the number of entrances in the open arms. On the contrary, the time of permanence and the number of entrances in the closed arms were decreased. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors. In the pentobarbital-induced sleeping time test, AMY at the same doses significantly increased the animals sleeping time duration. In the rota rod test, AMY did not alter motor coordination and, thus, was devoid of effects, as related to controls. Since AMY, at the doses of 10 and 25 mg/kg, showed a sedative effect in the open field test, lower doses (2.5 and 5.0 mg/kg) were used in the forced swimming test, producing a decrease in the immobility time, similarly to that of imipramine, the positive control. The effect of AMI was greater when it was administered 15 min after imipramine (10 mg/kg). However, the antidepressant AMY effects were not altered by the previous administration of paroxetine, a selective blocker of serotonin uptake. In addition, AMY effects in the forced swimming test were totally blocked by reserpine pretreatment, a drug known to induce depletion of biogenic amines. In conclusion, the present work evidenced sedative and anxiolytic effects of AMY that might involve an action on benzodiazepine-type receptors, and also an antidepressant effect where noradrenergic mechanisms will probably play a role.