Chemical Diversity and Therapeutic Effects of Essential Oils of Aniba Species from the Amazon: A Review

Lauraceae families have great diversity in the world’s tropical regions and are represented mainly by aromatic shrubs and trees with significant production of essential oils (EOs). This work presents a review of the EO chemical profiles from specimens of Aniba, including their seasonal variations, geographical distributions, and biological activities in the Amazon biome. Based on the survey, 15 species were reviewed, representing 167 oil samples extracted from leaves, twig barks, and woods. Brazilian Amazon was the most representative geographic area in the number of specimens, highlighting the locations Belém, (Pará state, PA) (3 spp., 37 samples), Santarém (PA) (3 spp., 10 samples), Carajás (PA) (3 spp., 7 samples), and Manaus (Amazonas state, AM) (3 spp., 16 samples). The main compound classes identified in oils were benzenoids and phenylpropanoids, represented by 1-nitro-2-phenylethane, benzyl salicylate, benzyl benzoate and methyleugenol, along with terpenoids, especially monoterpenes and sesquiterpenes, such as linalool, α-phellandrene, β-phellandrene, β-selinene, and spathulenol. The EOs from Aniba showed considerable variation in the chemical profiles according to season and collection site. The hierarchical cluster analysis classified the samples into two main groups according to chemical composition. This review highlights its comprehensive and up-to-date information on history, conservation, traditional uses, chemosystematics, pharmacological potential of Aniba species.


Introduction
The genus Aniba Alblet (1775) belongs to the Lauraceae family, considered one of the most primitive of the Magnoliids clade [1], and includes 48 accepted species, 25 of which occur in the Brazilian Amazon [2]. The genus originated in the Amazon because the center of species diversity is in the region of the Guianas and Central Amazon, spreading over the humid tropical plains, Antilles, Guyana, and Andes region, without occurrence in Central America [3]. In Brazil, they occur in regions with high rainfall, such as in the Amazon and dry areas in the central and southern regions of the country, with diverse phytophysiognomy such as ombrophilous forests, savannas, canga, and restinga vegetation [2,4].
The first records known about this genus are from an expedition made by Aublet through French Guiana between the years 1762 and 1764, in which the species Licaria guianensis Aubl. (1775) was registered in reference to the name "likari", a tree named by the Galibis Indians. However, Aublet gave this name without having analyzed the fertile parts and fragrance of the oils, suggesting high genetic variation in the specimens or adulteration resulted from a mixture of other Aniba oils [36].
Extractivism is the main activity for the commercial exploitation of aromatic plants from the Amazon. Many species are now under pressure from exploitation, deforestation, and habitat burning [52]. Predatory exploitation and destruction of natural habitats of species with restricted distribution, like some Aniba species, has led to the inclusion of several species in the Red List of Threatened Species [53] and the Brazilian Flora Red List [17,54]. From the species surveyed in this review, only A. canelilla and A. rosaeodora are included in local management programs and subject to ex-situ conservation. Concerning in-situ conservation in protected areas, only A. canelilla and A. parviflora are listed within the genus [53]. The conservation status of Aniba species sampled for the study of chemical composition and biological activity, raised in this review, points out that all of them are in a situation of mostly minor concern, except A. rosaeodora, which is endangered due to decades of predatory exploitation that this species has been facing, as the destruction of its natural habitats by logging, livestock, and agriculture, which has culminated in the continued decline of its natural population [54].
Studies have shown that the density of rosewood trees in the forest is low; about 1 tree per 7 hectares [55]. Even so, the rosewood oil intended for trade is obtained exclusively by steam distillation of trunk wood and bark from A. rosaeodora trees, consisting of a predatory and a high-risk method of reduction in genetic variability of the species [56]. The indiscriminate cutting of many trees of reproductive age has prevented natural regeneration, leading to a drastic reduction in natural populations, which permitted the Brazilian Institute for the Environment and Natural Resources (IBAMA) to include it in the list of endangered species [57]. Consequently, IBAMA promulgated a set of rules, allowing for the extraction and controlled commercialization of rosewood from the Amazon, only through the preparation and approval of sustainable management and reforestation plans [58]. Rosewood essential oil industry has long been threatened by the scarcity of raw materials and increased environmental regulatory requirements to prevent species extinction [56]. The main limitations for developing production technologies for the species occur because their natural regeneration is irregular and infrequent. Although the propagation by cuttings has a survival rate of about 70%, the availability of matrices for the production of seedlings on a large scale is limited [59,60]. Other limiting factors are the scarcity of information on natural variability, ecology, and distribution of the species [17]. In addition, there is a difficulty for A. rosaeodora to produce seedlings. Rosewood propagates naturally through seeds, but these are often preyed upon by birds and insects before maturation [61] and by rodents after maturation [62].
A project sponsored by the Benchimol award in 2005 was implemented to guarantee the sustainable supply of rosewood oil in the Brazilian Amazon [56]. As part of the proposal, a germplasm collection of A. rosaeodora and other Aniba species was created. Based on this, tissue culture studies were carried out, which demonstrated that the rosewood could be propagated satisfactorily in vitro from the cultivation of its stem apices [63]. These activities aimed to facilitate researchers' access to plant material and reintroduce representative germplasm in regions where the species had already been extirpated, aiming at its in vivo conservation. The researchers of the project highlighted that the articulation of the research sector, government agencies, and the productive sector, represented by distilleries, riverside communities, and small producers, was indispensable for the development of an efficient model of propagation and production of seedlings on a large scale, in order to restore populations in their natural environment [56].

Scope of Collected Data
In this review, data collection of Aniba species was performed electronically, based on published articles, conference proceedings, theses, and ethnobotanical textbooks. The research was carried out in the Google Scholar, Science Direct, Scopus, and PubMed databases focused on chemical diversity and biological activities of essential oils of Aniba species. The keywords used were "essential oils", "chemical profile", "biological activity", "chemical diversity", "chemical markers of Aniba species". The authors built the map of sample distribution based on the information of the collection sites, available in the bibliographic references to each access (see Figure 1). Based on the survey, there are reports on the species Aniba burchellii Kosterm., A. canelilla (Kunth) Mez, A. cinnamomiflora C.K. Allen, A. citrifolia (Nees) Mez, A. duckei Kosterm., A. fragrans Ducke, A. gardneri (Meisn.) Mez, A. guianensis Aubl., A. hostmanniana (Nees) Mez, A. panurensis (Meisn.) Mez., A. parviflora (Meisn) Mez., A. puchury-minor (Mart.) Mez., A. riparia (Nees) Mez., A. rosaeodora Ducke, and A. terminalis Ducke, corresponding to 167 samples of essential oils. Aniba species showed geographic distribution in four countries of the Amazon biome: Brazil, Bolivia, Venezuela, and French Guiana. The most representative geographic area in specimen number was Brazilian Amazon with highlight to Pará State (67 samples) and Amazonas State (35 samples), predominantly in the cities of Belém (PA) (3 spp., 37 samples) and Manaus (AM) (3 spp., 16 samples), respectively. Aniba rosaeodora (68 samples) and A. canelilla (22 samples) were the species with the most significant number of studies, followed by A. parviflora (9 samples) and A. duckei (6 samples). Additionally, studies on EO samples extracted from A. cinnamomiflora and A. hostmanniana were found only for specimens collected in Venezuela.

Multivariate Statistical Analysis Based on the Essential Oils of Aniba Species
A multivariate statistical analysis was performed to group the compound classes as chemical markers of the Aniba species. The EOs from specimens of Aniba were divided into two groups according to the tissue: leaf, thin twig, and branch; stem, bark, and trunk wood. Seventy-six specimens of A. canelilla, A. duckei, A. fragrans, A. gardneri, A. hostmanniana, A. panurensis, A. parviflora, A. puchury-minor, A. riparia, and A. rosaeodora showed 84 EO samples of leaves, thin twigs, and branches. In contrast, thirty-eight EO samples of stems, barks, and trunk woods of A. canelilla, A. cinnamomiflora, A. citrifolia, A. gardneri, A. guianensis, A. parviflora, A. puchury-minor, A. rosaeodora, and A. riparia were represented by thirty-one specimens (see Figure 2). Total percentage of the following compound classes, monoterpene hydrocarbons (MH), oxygenated monoterpenes (OM), sesquiterpene hydrocarbons (SH), oxygenated sesquiterpenes (OS), phenylpropanoids (PP), and benzenoids (BZ), present in the leaves, thin twigs, branches, stems, barks, and trunk woods was applied as variables. The data matrix was standardized by subtracting the mean from each compound's value and then subtracting it by the standard deviation. The values were submitted to Hierarchical Cluster Analysis (HCA) based on Ward binding and Euclidean distance, using the software Minitab 17 (free 390 version, Minitab Inc., State College, PA, USA).

Essential Oils from Leaves, Thin Twigs and Branches of Aniba Species
Based on the dendrogram obtained by HCA, using the classes of compounds as variables, 84 EO from the leaves, thin twigs, and branches of Aniba species were classified into two main clusters, presenting a similarity of −516.68%. Cluster I was composed of twenty-four oils of A. canelilla, A. puchury-minor, A. gardneri, A. hostmanniana, A. riparia, A. fragans, A. parviflora, A. rosaeodora, and A. terminalis. The samples of cluster I were divided into two subgroups with a similarity of −214.58%. Subgroup I-1 was formed by seven oils from A. canelilla with a high concentration of benzenoids, especially 1-nitro-2-phenylethane (68.7-95.3%), and with a similarity of 71.50%. On the other hand, subgroup I-2 comprised oils rich in terpenoids (traces-89.3%), benzenoids (traces-45.4%), and phenylpropanoids (traces-44.5%) with a similarity of −112.69%. In this I-2 subgroup, seventeen samples of A. fragrans, A. gardneri, A. hostmanniana, A. parviflora, A. riparia, A. parviflora, A. rosaeodora, A. terminalis, and A. puchury-minor were grouped.

Seasonal Variation in the Aniba Volatile Constituents
The essential oil chemical composition of Aniba species can be influenced by environmental factors, such as light, humidity, soil, harvest time, as well as by oil variation in the plant organs and their stage of development [84,[99][100][101]. Different responses in EO production by Aniba species can be evaluated to improve the oil productivity in natural or cultivation conditions [102].
Aniba canelilla leaf EO (Aca16), collected in Manaus (AM, Brazil) during the dry and rainy season, showed similar chemical profiles with contents of 1-nitro-2-phenylethane of 88.5% and 88.9%, respectively ( Figure 4) [22]. However, the EO composition from a specimen of A. canelilla (Aca19) collected in Itacoatiara (AM, Brazil) changed drastically according to season. The average percentages of 1-nitro-2-phenylethane identified in the leaves and thin twigs of A. canelilla were 52.2% and 92.7% in the rainy and dry season, respectively ( Figure 4) [102]. In another study, the content of 1-nitro-2-phenylethane in the leaves of A. canelilla (Aca21) collected in Itacotiara (AM, Brazil) showed a high variation during the months of collection. The dry season showed variable contents (13.17-74.55%) compared to the rainy season (31.22-84.33%). On the other hand, these abrupt changes of 1-nitro-2-phenylethane were not observed in the stems (Aca21) (Figure 4) [101].
Linalool production in the leaf oils of two specimens of A. duckei (Adu2), collected in Manaus (AM, Brazil), showed significant variations according to season. The leaf oil content was higher in the dry season (62.4-76.69%) than in the rainy season (56.26-60.38%) ( Figure 5) [103]. In another study, conversely, a higher percentage of linalool was observed in the rainy season (63.16%) in comparison to the dry season (54.5%) for the leaves of A. duckei (Adu5). However, the linalool content of the thin twigs was maintained between 69.38% and 71.98% in the rainy and dry seasons, respectively ( Figure 5) [99].

Biological Activities
The studies on biological activities of EOs of Aniba species from the Amazon correspond to 63 oil samples. Among them, six samples had no chemical composition analysis. Several oils presented more than one specific activity, and the most frequent were antibacterial, toxicological, antifungal, antioxidant, and cytotoxic activities. The percentages of biological activities report the essential oils of Aniba species from the Amazon, and their details of biological assays are presented in Figure 6 and Table 2.

Antibacterial Activity
Antibacterial properties of various Aniba essential oils were evaluated using the disk diffusion and plate microdilution bioassay.
Essential oils have been used in diets for chickens as alternative antibiotic products and growth promoters. Due to their antimicrobial properties, the trunkwood oil of A. rosaeodora, collected in Belém (PA, Brazil), was evaluated in vivo against E. coli from the gastrointestinal tract broiler of chickens. Linalool (84.8%), α-terpineol (2.9%), and geraniol (1.0%) were the main compounds in the tested oil. Broilers were fed with rosewood oil at 40 days of age, and samples from the gastrointestinal tracts were inoculated on plates. The rosewood oil was also evaluated as a growth promoter but did not influence broilers' growth or fattening performance. The oil at 0.45% reduced the relative weight of the intestines. The commercial growth promoter virginiamycin (100 ppm) was used as control [110].
The oil of leaves and thin branches from A. rosaeodora, sampled in Adolpho Ducke Forest Reserve (AM, Brazil), containing linalool (93.6%), α-terpinolene (3.3%), and cislinalool oxide (3.0%) was evaluated by disk-diffusion method against bacteria isolated from a marine environment. The MIC of A. rosaeodora oil ranged from 250 to 450 µg/mL, compared to standard linalool (550-650 µg/mL), and the antibiotics amoxicillin (8-16 µg/mL), gentamycin (2-8 µg/mL), and polymyxin B (16 µg/mL). Aniba rosaeodora oil was more efficient against Aeromonas caviae and Enterococcus faecalis than the standard linalool. Linalool exhibited more significant activity against Klebsiella pneumonia and Providencia stuartii compared to the oil, while the oil and linalool presented the same activity against Aeromonas hydrophila [81]. The oil from stems of A. rosaeodora was also tested against E. coli and S. aureus and presented MIC of 200 and 150 µg/mL, respectively. The inhibition halos ranging from 11 to 15 mm, and the minimum bactericidal concentration (MBC) ranging from 400-350 µg/mL [82].

Antifungal Activity
The fungistatic properties of oils from Aniba were tested by the disk diffusion method. The trunkwood oil of A. canelilla was evaluated against the human pathogenic fungi Candida albicans, C. krusei, and C. parapsilosis. oil (5 mg/mL) was active against these fungi with a halo of inhibition 25 mm to C. krusei and C. albicans and 18 mm to C. parapsilosis. The oil's main compounds were 1-nitro-2-phenylethane (73.0%), methyleugenol (19.2%), and safrole (3.7%). MIC values and standard controls were not reported [77].
Different oil concentrations of Aniba duckei branches were tested on the growth of phytopathogenic fungi Colletotrichum gloesporioides and Fusarium oxysporum, displaying a mycelial inhibition of 65.0% and 72.09%, respectively, at 2%, and 100% inhibition for both fungi, at 0.4%. The oil was dominated by linalool (93.60%) with lesser amounts of cis-linalool oxide (3.03%) and α-terpinolene (3.37%). A linalool experiment itself supported its influence on the antifungal activity with a mycelial inhibition of 100% at a concentration of 0.2% [29].
The essential oils of leaves and branches of A. rosaeodora collected in Manaus (AM, Brazil) in different seasons were dominated by linalool in the leaves (69.0-71.0%) and in the branches (78-84%). The samples and racemic linalool (Sigma-Aldrich, St. Louis, MO, USA) exhibited antifungal activity against phytopathogenic fungi. All oils showed significant activity against C. guaranicola, Colletotrichum sp., C. gloeosporioides and A. alternata with MIC values ranging from 0.62 to 5.0 µL/mL [28].

Antioxidant and Photoprotective Activities
Essential oils have been recognized as natural antioxidants, because they contain compounds such as terpenoids and phenylpropanoids capable of reacting with radicals and reducing or neutralizing oxidative stress [122]. All Aniba oils evaluated below were tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays.
The photoprotective capacity of A. canelilla leaf and branch oils was evaluated by spectrophotometric method, applying a wavelengths scan from 280 to 400 nm [123]. At a concentration of 1% in isopropanol, the oils collected during the dry and rainy seasons displayed solar protection factor (FPS) varying from 7.54 to 14.08 in the leaf oil and 5.49-6.93 in the branch oil. Quercetin (FPS 261.23), benzophenone (FPS 289.80), and commercial sunscreen (FPS 72.08) were used as standards [112]. According to Brazilian legislation, a product to be used in photoprotection cosmetics must have an SPF value of at least 6 [124].

Cardiovascular Activity
Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of A. canelilla were evaluated in rodents. The main compounds of the oil were 1-nitro-2-phenylethane (52.4%), methyleugenol (38.6%), and selin-11-en-4α-ol (2.5%). Hypotensive effects of essential oil from A. canelilla bark were assessed in pentobarbital-anesthetized and conscious rats. Intravenous injections of EO (1 to 20 mg/kg) induced immediate and dose-dependent decreases in mean aortic pressure and heartbeat at doses of 1 and 5 mg/kg, respectively, in both experiments. The EO (100 µg/mL) also showed smooth-muscle relaxant activity in aorta preparations containing endothelium previously contracted with potassium (60 mM) [85].
The constituent 1-nitro-2-phenylethane (NPE), isolated in high-grade purity (98%) from the A. canelilla wood bark oil, collected at Paragominas (PA, Brazil), was investigated for its vasodilator effect in rat aorta, using isolated vessel bioassays. The NPE (0. 7-1984.6  Thus, it is suggested that NPE appeared to exert vasodilatory effects compatible with a drug's profiles that induce stimulation and improve production in aortic tissues [114]. A study investigated the action of 1-nitro-2-phenylethane (NPE) (synthetic), the main constituent of A. canelilla oil, in the cardiovascular responses of spontaneously hypertensive rats (SHRs). Intravenous injections of oil (1-20 mg/kg) and NPE (1-10 mg/kg) elicited dose-dependent hypotensive and bradycardic effects. The vasorelaxant effect, induced by oil and NPE, was also tested in superior mesenteric artery from SHRs, at concentration 0.1-1000 µg/mL. Both oil and NPE relaxed superior mesenteric artery (SMA) preparations, pre-contracted with 75 mM KCl, with IC 50 values of 294.19 and 501.27 µg/mL, respectively. The inhibitory effects of oil and NPE on contractions were induced by the exogenous addition of Ca 2+ (75 mM) [24]. The mechanisms underlying the vascular effects of NPE were investigated in rat isolated thoracic aortic preparations, at concentration 0.1-100 µg/mL, in NPE relaxed endothelium-intact or endothelium-denuded aortic preparations pre-contracted with to KCl (60 mM) or phenylephrine (1 µM) [115].
The cytotoxicity of A. rosaeodora wood oil was evaluated through the maximum nontoxic concentration (MNTC). The analysis was determined microscopically by observing cell morphological changes at 24, 48, and 72 h of incubation, followed by MTT assay. The cells used were bovine kidney CRIB, chicken-embryo related CRER, mouse fibroblast cell L929, and feline kidney cell lines CRFK. The oil showed 50% cytotoxic concentrations (CC 50 ) of 104.8%, with a selectivity index of 5. The oil composition was not reported [120]. The A. rosaeodora leaf and thin branch oil containing linalool (93.60%), α-terpinolene (3.37%), and cis-linalool oxide (3.03%), linalool standard (1000-7.8 µg/mL) and the positive control benznidazole (200-0.78 µg/mL) were evaluated by MTT method on cell viability of peritoneal macrophages from Balb/C mice. The oil and linalool did not exhibit cell toxicity at the highest concentration analyzed (CC 50 > 1000 µg/mL) [81].
The A. parviflora bark oil, collected in Curuá, municipality of Santarém (PA, Brazil), containing linalool (16.3%), α-humulene (14.5%), δ-cadinene (10.2%), α-copaene (9.51%), and germacrene B (7.58%), was evaluated on the growth of human hepatocellular carcinoma cells in the culture and in the development of tumors in a xenograft model. The oil was selective for HepG2 cells with IC 50 values of 9.05 µg/mL. Based on their bibliographic survey, the authors considered essential oils with IC 50 values < 30 µg/mL the most promising for the development of cytotoxic drugs in cancer therapy. With respect to the development of tumors, the animals treated with the oil showed a reduction in tumor weights 0.40 g and 0.17 g at the 40 and 80 mg/kg doses of oil [119].

Nervous System Activity
Essential oils and their components can induce innumerable physiological actions in the central nervous system, such as analgesic, anxiolytic, relaxing, sedative, and behavior and perception effects, in addition to the treatment of epilepsy and degenerative diseases such as Alzheimer's and Parkinson's diseases [125].
The A. rosaeodora and A. parviflora leaf oils and linalool standard 97% were evaluated in the central nervous system of rodents, employing neurobehavioral tests. The sponta-neous locomotion was smaller in the group treated with 3.5 mg/kg of A. rosaeodora oil when compared with the non-treated control group. In the depressive type method, the A. rosaeodora oil (35 mg/kg) and linalool (30 mg/kg) caused a reduction in the latency period and an increase in the self-cleaning time, a similar behavior was noted for the control group, fluoxetine (10 mg/kg). Both oils and linalool standard significantly decreased the immobility time of the animals when compared to the positive control fluoxetine. The major components of the oil from A. rosaeodora were linalool (88.6%), while in A. parviflora were linalool (45.0%), β-phellandrene (17.3%), and α-phellandrene (4.1%) [71].
The oils from leaves of A. rosaeodora (linalool, 90.5%) and A. parviflora (linalool 29.6%, β-caryophyllene, 10.9%, and α-phellandrene, 10.5%), standard linalool 97%, and linalool isolated from the oil of A. rosaeodora were evaluated as anesthetics in young Colossoma macropomum fish. At concentrations of 0.025 and 0.05 µL/mL, the A. rosaeodora oil was twice as efficient in light sedation (123.0 s, 68.3 s), deep sedation (355 s, 204 s), and deep anesthesia (636.4 s) compared to A. parviflora oil, and standard and isolated linalool, which needed two-fold concentrations to provoke the same effects. Fish exposed to 0.05-0.2 µL/mL of A. rosaeodora oil, 0.1-0.3 µL/mL of A. parviflora oil, and both linalool samples reached deep anesthesia 1-10 min. The induction time for all anesthesia stages decreased with the increasing concentration of the anesthetics. The isolated linalool showed the lengthier time for anesthesia induction in some stages and recovery at 0.1 and 0.2 µL/mL, in comparison to standard linalool [118]. (3S)-(+)-Linalool and (3R)-(-)-linalool have different properties on the central nervous system, related to depressant effects, analgesic and anti-inflammatory activities [126].
The sedative effects of A. rosaeodora trunk wood oil in rats and mice were investigated and showed decreased latency and increased duration of sleeping time at doses of 200 and 300 mg/kg. On the other hand, the combination of the oil (100 mg/kg) and the sedative agent pentobarbital (40 mg/kg) increased the action. The blocking effect of oil for 30 min on rat sciatic nerves from 75.0% at 2 µg/mL to 95.0% at 100 µg/mL was irreversible. The main compounds of the EO were linalool (87.7%), α-terpineol (3.1%), trans-linalool oxide (1.5%), and cis-linalool oxide (1.5%) [92].
Relaxant and anticonvulsant activities on the central nervous system of A. rosaeodora wood oil and linalool were evaluated on adenylate cyclase activity (an enzyme that catalyzes cAMP hydrolysis) in a chick retina model. The decreased levels of cAMP protect against seizures in a variety of epilepsy models. The cAMP accumulation was stimulated by forskolin (10 µM), and inhibited by the EO (6 and 17.5 mM). The effects were also evaluated in the presence of the 3-isobutyl-1-methylxanthine (500 µM), an inhibitor of cAMP, which did not interfere with the positive effects of the EO (1-6 mM) on cAMP production. The oil, (3R)-(-)-linalool and racemic (±)-linalool displayed IC 50 values of 130, 310, and 300 µM, respectively. The inhibition of cAMP takes part in the molecular mechanisms underlying the relaxant and anticonvulsant effects of EO and linalool in the central nervous system. The trunk wood of A. rosaeodora collected in Belém (PA, Brazil) was mainly composed of linalool (84.8%), α-terpineol (2.9%), and geraniol (1.0%). Its enantiomeric distribution of linalool was analyzed by GC chiral column and revealed a nearly racemic mixture with the proportion 50.62% of (3R)-(-)-linalool and 49.38% of (3S)-(+)-linalool [90].
The anti-trypanosomal activity of A. canelilla stem EO, rich in 1-nitro-2-phenylethane (83.68%) and methyleugenol (14.83%), was evaluated against Trypanosoma evansi. The assays were performed using the oil, the two main isolated constituents, and a mixture (1:1) at concentrations ranging from 0.5 to 2.0%. The tested oil presented a trypanocidal profile similar to the positive control, diminazene aceturate (0.5%). After 6 h, no parasites were found alive (complete motility cessation) in all oil concentrations tested. The compound 1-nitro-2-phenylethane (0.5%) was able to reduce the number of live trypanosomes to zero after only 3 h; methyleugenol and the mixture (2.0%) caused the death of the trypanosomes after 1 h [86].
The antiviral activity of oil from A. rosaeodora trunkwood, collected at Zoobotanical Park of the Emilio Goeldi Museum, located in Belém (PA, Brazil), showed cytopathic effects through visual microscopic analysis and inhibited the viral growth of avian metapneumovirus (EC 50 : 20.86 µg/mL). The oil composition was not reported [120].

Biological Activities from Commercial Aniba Rosaeodora Essential Oils
Although most biological activities reported for commercial A. rosaeodora oils do not describe the plant's part or chemical composition, it is essential to know the wide application given to them. The antimicrobial activity of oils obtained from Sunspirit Oils Pty Ltd., Australia, was evaluated by agar dilution and broth microdilution methods and exhibited activity against Acinetobacter baumanii, Aeromonas sobria, and E. coli (MIC 1.2%), Salmonella typhimurium, S. aureus, and C. albicans (MIC 0.25%), E. faecalis, K. pneumoniae and Serratia marcescens (MIC 0.5%) using agar dilution assay; Mueller Hinton agar, with 0.5% (v/v) tween-20 was used as positive growth control. However, the assays performed by the microdilution method against C. albicans, E. coli and S. aureus showed MIC values of 0.12%, the EO composition and standard were not mentioned. The results obtained by each of these methods may differ as many factors vary between assays [129,130], these include differences in microbial growth, exposure of micro-organisms to the oil, the solubility of oil or oil components, and the use and quantity of an emulsifier. These and other elements may account for the significant differences in MICs obtained by the agar and broth dilution methods in this study [131].
A rosewood oil sample purchased from Erbamea (Istrana, Treviso, Italy), containing linalool (60.1%), limonene (19.2%), geraniol (7.8%), and cymene (4.1%) showed antibacterial activity by the broth microdilution method. The MIC values were 250 µg/mL to Bacillus cereus and A. baumannii, 500 µg/mL to B. subtilis, S. aureus and E. coli, and 2000 µg/mL to Serratia marcescens and Yersinia enterocolitica. In addition, the combination of the oil with the drug gentamicin was evaluated for its synergistic effect. The interaction was defined quantitatively as a fractional inhibitory concentration (FIC). the synergism is indicated when FIC values are below 0.5. The oil in association with gentamicin revealed a strong synergistic mode of action. MIC values were reduced to an interval varying from 10 to 100 µg/mL. Mueller Hinton Broth was used as positive growth control [95]. An A. rosaeodora wood oil, commercially obtained from Brazil, was mainly composed of linalool (80.0%) and exhibited antibacterial activity against B. cereus, Micrococcus luteus, Alcaligenes faecalis, and P. aeruginosa, with inhibition zones varying from 12 mm to 19 mm, and against S. aureus, S. faecalis, and Enterobacter cloacae with inhibition zones from 5 mm to 7 mm. The same oil indicated antifungal potential against C. albicans and Aspergillus niger, with inhibition zones of 33 mm and 32 mm, respectively, and Rhizopus oligosporus with only a 2 mm inhibition zone. The assays were performed by the disk diffusion method. The origin of the sample, MIC values, and reference standards was not reported [132]. Rosewood oil sample purchased from Stony Mountain Botanicals, Ltd. (Loudonville, OH, USA) was evaluated against Aeromonas salmonicida subsp. salmonicida, a bacterium that causes fish furunculosis, by the disk diffusion method. The inhibition zone of the oil was 16.7 mm, which is considered a moderate inhibition. The MIC value was not determined [133]. The diameter of inhibition zones, including the disc diameter, is considered as weak (10-13.9 mm), moderate (14-18 mm), or strong (>18 mm), according to [107]. Another rosewood oil sample, purchased from Anthémis Aromatherapie (Oosterstreek, The Netherlands), was evaluated by the broth dilution method against B. cereus and showed MIC value 1.0% to vegetative cells and MIC value >1.00% to spore germination [134].
The antifungal activity of a rosewood oil sample obtained from the Institute for Medicinal Plant Research "Dr. Josif Pancic", Serbia, containing 81.27% of linalool, was evaluated by the disk diffusion method. The inhibition of mycelial growth and inhibition of spore germination was performed by macro-dilution and micro-dilution assays. The oil was active against all fungi in the micro-dilution method, with MIC value from 1 to 10 µL/mL for Alternaria alternata, Aureobasidium pullulans, Cladosporium cladosporioides, C. fulvium, Fusarium tricinctum, F. sporotrichoides, Phomopsis helianthin, and Phoma macdonaldii. Meanwhile, in the macro-dilution method, the MIC ranged from 0.5 to 7.5 µL/mL for A. alternata, A. pullulans, C. fulvium, P. helianthin, and P. macdonaldii. Bifonazole was used as a positive control [94]. Rosewood oil samples obtained commercially in Pretoria and Johannesburg, South Africa, were tested against Geotrichum citri-aurantii, a postharvest pathogen of Citrus, by incorporating 0.5 µL/mL of oil into the culture medium, and showed mycelial growth inhibition of 12.1%, which was considered low. Kenopel ® 200SL (1 µL/mL) was used as positive control [135].
The nematicidal activity from A. rosaeodora oil purchased from Berje (Bloomfield, NJ, USA) was evaluated against Bursaphelenchus xylophilus by immersion bioassay during a 24-h exposure. The oil at 10 mg/mL had a significant lethal activity of 94% mortality and toxicity LC 50 2.99 mg/mL. Ethanol-Triton X-100 solution was used as control, and fenitrothion was used as a standard nematicide but was ineffective (LC 50 > 10 mg/mL) [136]. The lethal activity was considered strong, with mortality above 80% [137].
The cytotoxic potential of commercial A. rosaeodora oil was also evaluated. A sample of unknown origin containing linalool (80%) and α-terpineol (4.5%) was tested against human epidermoid carcinoma cell line (A431), human epidermal keratinocytes CRL-2404 (HEK001), immortalized HaCaT cells (HaCaT), and on normal primary human epidermal keratinocytes (NHEK). The MTT assay showed a reduction in cell viability observed in A431 and HaCaT cells (<20% viability) at 0.4 µL/mL of EO for 4 h, whereas HEK001 and NHEK cells were much less affected (>70% viability), the prolonged incubation for 12 h in the HEK001 and NHEK cells reduced viability to approximately 50%. The EO triggered the production of reactive oxygen species, induced depolarization of the mitochondrial membrane, and caused caspase-dependent cell death [97].
The insecticidal and larvicidal effects of commercial samples of rosewood oil have also been evaluated. A sample obtained from the Fragrance and Flavour Development Center, India, was tested as a repellent against A. aegypti using the cage and cone bioassay methods. The oil was effective as a repellent until 1.5 h, compared with synthetic repellents N,Ndiethyl-m-toluamide (DEET), and N,N-diethylphenylacetamide (DEPA), used as positive controls, and provided complete protection ranging from 5 to 6 h. The EO exhibited 10%, 66%, and 100% knockdown effects at 0.1%, 1%, and 5%, respectively, and showed a practical knockdown dose value (KT 50 ) of 2.029%. Malathion and acetone were used as positive and negative controls, respectively. The gas chromatograph coupled-electroantennogram detection showed that linalool and oxide linalool elicited a spick response in the antenna of A. aegypti female mosquito. However, the concentrations of these compounds were not mentioned [138]. A sample obtained from Edens Garden, San Clemente (CA, USA) was evaluated as a vapor for enhancement of deltamethrin efficacy in pyrethroid-susceptible and resistant strains of the A. aegypti mosquito. Vapor bioassays were made by exposing mosquitoes to the vapor of essential oil (100 µL), which showed 48.33% mortality, ( [139]). The larvicidal activity of EO from the heartwood of A. rosaeodora obtained from Guangzhou Yuxitang Cosmetics Co., Ltd. (China) was tested against Aedes albopictus larvae at 100 ppm the EO showed 5.0% of mortality [140].
Aniba rosaeodora oil, purchased from a commercial company with unknown origin, was tested regarding its anesthetic efficacy in goldfish (Carassius auratus). Linalool was the main compound from the oil (86.23%), followed by cis-linalool oxide (1.06%) and β-selinene (0.95%). The lowest effective concentration (LECs) for the oil was 0.25 µL/mL, which showed rapid induction and recovery of anesthetic effect. No mortality or adverse effects occurred with the fish. Thus rosewood oil was considered a new potential anesthetic agent for fish species [98].
A study showed the comparative effects of (3S)-

Conclusions
The genus Aniba has a predominantly Amazonian distribution and many species have been used as traditional herbal medicines. This review demonstrated the high chemical and biological potential of essential oils from their species. The multivariate analysis of the chemical classes present in the essential oils allowed the identification of chemical markers, which contributed to fill the morphological and phylogenetic gaps of the genus. The benzenoids and phenylpropanoid were well represented for A. canelilla, A. guianensis, A. gardineri and A. puchury-minor species. On the other hand, A. rosaeodora and A. duckei were characterized by the high concentration of oxygenated monoterpenes. The oils of A. fragrans, A. gardneri, A. hostmanniana, A. parviflora, A. riparia, A. parviflora, A. rosaeodora, A. terminalis, and A. puchury-minor showed significant chemical diversity for their main compound classes such as terpenoids, benzenoids, and phenylpropanoids.
Aniba essential oils and their compounds have a wide range of pharmacological activities: 1-Nitro-2-phenylethane, a major component in A. canelilla essential oils, is responsible for the cinnamon-like odor of the plant, and has shown hypnotic, anticonvulsant, anxiolytic, vasorelaxant, hypotensive, and anti-inflammatory activities. The essential oils of A. rosaeodora, A. duckei, A. fragrans and A. parviflora are rich in linalool, which give these species a floral-like odor. Linalool has shown antimicrobial, antiparasitic, antiinflammatory, and central nervous system effects. Both enantiomers of linalool have shown anxiolytic and anticonvulsant effects, but (3R)-(-)-linalool is apparently more active than (3S)-(+)-linalool in terms of sedative activity. The high concentrations of linalool or 1-nitro-2-phenylethane in Aniba essential oils likely account for the traditional uses of these plant species as well as the biological activities of the oils.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.