The Genus Psychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties

Psychotria genus (Rubiaceae) is featured into the angiosperm, being the most speciose genus comprising approximately 1600 species. The available references demonstrate that Psychotria has several uses on traditional medicine including spiritual and cultural purposes, and presents great potential on pharmacological properties, especially the one related to neurodegenerative diseases. Despite its wide biological properties, this genus has shown complex phylogenetic analysis due to lack of chemotaxonomic information. In recent years, the interest in these plants has increased considerably and many active compounds have been isolated. Phytochemical investigations described in the literature confirmed the indole alkaloids as the major compounds and besides that, another particular chemical constituent are cyclic peptides, known as cyclotides. This present review will cover the relevant literature from 1962 until 2015, and outlines the current data on taxonomy, chemotaxonomy, traditional uses, pharmacological properties, chemical composition and ecological approach from Psychotria genus.


Introduction
It is believed that about 80% of the population worldwide, especially Asian and African countries use plants and herbal medicines as a source of medicinal agents and primary health care.Traditional medicine is an important form of health care for many people and covers a wide variety of therapies and practices, which vary from country to country. 1 Many useful drugs were inspired from plants sources and nature continues to be a major source of new structural leads, and effective drug development. 2hus, based on this estimates it is of great importance the proper identification and classification of plant species.
The genus Psychotria belongs to the Rubiaceae family (subfamily Rubioideae, tribe Psychotrieae) and is the most speciose angiosperm genera (flowering plants) comprising approximately 1600 species.These species are mostly shrubs, although are known, vines, herbaceous and epiphytes, widely distributed in tropical and pantropical countries. 3,4In South America countries the leaves of P. viridis is largely used by Amazon indigenous peoples as a component of the hallucinogenic drink "ayahuasca".6][7][8] Some other plants from the genus Psychotria (leaves, roots and rhizomes) have been widely used in traditional medicines for treating bronchial and gastrointestinal disorders such as cough, bronchitis, ulcer and stomachache.Also, they are commonly used for infections of the female reproductive system. 9esides the variety of ethnopharmacology uses the taxonomy of Psychotria genus is very complex and a comprehensive phylogenetic analysis of this genus lack diagnostic characters.Until now, schizocarps and bacterial leaf nodules have been used for recognizing formal groups in Psychotrieae, but a robust phylogeny of the tribe, including their evolution and taxonomic value have not been described. 10n increasing number of phytochemical studies have been investigated in Psychotria plants in the last decade contributing significantly to the ethnobotanical, pharmacological and chemotaxonomic studies in addition to the molecular phylogenetic analysis. 11The genus Psychotria can be characterized as an abundant source of indole, monoterpene indole, quinoline and isoquinoline alkaloids as well as flavonoids, coumarins, terpenoids and cyclic peptides that might be responsible for a wide range of biological activities (cytotoxicity, analgesics, antivirals, antifungals and modulators of the activity of the central nervous system) found on those species. 12,13he purpose of this review is to provide an update of the recent ethnopharmacology, taxonomy, chemotaxonomy, chemical approach, pharmacological and ecological properties of the extracts and isolated compounds identified in some plants belonging to the genus Psychotria.

Method
In the present review, information on Psychotria genus was gathered via searching scientific databases including PubMed, Elsevier, Google Scholar, Scopus, Web of Science, Cybase and SciFinder by using the keyword Psychotria.
In order to retrieve the available literature pertaining to this genus and concisely illustrate it using an informative graph, a SciFinder search was performed in September 2015.Figure 1 shows the number of articles retrieved when using the keyword Psychotria for year, which demonstrate the relevance of this genus.It is remarkable the large increase in publications in recent years; whereas in 1995 had been described about 10 scientific papers, in 2014 more than 50 scientific papers have been published on Psychotria genus and this number continues to increase in 2015.

Taxonomy and Chemotaxonomic Approach of Genus Psychotria
The tribes Palicoureeae and Psychotrieae include about 91% of the species of the Psychotrieae alliance and about 24% of Rubiaceae as a whole.Members of these groups of plants are very important components of various terrestrial ecosystems throughout the tropics.The tribe Psychotrieae is well established, but the same does not occur for their genera.The Amaracarpus Blume, Calycosia A. Gray, Dolianthus C. H. Wright, Hedstromia A. C. Sm., and Hydnophytum Jack genera, for example, were nested within Psychotria L. rendering the latter genus paraphyletic. 10efore 2014, the relationships between among most members of tribes Psychotrieae and Palicoureae were still unknown partly, due to the poor or lack of sampling from some biodiversity hotspots.Schizocarpous fruits and bacterial nodules were used for recognizing authentic groups, but the evolution and taxonomic value of these characters have not been addressed based on a broadened sampling of the tribe.
In 2014, a robust phylogenetic study was done for establishing new generic circumscriptions between these tribes.Razafimandimbison et al. 10 established that Psychotria includes all its allied genera, rendering the tribe Psychotrieae monogeneric.It was confirmed the paraphyly of Psychotria, because the genera Amaracarpus, Calycosia, Camptopus, represented by its type C. mannii (= P. camptopus), Dolianthus, Hydnophytum, Grumilea Gaertn., represented by the type G. nigra (= Psychotria nigra), Mapouria, and all the WIOR genera (Apomuria, Cremocarpon, Psathura, Pyragra, and Trigonopyren) are nested within a broadly defined Psychotria. 10 A great variety of species of plants belonging to the genus Psychotria have been phytochemically investigated and several compounds have been isolated and identified.Thus, the phytochemical approach, which involves a range of compounds, became a very useful tool to understand and establish the chemotaxonomy of Psychotria.In this context, different classes of organic compounds have been reported. 11nalysis of the chemical profile of some species like P. borucana contributed to the taxonomic rearrangement, which was grouped together with P. ipecac in Carapichea genus. 14The comparative study of 57 methanol extracts of Psychotria clearly showed a distinct chemical separation of P. borucana due to the bigger accumulation of alkaloids type dopamine-iridoid rather than alkaloids type tryptamineiridoid, which is commonly found in other species.In this context stands out the borucoside alkaloid (1), which was first described in this species. 14s an example, the species Psychotria acuminata was renamed to Palicourea acuminata (Benth.)and from methanol extract of its leaves and stem bark, were isolated several alkaloids type tryptamine-iridoids.Among those structures, lagamboside (2) is a novelty because represents an unusual pattern of N-glycosylation and a iridoid closely related to the unusual alkaloid vallesiachotamine (3). 15lso, the co-occurrence of another rare alkaloid, the bahienoside B (4), comprising two iridoids structures, is of great interest and contributes to the chemotaxonomy of this species (Figure 2). 16esides the alkaloids, some other secondary metabolites also can be used as taxonomic markers.Vomifoliol (5), for example, is a megastigmane sesquiterpene that has been reported on Psychotria gitingensis from the Philippines.This compound has an α,β-unsaturated ketone that might be responsible for the observed orange spots in Dragendorff's test. 17It is well established that certain compounds can give false-positive alkaloid reactions with Dragendorff's spray reagent. 18lthough P. gitingensis from Philipines did not present alkaloids, is highly recommended to verify the absence of alkaloids in species collected in other regions.

Traditional Uses of Psychotria Species
Plants from the genus Psychotria (leaves, roots, barks and rhizomes) are commonly used in traditional medicines for treating bronchial and gastrointestinal disorders such as cough, bronchitis, ulcer and stomachache.Also they are used for infections of the female reproductive system. 9,19,20P. poeppigiana is a native plant widely used in Latin America for the treatment of a variety of diseases, particularly gastrointestinal disorders, stomachaches and fever. 21In Panama, this plant is also used in traditional medicine for the treatment of dyspnea. 22P. colorata is a plant commonly found in Amazon region of Brazil, which is used as painkiller for earache and abdominal pain by traditional rural communities. 23n Tamil Nadu (India) several tribes use the leaves, flowers and fruits from P. nudiflora Wt. & Arn. and P. nilgiriensis Deb.& Gan for rheumatism treatment.24 Other applications are anti-emetic and against snakebites in Central and South America countries.25,26 In S. Tomé and Príncipe (Africa), P. subobliqua is used to treat toothaches and mouth inflammation.27,28 P. ipecacuanha (Brot.)Stokes is another species important on traditional medicine. Itas an important history as emetic, expectorant, amebicide and also in the treatment of dysenteries.29 Besides the properties already described, some Psychotria species are also used against microbial infections (malaria, amoebiasis, viral and venereal diseases), cardiovascular and mental disorders.30,31 Figure 2. The structures from Psychotria genus.
The Genus Psychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties J. Braz.Chem.Soc.6][7][8] "Ayahuasca's" psychoactive effects are similar to LSD (lysergic acid diethylamide) and psilocybin. 83][34] A qualitative empirical study made by Anja and Rolf 35 explored the ritual use of "ayahuasca" in the treatment of addictions.The recently findings indicate that "ayahuasca" can serve as a therapeutic tool which catalyze neurological and psychological processes that support recovery from substance dependencies.Some Psychotria species distributed in China are used in folk medicines for swelling and relieving muscles, activating collaterals and strengthening bones and muscles. 36P. henryi is one of these species that has been used in traditional Chinese medicine for invigorating spleen to eliminate dampness and for regulating qi-flowing to relieve pain. 37

Alkaloids
Several classes of alkaloids found on Psychotria genus is already described in the literature and some others are still under investigation (Figure 3).

Terpenoids
The phytochemical study on P. yunnanensis allowed the isolation of four norisoprenoids (58-61) and one monoterpenic acid (62).From the aerial parts of this plant a new type of sesquiterpene derived from acorane, possessing rare spirobicyclic carbon skeleton, known as psycacoraone A, was identified (63). 36,93rom the leaves of P. cadigensis, an endemic species from Philippines, were isolated three nor-sesquiterpenes: vomifoliol (5), loliolide (61) and isololiolide (64).This was the first time that the phytochemical study of this species was described in the literature. 43In P. vellosiana Benth.was reported the presence of squalene (65), lupeol (66), a mixture of sitosterol (67) and stigmasterol (68) obtained from the aerial parts of the plant.Also according to the authors this is the first time that squalene was described on the genus. 89From the floral essential oil of P. eurycarpa Standl.were obtained some components such as linalool (69)  and α-terpineol (70). 49The extract from leaves and roots of P. stachyoides Benth.provided β-sitosterol (71) and stigmasterol glucosides (72) (Figure 4). 12

Tannins
A study realized for P. carthagenensis, P. leiocarpa, P. capillacea and P. deflexa showed not only high flavonoid concentration in the extracts, but also the presence of condensed tannins. 20,98For P. reevesii Wall.was realized a screening based on color reactions, high performance liquid chromatography (HPLC) analytical and nuclear magnetic resonance (NMR) spectroscopy.The obtained results revealed the presence of condensed tannins. 99

Cyclic peptides
Besides the presence of traditional secondary metabolites, another main chemical constituents are cyclic peptides, especially cyclotides.This peptide group is characterized by a peculiar cyclic structure with approximately 30 amino acids residues with cyclic cystine motif (CCK), conferring them a remarkable stability.All cyclotides sequences described in the literature from Psychotria species are presented on Table 2. 100,101

Neurodegenerative diseases
As previously demonstrated on section 4, plants from Psychotria genus commonly affect the central nervous system.Recently, several Psychotria alkaloids, mainly monoterpene indoles and β-carboline alkaloids have been reported for their inhibitory properties against acetylcholinesterase and monoamine oxidase proteins, which are enzymatic targets related with neurodegenerative diseases. 60,102Alkaloidal fractions of Psychotria suterella and Psychotria laciniata as well as two monoterpene indole alkaloids isolated from these fractions were evaluated against monoamine oxidases (MAO-A and MAO-B) obtained from rat brain mitochondria. 59The monoterpene indole alkaloids lyaloside (26) and strictosamide (22)  exhibited inhibitory effect on MAO-A (IC 50 50.04and 132.5 μg mL -1 , respectively) and MAO-B (IC 50 306.6 and 162.8 μg mL -1 , respectively). 59,60,84These data confirm the previous study made by McKenna et al. 5 which also demonstrated inhibition of MAO by alkaloids compounds present in hallucinogenic "ayahuasca" drink.
Some other effects on the central nervous system involving acetylcholinesterase (AChE), butilcolinesterase (BChE) have also been reported for various other alkaloids of Psychotria sp.The β-carboline quaternary alkaloids prunifoleine (84) and 14-oxoprunifoleine (21)  inhibited the enzymes AChE by a non-competitive mode  of inhibition, although inhibited both BChE and MAO by a time-dependent mode of inhibition.In addition, the monoterpene indole alkaloids angustine (36), vallesiachotamine lactone (85) and vallesiachotamine (3) also inhibited BChE and MAO. 59,60The monoterpene indole alkaloid strictosidinic acid (11) isolated from the leaves of Psychotria myriantha Mull.Arg.reduced levels of serotonin (5-HT) and DOPA C, a metabolite of dopamine neurotransmitter from the MAO action in rat hippocampus inhibiting probably the precursor enzyme of the biosynthesis of 5-HT.A reduction of 83.5% in 5-HT levels was observed after intra-hippocampal injection (20 μg μL -1 ).In addition, decreased levels of DOPA C suggests that strictosidinic acid (11) have action on the dopaminergic system by inhibiting MAO, which was confirmed by enzymatic assay in rat brain mitochondria.After treatment by intraperitoneal route (10 mg kg -1 ), a reduction of 63.4% in 5-HT levels and 67.4% in DOPA C values were observed. 69,71This monoterpene glycosylated indole alkaloid also showed peripheral analgesic and antipyretic activities on mice. 70,105hose findings suggest that species from genus Psychotria might be an interesting source for new MAO inhibitors.
The peptide cyclopsichotride A (Table 2), isolated from the extract of P. longipes inhibited the interaction of neurotensin radiolabeled with their membrane receptors on HT-29 cells (intestinal colon carcinoma) and stimulated the increase of calcium intracellular in two different cell lines not expressing neurotensin receptors.It suggests that this compound might be an antagonist of these types of receptors as well as also being able to act via other receptors. 65udies made by Hellinger and co-workers 104 described the bioactivity-guided isolation of a cyclotide from P. solitudinum as an inhibitor of a serine-type protease, namely, the human prolyl oligopeptidase (POP).It yielded the isolated peptide psysol 2 (Table 2), which exhibited an IC 50 of 25 μmol L -1 .The enzyme POP plays an important role in memory and learning processes, and it is currently being considered as a therapeutic target for some psychiatric and neurodegenerative diseases, such as schizophrenia and Parkinson's disease.

Antioxidant and analgesic properties
The monoterpene indole alkaloids psychollatine (6)  and brachycerine ( 14) isolated from P. umbellata and P. brachyceras, respectively, presented antioxidant and antimutagenic activity. 42,106,107In the study made by Both et al., 87 it was described the analgesic properties of isodolichantoside (49) isolated from P. umbellata.These same analgesic properties have also been reported to alkaloid hodgkinsine (39) isolated from another Psychotria species, P. colorata which is in agreement with the previous study made by Amador et al. 108 and Elisabetsky et al., 109 which reported the alkaloid analgesic activity of leaves and flower extracts.
The alkaloid fraction from the ethanol extracts of flowers and leaves of P. colorata consisted primarily of a mixture of pyrrolidinoindoline alkaloids quadrigemine C (40), calycanthine (56), isocalycanthine (57) which showed analgesic activity by inhibiting the interaction of naloxone [H 3 ] with proteins of the cell membrane and also inhibiting  the activity of the enzyme adenylate cyclase in rat.Thus, this suggests an action in opiodergic system since alkaloids did not inhibit the interaction of GMP [H 3 ]-pnp (guanylyl imidodiphosphate) with the proteins during the Tail-flick analgesic test. 46,47,1103.Anti-inflammatory activity Ten Psychotria species were collected in the Brazilian Atlantic Forest (P.pubigera, P. ruelliifolia, P. suterela, P. stachyoides, P. capitata, P. glaziovii, P. leiocarpa, P. nuda, P. racemosa and P. vellosiana) in order to check if they could inhibit the production of nitric oxide (NO) in macrophages and if they have free-radical scavenging properties.From the evaluated extracts for in vitro antiinflammatory activity, P. suterela, P. stachyoides and P. capitata were the most active in inhibiting macrophage NO production.Interestingly 5,6-dihydro-β-carboline alkaloids were found in all of the ten species evaluated, besides, indol alkaloids were also detected in P. nuda and P. suterela. 111

Antiviral activity
Ipecac alkaloids are secondary metabolites produced in the medicinal plant P. ipecacuanha.This species is known as a traditional herbal medicine, which was introduced to western medicine over 300 years ago and the syrup is commonly used as emetic for the treatment of patients who ingested poisons.Emetine (12) is one of the active compounds found in the syrup and the main alkaloid of Ipecac, which possesses a monoterpenoidtetrahydroisoquinoline skeleton and is formed by condensation of dopamine and secologanin. 56Ementine (12) was evaluated as an antiviral agent against human immunodeficiency virus (HIV).It inhibited HIV-1 replication by interfering with reverse transcriptase activity and the obtained results showed that in cellular models reduced about 80% of HIV-1 infection.It also blocked HIV-1 infection of RT M184V mutant in in vitro reactions with isolated HIV-1RT and intravirion. 95ix acetone subfractions of ethanolic extract from P. serpens significantly suppressed Herpes simplex virus type 1 replication on Vero cells.The viability of cells was not significantly decreased as well as deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein synthesis were unaffected showing that inhibitory mechanism of viral replication was not through cytotoxicity and/or blocking of Vero cells growth. 1126.Cytotoxic activity Some other bioactive compounds from the polypyrrolidinoindoline alkaloid family have been described as cytotoxic agents.The compounds quadrigemine A (88), quadrigemine B (89), isopsychotridine C (90) and psychotridine (42) isolated from P. forsteriana leaves showed cytotoxic activity in rat hepatoma cell line (HTC strain) and were more potent than vincristine, an antitumor agent.51,76 These same compounds also inhibited the aggregation of washed human platelets induced by adenosine diphosphate (ADP), collagen and thrombin.113 In addition, the compounds vatine (91), vatamine (92) and vatamidine (93) exhibited strong cytotoxic activity in rat hepatoma cells and in human leukemia cells.52 The bioguided fractionation of P. serpens allowed the isolation of the triterpenoid ursolic acid (94), which showed cytotoxicity in leukemic cells P-388, L-1210 and A-549 human lung carcinoma.It also showed moderate cytotoxicity in human colon tumor cells (HCT-8) and breast cancer cells (MCF-7).80 From Psychotria sp.Zhang et al. 114 isolated six new triterpenoid saponins called psychotrianosides A-F (95-100) and some other two compounds already known psychotrianoside G (101) and ardisianoside D (102).In vitro assays showed that the evaluated compounds reduced the viability of tumor cell lines like MDA-MB-231, MCF-7 and HepG2, and inhibited the growth of multi-drug resistant strains such MCF-7/ADM and HepG2/ADM.Among the evaluated saponins, the psychotrianoside C (97) showed the most potent cytotoxic effect and also induced cell death by apoptosis.
The alkaloid emetine (12) presented cytotoxic and apoptosis effects in leukemia cell lines via mitochondrial pathway. 56,115When tested with cisplatin (standard chemotherapeutic agent) it increased levels of apoptosis, inducing the expression of several proapoptotic genes and inhibiting expression of survival factors. 56he alkaloid psychotripine (23), a trimeric pyrroloindoline derivative with a hendecacyclic system bearing a hexahydro-1,3,5-triazine unit, was isolated from the leaves of P. pilifera.This compound was evaluated for cytotoxicity in five different tumor cell lines, HL-60 (leukemia), SMMC-7721 (liver cancer), A-549 (lung cancer), MCF-7 (breast cancer) and SW480 (colon cancer) although did not present any significant activity (IC 50 > 40 mmol L -1 ). 73he 1-hydroxybenzoisochromanquinone (psychorubrin) (86) isolated from P. rubra showed cytotoxic effect on tumor lineage KB.In addition, some other naphthoquinones derived from structural modifications exhibited cytotoxic activity higher than the natural product psychorubrin, thus demonstrating the importance of structure-activity study. 78rom the species P. leptothyrsa, six cyclotides were isolated (Psyle A-F) (see Tables 1 and 2), however only the cyclotides psyle A, C and E showed a potent cytotoxic effect (IC 50 = 0.64 > 10 μmol L -1 ) in breast cancer cell lines resistant (MCF-7/ADR) or not (MCF-7).It was demonstrated that the presence of cyclotides in MCF-7/ADR cell line significantly increased the cytotoxicity induced by doxorubicin (IC 50 = 0.39-0.76μmol L -1 ), revealing a chemosensitization effect of these compounds, as well as being promising against resistant breast cancer cell lines. 64,116

Bactericidal and antifungal activity
The compound quadrigemine B (89) isolated from P. rostrata showed bactericidal activity against Escherichia coli and Staphylococcus aureus. 76From the leaves of the same species were isolated some other alkaloids like psychotrimine (17) and psychopentamine (18), which showed anti-bactericidal activity against resistant grampositive bacteria Bacillus subtilis and S. aureus. 77,117n a study made by Moraes et al., 111 ten Psychotria species (P.pubigera, P. ruelliifolia, P. suterela, P. stachyoides, P. capitata, P. glaziovii, P. leiocarpa, P. nuda, P. racemosa and P. vellosiana) were evaluated for antimycobacterial activity, in an attempt to find new antituberculosis agents.From the evaluated extracts the species P. pubigera, P. ruelliifolia and P. stachyoides were the most active against Mycobacterium.

Other activities
The indole pyrrolidine alkaloids like psycholeine (105) and quadrigemine C (40) isolated from P. oleoides were subjected to the interaction study with radiolabeled somatostatin ([125 I] N-Tyr-SRIF), inhibition of the enzyme adenylate cyclase and somatostatin secretion of growth hormone (GH) by the rat pituitary cells.Psycholeine (105)  presented antagonistic properties at the SRIF receptor with an IC 50 of 10 -5 mol L -1 . 72,118

Ecological Approach of Psychotria Species
The production of secondary metabolites may also help the plants to develop and grow in the environment.The monoterpene indole alkaloid brachycerine (14), an antioxidant glucosidic indole alkaloid, is involved in the defense of P. brachyceras Muell.Arg. against the osmotic/ oxidative stress, contributing to the detoxification of hydroxyl radicals and superoxide anions.It was demonstrated that the agents responsible for inducing osmotic stress agents such as sodium chloride, sorbitol and polyethylene glycol lead to the alkaloid accumulation in leaves.Some other agents responsible for inducing oxidative stress such as exposure to aluminum, silver and abscisic acid also increased the amount of brachycerine (14).Nascimento et al. 119 described that brachycerine in not herbivore deterrent, but is involved in defense by modulating oxidative stress.
The major indole alkaloid N,β-D-glucopyranosyl vincosamide (15) from leaves of P. leiocarpa Cham.& Schltdl.showed broad antioxidant activity and may act against oxidative stress generated upon wounding, UV exposure and perhaps other environmental stresses. 97he study made by Matsuura and Fett-Neto 97 showed the antioxidant effect of GPV (N,β-D-glucopyranosyl vincosamide) (15) when evaluated in vitro tests against singlet oxygen, superoxide and hydroxyl radicals and in situ tests against hydrogen peroxide.It was demonstrated that this alkaloid protects the plant P. leiocarpa indirectly against oxidative stress generated in injury, exposure to UV rays and other environmental damage, although not directly against herbivory. 96sychotria plants are rich in secondary metabolites that could be toxic against Sitophilus zeamais (Coleoptera: Vol. 27, No. 8, 2016 Curculionidae) and Spodoptera frugiperda (Lepidoptera: Noctuidae) for maize protection.The study made by Tavares et al. 120 demonstrated that extracts (leaves or stems) from P. hoffmannseggiana, P. capitata and P. goyazensis were significantly toxic to these type of insects involving the following parameters such as hatching rate, weight, length, repellence and mortality.
The extract from the leaves of P. microphylla showed to be very toxic to the young forms of Clarias gariepinus, important species of catfish from Africa.The toxicity of the extract was time and dose-dependent.This extract may be useful in aquaculture to eradicate predators and competitors of wild fishpond in farmed ponds or stocking hatchery fish species commercially cultivated. 121pecies such as P. gabriellae and P. douarrei presented the ability to accumulate high amounts of nickel in their sprouts.Metabolites were identified in complexes with Ni including Ni-malonate from P. douarrei and the levels for some metabolites were found to correlate with the leaf Ni concentration. 122,123Studies conducted by Grison et al. 124 demonstrated the use of biomass obtained from P. douarrei enriched by nickel a catalyst type Lewis acid in organic synthesis as an alternative source of nickel used in the synthesis of antifungal compound monastrol, thus showing its potential to be used in Green Chemistry.

Conclusions
As demonstrated in our methods an increasing number of publications revealed a significant interest in Psycothria genus in recently years, due to their traditional uses and pharmacological activities.This review presents the main traditional uses as long as pharmacological properties, phytochemistry, chemotaxonomy and ecological approach.
The genus Psychotria presents a complex taxonomy and its phytochemical approach became a very useful tool to understand and establish the chemotaxonomy.Several classes of natural products are described for this genus, although, this study highlights the importance of some alkaloids and cyclic peptides, which are involved on central nervous system and neurodegenerative diseases.

Figure 1 .
Figure 1.Results of SciFinder search for Psychotria genus publications up to 2015.

Figure 4 .
Figure 4.The structures of terpenoids from Psychotria species.

Figure 5 .
Figure 5.The structures of flavonoids from Psychotria species.

Figure 6 .
Figure 6.The structures of coumarins from Psychotria species.

Table 2 .
Cyclic peptides identified from Psychotria species