Aspidosperma excelsum Benth. (Apocynaceae): ethnomedicinal applications, phytochemistry of indole alkaloids, and pharmacological potential of an Amazonian species

Aspidosperma excelsum Benth. (Apocynaceae): aplicações etnomedicinais, fitoquímica de alcalóides indólicos e potencial farmacológico de uma espécie amazônica

Abstract

Aspidosperma excelsum Benth. (Apocynaceae) is an Amazonian medicinal species traditionally used for treating malaria, inflammatory disorders, liver diseases, fever, and other health conditions. Despite growing scientific interest, knowledge regarding this species remains fragmented and complicated by taxonomic inconsistencies involving botanical synonyms. The present review critically compiled and integrated the available evidence regarding A. excelsum and its validated synonyms, emphasizing taxonomic aspects, ethnomedicinal applications, phytochemical composition, and pharmacological potential. Taxonomic standardization was performed using the Plants of the World Online database, and systematic literature searches identified 45 eligible studies after applying explicit search and eligibility criteria. Ethnobotanical evidence highlighted the widespread traditional use of stem bark preparations, particularly for malaria treatment across Amazonian communities. Phytochemical investigations revealed a remarkable diversity of indole alkaloids, alongside flavonoids, tannins, and terpenoids, reinforcing the species as a promising source of bioactive metabolites. Experimental studies demonstrated antiplasmodial, anti-inflammatory, antimicrobial, antioxidant, antileishmanial, and selective cytotoxic activities, partially supporting traditional therapeutic indications and suggesting convergence between ethnomedicinal knowledge and pharmacological evidence. However, most findings derive from in vitro and preclinical studies. This review consolidates fragmented information, addresses nomenclatural inconsistencies, and establishes a framework to guide future pharmacological investigations.

Keywords:
Aspidosperma excelsum; indole alkaloids; bioactive compounds; ethnopharmacology; bioprospecting

Resumo

Aspidosperma excelsum Benth. (Apocynaceae) é uma espécie medicinal amazônica tradicionalmente utilizada no tratamento da malária, processos inflamatórios, distúrbios hepáticos, febre e outras condições de saúde. Apesar do crescente interesse científico, o conhecimento sobre essa espécie permanece fragmentado e dificultado por inconsistências taxonômicas relacionadas a sinônimos botânicos. A presente revisão compilou e integrou criticamente as evidências disponíveis sobre A. excelsum e seus sinônimos validados, enfatizando aspectos taxonômicos, aplicações etnomedicinais, composição fitoquímica e potencial farmacológico. A padronização taxonômica foi realizada com base na base de dados Plants of the World Online, e a busca sistemática da literatura identificou 45 estudos elegíveis após aplicação de critérios explícitos de busca e elegibilidade. As evidências etnobotânicas destacaram o amplo uso tradicional de preparações da casca do caule, especialmente para o tratamento da malária em comunidades amazônicas. As investigações fitoquímicas revelaram uma notável diversidade de alcaloides indólicos, além de flavonoides, taninos e terpenoides, reforçando o potencial da espécie como fonte de metabólitos bioativos. Estudos experimentais demonstraram atividades antiplasmódica, anti-inflamatória, antimicrobiana, antioxidante, antileishmania e citotóxica seletiva, sustentando parcialmente indicações terapêuticas tradicionais e sugerindo convergência entre o conhecimento etnomedicinal e as evidências farmacológicas. Entretanto, a maior parte dos achados deriva de estudos in vitro e modelos pré-clínicos. Esta revisão consolida informações fragmentadas, aborda inconsistências nomenclaturais e estabelece uma base conceitual para orientar futuras investigações farmacológicas.

Palavras-chave:
Aspidosperma excelsum; alcaloides indólicos; compostos bioativos; etnofarmacologia; bioprospecção

1. Introduction

Medicinal plants remain an essential source of therapeutic resources worldwide and continue to have a central role in therapeutical care, particularly in tropical and low-resource regions which approximately 80% of the global population relies partially on traditional medicine practices, especially medicinal plants, for primary healthcare needs (WHO, 2019). In parallel, natural products have historically contributed substantially to drug discovery, serving as a source of clinically relevant drugs and pharmacological prototypes (Fabricant and Farnsworth, 2001; Heinrich et al., 2009).

The family Apocynaceae comprises approximately 400 genera and more than 5,000 species predominantly distributed in tropical regions and is recognized as an important source of secondary metabolites with pharmacological relevance, including alkaloids, flavonoids, terpenoids, and cardiac glycosides (Rapini, 2012; Simões et al., 2016; Almeida et al., 2019; Batista et al., 2024; Noradina et al., 2024). Within Apocynaceae, the genus Aspidosperma Mart. & Zucc. represents one of the most taxonomically complex and pharmacologically relevant groups of Neotropical flora. The genus comprises 64 recognized species distributed from Central to South America, with Brazil harboring most of this diversity, particularly in the Amazon region (Pereira et al., 2019).

Among these species, Aspidosperma excelsum Benth. is a large Amazonian tree traditionally used by riverine populations and other traditional communities for the treatment of malaria, inflammatory conditions, fever, liver disorders, infectious diseases, and other ailments (Pérez, 2002; Oliveira et al., 2015; Pedrollo et al., 2016; Trindade et al., 2016; Almeida et al., 2019). The species occurs throughout several Amazonian countries and has gained increasing scientific interest due to the convergence between traditional medicinal applications and preliminary experimental evidence supporting its pharmacological potential. Phytochemical investigations demonstrate that A. excelsum and its botanical synonyms constitute an important source of indole alkaloids, a class of secondary metabolites recognized for remarkable structural diversity and broad pharmacological properties under preclinical models in experimental studies, including antiplasmodial, antimicrobial, anti-inflammatory, antileishmanial, antioxidant, analgesic, and cytotoxic activities (Mitaine-Offer et al., 2002; Pereira et al., 2007; Almeida et al., 2019; Omar et al., 2021).

Despite growing scientific interest, knowledge regarding A. excelsum remains fragmented and frequently affected by taxonomic inconsistencies involving botanical synonyms such as Aspidosperma nitidum, which complicates data retrieval and limits broader interpretation of pharmacological evidence (Castello et al., 2022). Moreover, no previous study has critically integrated ethnobotanical knowledge, phytochemical diversity, pharmacological evidence, and taxonomic aspects specifically focused on A. excelsum and its validated synonyms.

Therefore, the present article comprises a systematic search and review, aiming to critically compile and integrate the available evidence regarding Aspidosperma excelsum Benth., emphasizing its taxonomic aspects, traditional medicinal applications, phytochemical profile, and pharmacological potential. By consolidating fragmented information and addressing nomenclatural inconsistencies, this review seeks to establish a conceptual foundation to support future pharmacological investigations and the sustainable valorization of this Amazonian species.

2. Material and Methods

This study was conducted as a systematic search and review (Grant and Booth, 2009), a typology that combines the strengths of a critical review with a comprehensive and transparent search strategy, ensuring both methodological rigor and analytical depth. The study was guided by the following research question: “What botanical, phytochemical, and bioactivity aspects of Aspidosperma excelsum Benth. (Apocynaceae) and its synonyms have been reported in the literature?”

2.1. Taxonomic standardization

Prior to the literature searches, taxonomic standardization of the species was performed based on the Plants of the World Online (POWO, 2025) database, adopted as the taxonomic reference authority in this study. The accepted name Aspidosperma excelsum Benth. and its validated synonyms (A. nitidum Benth. ex Müll.Arg., Macaglia excelsa (Benth.) Kuntze, A. aquaticum Ducke, and Thyroma nitida (Benth. ex Müll.Arg.) Miers) were all included as search terms in order to ensure comprehensive retrieval of the available literature on the species, regardless of the nomenclature used by the authors.

2.2. Search strategy

Searches were conducted between until May 2025 from scientific publications in international scientific journals indexed in Google Scholar, SciELO, PubMed, ScienceDirect, and Plants of the World Online (POWO) databases. The following search string combinations were applied: ("Aspidosperma excelsum" OR "Aspidosperma nitidum" OR "carapanaúba") AND ("indole alkaloids" OR "alcaloides indólicos" OR "bioactive compounds" OR "compostos bioativos" OR "ethnopharmacology" OR "etnofarmacologia" OR "bioprospecting" OR "bioprospecção" OR "medicinal plants" OR "plantas medicinais"), using the Boolean operators AND and OR for cross-referencing of terms. Searches were conducted in Portuguese, Spanish, English, and French.

2.3. Eligibility criteria

The following inclusion criteria were adopted: (i) peer-reviewed scientific articles; (ii) publications from 1950 to May 2025, in order to cover the historical evolution of knowledge on the species; (iii) studies reporting botanical, phytochemical, ethnopharmacological, or pharmacological data on A. excelsum or its validated synonyms; (iv) availability of the full text.

The following exclusion criteria were adopted: (i) incomplete publications; (ii) abstracts without full text available; (iii) duplicate articles identified across different databases; (iv) editorials, letters to the editor, and opinion articles; (v) publications without description of methodology or results; (vi) publications for which access to the full text was not possible.

2.4. Screening and selection process

Screening was conducted in two sequential phases. In the first phase, titles and abstracts of all identified records were assessed. In the second phase, pre-selected articles were read in full to verify eligibility criteria. Throughout the entire process, results from in vitro and in vivo studies were systematically distinguished, given that activity demonstrated in cell-based systems does not necessarily translate into clinical efficacy.

A total of 137 publications were initially identified from the consulted databases. After the exclusion of six duplicate records, 131 articles were submitted to the first phase of screening, in which titles and abstracts were assessed; of these, 25 were excluded. The remaining 106 articles were read in full and assessed against the eligibility criteria. Of these, 63 were excluded for presenting irrelevant or insufficient data for the objectives of this review. In the end, 43 publications were considered eligible and included in the data synthesis.

2.5. Data extraction and synthesis

Data were extracted using a standardized form covering the following categories: species or synonym studied, plant part used, extract or fraction evaluated, biological activity reported, experimental model, and main quantitative results. The extracted information was thematically organized into four analytical categories: (i) taxonomy and morphology; (ii) traditional uses; (iii) phytochemical profile; and (iv) pharmacological activities.

3. Results and Discussion

3.1. Taxonomic position, morphological characteristics, distribution and habitat

Aspidosperma excelsum Benth. belongs to the order Gentianales and is taxonomically classified within the kingdom Plantae, phylum Streptophyta, class Equisetopsida, subclass Magnoliidae, family Apocynaceae, genus Aspidosperma. The species has a homotypic synonym, Macaglia excelsa (Benth.) Kuntze, as well as heterotypic synonyms, including A. aquaticum Ducke, A. nitidum Benth. ex Müll.Arg., and Thyroma nitida (Benth. ex Müll.Arg.) Miers (POWO, 2025), all of which are mentioned in the scientific literature. This nomenclatural asymmetry evidences a persistent taxonomic confusion in the genus Aspidosperma, characterized by overlapping morphological characteristics, unpublished synonymizations, and the absence of integrative reviews of specific groups, which hinders the consolidation of knowledge on species of recurrent use in ethnobotany and pharmacognosy (Castello et al., 2022).

These taxonomic difficulties are particularly evident in the Amazon, where ecological complexity contributes to the phenotypic variability of species, making identification challenging due to morphological similarity and overlapping vegetative and reproductive traits (Pereira et al., 2016).

In addition, recent systematic studies demonstrate that species delimitation within the genus remains unstable (Rapini, 2012; Batista et al., 2024), reinforcing the need for taxonomic revisions based on morphological, anatomical, and molecular criteria. In this context, it is essential that scientific studies clearly identify the botanical synonyms used and acknowledge their equivalence with the accepted name, in order to ensure terminological consistency and integrity in the recovery of taxonomic and pharmacological data (Castello et al., 2022).

In Brazil, A. excelsum is popularly known as carapanaúba, a name that originates from the Tupi language, formed by "carapanã" ("mosquito") and "ubá" ("tree"), thus translated as "mosquito tree". This denomination is associated with the morphological characteristic of the species: the holes present in its trunk often accumulate water, creating environments suitable for mosquito reproduction (Sales, 2019). Among its morphological characteristics, its large stature stands out, with heights ranging between 10 and 40 meters. The species is widely valued by the timber industry due to its high production of superior quality hardwood. The trunk is tortuous and exudes a white latex; its branches are cylindrical, not suberous, sparsely lenticelled, and vary between pubescent and glabrous. The leaves are elliptical to narrow in shape, measuring 4.5 to 12 cm long by 2.5 to 5 cm wide, and the inflorescences can be terminal or subterminal, composed of numerous flowers ranging from very sparsely puberulent to glabrescent (Morales, 2005). The fruits are follicles measuring 4 to 7 cm in length and 4 to 6 cm in width, featuring wart-like spines, with seeds measuring between 3 and 5 cm in diameter (Morales, 2005).

This native Amazonian species occurs in several Latin American countries, including Brazil, Bolivia, Colombia, Costa Rica, Peru, Guyana, Panama, Suriname, and Venezuela. In Brazil, its distribution covers the northern region, especially in the states of Pará, Amazonas, Rondônia, and Roraima, where it is found in Terra-firme, Várzea, and Campinarana forests (POWO, 2025).

It should also be noted that a substantial portion of the pharmacological data reported in this article derives from studies conducted with A. nitidum, a heterotypic synonym of A. excelsum that may present chemical and biological variation in relation to the accepted taxon. Throughout this work, the nomenclature used in each original study is preserved. Conclusions specifically attributed to A. excelsum sensu stricto are restricted to studies that explicitly used that taxon, and the uncertainty introduced by the use of heterotypic synonyms is acknowledged as a limitation of the available evidence.

3.2. Traditional uses

Ethnomedical practices play a fundamental role in the construction of popular knowledge regarding the use of medicinal plants in the Amazon, especially among traditional communities, such as riverine populations, indigenous people, and “quilombolas” (Vásquez et al., 2014). A. excelsum and its botanical synonyms are used in folk medicine for the treatment of various health problems, especially as an antimalarial agent (Oliveira et al., 2015; Trindade et al., 2016; Pedrollo et al., 2016; Tomchinsky et al., 2017; Almeida et al., 2019;), antipyretic (Fouqué, 1981; Pérez, 2002; Trindade et al., 2016; Almeida et al., 2019;), anti-inflammatory (Pedrollo et al., 2016; Almeida et al., 2019) hepatoprotector (Pedrollo et al., 2016; Almeida et al., 2019) and for wound healing (Pedrollo et al., 2016). The relevance of this traditional knowledge not only reinforces the therapeutic value of the species but also subsidizes scientific research aimed at bioprospecting its bioactive constituents.

In this context, the ethnobotanical and ethnopharmacological records available in the literature on A. excelsum and synonyms were systematized, with emphasis on the parts of the plant used, forms of preparation, therapeutic instructions and places of occurrence. Table 1 presents the traditional uses of A. excelsum and its botanical synonyms, with emphasis on A. nitidum, which is widely used in Amazonian folk medicine, especially by communities in Brazil, Bolivia, Peru, and Guiana. The table shows the diversity of uses and the cultural importance of the species in the regions where it is traditionally used. In the studies consulted, the most frequently used part of the plant is the stem bark, usually prepared in the form of decoctions or infusions, and the main therapeutic indication recorded is in the treatment of malaria.

Table 1
Traditional uses of A. excelsum and its botanical synonyms.

Species / Synonym	Common name	Part of the plant used	Traditional use	Region / community	Reference
A. excelsum	remo caspi	stem bark	malaria, fever, jaundice, asthma, anti-inflammatory, disinfectant, earache and hepatitis	Ucayali – Peru, Bolívia, Suriname	Pérez (2002)
	carapanaúba	stem bark	malaria	Oriximiná, Brazil	Oliveira et al. (2015)
	carapanaúba	stem bark	malaria and fever	Santa Bárbara do Pará, Brazil	Trindade et al. (2016)
	carapanaúba	stem bark	malaria, inflammation, dysentery, urinary pains, washing of genitals, healing of skin, kidney and liver diseases	Jauaperi River, Amazonas, Brazil	Pedrollo et al. (2016)
A. nitidum	carapanaúba	leaves and bark	malaria, fevers, inflammation, diabetes, liver, contraceptive	Acre and Amazonas, Brazil, Bolívia and Peru	Almeida et al. (2019)
	carapanaúba	stem bark	malaria treatment	Roraima and Yanomami communities in Brazil	Almeida et al. (2019)
	carapanaúba	stem bark	febrifuge in cases of bronchitis and jaundice	Guianas and northern Brazil	Fouqué (1981)
	carapanaúba	stem bark	contraceptive, antimalarial, anti-inflammatory (uterus and ovary), anticarcinogenic, antidiabetic, leprosy and stomach problems	Amazon region, Brazil	Pereira et al. (2006b)
	carapanaúba	stem bark	fever and malaria	Amazon region, Brazil	Coutinho et al. (2013)
	carapanaúba	stem bark	malaria	Negro River region, Amazonas, Brazil	Tomchinsky et al. (2017)

Regarding the use of A. excelsum for the treatment of malaria, the main uses are in the form of infusion and decoction of the stem bark, and reports of popular uses come mainly from the Amazon region of South American countries. In addition, several reports also indicate the use of the plant for cases of fever in general.

In addition to malaria, ethnobotanical reports indicate the use of the species for the treatment of liver, kidney, inflammatory, and metabolic diseases, such as diabetes (Pedrollo et al., 2016; Almeida et al., 2019). Topical applications for wounds and infectious processes are also described, showing a therapeutic spectrum that ranges from systemic disorders to dermatological conditions (Pérez, 2002; Pedrollo et al., 2016).

These traditional uses provide a consistent basis for the scientific investigation of their bioactive constituents, with emphasis on indole alkaloids, and guide biological assays regarding their potential antimalarial, anti-inflammatory, and antimicrobial actions. The recurrence of the use of stem bark in traditional practices confers empirical legitimacy to this knowledge and reinforces its relevance as a starting point for pharmacological research. This convergence between traditional knowledge and scientific validation is also observed in other species of the genus, such as A. quebracho-blanco and A. ramiflorum, traditionally used as antipyretic and antiparasitic agents by the local population (Deutsch et al., 1994; Marques et al., 1996).

The convergence of ethnobotanical records from independent communities across different countries, particularly regarding the use of A. excelsum in the treatment of malaria, inflammatory processes, and infections, confers empirical consistency to this traditional knowledge and provides a rational basis for the pharmacological investigation systematized in Section 3.3. The recurrence of these therapeutic indications across distinct geographical and cultural contexts suggests that the antiplasmodial, anti-inflammatory, and antimicrobial activities reported experimentally may reflect, at least in part, real phytochemical properties of the species, especially those associated with its indole alkaloids.

3.3. Experimental pharmacological evidence

Several studies, using in vitro and in vivo preclinical experimental approaches, have investigated the pharmacological potential of A. excelsum and its synonyms, revealing a wide range of pharmacological activities and preliminary evidence of biological activities of pharmacological interest as shown in Table 2. Among the most promising effects are antiplasmodial, antileishmanial, antioxidant, antimicrobial and anti-inflammatory actions.

Table 2
Pharmacological activities described for A. excelsum and its botanical synonyms.

Activity	Species/ Synonym	Extract / Fraction	Result	Reference
Antioxidant	A. excelsum	Hydroalcoholic extract	IC50 = 1.84 mg/mL Chemical (DPPH)	Salazar-Díaz et al. (2021)
		Second extract	IC50 = 5.89 µg/mL Chemical (DPPH)	Rocha et al. (2019)
Anti-inflammatory	A. nitidum	Hydroethanolic extract	Reduction of carrageenan-induced edema, Reduction of TNF-α, IL-1β, IL-6	Torres-Rêgo et al. (2024)
		Ethanolic extract	Reduction of carrageenan-induced edema	Pereira et al. (2006a)
Antiplasmodial	A. excelsum	Ethanolic and methanolic fraction	IC50 = 4,6–12,4 µg/mL (Strain W2)	Coutinho et al. (2013)
		Hydroalcoholic extract	IC50 = 42,0 µg/mL (Strain 3D7)	Meneguetti et al. (2014)
		Alkaloid fraction	IC50 = 8.75 µg/mL (Strain W2)	Nascimento et al. (2019)
		Alkaloid fraction	IC50 = 1.6–7.6 µg/mL (Strain W2) and reduction of parasitemia (67%) in mice	Coutinho et al. (2013)
	A. nitidum	Alkaloid fraction	IC50 = 2.32 µg/mL	Brandão et al. (2020)
Antinociceptive	A. nitidum	Ethanolic extract	Peripheral antinociceptive effect with significant reduction of pain (formalin test, inflammatory phase)	Pereira et al. (2006a)
Antifungal	A. excelsum	Hydroalcoholic extract	MIC inactive > 5,000 µg/mL (C. albicans, C. glabrata, C. krusei, C. guilliermondii)	Rocha et al. (2019)
Antimicrobial	A. excelsum	Various indole alkaloids	Assets against Bacillus subtilis (MIC = 20-380 µg/mL)	Verpoorte et al. (1983)
	A. nitidum	Ethanolic extract (EE), alkaloid fraction (AF) and neutral fraction (NF)	Active against S. aureus (EE: MIC = 2,504g/mL; AF/NF = 5,000g/mL); weak against E. coli (MIC = 10,000 g/mL); inactive for other strains (P. aeruginosa, K. pneumoniae, P. mirabilis	Brígido et al. (2020)
		Hexane extract	Active against S. aureus; inactive against P. aeruginosa and partially active against E. coli	Siminski et al. (2015)
Cytotoxicity	A. excelsum	Ethanolic extract (EE), alkaloid fraction (AF) and neutral fraction (NF)	EE (CC50 = 410.7 µg/mL), AF (346.7 µg/mL), NF (452.5 µg/mL); HepG2 cells	Brandão et al. (2020)
		Ethanolic extract	CC50 > 100 µg/mL (HepG2, MRC5)	Arias et al. (2021)
		Hydroalcoholic extract	CC50 > 250 µg/mL; SI > 10.56 (HepG2)	Nascimento et al. (2019)
	A. nitidum	Hydroethanolic extract	Viability > 80% up to 1,000 µg/mL (NIH/3T3 and Vero E6)	Torres-Rêgo et al. (2024)
		Ethanolic extract (EE), alkaloid fraction (AF) and dichloromethane fraction (DCLFr)	EE (CC 50 = 491.8 µg/mL; low toxicity), AF (CC50 = 184.7 µg/mL; moderate), DCLFr (CC50 > 500 µg/mL); cell: murine peritoneal macrophages	Veiga et al. (2021)
Toxicity	A. nitidum	Hydroalcoholic extract	LD50 = 273.52 µg/mL (Artemia salina)	Rocha et al. (2019)
		Ethanolic extract	Safe upto 2,000 mg/kg (in vivo, mice)	Brígido et al. (2021)
Trypanocide	A. excelsum	Ethanolic extract	Inactive (IC50 > 500 µg/mL)	Arias et al. (2021)
Leishmanicide	A. nitidum	Ethanolic extract (EE), alkaloid fraction (AF) and dichloromethane fraction (DCLFr)	(EE: IC50 = 23.9 µg/mL, SI = 21; AF: IC50 = 18.5 µg/mL, SI = 11) active against amastigotes; DCLFr moderately active against promastigotes (IC50 = 105.7 µg/mL)	Veiga et al. (2021)
		Purified alkaloid subfractions (SF5-6, SF8 and SF9)	Active against promastigotes (IC50 = 38.4–100.3 µg/mL)	Veiga et al. (2022)
		Ethanolic extract	Reduction of parasitic load in vivo (42.5%)	Brígido et al. (2024)

• IC₅₀: Mean inhibitory concentration required to reduce 50% of the activity of the target organism or cell. CC₅₀: mean cytotoxic concentration required to reduce 50% of cell prediction. LD₅₀: lethal dose capable of killing 50% of organism’s saline test). MIC: minimum inhibitory concentration required to inhibit the growth of microorganisms. SI: selectivity index (ratio between CC₅₀ and IC₅₀), the higher the value, the more selective the compound is to the desired target. Phytochemical profile of A. excelsum.

The extracts and fractions evaluated demonstrated low cytotoxicity in different cell lines-including hepatocytes (HepG2), fibroblasts (MRC5 and NIH/3T3), epithelial cells (VERO E6), and murine macrophages, and demonstrated a good safety profile. Toxicity was also low in vivo tests with mice (Brígido et al., 2021), although the dry extract of A. excelsum showed toxicity in an assay with Artemia salina (Rocha et al., 2019). Nonetheless, all the extracts revealed promising selective profiles, with high rates of selectivity (SI) (Arias et al., 2021; Nascimento et al., 2019; Torres-Rêgo et al., 2024; Brígido et al., 2021; Veiga et al., 2021; Brandão et al., 2020).

The alkaloid fractions obtained from A. nitidum and A. excelsum demonstrated promising activity against P. falciparum (strain W2, resistance to chloroquine), with IC₅₀ values lower than 10 µg/mL (Coutinho et al., 2013; Nascimento et al., 2019; Brandão et al., 2020) in in vitro assays. These results indicate greater activity when compared to the crude extracts obtained from the same species, in which the extracts of the stem bark of A. excelsum presented IC₅₀ values ranging between 3.6 and 23.6 µg/mL (Coutinho et al., 2013; Brandão et al., 2020; Nascimento et al., 2019).

The alkaloid fraction derived from the ethanolic extract of A. nitidum stood out for presenting an IC₅₀ of 1.6 µg/mL, while still maintaining low cytotoxicity against BGM monkey kidney cells and HepG2 human hepatoma cells (Coutinho et al., 2013).

It is noteworthy that braznitidumine, the main alkaloid detected in these fractions by HPLC-DAD analysis, was found to be inactive when tested isolately against P. falciparum, suggesting that the observed antiplasmodial activity is likely attributable to the combined action of multiple alkaloids present in the fractions, indicating a pharmacological synergim among their components (Coutinho et al., 2013). In addition to the in vitro tests, fractions rich in alkaloids also demonstrated efficacy in vivo, reducing parasitemia by up to 67% in mice infected with P. berghei, after oral administration at a dose of 100 mg/kg (Coutinho et al., 2013).

Although these values indicate biologically relevant activity against the chloroquine-resistant W2 strain of P. falciparum, they are considerably higher than the IC₅₀ of chloroquine determined in the same assay as a positive control, which was 0.09 µg/mL (Nascimento et al., 2019). This demonstrates that the potency of the evaluated alkaloid fractions is substantially lower than that of the reference drug. These results, although promising from an ethnopharmacological perspective, indicate that additional studies focused on the isolation of pure compounds and the elucidation of their mechanisms of action are necessary before any therapeutic perspective can be considered.

The antiplasmodial activity documented in preclinical studies is consistent with the traditional use of A. excelsum in the Amazon, where P. falciparum represents the most severe form of malaria and where the species naturally occurs. This convergence between traditional use and experimental evidence follows a well-established pattern in antimalarial drug discovery, as clinically relevant drugs such as quinine and artemisinin were originally derived from traditionally used plants (Fabricant and Farnsworth, 2001).

Studies also indicate significant activity against leishmaniasis, again highlighting the alkaloid fraction as the most promising. The in vitro studies of Veiga et al. (2021) highlighted that the ethanolic extract obtained from the stem bark of A. nitidum presented an IC50 of 23.9 µg/mL against the amastigote forms of L. (L.) amazonensis, while the alkaloid fraction presented an IC50 of 18.5 µg/mL (Veiga et al., 2021) (Table 2).

For comparison, the EC₅₀ of amphotericin B against intracellular amastigote forms of Leishmania amazonensis was determined at 63.5 nM (equivalent to approximately 0.059 µg/mL) (Trinconi et al., 2014). This value is considerably lower than the IC₅₀ values obtained for the ethanolic extract (23.9 µg/mL) and the alkaloid fraction (18.5 µg/mL) of A. nitidum in the amastigote assays (Veiga et al., 2021). These results characterize the observed antileishmanial activity as biologically relevant, yet modest in relation to the reference drug, indicating that the isolation of pure compounds and the elucidation of their mechanisms of action represent necessary steps for the advancement of investigations.

Against promastigote forms, alkaloid subfractions obtained IC50 values ranging between 38.4 and 100.3 µg/mL, especially the indole alkaloid dihydrocorinanteol, isolated from one of the fractions, with an IC50 of 38.4 µg/mL (Veiga et al., 2022). When tested in vivo, the ethanolic extract and alkaloid fraction did not present such promising results in reducing parasitemia in a murine model. The ethanolic extract showed a reduction of 42.5% of parasitemia in the background of infected mice, while an alkaloid fraction showed a reduction of 22.1% (Brígido et al., 2024).

In addition to the observed results for the alkaloids of A. excelsum with potential activity against malaria and leishmaniasis, other studies have demonstrated the potential of this species against microorganisms. Extracts and isolated alkaloids have been tested for the prevention of bacteria such as Bacillus subtilis (Verpoorte et al., 1983), Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus mirabilis (Table 2) (Siminski et al., 2015; Brígido et al., 2020).

Regarding its activity against S. aureus, hexanic extracts, ethanolic, alkaloid fraction and a neutral fraction were able to inhibit growth (Siminski et al., 2015; Brígido et al., 2020), highlighting the moderate activity of the ethanolic extract, which presented a minimum inhibitory concentration (MIC) of 250 µg/mL. The inhibition of E. coli was weak in the two studies carried out, and there was no growth inhibition for the other strains tested (Siminski et al., 2015; Brígido et al., 2020).

This result deserves an important contextualization. For comparison purposes, oxacillin the reference antibiotic used in the treatment of Staphylococcus aureus infections, inhibits the growth of this bacterium at concentrations between 0.125 and 0.5 µg/mL when tested against the reference strain S. aureus ATCC 29213 (Humphries et al., 2021). The ethanolic extract of A. nitidum, in turn, required a concentration of 250 µg/mL to produce the same effect that is, a concentration approximately 500 to 2,000 times higher than that of the reference drug. This result classifies the antimicrobial activity of the extract as weak according to standardized criteria, indicating that, although the activity exists, but possibly not sufficient for therapeutic application. Additional studies with isolated compounds are necessary to identify possible constituents with greater antibacterial potential.

The study by Verpoorte et al. (1983) presented the most significant results regarding bacterial prevention, with indole alkaloids isolated from A. excelsum being active against Bacillus subtillis, and a MIC ranging between 20 and 380 µg/mL. However, this microorganism is not associated with human diseases.

The ethanolic and hydroethanolic extracts from the bark and core of the trunk of A. nitidum were also tested for antifungal, antioxidant, anti-inflammatory and antinociceptive activity, with additional results for the protection of free radicals and reduction of intensity of pain (Table 2). Although other species of the genus Aspidosperma showed significant results regarding antifungal activity, the results obtained for the prevention of strains of C. albicans, C. glabrata, C. krusei, and C. guilliermondii were not overwhelming (Rocha et al., 2019).

Given that several diseases are associated with oxidative stress, the antioxidant activity of Aspidosperma excelsum deserves further investigation, as studies indicate that both the hydroalcoholic extract and the dry extract of the species have antioxidant potential, with IC₅₀ values of 1.84 mg/mL (Salazar-Díaz et al., 2021) and 5.89 µg/mL (Rocha et al., 2019), respectively.

Finally, when evaluated for antinociceptive and anti-inflammatory activities, the ethanolic extract of A. nitidum impaired nociception in mice at a dose of 300 mg/kg and showed expressive antiedematogenic action, causing paw edema induced by carrageenan at concentrations of 200 and 300 mg/kg (Table 2) (Pereira et al., 2006a; Torres-Rêgo et al., 2024). The study by Torres-Rêgo et al. (2024) also showed a reduction in the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), as well as a decrease in polymorphonuclear leukocyte migration, total proteins and myeloperoxidase concentrations in the zymosan-air-pouch assay. In general, the extracts analyzed were predominantly composed of classes of triterpenes, steroids, and alkaloids, which may be associated with the observed activities, corroborating the traditional uses of the plant in the treatment of systemic and topical processes.

The anti-inflammatory and antioxidant activities documented experimentally are consistent with several traditional uses of A. excelsum recorded across Amazonian communities, including the treatment of fever, inflammatory conditions, pain, asthma, and liver disorders (Pérez, 2002; Pedrollo et al., 2016; Almeida et al., 2019). This correspondence between experimental findings and ethnomedicinal indications reinforces the biological plausibility of the traditional use of the species and supports its further pharmacological investigation, particularly regarding the isolation of the compounds responsible for these effects.

Taken together, these findings provide preliminary experimental support for the ethnopharmacological relevance of A. excelsum and suggest that the species merits prioritization in future pharmacological investigations. The biological activities documented so far justify directing research efforts toward the isolation of active compounds, the elucidation of mechanisms of action, and the development of more robust preclinical models, as necessary steps prior to any consideration of therapeutic application.

3.4. Phytochemical profile of A. excelsum

Although indole alkaloids represent the most investigated constituents of A. excelsum, previous phytochemical studies indicate that other classes of secondary metabolites are also present in the species. Preliminary analyses of extracts revealed the occurrence of flavonoids, tannins, and quinones, which are widely associated with antioxidant activities (Salazar-Díaz et al., 2021). Similarly, tannins, steroids, and pentacyclic triterpenes, chemical classes often related to anti-inflammatory and antimicrobial properties, have been recorded in A. nitidum (Siminski et al., 2015). These findings highlight the chemical diversity of the genus Aspidosperma and reinforce its potential as a source of different bioactive compounds.

Indole alkaloids represent one of the most important groups of secondary metabolites of plant origin, highly recognized for their structural diversity and high bioactive potential. In the genus Aspidosperma, these compounds act as chemical markers and have been associated with various pharmacological activities, including antiplasmodial, antimicrobial, and anti-inflammatory effects (Mitaine-Offer et al., 2002; Pereira et al., 2007; Almeida et al., 2019). Indole alkaloids stand out for their structural similarity with endogenous neurotransmitters, which confer marked activity on the central nervous system. In addition, several relevant bioactivities are reported, such as antiviral, antileishmanial, antimalarial, anticancer, anti-inflammatory, analgesic, antidiabetic and hypotensive actions (Omar et al., 2021).

The bark of the stem and roots are the most frequently used parts for the isolation of these alkaloids from plants of the genus Aspidosperma, with emphasis on substances such as yohimbine (1), aspidospermine (14), quebrachamina (23), and excelsinin (3), whose presence reinforces the pharmacological potential of the species (Verpoorte et al., 1983).

The group of monoterpenoid indole alkaloids with Corynanthean and Aspidospermatan-type skeletons accounted for the largest number of isolated molecules in the reviewed studies. In addition to these, β-carbonyl indole alkaloids and other indole alkaloids from several structural skeletons were isolated from the species A. excelsum and its synonyms.

Yohimbine (1), a monoterpenic indole alkaloid isolated from the stem bark of A. excelsum (Benoin et al., 1967; Burnell and Nguyen-Thi-Sen, 1971; Verpoorte et al., 1983; Nascimento et al., 2019) was tested for antiplasmodic activity and showed an IC₅₀ of 14.35 µg/mL. Although the IC₅₀ value was higher than that presented for the alkaloid fraction, this alkaloid was also considered active against the W2 strain of P. falciparum (Nascimento et al., 2019). In the same study, monoterpene indole alkaloids with a Corynanthean skeleton, geissoschizol (26) and corynan-17-ol (27), were identified as the main constituents of the alkaloid fraction, particularly with kopsanol/epikopsanol (28), aspidocarpine (30), and 6,7-dihydroobscurinervine (31). This fraction presented an IC₅₀ of 9.93 µg/mL, evidencing the possible synergistic action of these compounds in the inhibition of P. falciparum (Nascimento et al., 2019). In addition, other alkaloids that have the Corynanthean skeleton, such as O-acetyloimbine (2), excelsinin (3), and ajmalicin (19), among others, have also been isolated and identified in this species.

Reinforcing the importance of a synergistic action between compounds, the studies of Pereira et al. (2006b), and Coutinho et al. (2013), found that the indole alkaloid braznitidumina (35), isolated from the trunk bark of A. nitidum, was inactive in vitro against P. falciparum (Pereira et al., 2006b). However, later work demonstrated that fractions rich in alkaloids, containing this compound, contained antiplasmodic activity (Coutinho et al., 2013), indicating that antimalarial activity may result from the joint action of several alkaloids present in the fractions, and not from a single isolated compound.

The alkaloids with a Corynanthean skeleton, didemethoxycarbonyltetrahydrosecamine (5), 16-desmethoxycarbonyltetrahydrosecamine (6), tetrahydrosecamine (8), and the alkaloid with an Aspidospermatan skeleton, 11-methoxytubotaiwine (12), revealed interesting antimicrobial activity against the bacterium Bacillus subtilis. Alkaloids (5) and (6) had lower minimum inhibitory concentrations (MIC), of 0.10 and 0.07 mg/mL, respectively (Verpoorte et al., 1983).

The indole alkaloid with a Corynanthean skeleton, 3α,20β-18,19-dihydrocorynantheol (36), was isolated and tested for in vitro antipromastigote activity against L. amazonensis. The alkaloid had an IC₅₀ of 38.4 µg/mL, being considerably more active than the other fractions of alkaloids tested, indicating that, in relation to antipromastigote activity, the isolation of the compound may be important. In addition, through scanning electron microscopy and transmission electron microscopy, it was also observed that the alkaloid was able to induce morphological changes such as cytoplasmic disorganization and cell body retraction, among other changes in the structure of promastigote forms, showing that the compound can generate antileishmanial action through apoptosis mechanisms (Veiga et al., 2022).

Similarly, the ethanolic fraction of A. nitidum bark, containing mainly the alkaloids yohimbine (1) and corynantheol (37), and the alkaloid fraction, containing the alkaloid 3α,20β-18,19-dihydrocorynantheol (36) as the majority, were tested in vivo for antileishmanial activity in mice (Brígido et al., 2024). The results revealed that treatment with the fraction containing alkaloids (1) and (37) was able to reduce (37.42%) the size of the lesion in 28 days at a dose of 400 mg/kg. On the other hand, the fraction containing the alkaloid (43) did not have the same effect.

The main indole alkaloids isolated from A. excelsum and their reported biological activities are summarized in Table 3, whereas Table 4 compiles the principal alkaloids identified in A. nitidum along with their respective pharmacological effects. Together, these tables highlight the chemical diversity and bioactive potential of alkaloids associated with both species. In addition, the representative chemical structures of the indole alkaloids isolated from A. excelsum and its botanical synonyms are illustrated in Figure 1 and Figure 2, providing a structural overview that supports the discussion of their biological activities and reinforces the relevance of these compounds as key contributors to the pharmacological profile of the genus Aspidosperma.

Table 3
Main alkaloids isolated from A. excelsum and their biological activities.

Secondary metabolism	Part of the plant	Biological activity	Reference
Yohimbine (1); O-Acetyloimbine (2); Excelsinin (3)	Stem bark	Not evaluated	Benoin et al. (1967)
Yohimbine (1); O-Acetyloimbine (2); Excelsinin (3)	Not rep Part of the plant orted	Not evaluated	Burnell and Nguyen-Thi-Sen (1971)
Yohimbine (1); O-Acetyloimbine (2); Oclorifuanine A (4); Didemethoxycarbonyltetrahydrosecamine (5); 16-Desmethoxycarbonyltetrahydrosecamine (6); 16-Hydroxy-16-desmetoxicarboniltetra-hydro-secamine (7); Tetrahydrosecamine (8); 16-Hydroxytetrahydrosecamine (9); Compactinervine (10); 11-Methoxytubotaivine (11); N-Acetylaspidospermidine (12); 3α-Aricin (13); O-Demethylaspidospermine (14)	Root bark	Antimicrobial (B. subtilis): MIC: (5) = 0.10 mg/mL; (6) = 0.07 mg/mL; (8) = 0.11 mg/mL; (12) = 0.23 mg/mL.	Verpoorte et al. (1983)
Yohimbine (1); O-Acetyloimbine (2); 10-Methoxygeisoschizole (15); 10-Methoxy-yohimbine (16);	Stem bark	Not evaluated	Bolzani et al. (1987)
Compactinervine (10); 11-Methoxytubotaivine (11); N-Acetylaspidospermidine (12); 3α-Aricin (13); O-Demethylaspidospermine (14); Tubotaiwine (17); (+)-Ulein (18); Ajmalycine (19); 3α,5α,16β,17α,20β-10-Methoxycorinanthin (20); 3α,5α,16β,17α,20β-Yohimbine (21); 3α,15α,16 α,17α,20β-O-acetyl yohimbine (22); 3α,15α,16α,17β,20α-Quebraquine (23); Didemethoxycarbonyltetrahydrosecamine (5); Tetrahydrosecamine (8); 16-Desmethoxycarbonyltetrahydrosecamine (6); 16-Hydroxytetrahydrosecamine (9); 16-Hydroxy,16 desmethoxycarbonyltetrahydrosecamine (7); 3α-10-Methoxygeisoschizole (15); 17-(R)-Ocrolifuanine (4)	Stem bark	Not evaluated	Pereira et al. (2007)
Excelsinidine (24); Aspidodasycarpine (25)	Stem bark	Not evaluated	Layne et al. (2007)
Yohimbine (1); O-Acetyloimbine (2); Excelsinin (3); Oclorifuanine A (4); Tetrahydrosecamine (8); Compactinervine (10); 11-Methoxytubotaivine (11); N-acetylaspidospermidine (12); 3α-Aricin (13); O-Demethylaspidospermine (14); Tubotaiwine (17); 3Α-10- Methoxygeisoschizole (15); Geissosquizole (26); Corinan-17-ol (27); Copsanol/Epikopsanol (28); Condylocarpine (29); Aspidocarpine (30); 6,7-Di-hydroobscurinervine (31); Yohimban-16-carboxylic acid (32)	Stem bark	Antiplasmodial: (1) IC50 = 14.35 µg/mL	Nascimento et al. (2019)

• IC₅₀: Mean inhibitory concentration required to reduce 50% of the activity of the target organism or cell. MIC: minimum inhibitory concentration required to inhibit the growth of microorganisms.

Table 4
Main alkaloids isolated from A. nitidum and their biological activities.

Secondary metabolism	Part of the plant	Biological activity	Reference
10-Methoxydihydrocorinantheol (33)	-	Not rated	Arndt et al. (1967)
Harman-3-carboxylic acid (34)	Core	Not rated	Pereira et al. (2006a)
Braznitidumina (35)	Trunk bark	Antiplasmodial (inactive in vitro against P. falciparum, but active in the alkaloid fraction)	Pereira et al. (2006b); Coutinho et al. (2013)
3α, 20β-1819-Dihydrocorinantheol (36)	Trunk bark	Antileishmanial - IC50 =38.4 µg/mL	Veiga et al. (2022)
Yohimbine (1)	Trunk bark	Antileishmanial (ethanolic fraction (1) and (44) = reduction of damage at 37.42%)	Brígido et al. (2024)
3α, 20β-18,19-Dihydrocorinantheol (36)
Corynantheol (37)
3 Α, 20 Β -18,19-Dihydrocorinantheol (36); (3 R, 15 R, 16 R)-E-Isositsyricin (38); (3 R, 15 R, 16 S)-E-Isositsyricin (39); harman-5-carboxylic acid (40)	Stem bark	Not evaluated	Torres-Rêgo et al. (2024)

• IC₅₀: Mean inhibitory concentration required to reduce 50% of the activity of the target organism or cell. MIC: minimum inhibitory concentration required to inhibit the growth of microorganisms.

Figure 1
Representative chemical structures of indole alkaloids isolated from A.excelsum Benth. and its botanical synonyms.

Figure 2
Representative chemical structures of indole alkaloids isolated from A.excelsum Benth. and its botanical synonyms (continued).

These experimental studies indicate that these alkaloids have potent antiplasmodial actions as well as antimicrobial and antileishmanial activities (Coutinho et al., 2013; Nascimento et al., 2019; Veiga et al., 2022). This convergence between structural diversity and multiple biological effects reinforces the importance of A. excelsum as a promising source of bioactive molecules of pharmaceutical interest. Thus, the data systematized in Tables 3 and 4 and illustrated in Figure 1 and Figure 2 not only validate the traditional uses of the species but also support future research aimed at elucidating the mechanisms of action and the discovery of new therapeutic prototypes obtained from Amazonian biodiversity.

Structural complexity is a striking characteristic of the genus Aspidosperma and has been observed in other species such as A. ramiflorum, A. spruceanum, and A. pyrifolium, whose metabolic profiles reveal the presence of yohimbine and aspidosperma alkaloids, associated with various biological activities (Mitaine-Offer et al., 2002; Almeida et al., 2019). However, A. excelsum stands out for bringing together many reported compounds with a detailed chemical characterization, which reinforces its relevance within the group as a kind of model for phytochemical and pharmacological investigations.

4. Final Considerations

This systematic search and review gathered and critically analyzed the ethnobotanical, phytochemical, pharmacological and taxonomic data regarding Aspidosperma excelsum Benth. and its accepted botanical synonym A. nitidum. By compiling information dispersed in the literature, often compromised by synonymic and taxonomic inconsistencies, the study contributes to the consolidation of scientific knowledge regarding the species and advances the understanding of its biological potential.

The results reveal a partial correspondence between traditional uses and preliminary experimental evidence, particularly regarding antiplasmodial, antioxidant, antimicrobial, anti-inflammatory and selective cytotoxic activities. It must be emphasized, however, that the majority of the available evidence derives from in vitro and in vivo assays using preclinical models, which limits the conclusions that can be drawn about the therapeutic relevance of the species. The diversity of indole alkaloids identified reinforces the investigative potential of A. excelsum as a source of bioactive metabolites worthy of further pharmacological research.

In addition to organizing a hitherto fragmented body of data, this review establishes a conceptual foundation to guide future research. Subsequent studies should prioritize the isolation of pure compounds, the elucidation of mechanisms of action, the standardization of experimental protocols, and the development of more robust preclinical models. The integration between traditional knowledge and scientific evidence, combined with nomenclatural stabilization, represents a strategic path toward the sustainable valorization of this emblematic species of Amazonian biodiversity.

Nevertheless, some limitations of the available evidence must be acknowledged. First, most pharmacological studies rely on crude extracts or partially purified fractions, which prevents the attribution of biological activities to specific compounds. Second, a substantial portion of the data derives from studies conducted with A. nitidum, a heterotypic synonym that may present chemical and biological variation in relation to A. excelsum sensu stricto, introducing taxonomic uncertainty into the interpretation of results. Third, the considerable methodological heterogeneity among the reviewed studies, including differences in extraction protocols, experimental models, and activity thresholds, limits the direct comparability of results and the generalization of conclusions.

Data Availability Statement

All the data supporting the results of this study were published in the article itself.

References

• ALMEIDA, V.L., SILVA, C.G., SILVA, A.F., CAMPANA, P.R.V., FOUBERT, K., LOPES, J.C.D. and PIETERS, L., 2019. Aspidosperma species: a review of their chemistry and biological activities. Journal of Ethnopharmacology, vol. 231, pp. 125-140. https://doi.org/10.1016/j.jep.2018.10.039 PMid:30395977.
  » https://doi.org/10.1016/j.jep.2018.10.039
• ARIAS, M.-H., VALLEJO, G.A. and GARAVITO, G., 2021. Trypanocidal activity of traditional antiparasitic medicinal plants from the Amazon. Pharmacognosy Research, vol. 13, no. 4, pp. 8-17. https://doi.org/10.5530/pres.13.4.15
  » https://doi.org/10.5530/pres.13.4.15
• ARNDT, R.R., MARROM, S.H., LING, N.C., ROLO, P., DJERASSI, C., FERREIRA, J.M., GILBERTO, F.B., MIRANDA, C.E., FLORES, S.E., DUARTE, A.P. and CARRAZZONI, E.P., 1967. Alkaloid studies - LVIII: the alkaloids of six Aspidosperma species. Phytochemistry, vol. 12, no. 12, pp. 1653-1658. https://doi.org/10.1016/S0031-9422(00)82898-8
  » https://doi.org/10.1016/S0031-9422(00)82898-8
• BATISTA, S.G., ARAÚJO, W.V., ARRUDA, R.C.O. and FARINACCIO, M.A., 2024. Taxonomic delimitation in Aspidosperma sect. Pungentia (Apocynaceae) based on morphological and leaf anatomical traits. Flora (Jena), vol. 314, pp. 152494. https://doi.org/10.1016/j.flora.2024.152494
  » https://doi.org/10.1016/j.flora.2024.152494
• BENOIN, P.R., BURNELL, R.H. and MEDINA, J.D., 1967. Alkaloids of Aspidosperma excelsum Benth. Canadian Journal of Chemistry, vol. 7, no. 7, pp. 725-730. https://doi.org/10.1139/v67-118
  » https://doi.org/10.1139/v67-118
• BOLZANI, V.D.S., SERUR, L.M., DE MATOS, F.J.A. and GOTTLIEB, O.R., 1987. Indole alkaloid evolution in Aspidosperma. Biochemical Systematics and Ecology, vol. 2, pp. 187-200. https://doi.org/10.1016/0305-1978(87)90019-6
  » https://doi.org/10.1016/0305-1978(87)90019-6
• BRANDÃO, M.G.L., MARTINS, M.T., SILVA, A.O., ALMEIDA, A.D., DE PAULA, R.C., DE OLIVEIRA, A.B., COELHO-FERREIRA, M.R., GOMES, A.T.A., DE VASCONCELOS, F., PEREIRA, W.L.A., VALE, V.V., PERCÁRIO, S. and DOLABELA, M.F., 2020 [viewed 19 Jan 2026]. Anti-malarial activity and toxicity of Aspidosperma nitidum Benth: a plant used in traditional medicine in the Brazilian Amazon. Research, Society and Development [online], vol. 9, no. 10, pp. e5059108817. Available from: https://rsdjournal.org/index.php/rsd/article/view/8817
  » https://rsdjournal.org/index.php/rsd/article/view/8817
• BRÍGIDO, H.P.C., RAMOS, B.T.C., PAZ, M.K.B., BASTOS, M.L.C. and DOLABELA, M.F., 2020. Atividade antimicrobiana de Aspidosperma nitidum Benth (Apocynaceae). Revista Eletrônica Acervo Saúde, vol. 12, no. 10, pp. e4123. https://doi.org/10.25248/reas.e4123.2020
  » https://doi.org/10.25248/reas.e4123.2020
• BRÍGIDO, H.P.C., VARELA, E.L.P., GOMES, A.R.Q., BASTOS, M.L.C., FEITOSA, A.O., MARINHO, A.M.R., CARNEIRO, L.A., COELHO-FERREIRA, M.R., DOLABELA, M.F. and PERCÁRIO, S., 2021. Evaluation of acute and subacute toxicity of ethanolic extract and fraction of alkaloids from bark of Aspidosperma nitidum in mice. Scientific Reports, vol. 11, no. 1, pp. 18283. https://doi.org/10.1038/s41598-021-97637-1 PMid:34521944.
  » https://doi.org/10.1038/s41598-021-97637-1
• BRÍGIDO, H.P.C., VARELA, E.L.P., GOMES, A.R.Q., CRUZ, J.N., CORREA-BARBOSA, J., SIQUEIRA, J.E.S., CHAGAS, C.K.S., MARINHO, A.M.R., CARNEIRO, L.A., COELHO-FERREIRA, M.R., PERCÁRIO, S. and DOLABELA, M.F., 2024. Aspidosperma nitidum reduces parasite load and modulates cytokines in BALB/c mice infected with Leishmania (Leishmania) amazonensis. Frontiers in Chemistry, vol. 12, pp. e1492770. https://doi.org/10.3389/fchem.2024.1492770 PMid:39552719.
  » https://doi.org/10.3389/fchem.2024.1492770
• BURNELL, R.H. and NGUYEN-THI-SEN, 1971. α-Yohimbine from Aspidosperma excelsum. Phytochemistry, vol. 10, no. 4, pp. 895. https://doi.org/10.1016/S0031-9422(00)97166-8
  » https://doi.org/10.1016/S0031-9422(00)97166-8
• CASTELLO, A.C.D., PEREIRA, A.S.S., SHIMIZU, G.H., ZUNTINI, A.R., SIMÕES, A.O. and KOCH, I., 2022. Taxonomy and nomenclature of Aspidosperma (Apocynaceae). Phytotaxa, vol. 571, no. 3, pp. 239-277. https://doi.org/10.11646/phytotaxa.571.3.1
  » https://doi.org/10.11646/phytotaxa.571.3.1
• COUTINHO, J.P., AGUIAR, A.C.C., SANTOS, P.A., LIMA, J.C., ROCHA, M.G.L., ZANI, C.L., ALVES, T.M.A., SANTANA, A.E.G., PEREIRA, M.M. and KRETTLI, A.U., 2013. Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon. Memórias do Instituto Oswaldo Cruz, vol. 108, no. 8, pp. 974-982. https://doi.org/10.1590/0074-0276130246 PMid:24402150.
  » https://doi.org/10.1590/0074-0276130246
• DEUTSCH, H.F., EVENSON, M.A., DRESCHER, P., SPARWASSER, C. and MADSEN, P.O., 1994. Isolation and biological activity of aspidospermine and quebrachamine from an Aspidosperma tree source. Journal of Pharmaceutical and Biomedical Analysis, vol. 12, no. 10, pp. 1283-1287. https://doi.org/10.1016/0731-7085(94)00066-2 PMid:7841224.
  » https://doi.org/10.1016/0731-7085(94)00066-2
• FABRICANT, D.S. and FARNSWORTH, N.R., 2001. The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives, vol. 109, suppl. 1, pp. 69-75. https://doi.org/10.1289/ehp.01109s169 PMid:11250806.
  » https://doi.org/10.1289/ehp.01109s169
• FOUQUÉ, A., 1981 [viewed 19 Jan 2026]. Les plantes médicinales présentes en Fôret Guyanaise. Fruits [online], vol. 36, no. 4, pp. 223-240. Available from: https://agritrop.cirad.fr/414112/1/414112.pdf
  » https://agritrop.cirad.fr/414112/1/414112.pdf
• GRANT, M.J. and BOOTH, A., 2009. A typology of reviews: an analysis of 14 review types and associated methodologies. Health Information and Libraries Journal, vol. 26, no. 2, pp. 91-108. https://doi.org/10.1111/j.1471-1842.2009.00848.x PMid:19490148.
  » https://doi.org/10.1111/j.1471-1842.2009.00848.x
• HEINRICH, M., EDWARDS, S., MOERMAN, D.E. and LEONTI, M., 2009. Ethnopharmacological field studies: a critical assessment of their conceptual basis and methods. Journal of Ethnopharmacology, vol. 124, no. 1, pp. 1-17. https://doi.org/10.1016/j.jep.2009.03.043 PMid:19537298.
  » https://doi.org/10.1016/j.jep.2009.03.043
• HUMPHRIES, R.M., MAGNANO, P., BURNHAM, C.A.D., DIEN BARD, J., DINGLE, T.C., CALLAN, K. and WESTBLADE, L.F., 2021. Evaluation of surrogate tests for the presence of mecA-mediated methicillin resistance in Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus warneri. Journal of Clinical Microbiology, vol. 59, no. 1, pp. e02290-e20. https://doi.org/10.1128/JCM.02290-20 PMid:33115842.
  » https://doi.org/10.1128/JCM.02290-20
• LAYNE, T.H., MCLEAN, S., REYNOLDS, W.F. and TINTO, W.F., 2007. Excelsinidine: a quaternary alkaloid from Aspidosperma excelsum. Natural Product Communications, vol. 2, no. 6, pp. 649-652. https://doi.org/10.1177/1934578X0700200606
  » https://doi.org/10.1177/1934578X0700200606
• MARQUES, M.F.S., KATO, L., LEITÃO FILHO, H.F. and REIS, F.A.M., 1996. Indole alkaloids from Aspidosperma ramiflorum. Phytochemistry, vol. 41, no. 3, pp. 963-967. https://doi.org/10.1016/0031-9422(95)00660-5
  » https://doi.org/10.1016/0031-9422(95)00660-5
• MENEGUETTI, D.U.O., CUNHA, R.M., LIMA, R.A., OLIVEIRA, F.A.S., MEDEIROS, D.S.S., PASSARINI, G.M., MEDEIROS, P.S.M., MILITÃO, J.S.L.T. and FACUNDO, V.A., 2014 [viewed 19 Jan 2026]. Antimalarial ethnopharmacology in the Brazilian Amazon. Journal of Basic and Applied Pharmaceutical Sciences [online], vol. 35, no. 4, pp. 577-587. Available from: https://rcfba.fcfar.unesp.br/index.php/ojs/article/view/86
  » https://rcfba.fcfar.unesp.br/index.php/ojs/article/view/86
• MITAINE-OFFER, A.C., SAUVAIN, M., VALENTIN, A., CALLAPA, J., MALLIÉ, M. and ZÈCHES-HANROT, M., 2002. Antiplasmodial activity of Aspidosperma indole alkaloids. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 9, no. 2, pp. 142-145. https://doi.org/10.1078/0944-7113-00094 PMid:11995947.
  » https://doi.org/10.1078/0944-7113-00094
• MORALES, J.F., 2005 [viewed 19 Jan 2026]. Estudios en las Apocynaceae neotropicales XIX: la familia Apocynaceae (Apocynoideae, Rauvolfioideae) en Costa Rica. Darwiniana [online], vol. 43, pp. 90-191. Available from: https://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0011-67932005000100011&lng=es&nrm=iso
  » https://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0011-67932005000100011&lng=es&nrm=iso
• NASCIMENTO, M.S., PINA, N.D.P.V., SILVA, A.S.B., GOMES, L.F.S., VASCONCELOS, F., BRANDÃO, G.C., NASCIMENTO, M.F.A., OLIVEIRA, A.B. and BARBOSA, W.L.R., 2019. In vitro antiplasmodial activity and identification, using tandem LC-MS, of alkaloids from Aspidosperma excelsum, a plant used to treat malaria in Amazonia. Journal of Ethnopharmacology, vol. 228, pp. 99-109. https://doi.org/10.1016/j.jep.2018.09.012 PMid:30201230.
  » https://doi.org/10.1016/j.jep.2018.09.012
• NORADINA, N., RITONGA, I.L., HERLINA, M., HASIBUAN, P.A.Z., YUANDANI, Y., SALIM, E. and TANJUNG, R., 2024. Botany, phytochemistry, traditional uses, pharmacology of Apocynaceae family: a review. Community Practitioner, vol. 21, no. 7, pp. 1857-1867. https://doi.org/10.5281/zenodo.12799415
  » https://doi.org/10.5281/zenodo.12799415
• OLIVEIRA, D.R., KRETTLI, A.U., AGUIAR, A.C.C., LEITÃO, G.G., VIEIRA, M.N., MARTINS, K.S. and LEITÃO, S.G., 2015. Ethnopharmacological evaluation of medicinal plants used against malaria by quilombola communities from Oriximiná, Brazil. Journal of Ethnopharmacology, vol. 173, pp. 424-434. https://doi.org/10.1016/j.jep.2015.07.035 PMid:26231451.
  » https://doi.org/10.1016/j.jep.2015.07.035
• OMAR, F., TAREQ, A.M., ALQAHTANI, A.M., DHAMA, K., SAYEED, M.A., EMRAN, T.B. and SIMAL-GANDARA, J., 2021. Plant-based indole alkaloids: a comprehensive overview from a pharmacological perspective. Molecules (Basel, Switzerland), vol. 26, no. 8, pp. 2297. https://doi.org/10.3390/molecules26082297 PMid:33921093.
  » https://doi.org/10.3390/molecules26082297
• PEDROLLO, C.T., KINUPP, V.F., SHEPARD JÚNIOR, G.J.R. and HEINRICH, M., 2016. Medicinal plants at Rio Jauaperi, Brazilian Amazon: ethnobotanical survey and environmental conservation. Journal of Ethnopharmacology, vol. 186, pp. 111-124. https://doi.org/10.1016/j.jep.2016.03.055 PMid:27058631.
  » https://doi.org/10.1016/j.jep.2016.03.055
• PEREIRA, A.S.S., CASTELLO, A.C.D., SIMÕES, A.O. and KOCH, I., 2019. Reestablishment, new records, and a key for the species of Aspidosperma (Apocynaceae) from the Brazilian Amazon. Acta Botanica Brasílica, vol. 33, no. 1, pp. 1-20. https://doi.org/10.1590/0102-33062018abb0168
  » https://doi.org/10.1590/0102-33062018abb0168
• PEREIRA, A.S.S., SIMÕES, A.O. and SANTOS, J.U.M., 2016. Taxonomy of Aspidosperma Mart. (Apocynaceae, Rauvolfioideae) in the State of Pará, Northern Brazil. Biota Neotropica, vol. 16, no. 2, pp. e20150080. https://doi.org/10.1590/1676-0611-BN-2015-0080
  » https://doi.org/10.1590/1676-0611-BN-2015-0080
• PEREIRA, M.M., SOUZA JÚNIOR, S.N., ALCÂNTARA, A.F.C., PILÓ-VELOSO, D., ALVES, R.B., MACHADO, P.O., AZEVEDO, A.O., MOREIRA, F.H., CASTRO, M.S.A. and RASLAN, D.S., 2006a. Constituintes químicos e estudo biológico de Aspidosperma nitidum (Apocynaceae). Revista Brasileira de Plantas Medicinais, vol. 8, no. 3, pp. 1-8. https://doi.org/10.70151/ph1qd630
  » https://doi.org/10.70151/ph1qd630
• PEREIRA, M.M., ALCÂNTARA, A.F.C., PILÓ-VELOSO, D. and RASLAN, D.S., 2006b. NMR structural analysis of braznitidumine: a new indole alkaloid with 1,2,9-triazabicyclo[7.2.1] system, isolated from Aspidosperma nitidum (Apocynaceae). Journal of the Brazilian Chemical Society, vol. 17, no. 7, pp. 1274-1280. https://doi.org/10.1590/S0103-50532006000700012
  » https://doi.org/10.1590/S0103-50532006000700012
• PEREIRA, M.M., JÁCOME, R.L.R.P., ALCÂNTARA, A.F.C., ALVES, R.B. and RASLAN, D.S., 2007. Alcaloides indólicos isolados de espécies do gênero Aspidosperma (Apocynaceae). Química Nova, vol. 30, no. 4, pp. 970-983. https://doi.org/10.1590/S0100-40422007000400037
  » https://doi.org/10.1590/S0100-40422007000400037
• PÉREZ, D., 2002. Etnobotánica medicinal y biocidas para malaria en la región Ucayali. Folia Amazónica, vol. 13, no. 1–2, pp. 87-108. https://doi.org/10.24841/fa.v13i1-2.136
  » https://doi.org/10.24841/fa.v13i1-2.136
• PLANTS OF THE WORLD ONLINE – POWO, 2025 [viewed 19 Jan 2026]. Facilitated by the Royal Botanic Gardens, Kew [online]. Available from: https://powo.science.kew.org/
  » https://powo.science.kew.org/
• RAPINI, A., 2012. Taxonomy" under construction": advances in the systematics of Apocynaceae, with emphasis on the Brazilian Asclepiadoideae. Rodriguésia, vol. 63, no. 1, pp. 075-088. https://doi.org/10.1590/S2175-78602012000100007
  » https://doi.org/10.1590/S2175-78602012000100007
• ROCHA, N.A., BARBOSA, D.B., RAPOSO, F.J., LATALIZA, A.A.B., AMARANTE, C.B. and RAPOSO, N.R.B., 2019. Assessment of different biological capacities of Aspidosperma excelsum Benth. Journal of Multidisciplinary Engineering Science and Technology, vol. 6, no. 1, pp. 9384-9390.
• SALAZAR-DÍAZ, J., GUERRERO-MARINA, J. and RODRÍGUEZ-ESPEJO, Y., 2021. Actividad antioxidante de Aspidosperma excelsum Benth., Dracontium loretense Krause y Pothemorphe peltata (L.) Miq. La Revista Agrotecnológica Amazónica, vol. 1, no. 2, pp. 27-39. https://doi.org/10.51252/raa.v1i2.190
  » https://doi.org/10.51252/raa.v1i2.190
• SALES, M.L., 2019. Estudo fitoquímico de Aspidosperma nitidum (Benth) Manaus: Universidade Federal do Amazonas. Dissertação.
• SIMINSKI, T., SOUZA, J.S., ARAUJO, C.F.L., AÑEZ, R.B.S. and NUNES, R.A., 2015. Avaliação da atividade antimicrobiana das espécies Aspidosperma nitidum, Annona crassiflora e Annona mucosa frente a cepas ATCC. Enciclopédia Biosfera, vol. 11, no. 22, pp. 2882-2892. https://doi.org/10.18677/Enciclopedia_Biosfera_2015_008
  » https://doi.org/10.18677/Enciclopedia_Biosfera_2015_008
• SIMÕES, A.O., KINOSHITA, L.S., KOCH, I., SILVA, M.J. and ENDRESS, M.E., 2016. Systematics and character evolution of Vinceae (Apocynaceae). Taxon, vol. 65, no. 1, pp. 99-122. https://doi.org/10.12705/651.7
  » https://doi.org/10.12705/651.7
• TOMCHINSKY, B., MING, L.C., KINUPP, V.F., HIDALGO, A.F. and CHAVES, F.C.M., 2017. Ethnobotanical study of antimalarial plants in the middle region of the Negro River, Amazonas, Brazil. Acta Amazonica, vol. 47, no. 3, pp. 203-212. https://doi.org/10.1590/1809-4392201701191
  » https://doi.org/10.1590/1809-4392201701191
• TORRES-RÊGO, M., NOGUEIRA, P.C.N., SANTOS, S.P.D., DANIELE-SILVA, A., CAVALCANTI, F.F., OLIVEIRA, C.I.F.B., ROCHA, H.A.O., FERNANDES-PEDROSA, M.F., SILVEIRA, E.R. and ARAÚJO, R.M., 2024. Isolation of indole alkaloids and a new norneolignan of hydroethanol extract from the stem barks of Aspidosperma nitidum Benth: preclinical evaluation of safety and anti-inflammatory and healing properties. Journal of Ethnopharmacology, vol. 319, no. Pt 1, pp. 117076. https://doi.org/10.1016/j.jep.2023.117076 PMid:37619858.
  » https://doi.org/10.1016/j.jep.2023.117076
• TRINCONI, C.T., REIMÃO, J.Q., YOKOYAMA-YASUNAKA, J.K.U., MIGUEL, D.C. and ULIANA, S.R.B., 2014. Combination therapy with tamoxifen and amphotericin B in experimental cutaneous leishmaniasis. Antimicrobial Agents and Chemotherapy, vol. 58, no. 5, pp. 2608-2613. https://doi.org/10.1128/AAC.01315-13 PMid:24550333.
  » https://doi.org/10.1128/AAC.01315-13
• TRINDADE, R.C.S., KIKUCHI, T.Y.S., SILVA, R.J.F., VALE, V.V., OLIVEIRA, A.B., DOLABELA, M.F. and COELHO-FERREIRA, M.R., 2016. Estudo farmacobotânico das folhas de Aspidosperma excelsum Benth. (Apocynaceae). Revista Fitos, vol. 10, no. 3, pp. 220-372. https://doi.org/10.5935/2446-4775.20160019
  » https://doi.org/10.5935/2446-4775.20160019
• VÁSQUEZ, S.P.F., MENDONÇA, M.S. and NODA, S.N., 2014. Etnobotânica de plantas medicinais em comunidades ribeirinhas do município de Manacapuru, Amazonas, Brasil. Acta Amazonica, vol. 44, no. 4, pp. 457-472. https://doi.org/10.1590/1809-4392201400423
  » https://doi.org/10.1590/1809-4392201400423
• VEIGA, A.S.S., SILVEIRA, F.T., DA SILVA, E.O., DINIZ-JÚNIOR, J.A.P., ARAÚJO, S.C., CAMPOS, M.B., MARINHO, A.M.R., BRANDÃO, G.C., VALE, V.V., PERCÁRIO, S. and DOLABELA, M.F., 2022. Activity of alkaloids from Aspidosperma nitidum against Leishmania (Leishmania) amazonensis. Scientific Reports, vol. 12, no. 1, pp. 8662. https://doi.org/10.1038/s41598-022-12396-x PMid:35606396.
  » https://doi.org/10.1038/s41598-022-12396-x
• VEIGA, A.S.S., SILVEIRA, F.T., MARINHO, A.M.R., TRINDADE, R.C.S., CAMPOS, M.B. and DOLABELA, M.F., 2021. Leishmanicidal activity of Aspidosperma nitidum Benth. ex Müll. Arg. Research, Society and Development, vol. 10, no. 2, pp. e50210212646. https://doi.org/10.33448/rsd-v10i2.12646
  » https://doi.org/10.33448/rsd-v10i2.12646
• VERPOORTE, R., KOS-KUYCK, E., TSOI, A.T., RUIGROK, C.L., JONG, G. and SVENDSEN, A.B., 1983. Medicinal plants of Surinam. III: antimicrobially active alkaloids from Aspidosperma excelsum. Planta Medica, vol. 48, no. 4, pp. 283-289. https://doi.org/10.1055/s-2007-969935 PMid:6635013.
  » https://doi.org/10.1055/s-2007-969935
• WORLD HEALTH ORGANIZATION – WHO, 2019. WHO global report on traditional and complementary medicine 2019 Geneva: WHO.

Edited by

• Editor:
  Marcelo A.M. Esquisatto

Publication Dates

• Publication in this collection
  18 Sept 2026
• Date of issue
  2026

History

• Received
  19 Jan 2026
• Accepted
  07 July 2026