Four almost unexplored species of Brazilian Connarus (Connaraceae): Chemical composition by ESI-QTof-MS/MS-GNPS and a pharmacologic potential.

INTRODUCTION: Species of Connaraceae are globally used in traditional medicines. However, several of these have not been studied regarding their chemical composition, and some are even at risk of extinction without proper studies. Therefore, the chemical composition and pharmacological potential of Connarus blanchetii Planch., Connarus nodosus Baker, Connarus regnellii G. Schellenb., and Connarus suberosus Planch., which were previously unknown, were analyzed. OBJECTIVE: This work aims to investigate the pharmacological potential of these four Connarus species. The chemical composition of different extracts was determined by high-resolution mass spectrometry (HRMS), with subsequent analysis by the GNPS platform and competitive fragmentation modeling (CFM). MATERIALS AND METHODS: Leaf extracts (C. blanchetii, C. nodosus, C. regnellii, and C. suberosus) and bark extracts (C. regnellii and C. suberosus) were obtained by decoction, infusion, and maceration. LC/HRMS data were submitted to the GNPS platform and evaluated using CFM in order to confirm the structures. RESULTS: The HRMS-GNPS/CFM analysis indicated the presence of 23 compounds that were mainly identified as phenolic derivatives from quercetin and myricetin, of which 21 are unedited in the Connarus genus. Thus, from the analyses performed, we can identify different compounds with pharmacological potential, as well as the most suitable forms of extraction. CONCLUSION: Using HRMS-GNPS/CFM, 21 unpublished compounds were identified in the studied species. Therefore, our combination of data analysis techniques can be used to determine their chemical composition.

Connaraceae: An updated overview of research and the pharmacological potential of 39 species.

ETHNOPHARMACOLOGICAL RELEVANCE: An interdisciplinary scientific investigation of biologically active agents is fundamental to search for natural substances with therapeutic action. This review collected the most relevant information on traditional knowledge related to the use of plants of the Connaraceae family. This work is the first to compile all the published ethnobotanical, chemical, pharmacological, and toxicological information about this important plant family. AIM OF THE STUDY: Our objective was to provide the scientific community with an up-to-date overview of the pharmacological potential of Connaraceae species. MATERIAL AND METHODS: We searched NCBI Pubmed Central, Google Scholar, Scientific Electronic Library Online (SciELO), ScienceDirect, SciFinder, and Scopus databases to review the research on ethnobotanical, chemical, pharmacognostical, pharmacological, and toxicological studies with Connaraceaes. Books that address the theme were also included. DISCUSSION AND CONCLUSION: The literature review indicated that 39 species of Connaraceaes have pharmacological potentiality. Ethnobotany reports listed 36 of the 39 species discussed. Pharmacognostical studies have been conducted with 23 species and isolates, and chemical compounds have been identified for only 15 species. At least one study has been published concerning the pharmacological activities for 20 of the 39 species analyzed. For Agelaea pentagyna, Cnestis ferruginea, Connars suberosus, and Rourea minor, pharmacological activity experiments were performed using isolated compounds, which have the highest current pharmacological potential. Studies employing a toxicological approach cover only 10 of the 39 Connaraceaes species. Thus, scientific community should conduct much more research for a broader understanding of this plant family.

Chemical constituents of Rourea doniana

The chromatography fractionation of the hexane, chloroform and ethyl acetate extracts from the leaves and stems of Rourea doniana Baker, Connaraceae, resulted in the isolation of five triterpenes (lupeol, lupenone, α-amyrenone, β-amyrenone, and taraxerol), a flavonol (7,4'-dimethylkaempferol), a coumarin (scopoletin) and four phytosteroids (β-sitosterol, stigmasterol, β-sitosteryl-3-O-β- D-glucopyranoside and stigmasteryl-3-O-β-D-glucopyranoside). All compounds are being for the first time in this species and all triterpenes and the flavonol are being described for the first time in the family Connaraceae. These compounds were identified on basis of their IR and NMR (¹H, 13C, DEPT, HSQC, HMBC, and NOESY) spectral data and by comparison with literature data.

Phytochemical constituents and preliminary toxicity evaluation of leaves from Rourea induta Planch. (Connaraceae) / Constituintes fitoquímicos e avaliação preliminar de toxicidade folhas de Rourea Induta Planch. (Connaraceae)

Most active plants are toxic at high doses and it is therefore important to investigate the preliminary toxicity of plant extracts. The Rourea induta species is a potential drug with no phytochemical or biological studies registered in the literature. Thus, a phytochemical study and a toxicity analysis of the ethanolic extract obtained from the leaves of Rourea induta Planch., Connaraceae, was run. A long chain hydrocarbon, n-tetracosane, and four flavonoids were identified: quercetin, and three glycosylated derivates, quercetin-3-O-α-arabinofuranoside, quercetin-3-O-β-xyloside and quercetin-3-O-β-galactoside. This is the first time these have been isolated in this species. The structures were elucidated by 13C NMR, ¹H NMR, UV and IR spectroscopy. The toxicity evaluation of extracts was performed by the brine shrimp method and determination of hemolytic activity. The samples demonstrated no toxic potential by the analyzed methods.

A maioria das plantas ativas é tóxica em doses elevadas, portanto, é importante a investigação da toxicidade preliminar dos extratos das plantas. A espécie Rourea induta é uma droga potencial que não apresenta estudo fitoquímico ou biológico descrito na literatura. Assim, um estudo fitoquímico e análises toxicológicas foram realizados com o extrato etanólico obtido das folhas de Rourea induta Planch., Connaraceae. Foram obtidos um hidrocarboneto de cadeia longa, n-tetracosano, e quatro flavonóides, quercetina e três derivados glicosilados, quercetina-3-O-α-arabinofuranosideo, quercetina-3-O-β-xilosideo e quercetina-3-O-β-galactosideo. Esta é a primeira vez que estes compostos são isolados nesta espécie. As estruturas foram elucidadas por espectroscopia de RMN-13C, RMN-¹H, ultravioleta e infravermelho. A avaliação da toxicidade dos extratos foi analisada pelo método da Artemia salina e atividade hemolítica. Nenhuma das amostras testadas apresentou um potencial tóxico pelos métodos analisados.

Connaraceae endémicas del Perú

La familia Connaraceae es reconocida en el Perú por presentar tres géneros y 20 especies (Brako & Zarucchi, 1993; Ulloa Ulloa et al., 2004), principalmente lianas y arbustos. En este trabajo reconocemos tres especies endémicas en tres géneros. Las especies endémicas ocupan la región Bosques Húmedos Amazónicos, entre los 100 y 400 m de altitud. Una de estas especies está representada dentro del Sistema Nacional de Áreas Naturales Protegidas por el Estado.

The Connaraceae are represented in Peru by 20 species in three genera (Brako & Zarucchi, 1993; Ulloa Ulloa et al., 2004), mainly lianas and trees. Here we recognize three endemic species in three genera. Endemic species are found in Humid Lowland Amazonian Forests region, between 100 and 400 m elevation. One of these species has been recorded within Peru´s protected areas system.