Terpenes from Cecropia Species and Their Pharmacological Potential.

Cecropia is a genus of neotropical trees mainly distributed in Mexico and Central and South America. Currently, 63 species have been described, some of which have been used for centuries in traditional medicine to treat conditions such as diabetes, high blood pressure, and wound healing, among others. In recent times, modern phytochemical studies have succeeded in isolating individual compounds with potential specific medicinal applications. This review aims to examine the literature data regarding isolated terpenes and their correlation with pharmacological activities, with the goal of unveiling the future potential of the genus.

Correction: De Jesus et al. Body Temperature Drop as a Humane Endpoint in Snake Venom-Lethality Neutralization Tests. Toxins 2023, 15, 525.

In the original publication [...].

Assessment of the Quality, Chemometric and Pollen Diversity of Apis mellifera Honey from Different Seasonal Harvests.

The parameters for assessing the quality of honey produced by Apis mellifera are standardized worldwide. The physicochemical properties of honey might vary extensively due to factors such as the geographical area where it was produced and the season in which it was harvested. Little information is available on variations in honey quality among different harvest periods in tropical areas, and particularly in neotropical dry forests. This study describes variations in seventeen physicochemical parameters and the pollen diversity of honey harvested from beehives during the dry season in February, March, and April 2021, in the dry arc of Panama. Potassium is the most abundant mineral in honey samples, and its concentration increases during the harvest period from February to April. A PCA analysis showed significant differences among the samples collected during different harvest periods. The pollen diversity also differs among honey samples from February compared with March and April. The results indicate that climatic conditions may play an important role in the quality of honey produced in the dry arc of Panama. Furthermore, these results might be useful for establishing quality-control parameters of bee honey produced in Panama in support of beekeeping activities in seasonal wet-dry areas of the tropics.

Body Temperature Drop as a Humane Endpoint in Snake Venom-Lethality Neutralization Tests.

Snake venom neutralization potency tests are required for quality control assessment by manufacturers and regulatory authorities. These assays require the use of large numbers of mice that manifest severe signs associated with pain and distress and long periods of suffering. Despite this, many animals make a full recovery; therefore, the observation of clinical signs as a predictor of animal death is highly subjective and could affect the accuracy of the results. The use of a more objective parameter such as body temperature measurement could help establish a humane endpoint that would contribute to significantly reducing the suffering of large numbers of animals. We determined the temperature drop in BALB/c mice exposed to the mixtures of Bothrops asper or Lachesis stenophrys venom and a polyvalent antivenom by using an infrared thermometer. Our data show that, based on the temperature change from baseline, it is possible to predict which animals will survive during the first 3 h after inoculation. The data provided in this study may contribute to future reductions in animal suffering, in concordance with general trends in the use of laboratory animals for the quality control of biologicals.

Validation of an UPLC-DAD Method for the Quantification of Phenolic Acids, Verbascoside and 6-epi-aucubin in Crescentia cujete Fruit.

BACKGROUND: The fruit pulp decoction of Crescentia cujete, commonly known as calabash, is traditionally used for the treatment of several respiratory diseases and is available as syrup formulations. Unfortunately, there is no detailed investigation on the analytical methods for warranting the quality of these products. AIMS AND OBJECTIVES: To develop and validate an appropriate analytical method for the simultaneous quantification of trans-cinnamic acid, 4-hydroxybenzoic acid, verbascoside and 6- epi-aucubin in the decoction and commercial cough syrups of Crescentia cujete fruit. MATERIALS AND METHODS: A reversed-phase ultra-high-performance liquid chromatographic method coupled to a diode array detector (UPLC-DAD) was validated following the ICH guidelines. The chromatographic analysis was performed using a C18 column, the mobile phase system consisted of water and acetonitrile containing 0.1% formic acid, and UV chromatograms were recorded from 200 to 400 nm. RESULTS: A new UPLC-DAD method was validated for the simultaneous quantification of transcinnamic acid, 4-hydroxybenzoic acid, verbascoside and 6-epi-aucubin in calabash-derived products. After successful validation, this method was applied for the quantification of the selected chemical markers in an in-house decoction and three commercial cough syrups. Among the selected chemical markers, 6-epi-aucubin was the main compound in the calabash decoction, while trans-cinnamic acid and 4-hydroxybenzoic acid were the major compounds in the commercial products. Verbascoside and 6-epi-aucubin were below the limit of quantification in all syrup samples. CONCLUSION: The proposed method was successfully applied for the analysis of three commercial syrup formulations and can be useful for standardization and quality control of raw and pharmaceutical calabash preparations.

Pharmacognostic Evaluation of Ten Species of Medicinal Importance of Cecropia: Current Knowledge and Therapeutic Perspectives.

This work covers a systematic review of literature about the genus Cecropia from 1978 to 2020, emphasizing the analysis of 10 of the most relevant species and their associated biological activities. Cecropia is a neotropical genus, which comprises about 61 native species in the American continent where it is known to be part of the traditional medicine of numerous countries. Secondary metabolites described for this genus showed an elevated structural and functional diversity, where polyphenols have been the most abundant. Based on this diversity, Cecropia phytochemicals represent an important source of potential therapeutic agents yet to be exploited. This review also highlights the effectiveness of combining chemometrics and ultra-performance liquid chromatography-tandem mass spectrometry as a novel approach to successfully single out Cecropia species phytochemicals. While the medicinal use of Cecropia species is officially recognized in National Pharmacopoeias and Formularies of several Latin American countries, it is important to recognize that these phytomedicines are complex mixtures requiring a thorough understanding of their chemical composition and their correlation with biological activities to guarantee their quality, safety, and efficacy.

Simulated Gastrointestinal Biotransformation of Chlorogenic Acid, Flavonoids, Flavonolignans and Triterpenoid Saponins in Cecropia obtusifolia Leaf Extract.

It is well known that biotransformation processes in the human body are crucial to form potentially bioactive metabolites from particular classes of natural products. However, little research has been conducted concerning the bioavailability of polyphenols, especially in the colon. The gastrointestinal stability and colonic biotransformation of the crude extract of the leaves of Cecropia obtusifolia, rich in flavone C-glycosides, was investigated under in vitro conditions, and the processing and interpretation of results were facilitated by using an automated machine learning model. This investigation revealed that flavone C-glycosides and flavonolignans from C. obtusifolia were stable throughout their passage in the simulated gastrointestinal tract including the colon phase. On the other hand, the colon bacteria extensively metabolized chlorogenic acid, flavonol, and triterpenoid O-glycosides. This investigation revealed that the colonic microbiota has an important role in the biotransformation of some chemical constituents of this extract.

Ruby chocolate: A study of its phytochemical composition and quantitative comparison with dark, milk and white chocolate.

Ruby chocolate was introduced in 2017 as the fourth type of chocolate, in addition to white, milk and dark chocolate. However, until now not much is reported about its phytochemical composition. Therefore, we analyzed ruby chocolate by UPLC-HRMS, together with the three other types of chocolate. Feature-based molecular networking was carried out to aid in the identification, while a set of 51 reference compounds were analyzed simultaneously for targeted quantification. In this way, a total of 54 compounds could be (tentatively) identified in the chocolates, of which 43 were found in the ruby chocolate. Moreover, 19 compounds were quantified, of which 13 in the ruby chocolate. The compounds include flavan-3-ols, proanthocyanidins and methylxanthines, but also biogenic amines and alkaloids. In general, ruby chocolate contained lower levels of these constituents compared to dark chocolate. However, A-type proanthocyanidins were found to be characteristic for the ruby chocolate.

UPLC-MS/MS-based molecular networking and NMR structural determination for the untargeted phytochemical characterization of the fruit of Crescentia cujete (Bignoniaceae).

The fruit pulp of Crescentia cujete is traditionally used in folk medicine for the treatment of a variety of respiratory conditions and gastrointestinal disorders. Due to the lack of a comprehensive phytochemical description of the fruit of this plant, its active compounds and rational quality control parameters have not yet been described. An untargeted metabolomics approach combining UPLC-MS/MS-based molecular networking with conventional isolation and NMR methods was carried out for the phytochemical profiling of the fruit pulp of Crescentia cujete. Sixty-six metabolites, including nine n-alkyl glycosides, twenty-three phenolic acid derivatives (such as cinnamoyl and benzoyl derivatives), fifteen flavonoids, four phenylethanoid derivatives and fifteen iridoid glycosides were identified at different levels of confirmation: eighteen confirmed structures (Level 1), six probable structures (Level 2) and forty two tentative candidates (Level 3). Among these, all four phenylethanoid derivatives were described for the first time within this species. In addition, 8-epi-eranthemoside, crescentiol A and crescentiol B were reported as three undescribed iridoid glucosides. The use of molecular networking has resulted in a detailed phytochemical overview of this species. This work provides a useful tool for further development and validation of appropriate analytical methods for routine quality control assessment of commercially available products containing the fruit of this species and further interpretation of their related pharmacological effects.

Ultrasound-assisted extraction optimization and validation of an HPLC-DAD method for the quantification of polyphenols in leaf extracts of Cecropia species.

Cecropia species are traditionally used in Latin American folk medicine and are available as food supplements with little information warranting their quality. The optimum conditions for the extraction of chlorogenic acid (CA), total flavonoids (TF) and flavonolignans (FL) from leaves of Cecropia species were determined using a fractional factorial design (FFD) and a central composite design (CCD). A reversed-phase high-performance liquid chromatographic method coupled to a diode array detector (HPLC-DAD) was validated for the quantification of CA, TF and FL, following the ICH guidelines. Quantitative and Principal Component Analysis (PCA) was also performed. The extraction-optimization methodology enabled us developing an appropriate extraction process with a time-efficient execution of experiments. The experimental values agreed with those predicted, thus indicating suitability of the proposed model. The validation parameters for all chemical markers of the quantification method were satisfactory. The results revealed that the method had excellent selectivity, linearity, precision (repeatability and intermediate precision were below than 2 and 5%, respectively) and accuracy (98-102%). The limits of detection and quantification were at nanogram per milliliter (ng/mL) level. In conclusion, the simultaneous quantification of chemical markers using the proposed method is an appropriate approach for species discrimination and quality evaluation of Cecropia sp.

Phytochemical characterization and comparative studies of four Cecropia species collected in Panama using multivariate data analysis.

Plant species of the genus Cecropia (Urticaceae) are used as traditional medicine in Latin-America, and are commercially available as food supplements. The aim of this study was to characterize and compare the phytochemical constituents of four Cecropia species collected in Panama. The structures of 11 compounds isolated from leaves of C. obtusifolia were elucidated based on high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopic analysis; the polyphenolic constituents of leaves of all four Cecropia species and commercial products were characterized using high performance liquid chromatography-diode array detection-quadrupole time of flight-tandem high resolution mass spectrometry (HPLC-DAD-QTOF). Forty-seven compounds were fully identified or tentatively characterized. Thirty-nine of these have not been previously reported for the species under investigation. Multivariate analysis revelead that C. obtusifolia and C. insignis are the most related species, while C. hispidissima is the most segregated one. Considering the importance of the description of novel chemical entities and the increasing interest and use of natural products, this study may be of great help for chemotaxonomic purposes, the interpretation of medicinal properties and for quality assessment of herbal supplements containing Cecropia leaves.

Selection of chemical markers for the quality control of medicinal plants of the genus Cecropia.

CONTEXT: Several Cecropia (Cecropiaceae) species are traditionally used in Latin America for the treatment of a variety of diseases including diabetes, arterial hypertension, asthma, bronchitis, anxiety, and inflammation. At present, a number of commercial products based on these plants have been introduced into the market with very little information on methods for guaranteeing their quality and safety. OBJECTIVE: This work proposes potential chemical markers for the quality control of the raw materials of Cecropia obtusifolia Bertol., Cecropia peltata L., Cecropia glaziovii Snethl., Cecropia pachystachya Trécul, and Cecropia hololeuca Miq. METHODS: The Herbal Chemical Marker Ranking System (Herb MaRS) developed by the National Institute of Complementary Medicine (NICM) at the University of Western Sydney was used for selecting chemical markers for the quality control of selected medicinal species of Cecropia. This review covers the period from 1982 to 2016. RESULTS: Chlorogenic acid, flavonoidal glycosides (orientin, isoorientin, vitexin, isovitexin, and rutin), catechin, epicatechin, procyanidins (B2, B5, and C1), steroids (ß-sitosterol), and triterpenoids (α-amyrin, pomolic, tormentic and ursolic acids) were selected as chemical markers for the quality control of the leaves. CONCLUSION: It is necessary to establish comprehensive standards for guaranteeing quality, safety and efficacy of herbal drugs. The selection of adequate chemical markers for quality control purposes requires a good knowledge about the chemical composition of medicinal plants and their associated biological properties. To the best of our knowledge this review article is the first to address the identification and quantitative determination of the chemical markers for the genus Cecropia.