Salicylic Acid and Water Stress: Effects on Morphophysiology and Essential Oil Profile of Eryngium foetidum.

The exogenous application of bioregulators, such as salicylic acid (SA), has exhibited promising outcomes in alleviating drought stress. Nevertheless, its impact on culantro (Eryngium foetidum L.) remains unexplored. Thus, the aim of this study was to assess how SA impacts the growth, morphophysiology, and essential oil composition of culantro when subjected to drought. To achieve this, culantro plants were grown under three different watering regimes: well-watered, drought-stressed, and re-watered. Additionally, they were either treated with SA (100 µM) or left untreated, with water serving as the control. SA application did not mitigate the effects of drought in biomass production but increased biomass, leaf number, leaf area, and photosynthetic pigments under well-irrigated and re-watered conditions. After a drought period followed by re-watering, plants recovered membrane integrity independently of SA application. Water stress and the exogenous application of SA also modulated the profile of essential oils. This is the first report about SA and drought affecting growth and essential oil composition in culantro.

Water stress modulates terpene biosynthesis and morphophysiology at different ploidal levels in Lippia alba (Mill.) N. E. Brown (Verbenaceae).

Monoterpenes are the main component in essential oils of Lippia alba. In this species, the chemical composition of essential oils varies with genome size: citral (geraniol and neral) is dominant in diploids and tetraploids, and linalool in triploids. Because environmental stress impacts various metabolic pathways, we hypothesized that stress responses in L. alba could alter the relationship between genome size and essential oil composition. Water stress affects the flowering, production, and reproduction of plants. Here, we evaluated the effect of water stress on morphophysiology, essential oil production, and the expression of genes related to monoterpene synthesis in diploid, triploid, and tetraploid accessions of L. alba cultivated in vitro for 40 days. First, using transcriptome data, we performed de novo gene assembly and identified orthologous genes using phylogenetic and clustering-based approaches. The expression of candidate genes related to terpene biosynthesis was estimated by real-time quantitative PCR. Next, we assessed the expression of these genes under water stress conditions, whereby 1% PEG-4000 was added to MS medium. Water stress modulated L. alba morphophysiology at all ploidal levels. Gene expression and essential oil production were affected in triploid accessions. Polyploid accessions showed greater growth and metabolic tolerance under stress compared to diploids. These results confirm the complex regulation of metabolic pathways such as the production of essential oils in polyploid genomes. In addition, they highlight aspects of genotype and environment interactions, which may be important for the conservation of tropical biodiversity.

Water stress and exogenous carnitine on growth and essential oil profile of Eryngium foetidum L.

Water stress influences plant growth and metabolism. Carnitine, an amino acid involved in lipid metabolism, has been related to responses of plants to abiotic stresses, also modulating their metabolites. Culantro (Eryngium foetidum L.) is a perennial herb, rich in essential oils, native to Latin America, commonly used due to its culinary and medicinal properties. Here, we investigated the effect of exogenous carnitine on morphophysiology and the essential oil profile of culantro plants under water stress. For this, plants were grown under three water conditions: well-watered, drought stress, and re-watered; and sprayed with exogenous carnitine (100 µM) or water (control). Culantro growth was impaired by drought and enhanced by re-watering. Carnitine, in turn, did not reverse drought effects on growth, and impaired the growth of re-watered plants, also improving photosynthetic pigment content. Water conditions and carnitine application changed the essential oil profile of the plants. Drought and re-watering improved the production of eryngial, which was even increased with exogenous carnitine in re-watered plants. In addition, hydroquinone was only produced with the combination of re-watering and carnitine application. The application of exogenous carnitine can be a strategy to induce the production of essential oil compounds with cosmetic and pharmaceutical importance in culantro. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03757-y.

Aneuploids and its increment on diversity of Lippia alba polyploid complex: genetic aspects and origin.

BACKGROUND: Aneuploidy is associated with add or lack of individual chromosomes. The knowledge regarding aneuploidy is still rare in wild and tropical populations. Lippia alba is a tropical polyploid complex naturally formed, with 2x, 3x, 4x, 6x, and aneuploid individuals. The species presents pharmacological and medicinal importance, due to its essential oil compounds, which are related to the ploidal level. Considering the singularity of aneuploids emergence and stability, we proposed to investigate putative cytotypes involved in the aneuploids formation. METHODS AND RESULTS: Molecular, cytogenetic, reproductive, and chemical approaches were adopted. The results showed that the aneuploids possibly have independent origin considering the genetic, chemical and karyotypical profiles. The chemical composition of aneuploids is related to genetic similarity. The aneuploid origin may involve 2x and 3x cytotypes being possible to rise four scenarios of crosses to explain that. CONCLUSIONS: The results, in general, contribute to the comprehension of the origin of aneuploids and highlight the genetic profile of these accessions as a key element on the understanding of the chemical profile of L. alba accessions.

Evaluation of copaiba oil as enhancer of ibuprofen skin permeation

Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.

Anticancer and antileishmanial in vitro activity of gold(I) complexes with 1,3,4-oxadiazole-2(3H)-thione ligands derived from δ-D-gluconolactone.

Four gold(I) complexes conceived as anticancer agents were synthesized by reacting [Au(PEt3 )Cl] and [Au(PPh3 )Cl] with ligands derived from δ-d-gluconolactone. The ligands' structure was designed to combine desired biological properties previously reported for each group. Ligands were synthesized from δ-d-gluconolactone via ketal protection and hydrazide formation followed by cyclization with CS2 to produce the novel oxadiazolidine-2-thione 7 and 8. Increasing of the ligands' lipophilicity via ketal protection proved useful since all four gold(I) complexes showed anticancer and antileishmanial properties. The IC50 values are at low micromolar range, varying from 2 to 3 µm for the most active compounds. The free D-gluconate 1,3,4 oxadiazole-derived ligands were neither toxic nor presented anticancer or antileishmanial properties. Triethylphosphine-derived compounds 9 and 10 were more selective against B16-F10 melanoma cell line. Although similar in vitro antileishmanial activity was observed for the gold(I) precursors themselves and their derived complexes, the latter were three times less toxic for human THP-1 macrophage cell line; this result is attributed to an isomeric variation of the D-gluconate ligand and the oxadiazole portion, which was one of the key concepts behind this work. These findings should encourage further research on gold(I) complexes to develop novel compounds with potential application in cancer and leishmaniasis chemotherapy.

Induction of Synthetic Polyploids and Assessment of Genomic Stability in Lippia alba.

Polyploidy is widely recognized as a major evolutionary force in plants and has been reported in the genus Lippia (Verbenaceae). Lippia alba, the most studied species, has been documented as a polyploid complex involving at least four ploidal levels. L. alba presents remarkable chemical and genetic variation and represents a model for understanding genome organization. Although the economic and medicinal importance of the species has been widely described, no established polyploid induction protocol has been reported so far. Here, we describe the production of synthetic polyploid plants of L. alba using colchicine. The ploidal levels were estimated by flow cytometry and chromosome counting. In addition, FISH and molecular markers approaches were used to confirm the stability of the synthetic polyploids. The major component of the essential oils was estimated by GCMS to compare with the natural individuals. Tetraploids and triploids were produced providing new opportunities for investigating medicinal, pharmacological, and economic applications as well as addressing intrinsic questions involved in the polyploidization process in tropical plants.

Desenvolvimento e estabilidade de formulação cosmética obtida com corante natural azul / Development and stability of cosmetic formulation obtained with natural blue dye

Introdução: Dentre os corantes de fontes naturais disponíveis no mercado, os mais comuns são aquelas capazes de conferir as cores vermelha, roxa, laranja e amarela, sendo a coloração azul relativamente escassa. A espécie Ravenala madagascariensis, também conhecida como árvore dos viajantes, é uma planta oriunda da Ilha de Madagascar, África do Sul, característica por sementes recobertas por arilos fibrosos de coloração azul intensa. Objetivo: Descrever uma metodologia capaz de extrair e incorporar os corantes azuis presentes nos arilos em uma formulação dermocosmética estável. Metodologia: Foi realizado screening com distintos líquidos extratores para a obtenção do extrato dos arilos. O extrato em ciclometicone foi incorporado em preparações cosméticas empregando-se as bases Polawax® e Cold cream. Após a avaliação dos aspectos sensoriais, a formulação preparada com Polawax foi direcionada para avaliação de estabilidade acelerada (15 dias) de acordo com o protocolo definido pela ANVISA. Resultados: O melhor processo extrativo foi obtido pela utilização do ciclometicone, que é um excipiente compatível com o preparo de formulações cosméticas. O produto contendo 1% do extrato dos arilos em ciclometicone, incorporado à base Polawax, foi avaliado em relação às variáveis aspecto, cor (azul), odor, sensação ao tato e pH (5,5) e não apresentou alterações no ensaio de estabilidade acelerado. Conclusão: Com a metodologia apresentada, foi possível extrair e preparar uma formulação dermocosmética estável com nova proposta de corante azul, aplicável como excipiente para formulações.

Introduction: Among the dyes from natural sources available in the market, the most common are those capable of giving the colors red, purple, orange and yellow, being the blue coloration relatively scarce. The Ravenala madagascariensis species, also known as the traveler's tree, is a plant from Madagascar Island, South Africa, characterized by seeds covered by intense blue colored fibrous aryls. Objective: To describe a methodology capable of extracting and incorporating the blue dyes present in aryls in a stable dermocosmetic formulation. Methodology:Screening with different extracting liquids was performed to obtain the extract of the arils. The cyclomethicone extract was incorporated into cosmetic preparations using the Polawax® and Cold cream bases. After evaluation of sensory aspects, the formulation prepared with Polawax was directed to accelerated stability evaluation (15 days) according to the protocol defined by ANVISA. Results: The best extraction process was obtained by the use of cyclomethicone, which is an excipient compatible with the preparation of cosmetic formulations. The product containing 1% of the cyclomethicone aryl extract, incorporated into the Polawax base, was evaluated in relation to the variables appearance, color (blue), odor, touch sensation and pH (5.5) and showed no changes in the stability test accelerated. Conclusion:With the methodology presented, it was possible to extract and prepare a stable dermocosmetic formulation with new blue dye proposal, applicable as an excipient for formulations.

Isolation, spectral characterization, molecular docking, and cytotoxic activity of alkaloids from Erythroxylum pungens O. E. Shulz.

Stem bark, root bark, and leaf extracts of Erythroxylum pungens were subjected to phytochemical analysis. N,N-dimethyltryptamine (DMT) was isolated and characterized from E. pungens roots. This unprecedented result is remarkable since no indole alkaloid has been previously reported from Erythroxylaceae so far. Eleven known tropane alkaloids were identified by their mass spectra and 3-(2-methylbutyryloxy)tropan-6,7-diol as well as 3-(2-methylbutyryloxy)nortropan-6,7-diol were isolated and characterized based on mass spectrometry, 1H, 13C, COSY, and NOESY NMR analysis. The complete NMR data are reported for the first time. Inverse Structure-based and Ligand-Based virtual screening were carried out to identify possible targets for 3-(2-methylbutyryloxy)tropan-6,7-diol. The level of cytotoxicity of this tropane alkaloid aliphatic ester was discrete with potencies on the order of 0.3-1.0 mg/mL and better results against HeLa (50% cell viability reduction). Otherwise, atropine (0.3 mg/mL), a Solanaceae tropane alkaloid, and DMT (0.5 mg/mL) from E. pungens roots impaired at 50% the cell viability against HeLa, SiHa, PC3, and 786-0. This study stimulates scientific investigation of the impact of edaphoclimatic features in a semi-arid environment on tropane alkaloid biosynthesis.

Novel antitumor adamantane-azole gold(I) complexes as potential inhibitors of thioredoxin reductase.

Gold complexes that could act as antitumor agents have attracted great attention. Heterocyclic compounds and their metal complexes display a broad spectrum of pharmacological properties. The present study reports the preparation and characterization of four novel gold(I) complexes containing tertiary phosphine and new ligands 5-adamantyl-1,3-thiazolidine-2-thione, 3-methyladamantane-1,3,4-oxadiazole-2-thione. Spectroscopic data suggest that gold is coordinated to the exocyclic sulfur atom in all cases, as confirmed by X-ray crystallographic data obtained for complex (1) and supported by quantum-mechanical calculations. The cytotoxicity of the compounds has been evaluated in comparison to cisplatin and auranofin in three different tumor cell lines, colon cancer (CT26WT), metastatic skin melanoma (B16F10), mammary adenocarcinoma (4T1) and kidney normal cell (BHK-21). The gold complexes were more active than their respective free ligands and able to inhibit the thioredoxin reductase (TrxR) enzyme, even in the presence of albumin. Molecular modeling studies were carried out to understand the interaction between the compounds and the TrxR enzyme, considered as a potential target for new compounds in cancer treatment. The docking results show that the adamantane ring is essential to stabilize the ligand-enzyme complex prior the formation of covalent bond with gold center. The structure of the new gold compounds was established on the basis of spectroscopic data, DFT calculations and X-ray diffraction. TrxR inhibition was evaluated and the results correlated with the assays in tumor cells, suggesting the TrxR as possible target for these compounds.

Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: synthesis, characterization, molecular modeling, and cytotoxic activity.

A series of novel platinum(II) complexes derived from N-alkyl-ethanediamine and N-alkyl-propanediamine ligands were prepared and characterized. These complexes contain a long chain aliphatic diamine where the carbon length is variable and present a hydroxyl group in two different positions. The complexes with the ethanediamine derivatives were prepared from K(2)PtCl(4). Interestingly, the propanediamine derivatives did not react well with this platinum salt under the experimental conditions normally employed and could only be obtained from the more reactive K(2)PtI(4). A theoretical molecular modeling study was performed to understand this difference in reactivity and it showed that the conformation around the diamine plays an important role in the ring closure step of complex formation. The complexes had their cytotoxicity investigated in B16F1, CT26, B16F10, and MDA cell lines. Some of them demonstrated superior activity when compared to cisplatin and carboplatin. We were also able to confirm a structure-activity relationship between cytotoxicity and carbon chain length.