Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro.

Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid.

Copaifera mildbraedii Desf.: Phytochemical Composition of Extracts, Essential Oil, and In Vitro Biological Activities of Bark.

Copaifera mildbraedii Desf. is an evergreen tree with an umbrella-like crown. It is distributed from south-eastern Nigeria eastward to the Central African Republic (CAR). The aim of this study was to assess the chemical composition and biological activities of C. mildbraedii bark, as well as the chemical composition of the essential oil. Ethyl acetate (EtOAc) and methanol (MeOH) extracts showed a high total phenolic content (TPC) (149.9 and 148.8 mg GAE/g dry residue (dr), respectively), which was related to good antioxidant activity (DPPH) with an IC50 of 21.2 and 12.9 µg/mL, respectively. High-performance liquid chromatography coupled with diode array detector (HPLC-DAD) analysis revealed seven phenolic compounds with myricitrin (13.3 mg/g dr) and 2,4-dihydroxy-3,6-dimethyl benzoic acid (30.7 mg/g dr) as major compounds, while gas chromatography-mass spectrometry (GC-MS) analysis enabled detection of 13 volatile compounds (3 before and 10 after derivatization). Thirty compounds were identified in the essential oil, which corresponds to 65% of all identified compounds. Among the latter, E,E-farnesylacetone and γ-gurjunene were considered as major compounds (8.08 and 10.43%, respectively). The EtOAc extract showed a potent potential, simultaneously, against anti-acetylcholinesterase (AChE), anti-15-lipoxygenase (15-LOX), anti-xanthine oxidase (XOD), and cytotoxic (OVCAR) activities, whereas cyclohexane (CYHA) and dichloromethane (DCM) extracts showed a cytotoxic effect with high percentages of inhibition (95.2%).

Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice.

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Antibacterial, antibiofilm, and antivirulence potential of the main diterpenes from Copaifera spp. oleoresins against multidrug-resistant bacteria.

To evaluate the antibacterial, antibiofilm and antivirulence potential of the main diterpenes from Copaifera spp. oleoresins against multidrug-resistant (MDR) bacteria. Antimicrobial assays included determination of the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Minimum Inhibitory Concentration of Biofilm (MICB50), as well as synergistic and antivirulence assays for eight diterpenes against MDR. The tests revealed that two diterpenes (named 1 and 5) showed the best results, with MIC and MBC between 12.5 and 50 µg/mL against most MDR bacteria. These diterpenes exhibited promising MICB50 in concentration between 3.12-25 µg/mL but showed no synergistic antimicrobial activity. In the assessment of antivirulence activity, diterpenes 1 and 5 inhibited only one of the virulence factors evaluated (Dnase) produced by some strains of S. aureus at subinhibitory concentration (6.25 µg/mL). Results obtained indicated that diterpenes isolated from Copaifera oleoresin plays an important part in the search of new antibacterial and antibiofilm agents that can act against MDR bacteria.

Evaluation of anti-inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights.

BACKGROUND: Kaurenol, a diterpene alcohol found in Copaifera langsdorffii Desf. (known as "copaiba"), is historically used in traditional medicine for inflammatory conditions. OBJECTIVES: This study aims to comprehensively assess the potential anti-inflammatory and antinociceptive properties of kaurenol. METHODS: To this end, the following experiments were conducted to evaluated toxicity: locomotor performance and acute toxicity; nociception: acetic acid-induced writhing and formalin-induced antinociception; and anti-inflammatory activity: carrageenan and dextran-induced paw edema at 10, 20, and 40 mg/kg, and measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in macrophages at 1, 3, and 9 µg/ml. RESULTS: Kaurenol did not show significant locomotor changes, acute toxicity, and central analgesic activity in the first phase of formalin test at dosages tested. Kaurenol showed 53%, 64%, 64%, and 58% of inhibition in the acetic acid-induced writhing, second phase of formalin test, carrageenan and dextran-induced paw edema, respectively. CONCLUSION: The anti-inflammatory activity was associated with the regulation of NO release and probably with the regulation of mediators, such as serotonin and prostaglandin in vascular permeability, as well as by being associated with the regulation of IL-6 and IL-10. Kaurenol display anti-inflammatory activity but has no analgesic activity.

Cicatrização de feridas crónicas tratadas com oleorresina de copaíba / Chronic wound healing with copaiba oleoresin application / Cicatrización de heridas crónicas tratadas con oleorresina de copaiba

Resumo Enquadramento: As feridas crónicas representam um problema crescente de saúde em diversos países. Estudos etnobotânicos e pré-clínicos sugerem que a oleorresina de copaíba (Copaífera sp.) possui propriedades cicatrizantes. Objetivo: Avaliar a aplicação clínica da oleorresina de copaíba na cicatrização de feridas crónicas. Metodologia: Estudo retrospectivo de série de casos composta por 6 participantes com feridas crónicas tratadas com: oleorresina de copaíba a 7% com óleo de girassol ou creme de copaíba a 10%. O desfecho primário foi a percentagem de redução da área lesada ao final do seguimento. Resultados: Idade média dos participantes foi 54,5 (DP = 11,5) anos. As causas das feridas foram vasculares (n = 3), cirúrgicas (n = 2) e traumáticas (n = 1). Todos os participantes tiveram redução da área lesada variando entre 15,5% a 100%, durante o seguimento (8 a 15 semanas). Nenhuma complicação foi observada. Conclusão: O tratamento com a oleorresina de copaíba mostrou-se uma opção efetiva e segura no tratamento de feridas crónicas.

Abstract Background: Chronic wounds represent a growing health problem in several countries. Ethnobotanical and preclinical studies suggest that copaiba oleoresin (Copaifera sp.) has healing properties. Objective: To evaluate the clinical application of copaiba oleoresin in chronic wound healing. Methodology: Retrospective case series study consisting of 6 participants with chronic wounds treated with 7% copaiba oleoresin with sunflower oil or 10% copaiba ointment. The primary endpoint was the percentage reduction in wound area at the end of follow-up. Results: Mean age of participants was 54.5 (SD = 11.5) years. The causes of wounds were vascular (n = 3), surgical (n = 2), and traumatic (n = 1). All participants had a reduction of the wound area ranging from 15.5% to 100% during the follow-up (8 to 15 weeks). No complications were observed. Conclusion: Treatment with copaiba oleoresin proved to be an effective and safe option in chronic wound treatment.

Resumen Marco contextual: Las heridas crónicas representan un problema sanitario creciente en varios países. Estudios etnobotánicos y preclínicos sugieren que la oleorresina de copaiba (Copaífera sp.) tiene propiedades cicatrizantes. Objetivo: Evaluar la aplicación clínica de la oleorresina de copaiba en la cicatrización de heridas crónicas. Metodología: Estudio retrospectivo de serie de casos compuesta por 6 participantes con heridas crónicas tratadas con oleorresina de copaiba al 7% con aceite de girasol o crema de copaiba al 10%. El criterio de valoración primario fue el porcentaje de reducción de la zona lesionada al final del seguimiento. Resultados: La edad media de los participantes fue de 54,5 (DP = 11,5) años. Las causas de las heridas fueron vasculares (n = 3), quirúrgicas (n = 2) y traumáticas (n = 1). Todos los participantes presentaron una reducción de la zona lesionada que osciló entre el 15,5% y el 100% durante el seguimiento (de 8 a 15 semanas). No se observaron complicaciones. Conclusión: El tratamiento con oleorresina de copaiba ha demostrado ser una opción eficaz y segura en el tratamiento de heridas crónicas.

Copaifera langsdorffii Oleoresin-Loaded Nanostructured Lipid Carrier Emulgel Improves Cutaneous Healing by Anti-Inflammatory and Re-Epithelialization Mechanisms.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

Polyalthic Acid from Copaifera lucens Demonstrates Anticariogenic and Antiparasitic Properties for Safe Use.

This study aimed at evaluating the potential of Copaifera lucens, specifically its oleoresin (CLO), extract (CECL), and the compound ent-polyalthic acid (PA), in combating caries and toxoplasmosis, while also assessing its toxicity. The study involved multiple assessments, including determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against cariogenic bacteria. CLO and PA exhibited MIC and MBC values ranging from 25 to 50 µg/mL, whereas CECL showed values equal to or exceeding 400 µg/mL. PA also displayed antibiofilm activity with minimum inhibitory concentration of biofilm (MICB50) values spanning from 62.5 to 1000 µg/mL. Moreover, PA effectively hindered the intracellular proliferation of Toxoplasma gondii at 64 µg/mL, even after 24 h without treatment. Toxicological evaluations included in vitro tests on V79 cells, where concentrations ranged from 78.1 to 1250 µg/mL of PA reduced colony formation. Additionally, using the Caenorhabditis elegans model, the lethal concentration (LC50) of PA was determined as 1000 µg/mL after 48 h of incubation. Notably, no significant differences in micronucleus induction and the NDI were observed in cultures treated with 10, 20, or 40 µg/mL of CLO. These findings underscore the safety profile of CLO and PA, highlighting their potential as alternative treatments for caries and toxoplasmosis.

Mathematical and numerical analyses of cellular, molecular and angiogenic parameters of a rat skin wound healing model.

The inflammatory phase is an important event in the skin wound healing process. The deposition of granulation tissue in the wound bed and the rebuilding of the vascular network occur as inflammation diminishes. An angiogenic component in the formation of granulation tissue is the secretion of vascular endothelial growth factor, which assists in the chemotaxis, proliferation, and replication of fibroblasts. In this paper, we develop a mathematical model of skin wound healing angiogenic factors based on inflammatory cells (macrophages and neutrophils) and mediators (interleukin 6 and interleukin 10). We highlight the importance of this process in vascular endothelial growth factor release and in the formation of new capillary tips. We used a mathematical model of partial differential equations based on the reaction-diffusion-advection equations. In order to calibrate the parameters, we considered an in vivo model composed by four treatments: hydroalcoholic extract and oil-resin of Copaifera langsdorffii at 10% concentration, collagenase, and Lanette cream. Using the laboratory data for the wound edge, our mathematical model estimated the values of vascular endothelial growth factor concentration, and tips density in the center of the wound with a maximum error of 2.9%, and predicted healing time required for each treatment. The region of viability for the parameters, in the proposed model, was found through numerical simulations from the Interleukin 6 and 10 dysregulation and we obtained that, among the parameters analyzed, the greatest influencer in the dynamics of the system is the one, which represents the production of Interleukin 10 during phagocytosis.

Polyalthic acid and oleoresin from Copaifera trapezifolia Hayne reduce Toxoplasma gondii growth in human villous explants, even triggering an anti-inflammatory profile.

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection. We used human villous explants as an experimental model of human maternal-fetal interface. Uninfected and infected villous explants were exposed to the treatments; the parasite intracellular proliferation and the cytokine levels were measured. Also, T. gondii tachyzoites were pre-treated and the parasite proliferation was determined. Our findings showed that CTO and PA reduced efficiently the parasite growth with an irreversible action, but without causing toxicity to the villi. Also, treatments reduced the levels of IL-6, IL-8, MIF and TNF by villi, what configures a valuable treatment option for the maintenance of a pregnancy in an infectious context. In addition to a possible direct effect on parasites, our data suggest an alternative mechanism by which CTO and PA alter the villous explants environment and then impair parasite growth, since the pre-treatment of villi resulted in lower parasitic infection. Here, we highlighted PA as an interesting tool for the design of new anti-T. gondii compounds.

Toxicological Effects of Copaiba Oil (Copaifera spp.) and Its Active Components.

Vegetable oils are among the most important traditional resources of Amazonia. Oleoresins are a type of oil that have interesting characteristics and highly bioactive properties with pharmacological potential. Oleoresins produced in the trunks of Copaifera (Fabaceae) spp. trees, known as copaiba oils, are made up of terpenes from the sesquiterpene (volatile) and diterpene (resinous) classes, but in amounts that vary between species and depending on several factors, such as soil type. Despite being used for medicinal purposes, via topical and oral application, the toxic effects of copaiba oils and their constituents are little known. The current paper reviews the toxicological studies, both in vitro and in vivo, described in the literature for copaiba oils, as well as the cytotoxic characteristics (against microorganisms and tumor cells) in in silico, in vitro and in vivo models for the sesquiterpenes and diterpenes that make up these oils.

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy.

The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

Exploiting Copaifera salikounda compounds as treatment against diabetes: An insight into their potential targets from a computational perspective.

Accumulating evidence has shown that medicinal plants have been exploited for treatment purposes since time immemorial. Thus, this study investigated the mitigating potentials of the ligands; n-hexadecanoic acid, 9-octadecenoic acid and octadecanoic acid from Copaifera salikounda seed pond extract reported to have antidiabetic potentials in our previous study using computational techniques. Fatty acid-binding protein 4 (FABP4) and peroxisome proliferator-activated receptor alpha (PPARα) were identified as potential receptors. Both molecular docking and Estimated ΔGbind revealed that each ligand exhibited high binding affinity to the respective proteins; this is quite sufficient to be termed favourable. A critical examination of the type and the nature of binding interactions and energy contributions have identified Arg106, Arg126 and Tyr128 in FABP4 and Gln277, Ser280, Tyr314, His440 and Tyr464 in PPARα as consistently being responsible for the binding interactions and stabilizations of each ligand to the individual proteins. The establishment of hydrogen bonding type of interaction and activity between the carboxylic acid moieties of these ligands and these crucial/unique residues goes further to buttress our assertion. A general study of the conformational state of these protein via RMSF and PCA plots goes further validate the observed structural trends wherein the presence of ligands induced seemly structural rigidity. In depth structural stability investigations went further to reveal that the 3D structures of these protein didn't deviate from it known native conformational stable state when bound with these ligands. Our findings indicate that the ligands have considerable inhibitory action against FABP4 and PPARα corroborating the reported antidiabetic potential of the extract.

Conventional and PEGylated Liposomes as Vehicles of Copaifera sabulicola.

Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 µg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.

Chemical composition variation of essential oils of Copaifera langsdorffii Desf. from different vegetational formations.

This study aims to provide information about the chemical profile of the essential oil from C. langsdorffii resin in areas of Cerradão, Carrasco, and Humid Forest. In order to obtain the essential oils, oil-resin was submitted to hydrodistillation process, and the chemical components were analyzed by gas chromatography coupled to mass spectrometry (GC/MS). Twenty-six constituents were identified in the essential oil of C. langsdorffii resin, of which 12 were present in Cerradão, 15 in Carrasco and 18 in Humid Forest, with ß-bisabolene, caryophyllene oxide, γ-muurolene, α-caryophyllene and ß-caryophyllene common to the three phytophysiognomies. Among the studied areas, the resin collection varied from 2.652 g to 20.263 g, while the essential oil yield varied from 2.216 % to 11.764 %. A concentration range of 0.60 % to 84.57 % was recorded among the compounds in the three study areas. There was variation in chemical composition both among phytophysiognomies and among individuals from the same location, where ß-caryophyllene showed to be the majority for all areas studied, being present in all individuals from Cerradão, Carrasco and Humid Forest.

Comparative study of the oil repellent activity of Copaifera officinalis Linnaeus and Copaifera reticulata Ducke front nymphs of Periplaneta americana Linnaeus

Abstract To control urban pests, especially cockroaches of the Periplaneta americana species, various pesticides have been developed that are increasingly potent and effective. However, the unrestrained application of pesticides has had negative consequences, such as the disappearance of some useful insect species and, consequently, the appearance of new pests, both in the countryside and cities. Due to the current scenario, it was necessary to search for new alternatives for the control of these insects. Among the species studied, Copaíba stood out. The oils were analyzed using GC-MS, b-caryophyllene and a-bergamotene being the predominant compounds. Repellency tests were performed with three different concentrations of C. officinalis and C. reticulata, 500 μg/mL, 250 μg/mL and 125 μg/mL, in triplicate. It can be observed that the oil of C. officinalis was more repellent to the nymphs at concentrations of 500 μg/mL and 250 μg/mL, however, when the behavior in nymphs exposed to the concentration of 125 μg/mL was compared, it was noted that C. reticulata oil was more repellent at this concentration. Copaifera has shown promising activity as a repellent against arthropods owing to the complex chemical composition of its oils.

Copaiba Oil Resin Exerts an Additive Effect to Babassu Oil on Behavioral Changes in Human Endometriotic Cell Cultures.

BACKGROUND: Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu (Orbignya speciosa) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk (Copaifera langsdorffii) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC). METHODS: CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. RESULTS: After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production. CONCLUSIONS: Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.

Biological Activity of Copaiba in Damage to the Alveolar Bone in a Model of Periodontitis Induced in Rats.

Several studies have investigated the effects of natural products in the treatment of diseases. Traditional Amazonian populations commonly use copaiba due to its well-known anti-inflammatory, antibacterial, and healing properties. In this study, we aimed to investigate the effects of systemic administration of copaiba oleoresin (Copaifera reticulata Ducke) on ligature-induced periodontitis in rats. To do so, 21 adult rats were divided into three groups (n = 7 each): a control group, ligature-induced periodontitis group, and ligature-induced periodontitis group treated with copaiba oleoresin (200 mg/kg/day). The ligature remained from day 0 to 14, and the copaiba oleoresin was administered via oral gavage during the last seven days. On day 14, the animals were euthanized, and mandibles were collected for histopathological evaluation and microcomputed tomography analysis. Our data showed that the administration of copaiba considerably reduced the inflammatory profile. Moreover, copaiba oleoresin limited alveolar bone loss, increased trabecular thickness and bone-to-tissue volume ratio, and decreased the number of trabeculae compared with those of the untreated experimental periodontitis group. Our findings provide pioneering evidence that supports the potential of copaiba oleoresin in reducing periodontitis-induced alveolar bone damage in rats.

A reliable validated high-performance liquid chromatography-photodiode array detection method for quantification of terpenes in Copaifera pubiflora, Copaifera trapezifolia, and Copaifera langsdorffii oleoresins.

The Copaifera oleoresins are widely used in folk medicine to treat various diseases. The goal of this study was to develop a validated reverse-phase high-performance liquid chromatography method with photodiode array detection (RP-HPLC-PDA) to quantify eight terpenes: ent-hardwickiic acid, ent-copalic acid, ent-7α-acetoxy hardwickiic acid, ent-16-hydroxy-3,13-clerodadiene-15,18-dioic acid, ent-5,13-labdadiene-15-oic acid, junenol, ent-kaurenoic acid, and 13E-ent-labda-7,13-dien-15-oic acid in the oleoresins of Copaifera pubiflora L. (OCP), Copaifera trapezifolia L. (OCT) and Copaifera langsdorffii L. (OCL). The linearity of the method was confirmed in the range of 20.00-500 µg.mL-1 (r2 > 0.999). The limit of quantification was between 1,05 and 16.89 µg.mL-1. Precision and accuracy ranges were found to be %RSD <0.2 and 96% to 110%, respectively. Based on the obtained results, the developed analytical method is rapid, precise, accurate, and sensitive for quantifying these terpenes in Copaifera's oleoresins.

Correlation between the Skin Permeation Profile of the Synthetic Sesquiterpene Compounds, Beta-Caryophyllene and Caryophyllene Oxide, and the Antiedematogenic Activity by Topical Application of Nanoemulgels.

Sesquiterpene compounds are applied as permeation promoters in topical formulations. However, studies exploring their impact on nanostructured systems, changes in permeation profile, and consequently, its biological activity are restricted. This study aimed to investigate the correlation between the skin permeation of the major sesquiterpenes, beta-caryophyllene, and caryophyllene oxide from the oleoresin of Copaifera multijuga, after delivery into topical nanoemulgels, and the in vivo antiedematogenic activity. First, ten nanoemulgels were prepared and characterized, and their in vitro permeation profile and in vivo anti-inflammatory activity were evaluated. In equivalent concentrations, ß-caryophyllene permeation was greater from oleoresin nanoemulgels, resulting in greater in vivo antiedematogenic activity. However, an inverse relationship was observed for caryophyllene oxide, which showed its favored permeation and better in vivo anti-inflammatory effect carried as an isolated compound in the nanoemulgels. These results suggest that the presence of similar compounds may interfere with the permeation profile when comparing the profiles of the compounds alone or when presented in oleoresin. Furthermore, the correlation results between the permeation profile and in vivo antiedematogenic activity corroborate the establishment of beta-caryophyllene as an essential compound for this pharmacological activity of C. multijuga oleoresin.