In Vitro Leishmanicidal Activity of Copaiba Oil and Kojic Acid Combination on the Protozoan Leishmania (Leishmania) amazonensis and Host Cell.

(1) Background: Leishmaniasis refers to a group of anthropozoonotic diseases caused by Leishmania. The major chemotherapeutic agent used for its treatment is Glucantime®®, but the search continues for new compounds that are economically viable and act on the protozoan without causing damage to the host cell. As an alternative approach, this study used a combination of copaiba oil (CO) and kojic acid (KA) to determine their in vitro action on host cells, on the Leishmania (Leishmania) amazonensis protozoan and its interaction with macrophages. (2) Methods: In vitro culture, analysis of cytokine release and microscopy assays were performed. Statistical analysis was performed with ANOVA (GraphPad Prism). (3) Results: The combination did not induce cytotoxic effects on macrophages after treatment but promoted morphological changes in the protozoan, such as nuclear alterations (apoptotic characteristics), alterations in the cellular body and an increase in the number of electrodense structures and acidocalcisomes, observed mainly at the concentrations of CO20KA50 and CO30KA50 µg/mL. We observed reductions in the intracellular amastigote number and in the production of proinflammatory cytokines, such as IL-6 and TNF-α, after treatment with CO30KA at 50 µg/mL. (4) Conclusions: We report here, for the first time, that the combination of CO and KA may be a promising approach against Leishmania (Leishmania) amazonensis.

Evaluation of the biological activities of Copaiba (Copaifera spp): a comprehensive review based on scientometric analysis.

Copaíba oil-resin is extracted from the trunk of the Copaíba tree and has medicinal, cosmetic, and industrial properties. As a result, widespread knowledge about the use of Copaíba oil-resin has evolved, attracting the scientific community's attention. This paper aims to map the global knowledge production regarding the biological activities of Copaíba (Copaifera spp.). Bibliometric methodological instruments were used to conduct a search of the Web of Science-Core Collection database. The search resulted in 822 references. After screening titles and abstracts, 581 references did not meet the eligibility criteria, leaving 246 references for full-text examination. Subsequently, 15 studies were excluded, resulting in a final set of 232 records for the bibliometric analysis. In vitro was the most published study type, mainly from Brazil, from 2010 to 2020. Regarding the authors, Bastos, JK, and Ambrosio, SR were the ones with the most significant number of papers included. The most frequent keywords were Copaíba oil, Copaíba, and Copaifera. Our findings revealed global study trends about Copaíba, mainly related to its various effects and use over time. In general, all countries have conducted more research on antimicrobial and anti-inflammatory activities, also exposing its antioxidant and healing properties. Copaifera reticulata was the most investigated, followed by Copaifera langsdorffi and Copaifera multijuga in both in vitro and in vivo studies. Therefore, there is a need for human reports, given the promising results that Copaíba oils have been demonstrating.

Copaiba oil improves pulmonary nitric oxide bioavailability in monocrotaline-treated rats.

Oxidative stress is involved in increased pulmonary vascular resistance (PVR) and right ventricular (RV) hypertrophy, characteristics of pulmonary arterial hypertension (PAH). Copaiba oil, an antioxidant compound, could attenuate PAH damage. This study's aim was to determine the effects of copaiba oil on lung oxidative stress, PVR, and mean pulmonary arterial pressure (mPAP) in the monocrotaline (MCT) model of PAH. Male Wistar rats (170 g, n = 7/group) were divided into four groups: control, MCT, copaiba oil, and MCT + copaiba oil (MCT-O). PAH was induced by MCT (60 mg/kg i.p.) and, after 1 week, the treatment with copaiba oil (400 mg/kg/day gavage) was started for 14 days. Echocardiographic and hemodynamic measurements were performed. RV was collected for morphometric evaluations and lungs and the pulmonary artery were used for biochemical analysis. Copaiba oil significantly reduced RV hypertrophy, PVR, mPAP, and antioxidant enzyme activities in the MCT-O group. Moreover, increased nitric oxide synthase and decreased NADPH oxidase activities were observed in the MCT-O group. In conclusion, copaiba oil was able to improve the balance between nitric oxide and reactive oxygen species in lungs and the pulmonary artery and to reduce PVR, which could explain a decrease in RV hypertrophy in this PAH model.

Synthesis and Antibacterial Activity of Polyalthic Acid Analogs.

Polyalthic acid (PA) is a diterpene found in copaiba oil. As a continuation of our work with PA, we synthesized PA analogs and investigated their antibacterial effects on preformed biofilms of Staphylococcus epidermidis and determined the minimal inhibitory concentration (MIC) of the best analogs against planktonic bacterial cells. There was no difference in activity between the amides 2a and 2b and their corresponding amines 3a and 3b regarding their ability to eradicate biofilm. PA analogs 2a and 3a were able to significantly eradicate the preformed biofilm of S. epidermidis and were active against all the Gram-positive bacteria tested (Enterococcus faecalis, Enterococcus faecium, S. epidermidis, Staphylococcus aureus), with different MIC depending on the microorganism. Therefore, PA analogs 2a and 3a are of interest for further in vitro and in vivo testing to develop formulations for antibiotic drugs against Gram-positive bacteria.

Development, characterization and evidence of anti-endometriotic activity of Phytocannabinoid-Rich nanoemulsions.

During the last decades, the cannabinoid research for therapeutic purposes has been rapidly advancing, with an ever-growing body of evidence of beneficial effects for a wide sort of conditions, including those related to mucosal and epithelial homeostasis, inflammatory processes, immune responses, nociception, and modulating cell differentiation. ß-caryophyllene (BCP) is a lipophilic volatile sesquiterpene, known as non-cannabis-derived phytocannabinoid, with documented anti-inflammatory, anti-proliferative and analgesic effects in both in vitro and in vivo models. Copaiba oil (COPA) is an oil-resin, mainly composed of BCP and other lipophilic and volatile components. COPA is reported to show several therapeutic effects, including anti-endometriotic properties and its use is widespread throughout the Amazonian folk medicine. COPA was nanoencapsulated into nanoemulsions (NE), then evaluated regarding the potential for transvaginal drug delivery and providing endometrial stromal cell proliferation in vitro. Transmission electron microscopy (TEM) showed that spherical NE were obtained with COPA concentration that varied from 5 to 7 wt%, while surfactant was maintained at 7.75 wt%. Dynamic light scattering (DLS) measurements showed droplet sizes of 30.03 ± 1.18, 35.47 ± 2.02, 43.98 ± 4.23 and PdI of 0.189, 0.175 and 0.182, respectively, with stability against coalescence and Ostwald ripening during 90 days. Physicochemical characterization results suggest that NE were able to both improve solubility and loading capacity, and increase thermal stability of COPA volatile components. Moreover, they showed slow and sustained release for up to eight hours, following the Higuchi kinetic model. Endometrial stromal cells from non-endometriotic lesions and ectopic endometrium were treated with different concentrations of COPA-loaded NE for 48 h to evaluate its effect on cell viability and morphology. The results suggested significant decrease in cell viability and morphological modifications in concentrations higher than 150 µg/ml of COPA-loaded NE, but not when cells were treated with the vehicle (without COPA). Given the relevance of Copaifera spp. species in folk medicine and their bio economical importance in the Amazon, the development of novel formulations to overcome the technological limitations related to BCP and COPA, is promising. Our results showed that COPA-loaded NE can lead to a novel, uterus-targeting, more effective and promising natural alternative treatment of endometriosis.

Chemical Characterization and Quality Assessment of Copaiba Oil-Resin Using GC/MS and SFC/MS.

In recent years, the popularity of copaiba oil-resin has increased worldwide due to its medicinal value and wide applications in industry. Despite its popularity, the oil has not been standardized by industry or regulatory agencies. Product adulteration in order to maximize profits has become a problem. To address these issues, the current study describes the chemical and chemometric characterization of forty copaiba oil-resin samples by GC/MS. The results demonstrated, with the exception of commercial samples, that all sample groups contained six characteristic compounds (ß-caryophyllene, α-copaene, trans-α-bergamotene, α-humulene, γ-muurolene, and ß-bisabolene) in varying concentrations. Furthermore, compositional patterns were observed in individual groups which corresponded to sample origin. Within the commercial group, two samples did not contain or contained only one of the characteristic compounds. Principal component analysis (PCA) revealed distinct groups which largely corresponded to sample origin. Moreover, commercial samples were detected by PCA as outliers, and formed a group far removed from the other samples. These samples were further subjected to analysis using a SFC/MS method. Product adulteration with soybean oil was clearly detected, with each individual triglyceride in soybean oil being unambiguously identified. By combining these analytical techniques, the overall quality of copaiba oil-resin can be assessed.

Copaiba Oil-Based Emulsion as a Natural Chemotherapeutic Agent for the Treatment of Bovine Mastitis: In Vivo Studies.

Copaiba oil-resin (COR) extracted from Copaifera reticulata Ducke has been used as a natural chemotherapeutic agent for a wide range of therapeutic applications. This study presents an emulgel design with a high concentration of COR, designed to prevent and treat mastitis. The COR was stabilized in a gel matrix constituted by carbopol C934P and Pluronic® F127 (ECO formulation) ratios. The permeation study of ECO was accessed by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS). The results reveal a high capacity of ECO to permeate deep skin layers. Dairy cows with a history of mastitis were used as in vivo models and exposed to ECO treatment. Monitoring of the teat's inflammatory response showed that ECO effectively prevents mastitis. Furthermore, the ECO formulation was able to form a thin film gel on the application side, preventing fly proliferation and significantly reducing the pathogen load. This study reveals a drug that can used as an alternative application for mastitis in human or veterinary clinics.

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.

Copaiba Oil-Loaded Polymeric Nanocapsules: Production and In Vitro Biosafety Evaluation on Lung Cells as a Pre-Formulation Step to Produce Phytotherapeutic Medicine.

Copaiba oil has been largely used due to its therapeutic properties. Nanocapsules were revealed to be a great nanosystem to carry natural oils due to their ability to improve the bioaccessibility and the bioavailability of lipophilic compounds. The aim of this study was to produce and characterize copaiba oil nanocapsules (CopNc) and to evaluate their hemocompatibility, cytotoxicity, and genotoxicity. Copaiba oil was chemically characterized by GC-MS and FTIR. CopNc was produced using the nanoprecipitation method. The physicochemical stability, toxicity, and biocompatibility of the systems, in vitro, were then evaluated. Β-bisabolene, cis-α-bergamotene, caryophyllene, and caryophyllene oxide were identified as the major copaiba oil components. CopNc showed a particle size of 215 ± 10 nm, a polydispersity index of 0.15 ± 0.01, and a zeta potential of -18 ± 1. These parameters remained unchanged over 30 days at 25 ± 2 °C. The encapsulation efficiency of CopNc was 54 ± 2%. CopNc neither induced hemolysis in erythrocytes, nor cytotoxic and genotoxic in lung cells at the range of concentrations from 50 to 200 µg·mL-1. In conclusion, CopNc showed suitable stability and physicochemical properties. Moreover, this formulation presented a remarkable safety profile on lung cells. These results may pave the way to further use CopNc for the development of phytotherapeutic medicine intended for pulmonary delivery of copaiba oil.

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing.

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy's viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals' condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

Thermo and Photoresponsive Emulgel Loaded with Copaifera reticulata Ducke and Chlorophylls: Rheological, Mechanical, Photodynamic and Drug Delivery Properties in Human Skin.

Recently, the number of new cases of cutaneous leishmaniasis has been of concern among health agencies. Research that offers new therapeutic alternatives is advantageous, especially those that develop innovative drugs. Therefore, this paper presents the incorporation of Copaifera reticulata Ducke and chlorophyll extract into Pluronic®® F127 and Carbopol gels, under optimized polymer quantities. The chlorophyll extract (rich in photosensitizing compounds) was obtained by continuous-flow pressurized liquid extraction (PLE), a clean, environmentally friendly method. The system aims to act as as a leishmanicidal, cicatrizant, and antibiotic agent, with reinforcement of the photodynamic therapy (PDT) action. Rheological and mechanical analyses, permeation studies and bioadhesiveness analyses on human skin, and PDT-mediated activation of Staphylococcus aureus were performed. The emulgels showed gelation between 13° and 15 °C, besides pseudoplastic and viscoelastic properties. Furthermore, the systems showed transdermal potential, by releasing chlorophylls and C. reticulata Ducke into the deep layers of human skin, with good bioadhesive performance. The application of PDT reduced three logarithmic colony-forming units of S. aureus bacteria. The results support the potential of the natural drug for future clinical trials in treating wounds and cutaneous leishmania.

Design and Optimization of a Natural Medicine from Copaifera reticulata Ducke for Skin Wound Care.

In this study, we developed a bioadhesive emulsion-filled gel containing a high amount of Copaifera reticulata Ducke oil-resin as a veterinary or human clinical proposal. The phytotherapeutic system had easy preparation, low cost, satisfactory healing ability, and fly repellency, making it a cost-effective clinical strategy for wound care and myiasis prevention. Mechanical, rheological, morphological, and physical stability assessments were performed. The results highlight the crosslinked nature of the gelling agent, with three-dimensional channel networks stabilizing the Copaifera reticulata Ducke oil-resin (CrD-Ore). The emulgel presented antimicrobial activity, satisfactory adhesion, hardness, cohesiveness, and viscosity profiles, ensuring the easy spreading of the formulation. Considering dermatological application, the oscillatory responses showed a viscoelastic performance that ensures emulgel retention at the action site, reducing the dosage frequencies. In Vivo evaluations were performed using a case report to treat ulcerative skin wounds aggravated by myiasis in calves and heifers, which demonstrated healing, anti-inflammatory, and repellent performance for the emulsion-filled gel. The emulgel preparation, which is low in cost, shows promise as a drug for wound therapy.

In vivo study of anti-inflammatory and antinociceptive activities of Copaifera pubiflora Benth oleoresin.

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.

Design and Optimization of Stimuli-responsive Emulsion-filled Gel for Topical Delivery of Copaiba Oil-resin.

This study presents a phytotherapeutic emulsion-filled gel design composed of Pluronic® F127, Carbopol® C934P, and high level of copaiba oil-resin (PHY-ECO). Mathematical modeling and response surface methodology (RSM) were employed to access the optimal ratio between the oil and the polymer gel-matrix constituents. The chemometric approach showed robust mechanical and thermoresponsive properties for emulsion gel. The model predicts viscosity parameters at 35.0°C (skin temperature) from PHY-ECOs. Optimized PHY-ECOs were described by 18-20% (w/w) F127, 0.25% (w/w) C934P, and 15% (w/w) copaiba oil-resin, and showed interfacial layers properties that led to high physicochemical stability. Besides, it had thermal stimuli-responsive that led large viscosity range before and after skin administration, observed by oscillatory rheology. These behaviors give the optimized smart PHY-ECO high design potential to be used as a pharmaceutical platform for CO delivery, focusing on the anti-inflammatory therapy and skin wound care.

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.

Efeitos do Óleo de Copaíba em Marcadores Periféricos de Estresse Oxidativo em um Modelo de Cor Pulmonale em Ratos / Effects of Copaiba Oil in Peripheral Markers of Oxidative Stress in a Model of Cor Pulmonale in Rats

Resumo Fundamento Até o presente momento, os efeitos sistêmicos do óleo de copaíba jamais foram documentados no Cor pulmonale induzido por monocrotalina. Objetivos Investigar os efeitos do óleo de copaíba nos marcadores periféricos de stress oxidativo em ratos com Cor pulmonale. Métodos Ratos Wistar machos (170±20g, n=7/grupo) foram divididos em quatro grupos: controle (CO), monocrotalina (MCT), óleo de copaíba (O), e monocrotalina + óleo de copaíba (MCT-O). Foi administrada a MCT (60 mg/kg i.p.) e, depois de uma semana, foi iniciado o tratamento com óleo de copaíba (400 mg/kg/day-gavagem-14 dias). Foi realizado o ecocardiograma e, depois disso, foi coletado sangue do tronco para a realização de avaliações de stress oxidativo. Análise estatística: ANOVA de duas vias com teste Student-Newman-Keuls post hoc. P-valores <0,05 foram considerados significativos. Resultados O óleo de copaíba reduziu a resistência vascular pulmonar e a hipertrofia do ventrículo direito (VD) hipertrofia (Índice de Fulton (mg/mg)): MCT-O= 0,39±0,03; MCT= 0,49±0,01), e função sistólica melhorada (fração de encurtamento do VD, %) no grupo MCT-O (17,8±8,2) em comparação com o grupo de MCT (9,4±3,1; p<0,05). Além disso, no grupo MCT-O, espécies reativas do oxigênio e os níveis de carbonila foram reduzidos, e os parâmetros antioxidantes aumentaram no sangue periférico (p <0,05). Conclusões Os resultados deste estudo sugerem que o óleo de copaíba tem um efeito antioxidante sistêmico interessante, que se reflete na melhoria da função e na morfometria do VD nesse modelo de Cor pulmonale . A atenuação do Cor pulmonale promovida pelo óleo de copaíba coincidiu com uma redução no stress oxidativo sistêmico.

Abstract Background To date, copaiba oil's systemic effects have never documented in Cor pulmonale induced by monocrotaline. Objectives To investigate copaiba oil's effects in peripheral markers of oxidative stress in rats with Cor pulmonale. Methods Male Wistar rats (170±20g, n=7/group) were divided into four groups: control (CO), monocrotaline (MCT), copaiba oil (O), and monocrotaline+copaiba oil (MCT-O). MCT (60 mg/kg i.p.) was administered, and after one week, treatment with copaiba oil (400 mg/kg/day-gavage-14 days) was begun. Echocardiography was performed and, later, trunk blood collection was performed for oxidative stress evaluations. Statistical analysis: two-way ANOVA with Student-Newman-Keuls post-hoc test. P values<0.05 were considered significant. Results Copaiba oil reduced pulmonary vascular resistance and right ventricle (RV) hypertrophy (Fulton index (mg/mg): MCT-O=0.39±0.03; MCT=0.49±0.01), and improved RV systolic function (RV shortening fraction, %) in the MCT-O group (17.8±8.2) as compared to the MCT group (9.4±3.1; p<0.05). Moreover, in the MCT-O group, reactive oxygen species and carbonyl levels were reduced, and antioxidant parameters were increased in the peripheral blood (p<0.05). Conclusions: Our results suggest that copaiba oil has an interesting systemic antioxidant effect, which is reflected in the improvements in function and RV morphometry in this Cor pulmonale model. Cor pulmonale attenuation promoted by copaiba oil coincided with a reduction in systemic oxidative stress.

Prospective, Randomized, Double-Blind, Placebo-Controlled Study on Efficacy of Copaiba Oil in Silicone-Based Gel to Reduce Scar Formation.

INTRODUCTION: Scars are the end result of a biologic and natural process of wound repair after injury, surgery, acne, illness, burns, and infection. When skin is damaged, a fast and coordinated body response is triggered by four highly integrated and overlapping phases including homeostasis, inflammation, proliferation, and tissue remodeling. Healing of a skin wound may result in an abnormal scar if the balance among these four phases is lost during the healing process. Various topical treatments have been used for their ability to reduce unsightly scar formation. Recently, studies have shown improvement in scar appearance after treating with silicone gels containing natural herbal ingredients. The aim of this study is to evaluate the efficacy of a novel silicone-based gel containing copaiba oil (Copaderm) for prevention and/or appearance reduction of different types of abnormal scars. METHODS: This study was designed as a prospective, randomized, double-blind, placebo-controlled trial involving 42 patients with abnormal scars, divided into two groups. Each group received either a topical scar formulation consisting of copaiba oil in silicone gel or a placebo gel twice a day for 84 days. Assessments of the scars were performed at 0, 28, and 84 days following the onset of topical application using three methods: a clinical assessment using the Manchester Scar Scale, a photographic assessment to establish before and after treatment improvements, and at the end of the study period, patients completed a final satisfaction questionnaire. RESULTS: Of the original 42 patients, 32 completed the evaluation. There was a significant difference with respect to the overall score of the Manchester Scar Scale between the two groups from baseline to 84 days (P < 0.05). All patients with copaiba oil in silicone gel achieved improvement of their scars, based on overall score at 84 days. A visible scar reduction was observed with photographic assessment. Eighty-nine percent of subjects (n = 16) with copaiba oil in silicone gel rated as being satisfied or very satisfied after 84 days of treatment. CONCLUSION: Our findings support the hypothesis that copaiba oil in silicone-derivative gel was able obtain significant improvement in color, contour, distortion, and texture for different types of scar through the Manchester Scar Scale analysis. These findings contribute to reducing abnormal scar formation during the healing process.

(E)-2,6,10-Trimethyldodec-8-en-2-ol: An Undescribed Sesquiterpenoid from Copaiba Oil.

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.

Effect of Phonophoresis and Copaiba Oil on Oxidative Stress Biomarkers after Skeletal Muscle Injury in Rats.

The objective of this study was to analyze the effectiveness of phonophoresis with copaiba oil gel, in comparison to therapeutic pulsed ultrasound alone or topical application of copaiba oil gel, on oxidative stress after a traumatic muscle injury. Forty male Wistar rats were divided into five groups: control, muscle injury, therapeutic pulsed ultrasound (TPU), copaiba oil gel (CO) and TPU plus CO. TPU and CO application occurred at 2, 12, 24, 48, 72 and 96 h after injury. The gastrocnemius muscle was injured by mechanical trauma. Malondialdehyde (a lipoperoxidation marker) and superoxide dismutase and catalase (antioxidant enzymes) were assessed 98 h after muscle injury. All were elevated in the muscle injury group. There was a significant difference among treatment groups favoring TPU plus CO for reducing malondialdehyde levels, but all treatments reduced superoxide dismutase and catalase activity, with no between-groups difference. In conclusion, phonophoresis-the application of TPU plus CO-was superior to TPU or CO alone for reducing lipoperoxidation. Phonophoresis, TPU alone and CO were all effective in decreasing antioxidant enzyme activity after a traumatic skeletal muscle injury.