[Preparation stimulating hair growth possibly acts by inhibiting hair follicle ageing experiments on mice and transcriptome analysis].

Preparation stimulating hair growth (PSHG) was studied on mice of various strains (Balb/c, CBA, C57BI/6, and outbred). It was shown that a long-term (44 months) application of PSHG does not reliably affect the appearance of young healthy mice but does induce increase in the hair follicle size. No adverse consequences of the PSHG application were observed. Naturally occurring propagating regenerative hair waves peculiar to mice were preserved. In older mice (more than 2 years) with signs of alopecia, application of PSHG caused an overgrowing of bald patches within two months. Transcriptome analysis of the PSHG effect performed in fibroblast cell culture showed that PSHG stimulates processes of tissue development and remodeling. These observations together with previous findings showing that PSHG stimulates autophagy and induces death of cells subjected to oxidative stress may suggest that the mechanism of the PSHG effect involves stimulation of regeneration of skin and its derivatives owing to more efficient elimination of senescent and damaged follicle cells.

Antileishmanial activity of diterpene acids in copaiba oil.

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Treating a chronic wound in a nonadherent patient: a case study.

BACKGROUND: Limited evidence suggests that various formulations containing Balsam of Peru, castor oil, and trypsin (BCT) exert multiple actions that may promote wound healing such as shedding damaged skin cells, stimulation of localized blood flow, antimicrobial actions, and local analgesic actions. CASE: An 81-year-old man was referred to our home-based wound care center for treatment of an excoriation-induced chronic dehiscence of an abdominal surgical wound. He had failed multiple topical therapies, primarily owing to persistent pruritus of the wound and periwound skin, resulting in removal of his dressing to scratch the wound and periwound skin. We used a spray containing BCT to promote wound healing and relieve pruritus; this addition resulted in wound closure within 38 days of treatment. CONCLUSIONS: We recommend considering BCT spray when maintenance of dressing is impaired and wound healing delayed owing to pruritus. We found the BCT spray easy to use and well-accepted by our patient who was unable to tolerate other forms of topical therapy over a period of 6 months.

Chemical profiling and cytotoxic activity of 150-year old original sample of Jerusalem Balsam.

Herbal formulations have been used in ethnomedicine and pharmacy around the world for thousands of years. One of them is Jerusalem Balsam (JB), which came into use in the seventeenth century. Today, people still produce and use it regularly as prophylactic supplement. JB has been widely used in Europe since the nineteenth century, as a remedy possessing antibacterial, antifungal and anti-inflammatory activities. The composition of the product was not known, although possible formulations were reported. In this study the original sample, which dated back to 1870, was investigated for chemical composition and cytotoxic activity. The obtained results were compared with results from more recently produced samples. Several tests were carried out, namely GC-MS, UPLC-PDA-Q-TOF-MS and MTT. Only the 150-year old sample showed a significant cytotoxic activity on cancer cell lines. At a concentration of 125 µg/mL after 72 h of incubation, the original sample inhibited almost 90% of cell metabolic activity, while contemporary samples showed none or little activity. None of the tested samples showed a significant impact on normal cells. These results may be attributed to the activities of benzoic acid and its derivatives, cinnamic acid derivatives, vanillin, group of sesquiterpenes and cembrene.

Acute effect of Copaifera reticulata Ducke copaiba oil in rats tested in the elevated plus-maze: an ethological analysis.

OBJECTIVES: Copaiba oil oleoresin exuded from Copaifera reticulata Ducke (CRD) is commonly used in anti-inflammatory, healing and anti-tumoral folk medicines. The purpose of this study was to investigate the putative anxiolytic effect of acute administration of CRD. METHODS: CRD was administered (100, 400 and 800 mg/kg, p.o.) to male Wistar rats submitted to the elevated plus-maze model of anxiety using an ethopharmacological analysis. KEY FINDINGS: In comparison with control rats, CRD increased the percentage of entries in the open arms over the entire dose range tested (vehicle, 33.6 +/- 4.5; CRD 100 mg/kg, 44.67 +/- 3.68; CRD 400 mg/kg, 47.2 +/- 2.3; CRD 800 mg/kg, 50.7 +/- 2.2) and the percentage of time spent in the open arms of the elevated plus-maze at the highest dose (800 mg/kg) (vehicle, 26.4 +/- 5.7; CRD 800 mg/kg, 52.0 +/- 2.7). A standard anxiolytic, diazepam (3 mg/kg, p.o.), was used as a positive control. In a similar way, diazepam increased the percentage of entries and time spent in the open arms when compared with vehicle (% open entries: vehicle, 45.4 +/- 1.3; diazepam, 50.7 +/- 1.9; % time spent in open arms: vehicle, 28.2 +/- 0.9; diazepam, 38.9 +/- 1.2). Regarding ethological measures, CRD at the highest dose (800 mg/kg) reduced peeping out (anxiety-related behaviour) (vehicle, 3.1 +/- 0.6; CRD, 0.9 +/- 0.2) and increased end-arm activity (vehicle, 0.2 +/- 0.2; CRD, 2.0 +/- 0.4), indicating an enhanced tendency of the rats to explore actively the potentially dangerous areas of the maze. Diazepam decreased peeping out (vehicle, 3.3 +/- 0.3; diazepam, 1.0 +/- 0.2) and flat-back approach (vehicle, 0.8 +/- 0.2; diazepam, 0.2 +/- 0.1) and increased end-arm activity (vehicle, 0.3 +/- 0.1; diazepam, 2.5 +/- 0.3) and head-dipping (vehicle, 8.2 +/- 0.4; diazepam, 12.0 +/- 0.5). CONCLUSIONS: These data showed, for the first time, that acute treatment with CRD copaiba oil produced a dose-dependent anxiolytic-like effect over the dose range tested, on conventional and ethological parameters, without adversely affecting general activity levels.

Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne--a comparative study.

Copaiba oil is an oleoresin obtained from the Copaifera L. genus (Leguminoseae) commonly featured in anti-inflammatory recipe prescribed by Amazonian traditional medical practitioners and featured in Europe and North America pharmacopeias of the past. Chemical and anti-inflammatory activity investigations from the copaiba oils obtained from Copaifera multijuga Hayne, Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke species have proved that, although similar, these oleoresins possess varied composition and anti-inflammatory activity. Chromatographic studies showed that the main compound among sesquiterpenes was beta-caryophyllene (57.5, 19.7 and 40.9%, respectively), followed by alpha-humulene, alpha-copaene, alpha-bergamotene, delta-cadinene, with different amounts in each oleoresin. Among the diterpenes, copalic acid was the main component from Copaifera multijuga Hayne (6.2%) and was found in all the oleoresins studied. In Copaifera cearensis Huber ex Ducke, clorechinic (11.3%) and hardwickiic acids (6.2%) were the major diterpenes while kaurenoic (3.9%) and kolavenic acids (3.4%) predominated in Copaifera reticulata Ducke. The pharmacologic effects of the three oleoresins were evaluated in vitro by measuring the NO production by murine macrophages and in vivo using the zymosan induced pleurisy model in mice. The Copaiba Oil from Copaifera multijuga Hayne (100 mg/kg) was the most potent, inhibiting both NO production and the pleurisy induced by zymosan. The oleoresins from Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke were also able to inhibit NO production and the pleurisy but with less intensity.

Development and pharmacological evaluation of in vitro nanocarriers composed of lamellar silicates containing copaiba oil-resin for treatment of endometriosis.

In this work, newly developed nanocomposites based upon lamellar silicates are evaluated to determine their potential in controlling endometriosis. The preparation of the new nanocarriers is detailed, properties characterized and in vitro pharmacological evaluation performed. The nanocomposites in this study were obtained from the reaction of copaiba oil-resin (COPA) with the polymer polyvinylpyrrolidone (PVP K-30). COPA was selected due to its antiinflammatory and anticancer activities along with the organophilic derivatives of sodium montmorillonite, Viscogel B8, S7 and S4. The results indicated that it was feasible to obtain a good yield of a COPA nanocomposite using a simple process. Intercalation was confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). In vitro release experiments demonstrated that COPA was released from the nanocomposite in a delayed fashion. Whereas, in vitro pharmacological studies showed a reduction in viability and proliferation of endometriotic cell cultures upon COPA nanocomposite treatment, suggesting that the system developed here can be a promising alternative therapy for the oral treatment of endometriosis.

The Jerusalem Balsam: from the Franciscan Monastery in the old city of Jerusalem to Martindale 33.

The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture, was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old city of Jerusalem. Having gained fame, the Jerusalem Balsam was replicated and prepared in Europe. One can still find variations of the formula in current pharmacopoeias (B.P., 1998. The Stationary Office, London, p. 1510; Sweetman, S.C., Blake, P.S., McGlashan, J.M., Parsons, A.V., 2002. Martindale: The Extra Pharmacopeia, 33rd ed. Pharmaceutical Press, London, p. 1101). We report here, five different formulas, all referred to as "The Jerusalem Balsam". Three of those formulas were translated and two of these translations are presented in the text. A third one is available as Supplementary data online. As the formulas originate from different historical periods, the Jerusalem Balsam may be a good case study of the development of pharmaceutical formulations over a 250 years period. One of the formulas, found in a manuscript form in the archive of the monastery, contains four plants: olibanum (Boswellia spp.), myrrh (Commiphora spp.), aloe (Aloe sp.) and mastic (Pistacia lentiscus L.). We conducted pharmacological assays on this four-plant formula. It showed anti-inflammatory, as well as anti-oxidative, and anti-septic properties.

[Copaiba oil effect on urea and creatinine serum levels in rats submitted to kidney ischemia and reperfusion syndrome]. / Efeito do óleo de copaíba nos níveis séricos de ureía e creatinina em ratos submetidos à síndrome de isquemia e reperfusão renal.

PURPOSE: To evaluate the copaiba oil effect on urea and creatinine levels in rats submitted to kidney ischemia and reperfusion syndrome. METHODS: Eighteen Wistar rats (Rattus norvegicus albinus), aged between 90 and 120 days, weight between 200 g and 250 g, were allocated in 2 groups (n=9) and submitted to 50 minutes of renal ischemia and reperfusion and treated or not with copaiba oil (0.63 ml/kg daily seven days before ischemia). The nitrogen excrements were assessed at 24, 48 and 72 hours after ischemia period. RESULTS: The urea serum level was smaller (p d" 0,05) at 24 and 48 hours, and the creatinine serum level was smaller at 48 hours in animals treated with copaiba oil (GIRC) than the GIR. CONCLUSION: The copaiba oil decreased significantly the urea serum level at 24 and 48 hours and the creatinine level at 48 hours after kidney ischemia and reperfusion in rats.

[Copaiba oil effect on aminotransferases of rats with hepatic ischemia and reperfusion with and without ischemic preconditioning]. / Efeito do oleo de copaíba nas aminotransferases de ratos submetidos a isquemia e reperfusão hepática com e sem pré-condicionamento isquêmico.

PURPOSE: To study the copaiba oil effect in rats' aminotrasnferases submitted to hepatic ischemic and reperfusion with and without preconditioning. METHODS: 24 male and adults rats (Rattus norvegicus albinus, Wistar) were distributed into six groups: Standard Group (SG); Copaiba Group (CG), Ischemic-reperfusion Group (IRG), Ischemic-reperfusion + Copaiba Group (IRCG), Ischemic Preconditioning Group (IPCG) and Ischemic Preconditioning + Copaiba Group (IPCCG). The animals of CG, IRCG and IPCCG received copaiba oil, 0.63 ml/kg/day by gavage, during 7 days. It was realized total hepatic ischemic by 30 minutes and, in animals subbimited to ischemic preconditioning, it was realized 10 minutes of ischemia, following by 5 minutes of reperfusion and other ischemia by 30 minutes. All animals were subbmited to 24 hours of reperfusion. To realize surgery procedure, animals were anesthezied through ethilic eter breathing. On first post-operating day, blood was collected to dose aminotransferases. RESULTS: It was not observe alterations in AST level in animals which received copaiba oil. There was no statistic difference between IRCG and IRG ALT levels, however, this enzyme was increased in IPCCG when compared with IPCG. CONCLUSION: Copaiba oil did not change AST levels in groups studied. Analysing ALT, this oil did not change its values in animals were realized just hepatic ischemic-reperfusion, however, it had levels increase in IPCCG when compared to IPCG Between IRCG and IPCCG, ALT levels were not statistical different.

Immunomodulatory action of Copaifera spp oleoresins on cytokine production by human monocytes.

Copaifera spp oleoresins have been used in folk medicine for centuries; nevertheless, its immunomodulatory action has not been investigated. Thus, the goal of this study was to characterize different oleoresins and to verify their action on human monocytes regarding pro- and anti-inflammatory cytokine production (TNF-α and IL-10, respectively). The chemical composition of Brazilian Copaifera reticulata, Copaifera duckey and Copaifera multijuga oleoresins was analyzed by HPLC-MS. Cell viability was assessed by MTT method after incubation of cells with Copaifera spp. Noncytotoxic concentrations of oleoresins were incubated with human monocytes from healthy donors, and cytokine production was determined by ELISA. HPLC-MS analysis for terpenes allowed the identification of six diterpene acids and one sesquiterpene acid. Oleoresins exerted no cytotoxic effects on human monocytes. All oleoresins had a similar profile: LPS-induced TNF-α production was maintained by oleoresins, while a significant inhibitory action on IL-10 production was seen. Copaifera oleoresins seemed to exert an activator profile on human monocytes without affecting cell viability. Such effect may be due to the presence of either diterpene or sesquiterpene acids; however, further studies are necessary to determine the involvement of such compounds in Copaifera immunomodulatory effects.

Gastroprotective effect of Copaifera langsdorffii oleo-resin on experimental gastric ulcer models in rats.

The effects of oleo-resin obtained from the stem bark of Copaifera langsdorffii on ethanol, indomethacin and hypothermic restraint-stress induced gastric lesions were studied in rats. Oral administration of oleo-resin at doses of 200 and 400 mg/kg provided dose-dependent significant protection against gastric damage caused by ethanol and restraint stress, and at a dose of 400 mg/kg it also prevented the gastric ulceration induced by indomethacin. Further, in the 4 h pylorus ligated rats, the accumulation of gastric juice volume and the mucus secretion was significantly enhanced by oleo-resin whereas the total acidity was inhibited. These results highlight the gastroprotective potential of C. langsdorffii oleo-resin and the need for a systematic study on this traditional remedy.

The effect of different formulations of equivalent active ingredients on the performance of two topical wound treatment products.

Product selection for the management of pressure ulcers or perineal dermatitis is typically based on consideration of active ingredients, but a growing body of evidence suggests that delivery vehicles also may influence product safety and efficacy. A 10-day, randomized, controlled experimental study was conducted to compare the safety and efficacy of two prescription products used for the treatment of pressure ulcers and perineal dermatitis. Both products contain equivalent active ingredients (balsam of Peru, castor oil, and trypsin), but one product delivers these ingredients in an ointment base while the other uses an aerosol spray. Sixty healthy volunteers (> 65 years of age) underwent intentional creation of two equivalent skin wounds (approximately 6 mm in diameter) using an Erbium-YAG laser. Volunteers served as their own control. Wounds were randomized to treatment with one of the balsam of Peru products or saline. Wounds were evaluated every other day. Significant differences between treatments were observed for most outcome variables (edema, scabbing, erythema, epithelialization). Wounds managed with the ointment-based product had lower edema, scabbing, and erythema scores and higher epithelialization scores than the spray or saline managed wounds. The results of this study confirm that formulation of the vehicle base can have a significant effect on product safety and effectiveness.

Using a castor oil-balsam of Peru-trypsin ointment to assist in healing skin graft donor sites.

Skin graft donor sites are partial-thickness wounds that are commonly managed with gauze-type dressings. As such, they often cause more pain and difficulty in healing than the graft-recipient site. A retrospective study was conducted to ascertain the effects of using a castor oil-balsam of Peru-trypsin containing ointment on skin graft donor sites in 36 consecutive patients (16 female, 20 male). All donor sites were epithelialized after 11 days (range 6 to 11 days, mean 8 days) and no wound complications were observed. Given these healing results and product ease of use, this particular formulation has become the facilities' current treatment of choice and further study is indicated and warranted.

Rupture point analysis of intestinal anastomotic healing in rats under the action of pure Copaíba (Copaifera Iangsdorfii) oil.

PURPOSE: Analyze the mechanical strength of digestive tract scar after intestinal anastomosis surgery in animals treated with pure Copaíba oil. METHODS: 60 Wistar rats, male, about 250 days old and weighting around 350g were used. The rats were randomly divided into two groups: Group O, with 30 animals that received Copaíba oil and Group C, with 30 animals that received saline. Each group was subdivided into three subgroups, containing 10 rats each. They were designated O7, O14, O28, C7, C14 and C28, according to the post-operative assessment date at 7, 14 and 28 days, respectively. On these dates euthanasia was performed with the removal of the bowel segment containing the anastomosis and assigning the samples to tensile test for assessing Maximum Stress, Maximum Tensile Strength and Maximum Rupture Strength. RESULTS: On the three variables of the study, the results indicate that, for the three assessment periods (7, 14 and 28 days) there was no significant difference between the oil and control groups. CONCLUSION: For the mechanical tests proposed by this study, Copaíba oil didn t show any effectiveness in increasing the anatomosis strength.

Antileishmanial activity of diterpene acids in copaiba oil

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.