Chitosan-PEG Gels Loaded with Jatropha mollissima (Pohl) Baill. Ethanolic Extract: An Efficient and Effective Biomaterial in Hemorrhage Control.

A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.

Biocompatibility and mechanical properties evaluation of chitosan films containing an N-acylhydrazonic derivative.

The N-acylhydrazone subunit is considered a privileged structure in medicinal chemistry for its importance in pharmaceutical research. Also, alternative methods to deliver these molecules have a great pharmaceutical interest. Therefore, the objective of this work was to encapsulate JR19, an N-acyl hydrazone subunit, into chitosan films and evaluate several properties relevant for transdermal delivery, including biocompatibility using in vitro tests. CHI + JR19 film demonstrates greater strength, flexibility, water absorption capacity, low contact angle and higher surface roughness when compared to CHI. Agar diffusion and 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay show the absence of cytotoxicity and the higher cell viability for CHI + JR19 films. Therefore, the addition of JR19 in the system positively influenced mechanical properties and granted better compatibility with biological environments, showing the potential to treat skin inflammation.

A LC-MS validated method for quantification of rosmarinic acid and sesquiterpene lactones in Hedyosmum brasiliense.

The leaves of the aromatic neotropical shrub Hedyosmum brasiliense are employed popularly as a sedative, aphrodisiac and as a substitute for green tea. Sesquiterpene lactones and phenolic compounds were characterized as the main compounds of its aqueous extract, and some biological investigation demonstrated its anxiolytic, antidepressant and hypnotic effects. The quantification of podoandin, onoseriolide and rosmarinic acid in its infused tea was achieved by means of ultra high performance liquid chromatography coupled to a electronspray ionization interface and a high resolution mass detector. Quantification of the analytes was performed employing the areas of the extracted ion chromatograms of the analytes, negative ion mode for rosmarinic acid (1) and positive mode for podoandin (2) and onoseriolide (3). The method was validated by evaluating specificity, linearity, precision and accuracy and has been found to be sensitive, precise and accurate. When applied to analyze the hot water infusion extract of H. brasiliense, compounds 1, 2 and 3 were obtained to be 188 ± 1.45 mg/g, 1.9 ± 0.15 mg/g and 1.7 ± 0.02 mg/g of extract, respectively. The H. brasiliense tea was found to be a good source of the rosmarinic acid, also widely employed in the cosmetic industry.

Sesquiterpene lactones from Hedyosmum brasiliense induce in vitro relaxation of rat aorta and corpus cavernosum

Abstract Hedyosmum brasiliense Miq., Chloranthaceae, has been used in Southern Brazil as a sedative, anti-inflammatory, and aphrodisiac. In this study, endothelium-intact and endothelium-denuded rat aortic rings and strips of corpus cavernosum were used to investigate the relaxant effects of an hexane fraction of leaves of H. brasiliense and its sesquiterpene lactones 13-hydroxy-8,9-dehydroshizukanolide, podoandin, and elemanolide 15-acetoxy-isogermafurenolide. The incubation of hexane fraction of leaves of H. brasiliense resulted in significant relaxation of endothelium-intact aortic rings previously contracted by phenylephrine. In addition, 13-hydroxy-8,9-dehydroshizukanolide and podoandin displayed a clear concentration-dependent ability to relax endothelium-intact (∼85 to 90%) and endothelium-denuded (∼45 to 55%) rat aortic rings. A less pronounced vascular relaxation was recorded when 15-hydroxy-isogermafurenolide was tested. Interestingly, in tissues previously incubated with the nitric oxide synthase inhibitor L-NAME (100 µM), both 13-hydroxy-8,9-dehydroshizukanolide and podoandin had their effects in endothelium-intact vessels reduced to the same degree of relaxation observed in endothelium-denuded aortic rings. Podoandin, 13-hydroxy-8,9-dehydroshizukanolide, and 15-acetoxy-isogermafurenolide (100 µM) were also able to relax precontracted corpus cavernosum strips by 49.5 ± 3.9%, 65.9 ± 7.3% and 57.9 ± 5.5%, respectively. Our results demonstrated that 13-hydroxy-8,9-dehydroshizukanolide, podoandin and 15-acetoxy-isogermafurenolide, isolated from H. brasiliense, generate both endothelium-dependent and -independent relaxation of rat aortic rings, as well as being able to induce in vitro relaxation of rat corpus cavernosum. Importantly, the endothelium-dependent effect is fully dependent on nitric oxide production. Considering that penile erection depends on both relaxation of cavernosal smooth muscle and inflow of blood for the cavernous bodies, this is the first study reporting experimental evidence supporting the aphrodisiac properties of H. brasiliense.

Rosmarinic Acid--Pharmaceutical and Clinical Aspects.

The biosynthesis and biotechnological production of Rosmarinic acid, a phenolic ester that is widespread in the plant kingdom, has been widely investigated. This compound has shown many remarkable biological and pharmacological activities, which have led to its pharmaceutical and analytical development, as well as clinical studies, which are summarized and analyzed here for the first time. This review compiles data from the Pubmed, Scopus, Scifinder, Web Of Science, and Science Direct databases published between 1990 and 2015, restricting the search to works with the keywords "Rosmarinic acid" in the title. The initial search identified more than 800 articles; after an initial screening and removal of duplicate works, the search was further refined, resulting in approximately 300 articles that were scrutinized and comprise this review. The articles were organized to describe extraction and isolation, analytical methods, pharmaceutical development, and biological and pharmacological activities [divided into nonclinical (in vitro, in vivo) and clinical studies], pharmacokinetic studies, and stability studies.

Inhibitory effect of sesquiterpene lactones and the sesquiterpene alcohol aromadendrane-4ß,10α-diol on memory impairment in a mouse model of Alzheimer.

Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. Cerebral deposition of amyloid-ß peptide (Aß) is a critical feature of AD. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research. Sesquiterpene lactones and a sesquiterpene alcohol are compounds found in H. brasiliense that have several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether these compounds have neuroprotective effects in an amyloid-ß peptide-induced Alzheimer's disease mouse model. Mice were injected with Aß1-42 peptide intracerebroventricularly and were subsequently injected (i.c.v.) with 1µg/site of IGM-A (15-acetoxy-isogermafurenolide), IGM-H (15-hydroxy-isogermafurenolide), PDA (Podoandin), EHP (1,2-epoxy-10α-hydroxy-podoandin), HDS (13-hydroxy-8,9-dehydroshizukanolide), and ARD (aromadendrane-4ß,10α-diol). Seven days after treatments the animals had their memory tested in the inhibitory avoidance. After the behavioral testing of animals the brains were removed and subjected to biochemical tests for oxidative stress. The results showed that ARD, HDS and PDA significantly ameliorated the Aß1-42 peptide-induced memory impairment in the passive avoidance task (P<0.05). In addition, GSH activity was increased while the TBARS levels were decreased by treatment with these compounds. These results suggest that these compounds inhibit the cognitive deficit of animals induced peptide amyloid and may be potential candidates for Alzheimer's disease therapy.

Herbalists, traditional healers and pharmacists: a view of the tuberculosis in Ghana

This paper is the result of a visit by Brazilian researchers to Ghana, with the aim of improving understanding of the relationship between traditional healers and conventional health practices, specifically in relation to tuberculosis. Through this exploratory visit, this group of researchers promoted by the Edital Pro Africa (CNPq) had an opportunity to learn about, reflect on, and discuss the different social, economic and cultural realities and contexts that have led to the different health conditions and forms of healthcare in Ghana. Besides the direct relationship between the social and economic conditions of the country and the health of its population, it was also concluded that there is a clear distancing, in the Ghanaian reality, between the traditional healers and the conventional system, in terms of culture and modes of operation, each constituting isolated systems with little or no collaboration between them.The visit enabled us to see the difficulties involved in managing TB, including diagnosis, treatment, monitoring and co-infection with HIV. The majority of patients with TB only go to hospital after several attempts at self-medication, due to the non-specificity of the principal symptoms, and also to the trust in the traditional medicine. Initiatives to encourage research into medicinal plants in Ghana are seeking partnerships with developed countries, but not always with clear or secure national interests. For the traditional healers, there are high hopes that the information gathered by researchers from the local universities, on the plants and traditional methods they use, will result in affirmation and recognition of their practices, but they complain strongly that they receive no feedback on the research carried out.

Sesquiterpene lactones from the leaves of Hedyosmum brasiliense (Chloranthaceae).

Hedyosmum brasiliense Miq. is an endemic aromatic arborescent shrub that is the only representative of the Chloranthaceae in Brazil. There have been few studies seeking to determine its chemical constituents and/or pharmacological effects. This work describes the isolation and identification of sesquiterpene lactones from the leaves, including guaianolides, elemanolides and a lindenanolide. These were tested against Mycobacterium tuberculosis, together with podoandin, onoseriolide and some other common phenolics. The structures of the isolated compounds were determined based on extensive analysis of 1D and 2D NMR spectroscopic and MS data, as well as comparison with published data. The compounds found were the guaianolides, 1,2-epoxy-10α-hydroxy-podoandin and 1-hydroxy-10,15-methylenepodoandin, the elemenolide 15-acetoxy-isogermafurenolide and the lindenanolide 8α/ß,9α-hydroxy-onoseriolide, along with the previously isolated guaianolide podoandin, the lindenanolide onoseriolide and the elemenolide 15-hydroxy-isogermafurenolide. The phenolic compounds isolated were scopoletin, vanillin, vanillic acid, protocatechuic aldehyde and ethyl caffeate. The isolated sesquiterpene lactones did not show anti-mycobacterial activity against isoniazid-sensitive M. tuberculosis cultures at concentrations of 1-30 µM.

The antidepressant-like effect of Hedyosmum brasiliense and its sesquiterpene lactone, podoandin in mice: evidence for the involvement of adrenergic, dopaminergic and serotonergic systems.

We have recently shown that the ethanol extract of the leaves of Hedyosmum brasiliense exhibits an antidepressant-like effect in the tail suspension and forced swimming tests in mice. The present study investigates the mechanisms involved in the antidepressant-like effect of H. brasiliense extract, together with the antidepressant potential of podoandin, an isolated sesquiterpenoid. H. brasiliense (50mg/kg, i.p.) and podoandin (10mg/kg, i.p.) decreased the immobility time in the forced swimming test, without any accompanying changes in ambulation in the open-field test. The anti-immobility effect of the H. brasiliense extract was prevented by pre-treating the mice with ondansetron, NAN 190, pindolol, prazosin, yohimbine, haloperidol, SCH23390, and sulpiride. On the other hand, pre-treating the mice with: p-chlorophenylalanine (4 consecutive days), ketanserin, naloxone, naltrindole, bicuculline, phaclofen, or l-arginine did not block the antidepressant-like effect of H. brasiliense. In addition, pre-treatment of the animals with methylene blue, NG-nitro-l-arginine or 7-nitroindazole, at subeffective doses, did not cause a synergistic effect with H. brasiliense extract at an effective dose in the forced swimming test. The anti-immobility effect of podoandin was also prevented by pre-treating the mice with NAN-190, ondansetron, prazosin, yohimbine, sulpiride and haloperidol. The results indicate that the antidepressant-like effect of H. brasiliense (and podoandin) is dependent on the serotonergic, noradrenergic and dopaminergic systems, but not on the GABAergic, opioid and oxidonitrergic systems.