Calotropis procera (Aiton) Dryand (Apocynaceae): State of the art of its uses and Applications.

Calotropis procera (Aiton) Dryand (Apocynaceae), popularly known as milkweed, has been traditionally used to treat diseases particularly associated with gastric disorders, skin disease and inflammatory processes. The present study aimed to review the current scientific evidence regarding the pharmacological effects of C. procera extracted phytochemicals and possible research opportunities as complementary and alternative medicine. Scientific publications were searched in various electronic databases (PubMed, Scopus, Web of Science, Google Scholar, Springer, Wiley, and Mendeley) using the following search terms: Calotropis procera, medicinal plants, toxicity, phytochemical characterization, and biological effects. Collected data showed that cardenolides, steroid glycoside and flavonoids are the main classes of phytochemicals identified in C. procera latex and leaves. In addition, lignans, terpenes, coumarins, and phenolic acids have been reported. These metabolites have been correlated with their biological activities, including mainly antioxidant, anti-inflammatory, antitumoral, hypoglycemic, gastric protective, anti-microbial, insecticide, anti-fungal, anti-parasitic, among others. However, some of the studies were carried out with only a single dose or with a high dose not achievable under physiological conditions. Therefore, the validity of C. procera biological activity may be questionable. Not less important to highlight are the risks associated with its use and the possibility of accumulation of heavy metals that can be toxic. Furthermore, there are no clinical trials with C. procera to date. In conclusion, the need of bioassayguided isolation of bioactive compounds, bioavailability and efficacy, as well as pharmacological and toxicity studies, are needed using in vivo models and clinical trials in order to support the traditionally claimed health benefits.

Effects of acaricidal essential oils from Lippia sidoides and Lippia gracilis and their main components on vitellogenesis in Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae).

Rhipicephalus microplus is an important cattle tick, and resistant strains to synthetic compounds have been widespread. The combined effects of different essential oil compounds enhance biological activity and reduce selection for the development of target organism resistance. Essential oils of two different genotypes of each of Lippia sidoides and Lippia gracilis and their main components, the isomers thymol and carvacrol, have acted as acaricides against R. microplus. Little is known about the effects of the essential oils of L. sidoides and L. gracilis and thymol and carvacrol on the morphophysiology of R. microplus ovaries. This study aimed to identify the morphological changes in the ovaries of R. microplus females treated with essential oils from two different genotypes of each of L. sidoides (102 and 103) and L. gracilis (106 and 201) and the terpenes thymol and carvacrol through histological techniques. The LC50 and LC75 of essential oils and thymol and carvacrol were used for Adult Immersion Test (AIT) with groups of five fully engorged females of R. microplus. A negative control (DMSO 3% solution) was performed. Seven days after the AIT, the ticks were dissected to collect ovaries and their histologic analysis. Only the group treated with the essential oil of L. gracilis genotype 106 at the LC50 had no change compared with the control. The other groups showed the following changes in oocytes I to V: vacuolation, chorion deformation, disorganization of yolk granules, and irregularities at the cell periphery, causing incomplete process of vitellogenesis. Thus, the essential oils tested in this study may be potent products for the control of cattle ticks and thereby preventing further life cycles.

GC-MS Characterization of Antibacterial, Antioxidant, and Antitrypanosomal Activity of Syzygium aromaticum Essential Oil and Eugenol.

Syzygium aromaticum has a diversity of biological activities due to the chemical compounds found in its plant products such as total phenolic compounds and flavonoids. The present work describes the chemical analysis and antimicrobial, antioxidant, and antitrypanosomal activity of the essential oil of S. aromaticum. Eugenol (53.23%) as the major compound was verified by gas chromatography-mass spectrometry. S. aromaticum essential oil was more effective against S. aureus (MIC 50 µg/mL) than eugenol (MIC 250 µg/mL). Eugenol presented higher antioxidant activity than S. aromaticum essential oil, with an EC50 of 12.66 and 78.98 µg/mL, respectively. S. aromaticum essential oil and eugenol exhibited Trypanosoma cruzi inhibitory activity, with IC50 of 28.68 ± 1.073 and 31.97 ± 1.061 µg/mL against epimastigotes and IC50 of 64.51 ± 1.658 and 45.73 ± 1.252 µg/mL against intracellular amastigotes, respectively. Both compounds presented low cytotoxicity, with S. aromaticum essential oil displaying 15.5-fold greater selectivity for the parasite than the cells. Nitrite levels in T. cruzi-stimulated cells were reduced by essential oil (47.01%; p = 0.002) and eugenol (48.05%; p = 0.003) treatment. The trypanocidal activity of S. aromaticum essential oil showed that it is reasonable to use it in future research in the search for new therapeutic alternatives for trypanosomiasis.

Vernonia brasiliana (L.) Druce induces ultrastructural changes and apoptosis-like death of Leishmania infantum promastigotes.

The present study aimed to evaluate the antileishmanial effect, the mechanisms of action and the association with miltefosine of Vernonia brasiliana essential oil against Leishmania infantum promastigotes. This essential oil was obtained by hydrodistillation and its chemical composition was determined by gas chromatography-mass spectrometry (GC-MS). The antileishmanial activity against L. infantum promastigotes and cytotoxicity on DH82 cells were evaluated by MTT colorimetric assay. Ultrastructural alterations were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential, in the production of reactive oxygen species, and analysis of apoptotic events were determined by flow cytometry. The association between the essential oil and miltefosine was evaluated using the modified isobologram method. The most abundant component of the essential oil was ß-caryophyllene (21.47 %). Anti-Leishmania assays indicated an IC50 of 39.01 ±â€¯1.080 µg/mL for promastigote forms after 72 h of treatment. The cytotoxic concentration for DH82 cells was 63.13 ±â€¯1.211 µg/mL after 24 h of treatment. The effect against L. infantum was proven through the ultrastructural changes caused by the oil, such as kinetoplast and mitochondrial swelling, vesicles in the flagellar pocket, discontinuity of the nuclear membrane, nuclear fragmentation and condensation, and loss of organelles. It was observed that the oil leads to a decrease in the mitochondrial membrane potential (35.10 %, p = 0.0031), increased reactive oxygen species production, and cell death by late apoptosis (17.60 %, p = 0.020). The combination of the essential oil and miltefosine exhibited an antagonistic effect. This study evidences the antileishmanial action of V. brasiliana essential oil against L. infantum promastigotes.

Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.

The aim of this review was to identify anti-inflammatory and antioxidant therapeutic agents and their effects on patients with chagasic myocarditis. A systematic review of the MEDLINE, EMBASE, WEB OF SCIENCE, SCOPUS, LILACS and CENTRAL databases (Cochrane Library) was carried out without language restrictions. The descriptors used were: 'Chagas cardiomyopathy', 'treatment', 'Chagas disease', 'anti-inflammatory agents', 'Trypanosoma cruzi' and 'antioxidants'. A total of 4,138 articles was identified, six of which were selected for data extraction. Of these, four were related to antioxidant therapy with vitamins C and E supplementation, and two using anti-inflammatory therapy. The studies were carried out in Brazil and were published between 2002 and 2017. Antioxidant therapy with vitamin C and E supplementation increases the activity of antioxidant enzymes and reduces the oxidative markers. There is no conclusive data to support the use of vitamin supplementation and anti-inflammatory therapy in the treatment of chagasic cardiomyopathy. However, the studies indicate the possibility of vitamin supplementation as a new approach to the treatment of Chagas disease. Antioxidant therapy was proven to be a viable alternative for attenuating the oxidative damage caused by chronic chagasic cardiopathy, leading to a better prognosis for patients.

Aniba rosaeodora (Var. amazonica Ducke) Essential Oil: Chemical Composition, Antibacterial, Antioxidant and Antitrypanosomal Activity.

Aniba rosaeodora is one of the most widely used plants in the perfumery industry, being used as medicinal plant in the Brazilian Amazon. This work aimed to evaluate the chemical composition of A. rosaeodora essential oil and its biological activities. A. rosaeodora essential oil presented linalool (93.60%) as its major compound. The A. rosaeodora essential oil and linalool showed activity against all the bacteria strains tested, standard strains and marine environment bacteria, with the lower minimum inhibitory concentration being observed for S. aureus. An efficient antioxidant activity of A. rosaeodora essential oil and linalool (EC50: 15.46 and 6.78 µg/mL, respectively) was evidenced by the inhibition of the 2,2-azinobis- (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. The antitrypanosomal activity of A. rosaeodora essential oil and linalool was observed at high concentrations against epimatigote forms (inhibitory concentration for 50% of parasites (IC50): 150.5 ± 1.08 and 198.6 ± 1.12 µg/mL, respectively), and even higher against intracellular amastigotes of T. cruzi (IC50: 911.6 ± 1.15 and 249.6 ± 1.18 µg/mL, respectively). Both A. rosaeodora essential oil and linalool did not exhibit a cytotoxic effect in BALB/c peritoneal macrophages, and both reduced nitrite levels in unstimulated cells revealing a potential effect in NO production. These data revealed the pharmacological potential of A. rosaeodora essential oil and linalool, encouraging further studies.

Vernonia polysphaera Baker: Anti-inflammatory activity in vivo and inhibitory effect in LPS-stimulated RAW 264.7 cells.

Species of the Vernonia genius are widely distributed across the world. In traditional communities, they are commonly used in popular medicine for the treatment of inflammatory diseases. The objective of the present study was to evaluate the anti-inflammatory activity of Vernonia polysphaera Baker hydroalcoholic extract. A λ-carrageenan-induced paw edema and peritonitis model was established in BALB/c mice. The in vitro activity of the extract was measured on LPS-stimulated RAW 264.7 cells. There was no toxic effect on mice or on the cells treated with the extract. Animals treated with V. polysphaera extract demonstrated inhibition of paw edema in comparison with the untreated animals at all the analyzed doses. In peritonitis, treatment with the extract at a dose of 500 mg/kg resulted in a lower total leukocyte count in the peritoneal fluid and blood and lower levels of IL-1ß, IL-6, TNF-α and PGE-2 than the control group. Cells treated with 50 and 100 µg/mL of the extract exhibited lower levels of nitrite and pro-inflammatory cytokine production and lower COX-2, NF-κB expression. The V. polysphaera extract demonstrated an anti-inflammatory effect, interfering with cell migration, reducing pro-inflammatory cytokine levels and COX-2 expression and consequent interference with PGE-2, as well as inhibiting NF-κB transcription.

Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa Essential Oils: Chemical Composition, Antimicrobial and Antileishmanial Activity.

The resistance mechanisms of bacteria and protozoans have evidenced the need of discover new compounds with potential pharmaceutical activity against pathogenic microorganisms. Medicinal plants have been for centuries a promising alternative as sources of new drugs. The objective of this work was to evaluate the chemical composition, antimicrobial and antileishmanial activities of Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa essential oils. Chemical analysis was performed by gas chromatography-mass spectrometry. Antimicrobial activity was performed by disk diffusion and minimum inhibitory concentration (MIC) test. Antileishmanial activity was performed against antipromastigote and intracellular amastigote of Leishmania amazonensis. Cytotoxic and nitrite production were realized in BALB/c peritoneal macrophages. The major compounds of the essential oils were cinnamic aldehyde (46.30%) in C. zeylanicum, cis-p-menth-2-en-1-ol (33.88%) and linalyl acetate (13.90%) in O. vulgare, and turmerone (55.43%) in C. longa. The MIC showed significant antimicrobial activity of C. longa essential oil against S. aureus (83.3 ± 14.43 µg/mL). Antipromastigote activity showed IC50 values >500 µg/mL to C. zeylanicum, 308.4 ± 1.402 µg/mL to O. vulgare, and 405.5 ± 1.119 µg/mL to C. longa essential oil. Activity against intracellular amastigote of L. amazonensis showed IC50 of 63.3 ± 1.369 µg/mL and cytotoxic was not observed, resulting in selectivity index higher than 15.79 to parasite. C. longa essential oil decreased nitrite production in peritoneal macrophages, but not in Leishmania-infected cells. The chemical composition of the three essential oils is directly associated to its potential biological action, as the antimicrobial activity. C. longa presented a potent antileishmanial activity against promastigote and intracellular amastigote of L. amazonensis, although this activity is not linked to nitric oxide, since C. longa essential oil inhibits its production.

Carapa guianensis Aublet (Andiroba) Seed Oil: Chemical Composition and Antileishmanial Activity of Limonoid-Rich Fractions.

Leishmaniasis is a complex of diseases caused by protozoa of the genus Leishmania and affects millions of people around the world. Several species of plants are used by traditional communities for the treatment of this disease, among which is Carapa guianensis Aubl. (Meliaceae), popularly known as andiroba. The objective of the present work was to conduct a chemical study of C. guianensis seed oil and its limonoid-rich fractions, with the aim of identifying its secondary metabolites, particularly the limonoids, in addition to investigating its anti-Leishmania potential. The chemical analyses of the C. guianensis seed oil and fractions were obtained by electrospray ionization mass spectrometry (ESI-MS). The cytotoxic activity was tested against peritoneal macrophages, and antileishmanial activity was evaluated against promastigotes and intracellular amastigotes of Leishmania amazonensis. All the C. guianensis seed oil samples analyzed exhibited the same pattern of fatty acids, while the limonoids 7-deacetoxy-7-hydroxygedunin, deacetyldihydrogedunin, deoxygedunin, andirobin, gedunin, 11ß-hydroxygedunin, 17-glycolyldeoxygedunin, 6α-acetoxygedunin, and 6α,11ß-diacetoxygedunin were identified in the limonoid-rich fractions of the oil. The C. guianensis seed oil did not exhibit antileishmanial activity, and cytotoxicity was higher than 1000 µg/mL. Three limonoid-rich oil fractions demonstrated activity against promastigotes (IC50 of 10.53±0.050, 25.3±0.057, and 56.9±0.043µg/mL) and intracellular amastigotes (IC50 of 27.31±0.091, 78.42±0.086, and 352.2±0.145 µg/mL) of L. amazonensis, as well as cytotoxicity against peritoneal macrophages (CC50 of 78.55±1.406, 139.0±1.523, and 607.7±1.217 µg/mL). The anti-Leishmania activity of the limonoid-rich fractions of C. guianensis can be attributed to the limonoids 11ß-hydroxygedunin and 6α,11ß-diacetoxygedunin detected in the chemical analysis.

In vitro activity of Morinda citrifolia Linn. fruit juice against the axenic amastigote form of Leishmania amazonensis and its hydrogen peroxide induction capacity in BALB/c peritoneal macrophages.

OBJECTIVE: The current treatment of leishmaniasis induces strong side effects and increasing numbers of cases of resistance to reference drugs have been reported. The discovery of the therapeutic properties of active substances in plant extracts represents an interesting field of research into a more efficient treatment against leishmaniasis. Morinda citrifolia, commonly known as noni, has demonstrated promising results as antileishmanial and immunomodulator. Thus, the aim of this work was to evaluate activity against axenic amastigote and hydrogen peroxide induction capacity by M. citrifolia fruit juice. RESULTS: Phytochemical screening identified anthraquinones, flavonoids, alkaloids, terpenoids, steroids, saponins, coumarins, phenolic compounds, tannins, anthocyanidins and chalcones. Noni juice exhibited dose-dependent activity and an IC50 of 240.1 µg/mL for axenic amastigotes. An absence of endotoxins was observed at the concentrations analyzed, while no cytotoxic effects were identified. Noni juice induced hydrogen peroxide production in BALB/c peritoneal macrophages but not in macrophages infected with Leishmania amazonensis. M. citrifolia fruit juice exhibited antileishmanial activity against L. amazonensis axenic amastigotes and activated macrophages by hydrogen peroxide induction, asserting its potential for further research into new forms of leishmaniasis treatment.

Main lesions in the central nervous system of dogs due to Leishmania infantum infection.

BACKGROUND: Canine visceral leishmaniasis (CVL) is endemic in São Luís Maranhão/Brazil and it leads a varied clinical picture, including neurological signs. RESULTS: Histopathological evaluation showed that 14 dogs exhibited pathological alterations in at least one of the analyzed areas. Of these, mononuclear inflammatory reaction was the most frequent, although other lesions, such as hemorrhage, chromatolysis and gliosis were also observed. The presence of L. infantum amastigotes was confirmed in eight dogs, identified in four regions: telencephalon, hippocampus, thalamus and caudal colliculus, but only one presented neurological signs. Polymerase chain reaction results detected the DNA of the parasite in 11 samples from seven dogs. The positive areas were the telencephalon, thalamus, hippocampus, cerebellum, caudal and rostral colliculus. CONCLUSION: These results reveal that during canine visceral leishmaniasis, the central nervous system may display some alterations, without necessarily exhibiting clinical neurological manifestations. In addition, the L. infantum parasite has the ability to cross the blood brain barrier and penetrate the central nervous system.

One Plant, Many Uses: A Review of the Pharmacological Applications of Morinda citrifolia.

Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.

Morinda citrifolia Linn. fruit (Noni) juice induces an increase in NO production and death of Leishmania amazonensis amastigotes in peritoneal macrophages from BALB/c.

Leishmaniasis is a complex disease that is considered a serious public health problem. Due to the absence of an effective vaccine and debilitating chemotherapy better therapies are urgently needed. This situation has stimulated the search for alternative treatments such as the use of herbal medicines. Several studies conducted with Morinda citrifolia Linn. have shown various biological activities such as antitumor, immunomodulation and antileishmanial activity, however its mechanisms of action are still unknown. This study aimed to analyze the activity of M. citrifolia fruit juice against Leishmania amazonensis and its action on peritoneal macrophages from BALB/c infected with L. amazonensis. Activity against the promastigote forms showed IC50 at 275.3 µg/mL. Transmission electron microscopy was used to evaluate the ultrastructural alterations in the promastigotes treated with the juice and the results showed cytoplasmic vacuolization, lipid inclusion and increased activity of exocytosis. The juice treatment presented an IC50 at 208.4 µg/mL against intracellular amastigotes and led to an increased nitrite production in infected and non-infected macrophages. When macrophages were pre-treated with iNOS inhibitors, aminoguanidine or 1400W, the intracellular amastigotes increased, demonstrating the important role of NO production in M. citrifolia fruit activity. In conclusion, our results reveal that treatment with M. citrifolia fruit juice can increase NO production in peritoneal macrophages and this ability has an important role in the killing of L. amazonensis intracellular amastigotes.

Ultrastructural Changes and Death of Leishmania infantum Promastigotes Induced by Morinda citrifolia Linn. Fruit (Noni) Juice Treatment.

The search for new treatments against leishmaniasis has increased due to high frequency of drug resistance registered in endemics areas, side effects, and complications caused by coinfection with HIV. Morinda citrifolia Linn., commonly known as Noni, has a rich chemical composition and various therapeutic effects have been described in the literature. Studies have shown the leishmanicidal activity of M. citrifolia; however, its action on the parasite has not yet been elucidated. In this work, we analyzed leishmanicidal activity and ultrastructural changes in Leishmania infantum promastigotes caused by M. citrifolia fruit juice treatment. M. citrifolia fruit extract showed a yield of 6.31% and high performance liquid chromatography identified phenolic and aromatic compounds as the major constituents. IC50 values were 260.5 µg/mL for promastigotes and 201.3 µg/mL for intracellular amastigotes of L. infantum treated with M. citrifolia. Cytotoxicity assay with J774.G8 macrophages showed that M. citrifolia fruit juice was not toxic up to 2 mg/mL. Transmission electron microscopy showed cytoplasmic vacuolization, lipid inclusion, increased exocytosis activity, and autophagosome-like vesicles in L. infantum promastigotes treated with M. citrifolia fruit juice. M. citrifolia fruit juice was active against L. infantum in the in vitro model used here causing ultrastructural changes and has a future potential for treatment against leishmaniasis.

Leishmanicidal, cytotoxicity and wound healing potential of Arrabidaea chica Verlot.

BACKGROUND: Leishmaniasis includes a wide complex of diseases that affect humans and other mammals, and can range from a mild cutaneous form to a severe visceral type. The safety of the standard treatment using pentavalent antimony is a concern due to its toxic effects. The search for alternative, effective and less toxic treatments has led to the testing of natural products. The present study aimed to evaluate the cytotoxic, leishmanicidal and healing potential of Arrabidaea chica. METHODS: The crude ethanolic extract, as well as the chloroform, methanol and ethyl acetate fractions of A. chica were prepared and phytochemical analysis was performed. Cytotoxic evaluation was carried out through MTT colorimetric assay, and the 50% cellular cytotoxicity was determined. After that, the effect of the extract and fractions against Leishmania amazonensis promastigotes, at intervals of 24, 48 and 72 h, was analyzed, and 50% inhibitory concentration was determined. The healing effect of the plant was also tested in surgical lesions in Swiss mice skin. RESULTS: Phytochemical screening showed that the crude extracts contained flavonoids, tannins, anthocyanidins and chalcones. The leishmanicidal potential of A. chica produced satisfactory results in concentrations of between 60 and 155.9 µg/mL. Cytotoxic assay revealed a 50% reduction in viable cells at a concentration of 189.9 µg/mL. The healing results indicated that the treated group exhibited more pronounced signs of lesion resolution in the early period, but this pattern did not persist throughout the treatment. CONCLUSIONS: The results of the present study demonstrate that A. chica has cytotoxic and leishmanicidal potential but its healing effect must be better studied.

In Vitro Antileishmanial Activity of Essential Oil of Vanillosmopsis arborea (Asteraceae) Baker.

The search for new immunopharmacological chemical agents to treat various diseases caused by bacteria, fungi, and protozoa, such as leishmaniasis, for example, has led to the exploration of potential products from plant species and their main active ingredients. Antimonial drugs are the current treatment for leishmaniasis. These drugs cause major side effects and frequent discontinuation of treatment. In this study, we evaluated the in vitro leishmanicidal activity of essential oil of Vanillosmopsis arborea (VAEO) and its major compound α -bisabolol against Leishmania amazonensis. The essential oil and α -bisabolol showed activity against promastigotes (IC50 7.35 and 4.95 µ g/mL resp.) and intracellular amastigotes (IC50 12.58 and 10.70 µ g/mL, resp.). Neither product showed any cytotoxicity on treated macrophages. The ultrastructural analysis of promastigotes incubated with VAEO or α -bisabolol at 30 µ g/mL, showed morphological changes with the accumulation of vesicles electrodense lipid inclusions. The results give evidence that both VAEO and α -bisabolol have potential as new therapeutic agents against leishmaniasis.