Baccharis dracunculifolia DC (Asteraceae) Root Extract and Its Triterpene Baccharis Oxide Display Topical Anti-Inflammatory Effects on Different Mice Ear Edema Models.

B. dracunculifolia is popularly used to treat skin diseases. This work aimed to evaluate the topical anti-inflammatory properties of B. dracunculifolia root extract (BdR) and its major compound baccharis oxide (BOx) on mice ear edema models. BdR was analyzed by GC-MS, and BOx was isolated by chromatographic fractionation. Topical anti-inflammatory activities were determined by using the croton oil, capsaicin, histamine, and phenol-induced mouse ear edema models. N-acetyl-ß-D- glucosaminidase (NAG) and myeloperoxidase (MPO) activities, as well as NO dosage and histopathological analyses, were also evaluated. Phytochemical analysis of BdR showed BOx as one of the major constituents. BdR and BOx (both at 0.1, 0.5, and 1.0 mg/ear) significantly reduced croton oil, histamine, and phenol-induced ear edema, while only BOx was effective in reducing capsaicin-induced edema. MPO and NAG activities, as well as NO production, were significantly inhibited by BdR and BOx. Histopathological analysis confirmed the topical anti-inflammatory properties of BdR and BOx. Our findings showed that BdR and BOx demonstrated significant topical anti-inflammatory effects in mouse ear edema induced by different agents, suggesting their possible application on skin inflammatory diseases.

Antiparasitic properties of 4-nerolidylcatechol from Pothomorphe umbellata (L.) Miq. (Piperaceae) in vitro and in mice models with either prepatent or patent Schistosoma mansoni infections.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis. However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species. AIMS OF THIS STUDY: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis. MATERIALS AND METHODS: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound. RESULTS: PuE (EC50: 18.7 µg/mL) and PuH (EC50: 9.2 µg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC50 of 2.9 µM (0.91 µg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%. CONCLUSIONS: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.

Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells.

BACKGROUND: Breast Cancer (BC) is the most common cancer in women worldwide and, although 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients' survival is comprised by resistance to endocrine therapy. Brazilian flora, especially the Amazon biome, is one of the richest global sources of native species with potentially bioactive compounds. Arrabidaea chica is a plant native to the Amazon that has been used in the treatment of different diseases. However, its action on BC remains unclear. METHODS: Herein the biological effects of the chloroform extract of A. chica (CEAC) were evaluated on BC cells and in in vivo model. After confirmation of CEAC antioxidant capacity, cells were treated with CEAC and Tam, alone and with CEAC+Tam. The cell viability was evaluated by MTT and hormone receptor transcripts levels were assessed (ESR1, ESR2 and AR). Finally, anticarcinogenicity of CEAC was recorded in Drosophila melanogaster through Epithelial Tumor Test (ETT). RESULTS: The study confirmed the antioxidant activity of CEAC. CEAC was selective for MCF-7, downregulating ESR2 and AR transcripts and upregulating ESR2 expression. The modulatory effects of CEAC on ERs did not differ between cells treated with Tam and with CEAC+Tam. Interestingly, previous treatment with CEAC, followed by treatment with Tam promoted a significant decrease in cell viability. The extract also presented anticarcinogenic effect in in vivo assay. CONCLUSION: The bioassays on breast tumor cells demonstrated the antiproliferative activity of the extract, which modulated the expression of hormone receptors and sensitized luminal tumor cells to Tam. These results suggest that CEAC could be a complementary treatment for BC.

Assessment of the In Vitro Antischistosomal Activities of the Extracts and Compounds from Solidago Microglossa DC (Asteraceae) and Aristolochia Cymbifera Mart. & Zucc. (Aristolochiaceae).

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is a neglected tropical disease that afflicts over 230 million people worldwide. Currently, treatment is achieved with only one drug, praziquantel (PZQ). In this regard, the roots of Solidago microglossa (Asteraceae) and Aristolochia cymbifera (Aristolochiaceae) are popularly used as anthelmintic. Despite their medicinal use against helminthiasis, such as schistosomiasis, A. cymbifera, and S. microglossa have not been evaluated against S. mansoni. Then, in this work, the in vitro antischistosomal activity of the crude extracts of A. cymbifera (Ac) and S. microglossa (Sm) and their isolated compounds were investigated against S. mansoni adult worms. Sm (200 µg/mL) and Ac (100-200 µg/mL) were lethal to all male and female worms at the 24 h incubation. In addition, Sm (10-50 µg/mL) and Ac (10 µg/mL) caused significant reduction in the parasite's movements, showing no significant cytotoxicity to Vero cells at the same range of schistosomicidal concentrations. Confocal laser scanning microscopy revealed that Sm and Ac caused tegumental damages and reduced the numbers of tubercles of male schistosomes. Chromatographic fractionation of Sm leads to isolation of bauerenol, α-amirin, and spinasterol, while populifolic acid, cubebin, 2-oxopopulifolic acid methyl ester, and 2-oxopopulifolic acid were isolated from Ac. At concentrations of 25-100 µM, bauerenol, α-amirin, spinasterol, populifolic acid, and cubebin showed significant impact on motor activity of S. mansoni. 2-oxopopulifolic acid methyl ester and 2-oxopopulifolic acid caused 100% mortality and decreased the motor activity of adult schistosomes at 100 µM. This study has reported, for the first time, the in vitro antischistosomal effects of S. microglossa and A. cymbifera extracts, also showing promising compounds against adult schistosomes.

Copaiba oil suppresses inflammation in asthmatic lungs of BALB/c mice induced with ovalbumin.

Asthma is a chronic inflammatory disease that represents high hospitalizations and deaths in world. Copaiba oil (CO) is popularly used for relieving asthma symptoms and has already been shown to be effective in many inflammation models. This study aimed to investigate the immunomodulatory relationship of CO in ovalbumin (OVA)-induced allergic asthma. The composition of CO sample analyzed by GC and GC-MS and the toxicity test was performed in mice at doses of 50 or 100 mg/kg (by gavage). After, the experimental model of allergic asthma was induced with OVA and mice were orally treated with CO in two pre-established doses. The inflammatory infiltrate was evaluated in bronchoalveolar lavage fluid (BALF), while cytokines (IL-4, IL-5, IL-17, IFN-γ, TNF-α), IgE antibody and nitric oxide (NO) production was evaluated in BALF and lung homogenate (LH) of mice, together with the histology and histomorphometry of the lung tissue. CO significantly attenuated the number of inflammatory cells in BALF, suppressing NO production and reducing the response mediated by TH2 and TH17 (T helper) cells in both BALF and LH. Histopathological and histomorphometric analysis confirmed that CO significantly reduced the numbers of inflammatory infiltrate in the lung tissue, including in the parenchyma area. Our results indicate that CO has an effective in vivo antiasthmatic effect.

In Vitro Schistosomicidal Activity of the Alkaloid-Rich Fraction from Ruta graveolens L. (Rutaceae) and Its Characterization by UPLC-QTOF-MS.

Schistosomiasis is a neglected tropical disease that affects million people worldwide, mostly in developing countries. Ruta graveolens (Rutaceae) is a plant used in folk medicine to treat several diseases, including parasitic infections. In this study, we reported the in vitro schistosomicidal activity of the R. graveolens extract (Rg) and its active fraction (Rg-FAE). Also, the characterization of Rg-FAE by UPLC-ESI-QTOF-MS analysis and its in vitro antileishmanial activity against Leishmania braziliensis were also performed. In vitro schistosomicidal assays were assessed against adult worms of S. mansoni, while cell viability against peritoneal macrophages was measured by MTT assay. Rg (100 µg/mL) exhibited noticeable schistosomicidal activity, causing 100% mortality and decreasing motor activity of all adult male and female schistosomes, but with low activity against L. braziliensis. After chromatographic fractionation of Rg, fraction Rg-FAE was obtained, showing high activity against adult schistosomes. UPLC-ESI-QTOF-MS analysis of Rg-FAE revealed the presence of eleven alkaloids and one furanocoumarin. No significant antileishmanial activity was found for Rg, while Rg-FAE exhibited activity against L. braziliensis promastigotes. We demonstrated, for the first time, that the R. graveolens extract (Rg) and its alkaloid-rich fraction (Rg-FAE) are active against adult worms of S. mansoni, with no significant cytotoxicity on macrophages. Our findings open the route to further antiparasitic studies with the active fraction of R. graveolens and its identified compounds, especially alkaloids.

In vitro schistosomicidal and antiviral activities of Arctium lappa L. (Asteraceae) against Schistosoma mansoni and Herpes simplex virus-1.

Schistosomiasis and herpes diseases represent serious issues to the healthcare systems, infecting a large number of people worldwide, mainly in developing countries. Arctium lappa L. (Asteraceae), known as "bardana" and "burdock", is a medicinal plant popularly used for several purposes, including as antiseptic. In this study, we evaluated the in vitro schistosomicidal and antiherpes activities of the crude extract of A. lappa, which have not yet been described. Fruits of A. lappa L. were extracted by maceration with ethanol: H2O (96:4 v/v) in order to obtain the hydroalcoholic extract of A. lappa (AL). In vitro schistosomicidal assays were assessed against adult worms of Schistosoma mansoni, while the in vitro antiviral activity of AL was evaluated on replication of Herpes simplex virus type-1 (HSV-1). Cell viability was measured by MTT assay, using Vero cells and chemical composition of AL was determined by qualitative UPLC-ESI-QTOF-MS analysis. UPLC-ESI-QTOF-MS analysis of AL revealed the presence of dibenzylbutyrolactone lignans, such as arctiin and arctigenin. Results showed that AL was not cytotoxic to Vero cells even when tested at 400µg/mL. qPCR results indicated a significant viral load decreased for all tested concentrations of AL (400, 50, and 3.125µg/mL), which showed similar antiviral effect to acyclovir (50µg/mL) when tested at 400µg/mL. Also, AL (400, 200, and 100µg/mL) caused 100% mortality and significantly reduction on motor activity of all adult worms of S. mansoni. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after treatment with AL. This report provides the first evidence for the in vitro schistosomicidal and antiherpes activities of AL, opening the route to further schistosomicidal and antiviral studies with AL and their compounds, especially lignans.

Antiparasitic activity of nerolidol in a mouse model of schistosomiasis.

Schistosomiasis is a major public health problem worldwide, especially in poor communities. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new antischistosomal drugs. Nerolidol is a sesquiterpene present as an essential oil in several plants that has been approved by the FDA. This study evaluated the in vivo antischistosomal activity of nerolidol in a mouse model of schistosomiasis infected with either adult or juvenile stages of Schistosoma mansoni. A single dose of nerolidol (100, 200 or 400 mg/kg) administered orally to mice infected with adult schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest nerolidol dose (400 mg/kg) caused significant reduction in a total worm burden of 70.06% (P < 0.001). Additionally, the technique of quantitative and qualitative oograms showed that a single 400 mg/kg nerolidol dose achieved an immature egg reduction of 84.6% (P < 0.001). In faecal samples, the Kato-Katz method also revealed a reduction of 75.2% in eggs/g at a dose of 400 mg/kg (P < 0.001). Furthermore, scanning electron microscopy revealed that nerolidol-mediated worm killing was associated with tegumental damage. In contrast to activity against adult S. mansoni infection, oral treatment with nerolidol 400 mg/kg had low efficacy in mice harbouring juvenile schistosomes. Since nerolidol is already in use globally as a food additive and has a proven safety record, evaluation of this natural compound's potential for treatment of schistosomiasis could be entirely cost effective in the near future.

ß-Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. ß-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40µM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40µM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.

Parthenolide Modulates Immune Response in Cells from C57BL/6 Mice Induced with Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis is a chronic inflammatory and autoimmune disease of the central nervous system that affects more than 2.5 million people worldwide. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. Parthenolide, a natural sesquiterpene lactone found in Tanacetum parthenium L., is known for its strong anti-inflammatory activity. Herein, we have investigated the in vitro immunomodulatory effects of parthenolide on cytokine production and nitric oxide in cultured cells from myelin oligodendrocyte glycoprotein 35-55 amino acid peptide mice. Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide, and parthenolide was isolated from T. parthenium. Splenocytes and peritoneal cells were obtained from experimental autoimmune encephalomyelitis-induced mice and incubated with parthenolide (1, 5, and 20 µM). After in vitro treatment with parthenolide, supernatants were collected, and nitric oxide and cytokines were measured. The results suggested that parthenolide may regulate the activity of Th17 and Th1 cells, mainly by decreasing IL-17, TNF-α, and interferon gamma production. This modulation may be related to the lower levels of IL-12p40 and IL-6 after treatment with parthenolide. It was shown, for the first time, that parthenolide presents in vitro immunomodulatory effects on inflammatory mediators produced by cells from experimental autoimmune encephalomyelitis-induced mice.

Flavonoids and Sesquiterpene Lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni Worms.

Human schistosomiasis, caused by trematode worms of the genus Schistosoma, is one of the most significant neglected tropical diseases, affecting more than 200 million individuals worldwide and praziquantel is the only available drug to treat this disease. Artemisia absinthium L. and Tanacetum parthenium L. are species popularly used as anthelmintics. We investigated the in vitro schistosomicidal activity of crude extracts of A. absinthium (AA) and T. parthenium (TP) and their isolated compounds. AA and TP, at 200 µg/mL, were active, causing 100% mortality of all adult worms. Chromatographic fractionation of AA leads to isolation of artemetin and hydroxypelenolide, while santin, apigenin, and parthenolide were isolated from TP. Artemetin, hydroxypelenolide, santin, and apigenin, at 100 µM, were inactive against adult worms. Parthenolide (12.5 to 100 µM) caused 100% mortality, tegumental alterations, and reduction of motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms. This report provides the first evidence for the in vitro activity of parthenolide against adult worms of S. mansoni, opening the route to further schistosomicidal studies with this compound.

Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae).

Schistosomiasis is one of the world's major public health problems, and its treatment is widely dependent on praziquantel (PZQ), the only available drug. Schistosoma mansoni ATP diphosphohydrolases are ecto-enzymes localized on the external tegumental surface of S. mansoni and considered an important target for action of new drugs. In this work, the in vitro schistosomicidal activity of the crude extract of Glycyrrhiza inflata roots (GI) and its isolated compounds echinatin, licoflavone A and licoflavone B were evaluated against S. mansoni adult worms. Results showed that GI (200 µg/mL) was active against adult schistosomes, causing 100% mortality after 24 h of incubation. Chromatographic fractionation of GI led to isolation of echinatin, licoflavone A and licoflavone B. Licoflavone B (25-100 µM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms, without affecting mammalian Vero cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after incubation with licoflavone B. Licoflavone B also showed high S. mansoni ATPase (IC50 of 23.78 µM) and ADPase (IC50 of 31.50 µM) inhibitory activities. Docking studies predicted different interactions between licoflavone B and S. mansoni ATPDase 1, corroborating with the in vitro inhibitory activity. This report demonstrated the first evidence for the schistosomicidal activity of licoflavone B and suggests that its mechanism of action involve the inhibition of S. mansoni ATP diphosphohydrolases.

Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase.

BACKGROUND: Schistosomiasis is one of the world's major public health problems, and praziquantel (PZQ) is the only available drug to treat this neglected disease with an urgent demand for new drugs. Recent studies indicated that extracts from Piper aduncum L. (Piperaceae) are active against adult worms of Schistosoma mansoni, the major etiological agent of human schistosomiasis. PURPOSE: We investigated the in vitro schistosomicidal activity of cardamonin, a chalcone isolated from the crude extract of P. aduncum. Also, this present work describes, for the first time, the S. mansoni ATP diphosphohydrolase inhibitory activity of cardamonin, as well as, its molecular docking with S. mansoni ATPDase1, in order to investigate its mode of inhibition. METHODS: In vitro schistosomicidal assays and confocal laser scanning microscopy were used to evaluate the effects of cardamonin on adult schistosomes. Cell viability was measured by MTT assay, and the S. mansoni ATPase activity was determined spectrophotometrically. Identification of the cardamonin binding site and its interactions on S. mansoni ATPDase1 were made by molecular docking experiments. RESULTS: A bioguided fractionation of the crude extract of P. aduncum was carried out, leading to identification of cardamonin as the active compound, along with pinocembrin and uvangoletin. Cardamonin (25, 50, and 100 µM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner. Cardamonin also inhibited S. mansoni ATP diphosphohydrolase (IC50 of 23.54 µM). Molecular docking studies revealed that cardamonin interacts with the Nucleotide-Binding of SmATPDase 1. The nature of SmATPDase 1-cardamonin interactions is mainly hydrophobic and hydrogen bonding. CONCLUSION: This report provides evidence for the in vitro schistosomicidal activity of cardamonin and demonstrated, for the first time, that this chalcone is highly effective in inhibiting S. mansoni ATP diphosphohydrolase, opening the route to further studies of chalcones as prototypes for new S. mansoni ATP diphosphohydrolase inhibitors.

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 µg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity.

Copaiba oil suppresses inflammatory cytokines in splenocytes of C57Bl/6 mice induced with experimental autoimmune encephalomyelitis (EAE).

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35-55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

Protective effects of Baccharis dracunculifolia leaves extract against carbon tetrachloride- and acetaminophen-induced hepatotoxicity in experimental animals.

In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75±0.43 µg/mL), and high total phenolic (142.90±0.77 mg GAE/g) and flavonoid (51.47±0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.

Anthelmintic activity of crude extract and essential oil of Tanacetum vulgare (Asteraceae) against adult worms of Schistosoma mansoni.

Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus Schistosoma, affects more than 200 million people worldwide, and its control is dependent on a single drug, praziquantel. Tanacetum vulgare (Asteraceae) is used in folk medicine as a vermifuge. This study aimed to investigate the in vitro schistosomicidal activity of the crude extract (TV) and the essential oil (TV-EO) from the aerial parts of T. vulgare. TV-EO was obtained by hydrodistillation and analyzed by GC/MS, which allowed the identification of ß-thujone (84.13%) as the major constituent. TV and TV-EO, at 200 µg/mL, decreased motor activity and caused 100% mortality of all adult worms. At 100 and 50 µg/mL, only TV caused death of all adult worms, while TV-EO was inactive. TV (200 µg/mL) was also able to reduce viability and decrease production of developed eggs. Confocal laser scanning microscopy showed morphological alterations in the tegument of the S. mansoni surface after incubation with TV (50 and 100 µg/mL). Quantitative analysis on the schistosomes tegument showed that TV caused changes in the numbers of tubercles of S. mansoni male worms in a dose-dependent manner. The findings suggest that T. vulgare is a potential source of schistosomicidal compounds.

Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis.

OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. Herein, we have investigated the immunomodulatory effect of licochalcone A (LicoA) on NO, H2 O2 , tumour necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ) and IL-17 production in cultured cells from EAE mice. METHODS: EAE was induced in C57Bl/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55 ). LicoA was isolated from the roots of Glycyrrhiza inflata. Splenocytes were obtained from EAE mice and incubated with LicoA (4, 20 and 40 µm). Peritoneal cells were obtained from EAE mice treated with LicoA (15 and 30 mg/kg/day. p.o.). H2 O2 , NO, IFN-γ, TNF-α and IL-17 production was determined in the presence or absence of concanavalin (ConA) or MOG35-55 stimulation. KEY FINDINGS: LicoA (40 µm) inhibited H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in splenocytes spontaneously or after both ConA and MOG35-55 stimulation. LicoA (30 mg/kg/day) reduced clinical score and severity of EAE mice, and inhibited TNF-α, IFN-γ and IL-17 production in peritoneal cells. CONCLUSIONS: LicoA possesses immunomodulatory effects on H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in cells from EAE mice. It is suggested that LicoA acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

In vitro schistosomicidal activity of balsaminol F and karavilagenin C.

Five cucurbitane-type triterpenes (1-5), previously isolated from the African medicinal plant Momordica balsamina, along with five ester derivatives (6-10) of karavilagenin C (2), were evaluated for their potential schistosomicidal activity against Schistosoma mansoni adult worms. The natural compounds were isolated from the ethyl acetate-soluble fraction of the methanol extract of the aerial parts of M. balsamina. In a preliminary study, a significant schistosomicidal activity was observed for both the crude methanol extract and the ethyl acetate fraction. The compounds responsible for the activity were found to be balsaminol F (1) and karavilagenin C (2) with LC50 values of 14.7 ± 1.5 and 28.9 ± 1.8 µM, respectively, after 24 h of incubation (positive control praziquantel, LC50 = 1.2 ± 0.1 µM). Both compounds (1, 2), at 10-50 µM, induced significant reductions in the motor activity of the worms and significantly decreased the egg production. Furthermore, they were able (at 10-100 µM) to separate the adult worm pairs into male and female after 24 h. Compounds 3-5, bearing a sugar moiety as a substituent, and the acylated derivatives of karavilagenin C (6-10) were inactive, suggesting that the presence of free hydroxyl groups in the tetracyclic skeleton might be important for the activity. A correlation between activity and the molecular volume/weight of compounds was also found.

Fungal transformation and schistosomicidal effects of pimaradienoic acid.

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 µM. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.