Bisbenzylisoquinoline Alkaloids of Cissampelos Sympodialis With in Vitro Antiviral Activity Against Zika Virus.

In search of new antiviral compounds against Zika virus we conducted a bioassay-guided fractionation of bisbenzyilisoquinoline alkaloids isolated from Cissampelos sympodialis (Menispermaceae), a medicinal plant species endemic to Brazil. Six subfractions were obtained from a tertiary alkaloidal fraction of the rhizomes (TAFrz) using preparative high-performance liquid chromatography. All the subfractions were tested against Zika virus-infected Vero cells as the cellular model to evaluate cytotoxicity and antiviral effective concentrations. The results showed that three of the six TAFrz subfractions tested were active. The most active ones were the subfraction 6 (that consisted of the alkaloids methylwarifteine and warifteine present as a mixture at a ratio of 8.8:1.2 respectively) and the subfraction 5, that was later identified as warifteine, the major tertiary alkaloid of this species. Warifteine was able to significantly reduce virus titer in Zika virus-infected Vero cells with an IC50 of 2.2 µg/ml and this effect was selective (selectivity index, SI = 68.3). Subfraction 6 had an IC50 = 3.5 µg/ml and was more cytotoxic than pure warifteine, with SI = 6.14. Fraction 5 and fraction 6 were more potent in decreasing the viral titer of Zika virus-infected Vero cells than 6-methylmercaptopurine riboside (IC50 = 24.5 µg/ml and SI = 11.9), a mercaptopurine riboside with ZIKV antiviral activity used as a positive control. Our data demonstrate that alkaloids of the bisbenzylisoquinoline type may be explored as new antiviral agents or as an useful pharmacophore for investigating ZIKV antiviral activity.

Bisbenzylisoquinoline alkaloids of Cissampelos sympodialis with antiviral activity against dengue virus.

A number of bisbenzyilisoquinoline alkaloids have been previously isolated from Cissampelos sympodialis (Menispermaceae). The tertiary alkaloid fraction of the rhizomes (TAFrz) was prepared and the major alkaloid warifteine was isolated. Five TAFrz subfractions in addition to warifteine were tested against Dengue virus (DENV). We then used an epithelial (Vero) cell line to evaluate the cytotoxicity and effective concentrations of the samples against DENV. All TAFrz subfractions were active, but subfraction 6 (a mixture of the alkaloids methylwarifteine and warifteine) in particular showed a promising antiviral effect against DENV-2 with an IC50 of 2.00 µg/mL and a selectivity index (SI) of 10.74. Warifteine was the second most active sample and had an IC50 of 8.13 µg/mL and SI = 10.94. The antiviral activity of the samples compared favorably with that of 6-methylmercaptopurine riboside (IC50 = 7.31 µg/mL and SI = 11.8). These results suggest that bisbenzylisoquinoline alkaloids may prove interesting leading antiviral compounds.

Warifteine and methylwarifteine inhibited the type 2 immune response on combined allergic rhinitis and asthma syndrome (CARAS) experimental model through NF-кB pathway.

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of TH2 cytokine gens.

Ethanol extract of Cissampelos sympodialis ameliorates lung tissue damage in streptozotocin-induced diabetic rats

Diabetes Mellitus (DM) is a metabolic syndrome characterized by hyperglycemia. Chronic complications affect a number of organs, including the lungs. Cissampelos sympodialis Eichl (Menispermaceae) is a plant used to treat respiratory diseases. The aim of this study was to evaluate the effect of Cissampelos sympodialis extract (CSE) in lungs of diabetic rats. We used 30 Wistar rats divided into three groups: control group (CG), diabetic group (DG) and diabetic Cissampelos sympodialis treatment group (DTG). Diabetes was induced by streptozotocin (40 mg/kg i.v.). The CSE (400 mg/kg, po) was administered daily, during four weeks, beginning one week after the onset of DM. The treatment with CSE was not able to reduce blood glucose levels after streptozotocin injection. However, it was able to decrease cholesterol and triglycerides and prevent damage on pancreatic islets morphology. Additionally, morphological alterations such as alveolar septa loss, inflammatory infiltrate and fibrosis were seen in lung tissue of rats with DM, and treatment with CSE apparently reversed these histopathological findings. Thus, CSE treatment reduced the lipid profile and restored the lung architecture of diabetic animals by a mechanism independent of glycemia and which might be associated with the reduction of the damage on the pancreatic islets.

Antibiotic-Potentiating Activity of Phanostenine Isolated from Cissampelos sympodialis Eichler.

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance-modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub-inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm). The evaluation of aminoglycoside antibiotic resistance-modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.

Milonine, an Alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae) Inhibits Histamine Release of Activated Mast Cells.

Milonine is an alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae), a plant used in the northeast of Brazil to treat allergies such as asthma, rhinitis, and other conditions. Previously, several alkaloids were isolated from its roots and leaves with pharmacological properties in asthma and acute inflammation models. Therefore, the aim of this study was to evaluate the milonine effect on mast cells degranulation in vivo and in vitro. Swiss mice (n = 8) were used in models of paw edema induced by carrageenan, compound 48/80, or histamine. One hour before challenge, the animals were treated with milonine (at different doses) or standard drugs and, at different time points, the edema formation was measured. In addition, other different methods, such as anaphylactic shock reaction and scratching behavior models both induced by compound 48/80, a mast cell degranulator, were used to assess milonine effect histamine release in vivo. Moreover, milonine effect on mast cell degranulation in vitro was also carried out. Firstly, it was observed that milonine significantly decreased the carrageenan edema formation only at the beginning of the reaction (i.e., up to 2 h after challenge). Furthermore, this alkaloid decreased the edema induced by compound 48/80, maintained the paw tissue integrity, without modulating histamine-induced paw edema. In anaphylactic shock reaction, milonine increased the time of animal survival when compared with compound 48/80 group. Milonine also significantly decreased the scratching behavior induced by compound 48/80 with decreasing of mast cell degranulation in vitro. Therefore, these data indicated that milonine presents anti-allergic properties by decreasing mast cell degranulation rather than acting on histamine effect.

Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1ß Production.

Milonine is a morphinandienone alkaloid from Cissampelos sympodialis Eichl (Menispermaceae), a plant used in Brazil to treat inflammatory disorders. In this study, we evaluated the anti-inflammatory and analgesic activity of milonine (MIL) by using classical experimental models of inflammation and nociception. The results showed that MIL reduced the paw edema formation induced by lipopolysaccharide, prostaglandin E2, and bradykinin, without interfering with the serotonin-induced edema. With respect to the nociception experiments, MIL decreased the exudate into the peritoneum induced by acetic acid, maintaining the tissue morphology. The alkaloid was able to inhibit the peritonitis induced by carrageenan, decreasing mainly the migration of polymorphonuclear cells, without altering the mononuclear cell number, and reduced the levels of TNF-α and IL-1ß in the peritoneum. In addition, MIL was able to decrease the frequency of abdominal writhing induced by acetic acid but did not increase the latency time of the animals in the hot plate test. MIL significantly reduced the nociceptive behavior of paw licking induced by formalin only at the second phase of the test. In conclusion, we demonstrate that milonine has anti-inflammatory and anti-nociceptive activities by inhibiting mediators essential for the inflammatory process.

In silico and In vivo Toxicological Evaluation of Cissampelos Sympodialis Secondary Metabolites in Rattus Norvegicus.

Cissampelos sympodialis is a plant in northeastern Brazil used by the populace for treating respiratory diseases. Several studies have shown that ethanol leaf extracts have immunomodulatory and anti-inflammatory activities. Infusions are widely used, popular, and an ancient technique in traditional medicine, using hot water alone as the means of extraction. This study aimed to investigate acute toxicological potential of leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg to Rattus norvegicus, combined with an in silico study of 117 alkaloids present in the Cissampelos genus; five (5) of which were determined to have high toxicity (21, 8, 93, 32 and 88), and five (5) having both low toxicity (57, 77, 28, 25 and 67) and low liver metabolism. The in vivo toxicological evaluation showed that male water consumption decreased, and the feed intake decreased in both sexes. Yet, the figures as to change in weight gain of the animals were not statistically sufficient. As for the biochemical parameters, there was an increase in urea, and decreases in uric acid and AST in males. In females, there was a decrease in albumin and globulin which consequently leads to a total protein decrease. Despite biochemical changes suggestive of kidney damage, the histological sections revealed no kidney or liver changes. The results therefore indicate that despite presenting alkaloids which may be toxic, the genus Cissampelos, or leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg present low toxicity.

Medicinal plants used to treat snakebite in Central America: Review and assessment of scientific evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Every year between 1.2 and 5.5 million people worldwide are victims of snakebites, with about 400,000 left permanently injured. In Central America an estimated 5500 snakebite cases are reported by health centres, but this is likely to be an underestimate due to unreported cases in rural regions. The aim of this study is to review the medicinal plants used traditionally to treat snakebites in seven Central American countries: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama. MATERIALS AND METHODS: A literature search was performed on published primary data on medicinal plants of Central America and those specifically pertaining to use against snakebites. Plant use reports for traditional snakebite remedies identified in primary sources were extracted and entered in a database, with data analysed in terms of the most frequent numbers of use reports. The scientific evidence that might support the local uses of the most frequently reported species was also examined. RESULTS: A total of 260 independent plant use reports were recorded in the 34 sources included in this review, encompassing 208 species used to treat snakebite in Central America. Only nine species were reported in at least three studies: Cissampelos pareira L., Piper amalago L., Aristolochia trilobata L., Sansevieria hyacinthoides (L.) Druce, Strychnos panamensis Seem., Dorstenia contrajerva L., Scoparia dulcis L., Hamelia patens Jacq., and Simaba cedron Planch. Genera with the highest number of species used to treat snakebite were Piper, Aristolochia, Hamelia, Ipomoea, Passiflora and Peperomia. The extent of the scientific evidence available to understand any pharmacological basis for their use against snakebites varied between different plant species. CONCLUSION: At least 208 plant species are traditionally used to treat snakebite in Central America but there is a lack of clinical research to evaluate their efficacy and safety. Available pharmacological data suggest different plant species may target different symptoms of snakebites, such as pain or anxiety, although more studies are needed to further evaluate the scientific basis for their use.

Secondary Metabolites from Cissampelos, A Possible Source for New Leads with Anti-Inflammatory Activity.

The genus Cissampelos comprises of 21 species which have a wide global distribution and various pharmacological activities such as analgesic and antipyretic, antiinflammatory, anti-allergic, bronchodilation, and immunomodulation among others. Several compounds, mainly alkaloids with differing biological activities have been isolated from this genus. We will highlight antipyretic activities, anti-inflammatory, antiallergic, bronchodilatory, and immunomodulatory activities. In addition, we applied ligand-based-virtual screening associated with structure-based-virtual screening of a small dataset of 63 secondary metabolites from the Cissampelos genus of an in-house data bank, in order to select compounds with potential anti-inflammatory activity. Affinities were observed for hayatine (26), isochondrondendrine (30), pelosine (52), sepeerine (59), and warifteine (63) to the inhibiting enzymes MAPK p38 alpha, PKC beta, PKC theta and PKC zeta. The cissampeloflavone compound (8) alone showed no potential inhibitory activity for PKC zeta, or affinity for the PKC alpha. The compounds can be used as starting points for further studies on structures with potential anti-inflammatory activity.

Cissampelos sympodialis has anti-viral effect inhibiting dengue non-structural viral protein-1 and pro-inflammatory mediators

ABSTRACT Dengue is the most important viral infection transmitted among humans by arthropod-borne. There are currently no vaccines or specific therapeutical treatment. Therefore, immunomodulatory compounds from plants have been widely examined for their antiviral effects. Cissampelos sympodialis Eichler, Menispermaceae, has scientifically proven to present immunomodulatory activities. Here we assessed the antiviral activity of leaf hydroalcoholic extract, warifteine or methylwarifteine from C. sympodialis in an in vitro dengue virus infection model. The results demonstrated that leaf hydroalcoholic extract or warifteine/methylwarifteine treatment did not reduce dengue virus-Ag+ hepatocyte (Huh-7 cell) rates in present experimental conditions. However, we assessed the potential antiviral effect of leaf hydroalcoholic extract or warifteine/methylwarifteine on dengue virus-infection by the production of inflammatory molecules, TNF-α, MIF, IL-8 and PGE2. Dengue virus infection enhanced TNF-α, MIF, IL-8 and PGE2 production in infected Huh-7 cells and leaf hydroalcoholic extract but not warifteine/methylwarifteine treatments, significantly reduced these molecules in infected cells. In dengue virus-infected Huh-7 cells, non-structural protein-1 is produced and leaf hydroalcoholic extract significantly inhibited it independently of alkaloids. Our findings imply that leaf hydroalcoholic extract may attenuate dengue virus infection in Huh-7 cells by inhibiting the enhanced of pro-inflammatory mediators and non-structural protein-1 production induce by dengue virus independently of warifteine/methywarifteine its major compound.

Clinical safety evaluation of a tea containing Cissampelos sympodialis in healthy volunteers

ABSTRACTCissampelos sympodialis Eichler, Menispermaceae, is widely used by Indian tribes and folk medicine to treat various inflammatory disorders, including asthma. Clinical toxicological trials were made with the tea of C. sympodialis, a medicinal plant. The study took place at Lauro Wanderley Hospital/UFPB-PB, where seventeen healthy volunteers were chosen, among those six men and eleven women who orally ingested, during four weeks uninterruptedly, 150 ml of the tea, once a day. Before the first ingestion and after the last one, the participants were subjected to clinical and laboratorial tests for their overall conditions in order to analyze the toxicity of the plant. The results demonstrated that the volunteers neither experience clinical nor laboratorial alterations, as well as no significant adverse effects, apart from little change detected in their hematological tests. Nevertheless, none demonstrated any pathological conditions, just alterations of the normal human being physiology. Therefore, it is concluded that these data complement that obtained during pre-clinical studies and confirm a low toxicity of this plant.

A new species of Cissampelos (Menispermaceae) from Bolivia and Paraguay.

The new species Cissampelos arenicola M. Nee & R. Ortiz, from the Bolivian and Paraguayan Chaco is described, its affinities are discussed, and its preliminary conservation status is evaluated. The species is at present known from 13 collections from sand dunes or dry forests. Cissampelos arenicola is distinguished from all other American species in the genus by its ovate- to subreniform-trilobed leaves, 8-locular synandria, and relatively large, and scarcely ornamented endocarps. The most common perianth condition in the pistillate flowers of Cissampelos is one sepal and one antesepalous petal, and while these may vary in number, they are always found adaxial to the carpel, and although the southern African taxon called Cissampelos capensis, whose generic position is uncertain, superficially resembles Cissampelos arenicola, its sepals and petals are consistently lateral to the carpel and not adaxial.

Managing murine food allergy with Cissampelos sympodialis Eichl (Menispermaceae) and its alkaloids.

Food allergy is a severe human disease with imminent risk of life. Cissampelos sympodialis (Menispermaceae) is a native Brazilian plant used in Brazilian folk medicine for the treatment of respiratory allergies. In this study the experimental model of food allergy induced by ovalbumin (OVA) was used to determine whether the alcoholic extract of the plant (AFL) and its alkaloids match a therapeutic approach for this disease. Animal weight, diarrhea, OVA-specific IgE levels, inflammatory cell and cytokine profiles, mucus production and proportion of T cells on the mesenteric lymph node (MLN) were evaluated. Warifteine (W) or methyl-warifteine (MW) alkaloids slightly improve diarrhea score independently of AFL and all treatments decreased the OVA-specific IgE levels. Stimulated mesenteric lymph node (MLN) cells in the presence of the alkaloids diminished the IL-12p70 levels independently of IFN-γ or IL-13 secretion. The alkaloids increased the number of Treg cells on MLN and reduced the number of eosinophils and mast cells as well as mucus production in the gut. Therefore, the alkaloids modulate the immune response in food allergy by increasing regulatory T cells in MLN independently of Th1 or Th2 profiles.

Studies with Cissampelos sympodialis: the search towards the scientific validation of a traditional Brazilian medicine used for the treatment of asthma

The paper is a review of the literature on the ethnobotanical, chemical and pharmacological aspects of the species Cissampelos sympodialis Eichler, Menispermaceae, in order to assess its potential for the treatment of asthma. The aqueous infusion from the leaves of this Brazilian plant is used in the traditional medicine for the treatment of respiratory conditions, including colds, bronchitis and asthma. A multidisciplinary approach has led to the elucidation of the main chemical biomarkers and of the mechanism of action of the extract and its isolated constituents in animal models of inflammation and asthma. A comprehensive review of the literature on the species and its related chemical constituents was conducted using Pubmed, Web of Sciences, Lilacs, SciFinder, as well as conference proceedings. Retrieved literature data demonstrates that the aqueous fraction of the ethanolic extract from the leaves exerts an immunomodulatory activity in different animal models of asthma. This include an increase in the levels of anti-inflammatory cytokines, a decrease in the production of antigen-specific immunoglobulin, a decrease in mucus production and deposition in the airways, and a direct bronchodilator activity. These preclinical results clearly demonstrate the potential of this species for the treatment of asthma and points to the need for well-designed clinical trials to finally validate the traditional use of this herbal medicine.

Analgesic effect of hydroalcoholic extract of Cissampelos sympodialis Eichl leaves / Efecto analgésico del extracto hidroalcoholico de las hojas de Cissampelos sympodialis Eichl

Cissampelos sympodialis Eichl is a species of the family Meniespermaceae known as “Milona”, which extracts showed low toxicity and several pharmacological activities as anti-inflammatory, anti-allergic or anti-depressive. In the present study two classic analgesia models in mice were used to evaluate the hydroalcoholic extract of C. sympodialis leaves (HAECs) at doses of 50, 100 and 200 mg/kg, i.p. In the test of writhing by acetic acid HAECs- treatment induced a significant reduction in the number of abdominal contortions in a dose-dependent manner (p <0,05). In the formalin test, HAECs-200 mg/kg induced a significant inhibition of the second phase (15-30 minutes) (p <0,05). Results suggest that the HAECs presented outlying antinociceptive peripheral activity probably related with the alleged anti-inflammatory proprieties of extracts of this plant.

Existen varios estudios que evidencian que la Cissampelos sympodialis posee atividad anti-inflamatoria, antialérgica, antidepresiva y de baja toxicidad. Este estudio evaluó los efectos de la administración intraperitoneal, del extracto hidroalcohólico de hojas de cissampelos sympodialis (EHACS), en las dosis de 50, 100 y 200 mg/Kg, en modelos de analgesia en camumdongos. En el modelo de las contracciones inducidas por el ácido acético (0,85 por ciento) fue encontrada una reducción en el número de contracciones proporcional a las dosis usadas (p<0,05). En el test de la reacción al formaldeído las dosis utilizadas no presentaron efecto significante en la primera fase del test (0-5 minutos). Sin embargo, la dosis de 200mg/Kg presentó una significante inhibición en la segunda fase (15 – 30 minutos) del test (p<0,05). Los resultados mostraron que el EHACS presentó una actividad antinociceptiva periférica probablemente relacionada con la alegada actividad anti-inflamatoria.

Leaf epidermal characteristics of Cissampelos L. (Menispermaceae) species from Northeastern Brazil.

The morphological similarities among the species of Cissampelos are remarkable and the difficult to distinguish them as well. This article presents a comparative anatomical study of the leaves of common Northeastern Brazilian species of Cissampelos, carried out using light and scanning electron microscopy. The leaf epidermal was studied to obtain data on epidermal characteristics and to evaluate their taxonomic significance. As results, some micromorphological characters on the leaf epidermal like the cuticular waxes, the presence of papillae in epidermis and nonglandular trichomes, the anticlinal walls epidermal cells, the distribution, density and type of trichomes, and also the type and distribution of epicuticular wax proved to be the most useful characteristics to distinguish the species in taxonomic studies.

A Ação do Cissampelos Sympodialis Eichl: uma Perspectiva para o Tratamento da Asma / The Action of Cissampelos Sympodialis Eich: a Perspective in the Asthma’s Treatment

A espécie Cissampelos sympodialis (Menispermaceae) éutilizada na medicina popular e indígena para o tratamento dedesordens inflamatórias, incluindo a asma. O objetivo dopresente estudo foi revisar a literatura sobre os estudoscom a espécie Cissampelos sympodialis (Menispermaceae).A pesquisa bibliográfica deste trabalho foi realizada nosbancos de dados eletrônicos: Pubmed, Bireme, Portal Capes-Periódicos, Scielo. A asma tem como principal característicafisiopatogênica a inflamação e o broncoespasmo. Estudosfitoquímicos com espécies vegetais utilizadas no tratamentodessa patologia têm sido realizados com o objetivo deencontrar novas perspectivas terapêuticas que apresentemmenos efeitos adversos em relação aos tratamentos atuais.Estudos comprovaram que a planta é capaz de inibir tanto oinfluxo de eosinófilos quanto a produção de leucotrienoscisteínicos desencadeados pelo processo alérgico da asma.Com isso, de acordo com a literatura revisada, os estudospré-clínicos com as folhas de C. sympodialis viabilizamensaios clínicos que possam comprovar a segurança e aeficácia do C. sympodialis em seres humanos, tornandoprovável a liberação do registro como um fitomedicamento epossibilitando uma ampliação das opções terapêuticas depacientes portadores de patologias crônicas, como a asma,que cursam com broncoespasmo e inflamação...

The species Cissampelos sympodialis (Menispermaceae)is used in the popular and indigenous medicine for the treatmentof inflammatory disorders, including the asthma. The aim ofthe present study was to revise the literature about thespecies Cissampelos sympodialis (Menispermaceae). Thebibliographical research of this study was accomplished inthe electronic databases: Pubmed, Bireme, Portal Capes-Periódicos, Scielo. The asthma has as main physiopathogeniccharacteristic the inflammation and the bronchoconstriction.Phytochemical studies with vegetable species used in thetreatment of that pathology have been accomplished withthe objective of finding new therapeutic perspectives thatpresent less adverse effects in relation to the currenttreatments. Studies showed that the plant is able to inhibitboth the eosinophilic influx and the production of cysteinylleukotrienes unchained by the allergic process of the asthma.Therefore, in agreement with the revised literature, preclinicalstudies with the leaves of C. sympodialis make possible theconduction of clinical rehearsals that can prove safety andeffectiveness of the C. sympodialis in human beings, makingprobable the liberation of its registration as a phytomedicationas well as enlarging the therapeutic options of patientsaffected by chronic pathologies, like asthma, that coursewith bronchoconstriction and inflammation...

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents / Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodialis Eichler em roedores

A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modificou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.

The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF) of Cissampelos sympodialis Eichler (Menispermaceae) on two animal models of depression: a) forced swim test and b) reserpine test. Treatment of mice with TTAF (12.5 mg/kg) reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.

Estudo farmacobotânico de folhas de Cissampelos sympodialis Eichl. (Menispermaceae) / Pharmacobotanical study of the leaves of Cissampelos sympodialis Eichl., (Menispermaceae)

Cissampelos sympodialis Eichl. é uma espécie empregada na medicina popular do Nordeste do Brasil, cujos estudos farmacológicos são bastantes promissores no tratamento de doenças do trato respiratório. Neste trabalho realizou-se um estudo farmacobotânico de suas folhas, com o objetivo de elaborar morfodiagnoses macroscópicas e microscópicas que auxiliem sua caracterização. Realizaram-se secções paradérmicas (lâminas) e transversais de folhas (lâmina e pecíolo), posteriormente clarificadas e coradas com safranina e safrablue, respectivamente, e observadas ao microscópio óptico. Cissampelos sympodialis caracteriza-se pelas folhas peltadas, com as lâminas deltóides, nervação actinodroma-broquidodroma, e o pecíolo espessado nas extremidades. A epiderme é hipoestomática, com células de paredes anticlinais ondeadas na face adaxial e irregularmente sinuosa a ondeada na abaxial. O mesofilo é dorsiventral e o sistema vascular do pecíolo é formado de um anel de feixes isolados colaterais. Esparsos idioblastos de cristais prismáticos foram observados no parênquima peciolar. A morfologia foliar em conjunto com a anatomia da epiderme são caracteres distintivos para Cissampelos sympodialis.

Cissampelos sympodialis Eichl. is a plant species used in popular medicine in Northeast of Brazil, whose pharmacological studies are very promising in the treatment of diseases of the respiratory tract. In this work, a pharmacobotanical study of the leaves was performed with the objective to elaborate a macroscopical and microscopical morphodiagnosis to support its characterization. The microscopical morphodiagnosis was done with paradermic sections on the blades and cross sections on the blades and petioles followed by clarification and coloring with safranin and safrablue, respectively, and examined by optical microscopy. Cissampelos sympodialis has peltate leaves with deltoid blades with actinodromous -brochidodromous nervation, and the petioles are swollen at the extremities. The epidermis is hipostomatic with anticlinal walls of epidermal cells waved in the upper surface and irregularly sinuate to wavy on the lower surface. The mesophyll is dorsiventral and the vascular system of the petiole is formed by a ring of 6-7 free collateral bundles. Sparce idioblasts of prismatic crystals in parenchyma of petiole were observed. The morphology of the leaves and the anatomy of epidermis are distinguishing characters of Cissampelos sympodialis.