Assessment of pharmacological activities of Lygodium microphyllum Cav. leaves in the management of pain, inflammation, pyrexia, diarrhea, and helminths: In vivo, in vitro and in silico approaches.

Lygodium microphyllum Cav. (Family: Lygodiaceae) is a perennial, snake fern and an invasive weed in Florida and also known as old world climbing fern. This study is intended to evaluate the antipyretic, analgesic, anti-inflammatory, antidiarrheal and anthelmintic activity of methanol extract of Lygodium microphyllum Cav. leaves (MELM) by in vivo, in vitro and in silico approaches. In addition, Biovia, PyRx autoDock Vina, UCSF Chimera have been applied to investigate the docking study in order to evaluate the binding interaction and an online tool was used to explore the ADME/T properties of selected bioactive compounds. In acetic acid induced writhing study, MELM inhibited 44.28% and 56.61% of writhes at 200 and 400 (mg/kg) respectively compared to standard drug Diclofenac-Na (10 mg/kg) (74.42% inhibition). In anti-inflammatory experiment by formalin triggered licking method, MELM caused significant (p < 0.05) inhibition of licking in both early phase (42.97%, 63.30%) and late phase (43.35%, 63.03%) at the doses of 200 and 400 mg/kg respectively, whereas reference drug Ibuprofen inhibited paw licking 77.18% in early phase and 76.86% in late phase. MELM also showed promising antipyretic potential where the maximum reduction of fever was produced by MELM 400 mg/kg whose fever lowering capacity is close to the prescribe drug Indomethacin 4 mg/kg, i.p. In Castor oil triggered diarrhea method, MELM delayed the onset time of diarrhea, continuous persistence of wet feces, and decreased the weight of wet feces remarkably. Defection inhibition was achieved 27.56% and 51.72%, for MELM 200 and at 400 (mg/kg) respectively while loperamide 2 (mg/kg) yields 55.17% inhibition of the diarrheal defecation. In anthelmintic bioassay, MELM took 5.83 ± 0.83 and 41.67 ± 1.78 min respectively for paralyzing and death compared to standard drug albendazole; (paralysis time 4.00 ± 0.73 min and death time 31,00 ± 1.71 min). Isoeleutherol, isoquercetin and quercetin were found prominent in molecular docking study and ADME/T analysis verified their drug likeliness. The research validates the moderate analgesic, anti-inflammatory, and remarkable antipyretic, antidiarrheal, anthelmintic activities of the plant extract which can be used an alternative source of novel therapeutics.

Intoxicação crônica por Pteridium arachnoideum em bovinos no nordeste do estado do Rio Grande do Sul, Brasil / Chronic poisoning by bracken fern (Pteridium arachnoideum) in cattle in the northeast region of the state of Rio Grande do Sul, Brazil

Pteridium spp., popularmente conhecida como samambaia, comumente encontrada em solos ácidos, arenosos e de baixa fertilidade. A intoxicação ocorre quando os animais passam por privação alimentar ou ingestão acidental. O objetivo deste estudo é relatar a ocorrência de dois casos de intoxicação crônica por samambaia em bovinos na região nordeste do estado do Rio Grande do Sul, Brasil. Ambos os casos cursaram com sinais clínicos de disfagia, halitose, salivação e presença de tumores na orofaringe. A baixa oferta e qualidade de forragem, superlotação das áreas de pasto, manejo inadequado das pastagens, a presença de Pteridium arachnoideum, os sinais clínicos em conjunto com os achados de necropsia e o exame histopatológico confirmaram o diagnóstico de intoxicação crônica.

Pteridium spp., commonly known as fern, is commonly found in acidic, sandy and low fertility soils. Poisoning occurs when animals go through food deprivation or accidental ingestion. The objective of this study is to report the occurrence of two cases of chronic intoxication in cattle in the northeast region of the state of Rio Grande do Sul, Brazil. Both cases had clinical signs of dysphagia, halitosis, salivation and the presence of tumors in the oropharynx. Low supply and quality of forage, overcrowding of pasture areas, inadequate pasture management, presence of Pteridium arachnoideum, clinical signs, necropsy and histopathological of lesions confirmed the diagnosis of chronic intoxication.

Toxicological assessment of Diplazium esculentum on the reproductive functions of male Swiss albino mouse.

CONTEXT: Diplazium esculentum, a commonly consumed seasonal vegetable, has been reported to have some pathological effects in some animals. But, its effect on the male reproductive function has not yet been studied. OBJECTIVE: To investigate the effects of boiled D. esculentum (BDE), the form which human consumes, on male reproductive functions of Swiss albino mice. MATERIALS AND METHODS: Male (120 in no.) and female (80 in no.) Swiss albino mice (6-8 weeks of age) were fed orally with 80, 160 and 320 mg/kg bw of BDE within a span of 180 d. After the treatment, body weight, absolute- and relative-testis weight, relative-weight of other organs, their biochemical parameters, hypo-osmotic swelling test (HOST) of spermatozoa, testis histology and fertility and fecundity tests were performed to justify the toxic effects of D. esculentum on male reproductive functions. RESULTS: Significant dose- and time-dependent decreases were observed in body weight, absolute- and relative-testis weight, relative-weights of other organs and their biochemical parameters, percentage of live spermatozoa and percentage of fertility and fecundity in BDE fed mice. Significant decreases were observed in diameter, perimeter and area of the seminiferous tubules of mice treated for 180 d. The percentage of empty seminiferous tubules was increased significantly in BDE treated mice when compared to the controls. DISCUSSION AND CONCLUSION: These results suggest that the intake of D. esculentum, even after cooking, may induce infertility by altering the male reproductive function, and therefore, should be evaluated further as a potential antifertility agent.

Citotocixidade e atividade antiparasitária de Lygodium venustum SW / Cytotoxic and antiparasitic activity of Lygodium venustum SW

. Doenças parasitárias infecciosas como leishmaniose e doença de Chagas tem se difundido nas últimas décadas a locais onde antes não se observava sua ocorrência. São consideradas negligenciadas por assolarem países pobres e serem marginalizadas farmacologicamente. O tratamento não apresenta muitas opções de fármacos e estes demonstram relevante toxicidade contribuindo para o aparecimento de diversos efeitos colaterais. A pesquisa com produtos naturais tem se mostrado uma interessante alternativa para a procura por novos fármacos. Lygodium venustum é uma samambaia cosmopolita de hábito lianescente encontrada na encosta na Chapada do Araripe, considerada por algumas populações americanas como planta medicinal para o tratamento de dermatoses, infecções, micoses e tricomoníases. Neste estudo foi avaliada sua atividade anti-parasitária contra Leishmania brasiliensis e Trypanosoma cruzi, bem como sua citotoxicidade através de ensaios n vitro. Foram testadas a fração hexânica e o extrato etanólico obtido das folhas de Lygodium venustum em diferentes concentrações. Para os testes in vitro de T. cruzi, foi utilizado o clone CL-B5 e para Leishmania brasiliensis foram utilizadas formas promastigotas. O ensaio de citotoxicidade foi realizado com linhagens de fbroblastos. L. venustum não apresentou atividade antiparasitária clinicamente relevante na forma de extrato etanólico bruto nem como fração hexânica contra Leishmania. A fração hexânica apresentou uma atividade intermediária contra T. cruzi, porém a concentração de efeito moderado possui citotoxicidade máxima tornando-se inviável para aplicação clínica. Entretanto, a citoxicicidade apresentada poderá ser útil em pesquisas sobre atividade antineoplásica em células tumorais.

Infectious and parasitic diseases like leishmaniasis and Chagas disease have spreading recent decades to places not observed before. They are considered neglected by desolating poor countries and marginalized pharmacologically. There are not many options for the treatment and these drugs have shown signifcant toxicity contributing to the appearance of several side effects. Research on natural products has been shown to be an interesting alternative to the search for new drugs. Lygodium venustum is a cosmopolitan fern with latescence habit found on the Chapada do Araripe, considered by some American popula-tions as a medicinal plant for the treatment of skin diseases, infections, fungal infections and trichomoniasis. This study evaluated its antiparasitic activity against Trypanosoma cruzi and Leishmania brasiliensis, as well as its cytotoxicity through trials in vitro. We tested the ethanolic extract and hexane fraction obtained from the leaves of L. venustum at different concentrations. For in vitro tests of T. cruzi, we used the clone CL-B5 and for L. brasiliensis we used promastigotes. The cytotoxicity assay was performed with strains of fbroblasts. L.venustum showed no antiparasitic activity clinically relevant in the form of crude ethanolic extractor as the hexane fraction against Leishmania. The hexane fraction showed an intermediate activity against T.cruzi, but the concentration of moderate effect has maximum cytotoxicity becoming unfeasible for clinical application. However, the cytotoxicity presented may be useful in research on antineoplastic activity in tumor cells.

Bovine papillomavirus type 2 infects the urinary bladder of water buffalo (Bubalus bubalis) and plays a crucial role in bubaline urothelial carcinogenesis.

Bovine papillomavirus type 2 (BPV-2) has been shown to infect and play a role in urinary bladder carcinogenesis of buffaloes grazed on pastures with ferns from the Marmara and Black Sea Regions of Turkey. BPV-2 DNA has been found in both neoplastic and non-neoplastic lesions of the urinary bladder. Furthermore, this virus may be a normal inhabitant of the urinary bladder since BPV-2 DNA has also been detected in clinically normal buffaloes. The viral activation by fern immunosuppressant or carcinogen may trigger the urothelial cell transformation. The E5 oncoprotein was solely detected in urothelial tumours and appeared to be co-localized with the overexpressed and phosphorylated platelet derived growth factor (PDGF) ß receptor in a double-colour immunofluorescence assay. Our results indicate that the E5-PDGF ß receptor interaction also occurs in spontaneous tumours of the bubaline urinary bladder, revealing an additional role of BPV-2 in bladder carcinogenesis of buffaloes.

In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity.

The aim of this study was to evaluate the antitumor potential of Macrothelypteris torresiana by studying in vitro antitumor activity of the protoapigenone, as well as in vivo antitumor activity and acute/subacute oral toxicity of the total flavonoid fraction from the roots of M. torresiana. Considering that the protoapigenone is a main constituent of the total flavonoid fraction and it might play a key role in the antitumor activity of M. torresiana, the MTT assay was used to investigate the in vitro antitumor activity of the protoapigenone. Our study revealed that the protoapigenone of M. torresiana showed significant antitumor activity towards Hep G2, Tca-8113, MCF-7, M5 and K562 with IC(50) values of 2.3, 0.6, 0.8, 0.3 and 0.9 µg/ml, respectively. The antitumor potential of the total flavonoid fraction was evaluated using preparations 1, 2 and 3, which were prepared by total flavonoid fraction directly diluted with sterile saline, dissolved using sodium carboxymethyl cellulose (CMC-Na) and included by hydroxypropyl-ß-cyclodextrin, respectively. These were investigated in vivo using mouse sarcoma S-180 in BALB/c mice after completing tumor inoculation for 24h. Pronounced antitumor activity was observed in the treated groups for preparations 2 and 3, and the high and medium doses in particular showed very high inhibition ratio of tumor growth (>50%). No significant difference was observed when compared to the positive control group (5-fluorouracil). The acute/subacute oral toxicity test was performed, and the results of acute oral toxicity showed that the LD(50) values of preparations 2 and 3 were 2.76 and 0.87 g/kg body wt., respectively. According to the results of the subacute oral toxicity study, the total flavonoid fraction had low toxicity. The overall results of this study suggest that the total flavonoid fraction from the roots of M. torresiana shows significant antitumor activity and represents a potential source of medicine for the treatment of cancer.

Neoplasias do trato alimentar superior de bovinos associadas ao consumo espontâneo de samambaia (Pteridium aquilinum) / Neoplasms of the upper digestive tract of cattle associated with spontaneous ingestion of bracken fern (Pteridium aquilinum)

Foram estudados 30 bovinos com neoplasias no trato alimentar superior (TAS) associadas ao consumo espontâneo de samambaia (Pteridium aquilinum) provenientes de 27 propriedades rurais, sendo 23 no município de Jaguari e quatro em Nova Esperança do Sul, Rio Grande do Sul. A população bovina total das 27 propriedades em que ocorreram os casos era de 1.090 bovinos e havia quantidade abundante de samambaia nas áreas de pastoreio dos animais. Vinte e seis bovinos eram vacas e 4 eram machos castrados. A idade variou de 3 a 13 anos, sendo o maior número de casos entre 7 e 8 anos (46,6 por cento). Os sinais clínicos observados incluíram emagrecimento progressivo, atonia ruminal, tosse, disfagia, regurgitação, halitose, diarréia e timpanismo. Outros sinais clínicos menos freqüentes foram apetite seletivo, dispnéia e salivação. Dois bovinos tiveram morte espontânea e 28 foram submetidos à eutanásia em estágios avançados da doença e necropsiados. Os principais achados macroscópicos e histológicos observados nos 30 bovinos localizavam-se nos mesmos locais do TAS e consistiram de papilomas, papilomas em transformação para carcinomas de células escamosas (CCEs) e CCEs. Metástases de CCEs para linfonodos regionais e outros órgãos (como fígado e pulmões) foram também observadas (18/30). Vinte e nove bovinos tinham papilomas de diversos tamanhos, sendo a quantidade variável entre leve (45 por cento), moderada (38 por cento) e acentuada (17 por cento). Nos papilomas examinados microscopicamente, foram observadas três fases de desenvolvimento: a) fase de inicial de crescimento, b) fase de desenvolvimento, e c) fase de regressão. Em 16 bovinos, observou-se a transformação maligna de papilomas em CCEs. Os CCEs eram únicos (12/30) ou múltiplos (18/30) e variaram quanto ao grau de diferenciação celular entre bem, moderadamente ou pouco diferenciados. Quando a distribuição dos CCEs de maior extensão foi agrupada em regiões cranial (base da língua, faringe/orofaringe, epiglote), média...

Thirty bovine with neoplasms of the upper digestive tract (UDT) associated with spontaneous ingestion of bracken fern (Pteridium aquilinum) were studied. They were from 27 farms, located in the municipalities of Jaguari (23) and Nova Esperança do Sul (4), Rio Grande do Sul, Brazil. The total cattle population in those farms was 1,090 and large amounts of bracken fern were found in the pastures. Twenty-six of the affected cattle were cows and four were castrated males, 3-13 years of age; most of them were 7-8 years old (46,6%). Clinical signs observed in the affected animals were progressive weight loss, absence of ruminal movements, cough, dysphagia, regurgitation, halitosis, diarrhea, and bloat. Less frequent signs were selective appetite, dyspnea, and salivation. Two bovine died and 28 were submitted to euthanasia in advanced stage of disease and necropsied. The main gross and microscopic alterations were found in identical areas of the UDT. They consisted of papillomas, transforming papillomas, and squamous cell carcinomas (SCCs). Metastases of SCCs to regional lymph nodes and other organs, such as liver and lungs, were also observed (18/30). Twenty-nine bovine had papillomas of various sizes in several areas of the UDT. The digestive papillomatosis ranged from mild (45%), to moderate (38%), to severe (17%). Three developing phases were observed microscopically in the examined papillomas: an early growing phase, a developing phase, and a regressing phase. In 16 cases, there was malignant transformation of papillomas into SCCs. The SCCs were solitary (12/30) or multiple (18/30) and were histologically well, moderately, or poorly differentiated. Grouping the distribution of SCCs of larger extension in the UDT into cranial region (base of the tongue, pharynx/oropharynx, and epiglottis), medial region (esophagus), and caudal region (cardia and rumen), the distribution was cranial in 39%, middle in 16%, and caudal in 45% of the cases. By the same grouping...

Evaluación de la toxicidad por administración única del producto QT2B21 en ratas Sprague Dawley / Evaluation of toxicity by the sole administration of the QT2B21 product in Sprague Dawley rats

Se realizó un estudio de toxicidad aguda en ratas Sprague Dawley de ambos sexos mediante la administración oral única del producto QT2B21 obtenido a partir de la especie de helecho Nephrolepis cordifolia, para determinar su toxicidad. Fueron evaluados 3 niveles de dosis: 33,33, 133,32 y 533,28 mg/kg. Se determinaron algunos índices hematológicos sin encontrar efectos tóxicos atribuibles a la administración del producto. Se realizaron los estudios anatomopatológico (por inspección macroscópica) e histopatológico de los principales órganos. La inspección de estos no demostró alteraciones macroscópicas. Según el resultado del estudio histopatológico, sólo fueron observadas diferencias estadísticamente significativas en el porcentaje de peso relativo de los testículos en el grupo tratado con la dosis intermedia con respecto al grupo control. Este efecto no fue dependiente de la dosis. Se concluyó que la administración única por vía oral del producto QT2B21, no produjo alteraciones por toxicidad que pudieran ser atribuidas al mismo. Se consideró este producto como tolerable en ratas Sprague Dawley de ambos sexos en el rango de dosis desde 33,33 hasta 533,28 mg/kg de peso.(AU)

A preliminary study on the carcinogenicity of the common fern Onychium contiguum.

Onychium contiguum (Family Cryptogrammaceae) is a common terrestrial fern in the Himalayas and in many other parts of the world. It is also present on the pastures in areas where grazing animals suffer from bovine urinary bladder cancer. This fern is occasionally grazed by animals and in some areas it is present as a contaminant in grasses stored for winter feeding. Certain species of the genus Onychium are used in folk medicine. Long-term exposure of experimental animals to O. contiguum appeared to cause tumours of the ileum. urinary bladder and mammary glands.