lignans and Schistosomiasis-mansoni

Schistosomiasis is a tropical parasitic disease, in which the major clinical manifestation includes hepatosplenomegaly, portal hypertension, and organs fibrosis. Clinically, treatment of schistosomiasis involves the use of praziquantel (PZQ) and supportive care, which does not improve the patient's outcome as liver injuries persist. Here we show the beneficial effects of using PZQ in combination with Schisandrin B (Sch B). Concomitant treatment with PZQ and Sch B resulted in a significant improvement of hepatosplenomegaly and fibrosis, compared with single-agent treatment. We also demonstrated that PZQ-Sch B treatment ameliorates injuries in the lungs and intestine better than the sole use of PZQ or Sch B. In addition, PZQ-Sch B treatment improves the survival of S. mansoni-infected mice, and the treatment combination yields better therapeutic outcomes, as indicated by a partial improvement in neurological function. These results were accompanied by a reduction in neurological injuries. Collectively, we suggest that PZQ-Sch B concomitant therapy may be useful to alleviate schistosomiasis-associated liver injuries and prevent systemic complications.

Topics: Animals; Anthelmintics; Cyclooctanes; Lignans; Mice; Polycyclic Compounds; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively.

Topics: Animals; Caproates; Lactones; Lignans; Mice; Nanoparticles; Polyesters; Schistosoma mansoni; Schistosomiasis mansoni; Schistosomicides

Schistosomiasis, a parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, especially in developing countries. Despite the significant economic and public health consequences, only one drug is currently available for treatment of schistosomiasis, praziquantel. Thus, there is an urgent demand for new anthelmintic agents. Based on our continuous studies involving the chemical prospection of floristic biodiversity aiming to discover new bioactive compounds, this work reports the in vitro antiparasitic activity against Schistosoma mansoni adult worms of neolignans threo-austrobailignan-6 and verrucosin, both isolated from Saururus cernuus L. (Saururaceae). These neolignans showed a significant in vitro schistosomicidal activity, with EC

Topics: Animals; Humans; Lignans; Saururaceae; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni

Schistosomiasis is a widespread human parasitic disease currently affecting over 200 million people, particularly in poor communities. Chemotherapy for schistosomiasis relies exclusively on praziquantel (PZQ). Previous studies have shown that licarin A (LIC-A), a dihydrobenzofuran neolignan, exhibited in vitro antiparasitic activity against Schistosoma mansoni adult worms. This study aimed to investigate the potential of LIC-A, isolated as main metabolite from leaves of Nectandra oppositifolia Nees & Mart. (Lauraceae), as an antischistosomal agent orally active in schistosomiasis animal model. PZQ was used as a reference compound. As result, LIC-A showed, at a single dose of 400 mg/kg, to be able to partially cure infected mice (worm burden reductions of ~50%). Parasite eggs, that are responsible for a variety of pathologies and transmission of schistosomiasis, were also moderately inhibited by LIC-A (egg burden reductions of ~50%-60%). Furthermore, it was observed that LIC-A achieved a slight reduction of hepatomegaly and splenomegaly. Collectively, although LIC-A was partially active when administered orally, these results give support for the antiparasitic potential LIC-A as lead compound for novel antischistosomal agent.

Topics: Animals; Lauraceae; Lignans; Mice; Parasite Egg Count; Schistosoma mansoni; Schistosomiasis mansoni

Schistosomiasis is second only to malaria as the most devastating parasitic disease in the world. It is caused by the helminths Schistosoma mansoni (S. mansoni), S. haematobium, or S. japonicum. Typically, patients with schistosomiasis suffer from symptoms of liver fibrosis and hepatosplenomegaly. Currently, patients were treated with praziquantel. Although praziquantel effectively kills the worm, it cannot prevent re-infection or resolve liver fibrosis. Also, current treatment options are not ample to completely cure liver fibrosis and splenic damages. Moreover, resistance of praziquantel has been reported in vivo and in vitro studies. Therefore, finding new effective treatment agents is urgently needed. Schisandrin B (Sch B) of Schisandra chinensis has been shown to protect against different liver injuries including fatty liver disease, hepatotoxicity, fibrosis, and hepatoma. We herein investigate the potential of using Sch B to treat S. mansoni-induced liver fibrosis. Results from the present study demonstrate that Sch B is beneficial in treating S. mansoni-induced liver fibrosis and splenic damages, through inhibition of inflammasome activation and apoptosis; and aside from that regulates host immune responses. Besides, Sch B treatment damages male adult worm in the mice, consequently helps to reduce egg production and lessen the parasite burden.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cyclooctanes; Inflammasomes; Lignans; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Polycyclic Compounds; RAW 264.7 Cells; Schistosoma mansoni; Schistosomiasis mansoni; Spleen

Theoretical models for exploring the antischistosomal activity of a dataset of 18 synthetic neolignans are built using the multivariate image analysis applied to structure-activity relationships (MIA-SAR) approach. The obtained models were validated using the accuracy (Acc) in leave-one-out cross-validation, external validation and Y-randomization procedures, yielding correct classification superior to 80%, 70% and 60%, respectively. Additionally, a comparison was made of the models obtained from binary (black and white) and coloured images; the colours (pixel values) were selected to correspond to chemical properties. It was observed that the models obtained from coloured images with pixel values corresponding to electronegativity (known as the aug-MIA-SAR(colour) approach) generally yielded superior statistical parameters compared with those obtained from binary images (MIA-SAR) and randomly coloured images (atoms are coloured according to their type) with atomic sizes corresponding to Van der Waals radius (aug-MIA-SAR), respectively. Mechanistic interpretation of the influence of different substituents on the antischistosomal activity revealed that methoxy substituents in the R1 (or R2) and R5 positions of the neolignan scaffold are indispensable for the antischistosomal activity. The obtained results provide knowledge of the possible structural modifications to yield novel neolignan compounds with antischistosomal activity.

Topics: Animals; Computer Simulation; Lignans; Models, Biological; Multivariate Analysis; Quantitative Structure-Activity Relationship; Rats; Rodent Diseases; Schistosoma mansoni; Schistosomiasis mansoni; Schistosomicides

The chemotherapy of schistosomiasis relies on the use of praziquantel. However, concerns over drug resistance have encouraged the search for new drug leads. This paper is the first report on the in vitro and in vivo activity of (-)-6,6'-dinitrohinokinin (DNK) against Schistosoma mansoni. In vitro, the lethal concentrations for 50% of parasites (LC50) of DNK against adult worms were 103.9±3.6 and 102.5±4.8μM at 24 and 72h, respectively. Scanning electron microscopy images showed extensive tegumental alterations such as peeling and smaller numbers of tubercles in the spine of adult worms. DNK also elicited high mortality of schistosomula, with LC50 values of 57.4±2.3, 32.5±0.9, and 20.4±1.2μM at 24, 48, and 72h, respectively. DNK displayed moderate activity against the juvenile liver parasite, with an LC50 value of 179.5±2.3 μM at 72h. This compound reduced the total number of eggs by over 83%, and it affected the development of eggs produced by adult worms. The selectivity index showed that at 24h, DNK was 8.5 and 15.4 times more toxic to the adult worms and schistosomula than to Chinese hamster lung fibroblast cells, respectively. Treatment of infected mice with DNK moderately decreased worm burden (33.8-52.3%), egg production (40.7-60.0%), and spleen and liver weights. Together, our results indicated that DNK presents moderate in vitro and in vivo activities against S. mansoni, and it might therefore be interesting to explore the structure-activity relationship of the antischistosomal activity of this compound.

Topics: 4-Butyrolactone; Animals; Anthelmintics; Benzodioxoles; Cricetinae; Cricetulus; Female; Fibroblasts; In Vitro Techniques; Lignans; Liver; Lung; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Schistosoma mansoni; Schistosomiasis mansoni