Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides.

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

In vitro activity, ultrastructural analysis and in silico pharmacokinetic properties (ADMET) of thiazole compounds against adult worms of Schistosoma mansoni.

The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 µM against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 µM, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 µM. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 µM) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.

Evaluation of ß-lapachone-methyl-ß-cyclodextrin inclusion complex prepared by spray drying and its application against different developmental stages of Schistosoma mansoni in murine model.

BACKGROUND: ß-lapachone (ß-lap) is a naphthoquinone widely found in species of vegetables. However, its poor aqueous solubility limits its systemic administration and clinical applications in vivo. To overcome this limitation, several studies have been carried out in order to investigate techniques that can enhance the solubility and dissolution rate of ß-lap, such as the use of inclusion complexes with cyclodextrin. PURPOSE: To evaluate the in vivo effect of ß-lap complexed in methyl-ß-cyclodextrin (MßCD) on the evolutionary stages of Schistosoma mansoni in a murine model. METHODS: The development and characterization of the physicochemical properties of the inclusion complex of ß-lap in ß-lap:MßCD was prepared by solubility and dissolution tests, FTIR, DSC, X-RD and SEM. The mice were infected and subsequently treated with ß-lap:MßCD orally with 50 mg/kg/day and 100 mg/kg/day for 5 consecutive days, starting therapy on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms) and 45th (adult worms) days after infection. Control groups were also formed; one infected untreated, treated with MßCD, and the other treated with PZQ. RESULTS: The loss of the crystalline form of ß-lap in the ß-lap:MßCD complex obtained by spray drying was proven through physical-chemical characterization analyses. ß-lap:MßCD caused reduction in the number of worms of the 33.56%, 35.7%, 35.45% and 36.45%, when the dose was at 50 mg/kg, and 65.00%, 60.34%, 52.72% and 65.01%, in the dose 100 mg/kg; when treatment was started in the 1st, 14th, 28th and 45th days after infection, respectively. It was also possible to observe a significant reduction in the number of immature eggs and an increase in the number of ripe and dead eggs and, consequently, a reduction in the damage caused by the egg antigens to the host tissue, where we attributed the reduction in the average diameter of the granulomas to the ß-lap. CONCLUSION: The dissolved content of ß-lap:MßCD by spray drying reached almost 100%, serving for future formulations and delineation of the mechanisms of action of ß-lap against S. mansoni.

Effect of Bauhinia monandra Kurz Leaf Preparations on Embryonic Stages and Adult Snails of Biomphalaria glabrata (Say, 1818), Schistosoma mansoni Cercariae and Toxicity in Artemia salina.

Biomphalaria glabrata snails constitute the main vector of schistosomiasis in Brazil, and Bauhinia monandra Kurz, the leaves of which contain BmoLL lectin with biocidal action, is a plant widely found on continents in which the disease is endemic. This work describes the composition of B. monandra preparations and the effect on embryos and adult snails, their reproduction parameters and hemocytes. We also describe the results of a comet assay after B. glabrata exposure to sublethal concentrations of the preparations. Additionally, the effects of the preparations on S. mansoni cercariae and environmental monitoring with Artemia salina are described. In the chemical evaluation, cinnamic, flavonoid and saponin derivatives were detected in the two preparations assessed, namely the saline extract and the fraction. Both preparations were toxic to embryos in the blastula, gastrula, trochophore, veliger and hippo stages (LC50 of 0.042 and 0.0478; 0.0417 and 0.0419; 0.0897 and 0.1582; 0.3734 and 0.0974; 0.397 and 0.0970 mg/mL, respectively) and to adult snails (LC50 of 6.6 and 0.87 mg/mL, respectively), which were reproductively affected with decreased egg deposition. In blood cell analysis, characteristic cells for apoptosis, micronucleus and binucleation were detected, while for comet analysis, different degrees of nuclear damage were detected. The fraction was able to cause total mortality of the cercariae and did not present environmental toxicity. Therefore, B. monandra preparations are promising in combating schistosomiasis since they can control both the intermediate host and eliminate the infectious agent, besides being safe to the environment.

The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons.

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.

Anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic activities of Plinia cauliflora (Mart.) Kausel (Brazilian grape) epicarp.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known in Brazil as jabuticaba or jaboticaba has been used by Brazilian native populations for medicinal purposes, including those related to inflammatory conditions, such as asthma, diarrhea, disorders in female genitourinary tract, and tonsillitis. Inflammation has emerged as a main factor for the oxidative stress, hyperglycemia, and dyslipidemia present in chronic noncommunicable diseases (NCDs). Such disturbances have been a leading cause of death worldwide for decades, despite significant efforts in developing new therapies. Therefore, strengthening the relevance of ethnobotanic approaches, as P. cauliflora has the potential to become a natural, native, and traditional product to prevent and treat inflammation-associated diseases more effectively for more people. AIM OF THE STUDY: Evaluate anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic properties of hydroethanolic extract of P. cauliflora epicarps (PcE). MATERIALS AND METHODS: Phytochemical compound from the PcE were identified through HPLC-DAD-ESI-MSn analysis. Antioxidant activity was determined by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The anti-inflammatory potential was investigated by carrageenan-induced paw edema and peritonitis in mice. Analgesic effect was assessed, in mice, though hot plate test and acetic acid-induced abdominal writhing. Antidiabetic and hypolipidemic potential were evaluated using alloxan-induced diabetic mice. RESULTS: Tannins, phenolic acids, and their derivatives were the predominant phytochemicals found. Overall, PcE showed different properties related to the treatment of clinical conditions associated with chronic diseases as a potent antioxidant activity, demonstrating a radical scavenging action similar to gallic acid. PcE oral administration also significantly reduced inflammation induced by paw edema and partially blocked leukocyte migration. Moreover, PcE produced peripheral and central analgesic effects, as evaluated in the writhing model and hot plate tests. Treatment with PcE significantly improved glucose levels and lipid markers in diabetic mice. CONCLUSIONS: P. cauliflora fruits are rich sources of secondary metabolites, mainly tannins and phenolic acids with high biological potential, which can effectively contribute to the approach of preventing and controlling chronic NCDs.

Study of genotoxic and cytotoxic effects after acute and chronic exposures to industrial sewage sludge on Biomphalaria glabrata hemocytes.

Industrial development has provided numerous benefits to improve quality of life in modern times, however, it has also led to the development and use of a large number of toxic chemicals which have caused damage to various ecosystems. Consequently, knowledge of techniques and organisms that can be used to monitor, identify and quantify environmental pollutants has become increasingly relevant. Therefore, the objective of this study was to use the mollusk Biomphalaria glabrata to analyze biomarker and biomonitoring parameters of industrial sewage sludge. To perform the tests, concentrations of 50, 100, 150 and 500 mg L-1 of industrial sewage sludge were standardized. All the tests were performed after the animals were exposed to the sludge in acute and chronic forms. Embryos exposure to sludge did not show a significant percentage of the animals non-viable when compared to the control group. Subsequently, hemocytes were analyzed for the presence of cytoplasmic and nuclear alterations. Finally, the comet test was performed to quantify the genotoxic damage caused by exposure to industrial sludge. Analysis hemocytes showed a significant number of cellular alterations was observed, mainly due to the high frequency of apoptosis. Moreover, during the analysis of nucleoids several degrees of nuclear damage were identified, with the groups exposed to the highest concentrations presenting the greatest genotoxic damage. Thus, we can conclude that the parameters evaluated in the mollusk Biomphalaria glabrata have proven to be a good tool, along with other techniques and complementary organisms, to assist aspects related to biomonitoring of freshwater ecosystems.

Dataset on schistosomiasis control using potassium usnate against Biomphalaria glabrata at different developmental stage and Schistosoma mansoni cercariae.

This text presents complementary data corresponding to schistosomiasis mansoni׳s vector control and toxicity on Schistosoma mansoni cercariae using potassium usnate. This information support our research article "Potassium Usnate Toxicity Against Embryonic Stages of the Snail Biomphalaria glabrata and Schistosoma mansoni Cercariae" [1], and focuses on the analysis of the detailed data regarding the different concentrations of potassium usnate and their efficiency to B. glabrata mortality and non-viability and S. mansoni cercariae mortality etiologic agent of the disease.