Improving Riparin-A Dissolution through a Laponite Based Nanohybrid.

(1) Background: Riparin-A presents several pharmacological activities already elucidated, such as antimicrobial modulator, antileishmania, anxiolytic, anti-inflammatory, antinociceptive, and antioxidant. Even with important bioactive effects, the applicability of Riparin-A is limited due to its low solubility in water, impairing its dissolution in biological fluids. Thus, the objective of this study was to develop a nanohybrid based on Riparin-A and Laponite to obtain a better dissolution profile and evaluate its cytotoxic potential. (2) Methods: The formation of a hybrid system was highlighted by X-ray powder diffraction, infrared spectroscopy, and thermal analysis. Solubility, dissolution, and cytotoxicity studies were performed; (3) Results: An increase in the solubility and aqueous dissolution rate of Riparin-A was observed in the presence of clay. Diffractometric analysis of the hybrid system suggests the amorphization of Riparin-A, and thermal analyses indicated attenuation of decomposition and melting of the Riparin-A after interaction with clay. Furthermore, the nanosystem did not exhibit cytotoxic activity on normal and tumorigenic lines. (4) Conclusions: These results are promising for the development of the Riparin-A/Laponite nanosystem for therapeutic purposes, suggesting an increase in the range of possible routes of administration and bioavailability of this bioactive compound.

Palmatine antioxidant and anti-acetylcholinesterase activities: A pre-clinical assessment.

There is evidence that palmatine (PA), an alkaloid isolated from the Guatteria friesiana plant, has some important biological activities, including anti-inflammatory and antidepressant effects. In this study, the antioxidant and anti-acetylcholinesterase (AChE) effects of PA were assessed. The antioxidant capacity was evaluated in vitro and in vivo through 7 distinct assays, and the anti-AChE activity was determined in vitro. The standards, trolox and ascorbic acid were used for the in vitro antioxidant test, while hydrogen peroxide was selected as a stressor for the Saccharomyces cerevisiae test. Additionally, PA was also combined with trolox and ascorbic acid to determine the likelihood of synergistic effects occurrence to what concerns to antioxidant potential. PA exhibited a potent and concentration-dependent antioxidant potential, although a stronger antioxidant activity was stated using the PA + trolox combination. PA was also found to inhibit AChE activity when compared to the negative control. Thus, PA may be viewed as a promissory phytotherapeutic agent to manage oxidative stress-mediated neurological diseases, especially the Alzheimer's and Parkinson's diseases.

Antioxidant, anti-inflammatory and cytotoxic/antitumoral bioactives from the phylum Basidiomycota and their possible mechanisms of action.

Biologically active compounds from species of the phylum Basidiomycota have been shown a wide range of pharmacological activities and provide a vast reservoir of potential innovational drugs. The aim of this review is to discuss some mechanisms of action involved in antioxidant, anti-inflammatory and cytotoxic/antitumoral activities attributed to the bioactive compounds from species of the phylum Basidiomycota. We show that isolated compounds from extracts, secondary metabolites and polysaccharides that presented antioxidant properties have mechanisms of action involved in the elimination/capture of free radicals and reduction of lipid peroxidation. Also, some bioactives with anti-inflammatory activity were reported to enhance innate and cell-mediated immune responses. Finally, compounds that presented cytotoxic/antitumoral activity induces increased free radical production, collapse of the mitochondrial membrane potential and increased expression of proteins responsible for cell cycle arrest and apoptosis. Investigating the mechanisms of action of biologically active compounds will facilitate further efforts to accelerate the discovery of novel therapeutic strategies.

Mycotoxin-assisted mitochondrial dysfunction and cytotoxicity: Unexploited tools against proliferative disorders.

Mitochondria are the powerhouse of cells, which upon dysfunctions may lead to several diseases. Mycotoxins are the toxic secondary metabolites from fungi which are capable of causing diseases and death in humans and animals. They have a versatile mechanism of action in biological systems and can be used as lead compounds to treat some diseases including cancer. The present work encompasses analysis on the effects of mycotoxins on mitochondrial dysfunction. Electronic databases such as PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar were thoroughly searched for up-to-date published information associated with those mycotoxins and their effect on mitochondrial dysfunction. Findings suggest that mycotoxins such as citrinin, aflatoxin, and T-2 toxin exert multi-edged sword-like effects in test systems causing mitochondrial dysfunction. Mycotoxins can induce oxidative stress even at low concentration/dose that may be one of the major causes of mitochondrial dysfunction. On the other hand, activation of apoptotic caspases and other proteins by mycotoxins may lead to apoptotic cell death. Thus, mycotoxins-mediated mitochondrial dysfunction may be related to several chronic diseases which also makes these mycotoxins considerable as lead compounds for inducing toxic effects in cells. Their cytotoxic effects on cancer cells suggest their possible application as chemotherapeutic tools. © 2018 IUBMB Life, 70(11):1084-1092, 2018.

A comprehensive review on biological properties of citrinin.

Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.

Diterpenes as lead molecules against neglected tropical diseases.

Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.

Trypanocidal and cytotoxic activities of essential oils from medicinal plants of Northeast of Brazil.

Chagas disease, caused by Trypanosoma cruzi, is an important cause of mortality and morbidity in Latin America. There are no vaccines available, the chemotherapy used to treat this illness has serious side effects and its efficacy on the chronic phase of disease is still a matter of debate. In a search for alternative treatment for Chagas disease, essential oils extracted from traditional medicinal plants Lippia sidoides, Lippia origanoides, Chenopodium ambrosioides, Ocimum gratissimum, Justicia pectorales and Vitex agnus-castus were investigated in vitro for trypanocidal and cytotoxic activities. Essential Oils were extracted by hydrodistillation and submitted to chemical analysis by gas chromatography/mass spectrometry. The concentration of essential oils necessary to inhibit 50% of the epimastigotes or amastigotes growth (IC(50)) and to kill 50% of trypomastigote forms (LC(50)) was estimated. The most prevalent chemical constituents of these essential oils were monoterpenes and sesquiterpenes. All essential oils tested demonstrated an inhibitory effect on the parasite growth and survival. L. sidoides and L. origanoides essential oils were the most effective against trypomastigote and amastigote forms respectively. No significant cytotoxic effects were observed in mouse peritoneal macrophages incubated with essential oils which were more selective against the parasites than mammalian cells. Taken together, our results point towards the use of these essential oils as potential chemotherapeutic agent against T. cruzi.

In vitro antileishmanial activity and cytotoxicity of essential oil from Lippia sidoides Cham.

Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. There is no vaccine available for Leishmania infections and conventional treatments are very toxic to the patients. Therefore, antileishmanial drugs are urgently needed. In this study we have analyzed the effects of essential oils from Lippia sidoides (LSEO) and its major compound thymol on the growth, viability and ultrastructure of Leishmania amazonensis. The essential oil and thymol showed significant activity against promastigote forms of L. amazonensis, with IC(50)/48 h of 44.38 and 19.47 µg/mL respectively. However, thymol showed toxicity against peritoneal macrophages and low selectivity against the promastigotes when compared with the crude LSEO. On the other hand, no cytotoxic effect was observed in macrophages treated with the crude essential oil. Incubation of L. amazonensis-infected macrophages with LSEO showed a marked reduction in amastigote survival within the macrophages. Significant morphological alterations as accumulation of large lipid droplets in the cytoplasm, disrupted membrane and wrinkled cells were usually seen in treated parasites. The LSEO's activity against both promastigote and the amstigote forms of L. amazonensis, together with its low toxicity to mammalian cells, point to LSEO as a promising agent for the treatment of cutaneous leishmaniasis.