No abstract

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from Silybum marianum, commonly known as milk thistle or St. Mary’sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases.

Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

No abstract

Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.