Oxidative stress, inflammation, and gut microbiota impairments have been implicated in the development and maintenance of diabetes mellitus. Strategies capable of recovering the community of commensal gut microbiota and controlling diabetes mellitus have increased in recent years. Some lactobacilli strains have an antioxidant and anti-inflammatory system capable of protecting against oxidative stress, inflammation, and diabetes mellitus. Experimental studies and some clinical trials have demonstrated that Limosilactobacillus fermentum strains can beneficially modulate the host antioxidant and anti-inflammatory system, resulting in the amelioration of glucose homeostasis in diabetic conditions. This review presents and discusses the currently available studies on the identification of Limosilactobacillus fermentum strains with anti-diabetic properties, their sources, range of dosage, and the intervention time in experiments with animals and clinical trials. This review strives to serve as a relevant and well-cataloged reference of Limosilactobacillus fermentum strains capable of inducing anti-diabetic effects and promoting health benefits.

Quercetin supplementation during pregnancy and lactation has been linked to a lower risk of maternal cardio-metabolic disorders such as gestational diabetes mellitus (GDM), dyslipidemia, preeclampsia, attenuation of malnutrition-related conditions, and gestational obesity in animal studies. Pre-clinical studies have shown that maternal supplementation with quercetin reduces cardio-metabolic diseases in dams and rodents’ offspring, emphasizing its role in modifying phenotypic plasticity. In this sense, it could be inferred that quercetin administration during pregnancy and lactation is a viable strategy for changing cardio-metabolic parameters throughout life. Epigenetic mechanisms affecting the AMP-activated protein kinase (AMPK), nuclear factor-kappa B (NF-κB), and phosphoinositide 3-kinase (PI3 K) pathways could be associated with these changes. To highlight these discoveries, this review outlines the understanding from animal studies investigations about quercetin supplementation and its capacity to prevent or decrease maternal and offspring cardio-metabolic illnesses and associated comorbidities.

Background: Leishmaniasis is a neglected disease that does not have adequate treatment. It affects around 12 million people around the world and is classified as a neglected disease by the World Health Organization. In this context, strategies to obtain new, more active and less toxic drugs should be stimulated. Sources of natural products combined with synthetic and chemoinformatic methodologies are strategies used to obtain molecules that are most likely to be effective against a specific disease. Computer-Aided Drug Design has become an indispensable tool in the pharmaceutical industry and academia in recent years and has been employed during various stages of the drug design process. Objectives: Perform structure- and ligand-based approaches, synthesize and characterize some compounds with materials available in our laboratories to verify the method’s efficiency. Methods: We created a database with 33 cyclic imides and evaluated their potential anti- Leishmanial activity (L. amazonensis and L. donovani) through ligand- and structure-based virtual screening. A diverse set selected from ChEMBL databanks of 818 structures (L. donovani) and 722 structures (L. amazonensis), with tested anti-Leishmanial activity against promastigotes forms, were classified according to pIC50 values to generate and validate a Random Forest model that shows higher statistical indices values. The structures of four different L. donovani enzymes were downloaded from the Protein Data Bank and the imides’ structures were submitted to molecular docking. So, with available materials and technical feasibility of our laboratories, we have synthesized and characterized seven compounds through cyclization reactions between isosafrole and maleic anhydride followed by treatment with different amines to obtain new cyclic imides to evaluate their anti-Leishmanial activity. Results: In silico study allowed us to suggest that the cyclic imides 516, 25, 31, 24, 32, 2, 3, 22 can be tested as potential multitarget molecules for leishmanial treatment, presenting activity probability against four strategic enzymes (Topoisomerase I, N-myristoyltransferase, cyclophilin and Oacetylserine sulfhydrylase). The compounds synthesized and tested presented pIC50 values less than 4.7 for Leishmania amazonensis. Conclusion: After combined approach evaluation, we have synthesized and characterized seven cyclic imides by IR, 1H NMR, 13C-APT NMR, COSY, HETCOR and HMBC. The compounds tested against promastigote forms of L. amazonensis presented pIC50 values less than 4.7, showing that our method was efficient in predicting true negative molecules.

Leishmaniasis is a neglected disease that does not have adequate treatment. To try to solve this problem, we have tested a database with 33 cyclic imides and evaluated their potential antiLeishmanial activity (L. donovani) through ligand-based and structure based virtual screening. A diverse set selected from CHEMBL databanks of 818 structures (L. donovani) with tested antileishmanial activity against promastigotes forms, were classified according pIC50 values in order to generate and validate Random Forest model that show higher statistical indices values. The structure of four different L. donovani enzymes were downloaded from PDB databank and imides structures were submitted to molecular docking. In silico study allowed us to suggest that the cyclic imide 527 can be tested as a potential multitarget molecule for leishmanial treatment, presenting activity against four strategic enzymes to treatment with probability of activity of 60%.