Propolis is a resinous mixture with a complex chemical composition, produced by honeybees and stingless bees from a variety of vegetal sources. In the last decades, propolis was extensively researched, multiple studies confirming its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. More recently, due to an exponential increase in the number of patients with metabolic diseases, there is also a growing interest in the study of antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis. The aim of this review was to evaluate the potential role of propolis in the prevention and treatment of metabolic diseases like diabetes mellitus, dyslipidemia, and obesity. The preclinical in vivo and in vitro pharmacological models investigating antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis were reviewed with a focus on the putative mechanisms of actions of several chemical constituents. Additionally, the available clinical studies and an evaluation of the safety profile of propolis were also presented.

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole derivatives 5a–l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g, 5i, 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between −1.25 and −0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

Two series, “a” and “b”, each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABA_A receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D_1–3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABA_A receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABA_A receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a–9a and 1b–9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the “b” series, particularly for compound 8b.

The aim of this study was to determine the anti-inflammatory, analgesic and antioxidant effects and the polyphenols composition of Tetracera alnifolia Willd and Heinsia crinita Afz. G. Taylor extracts. The anti-inflammatory effect of the hydro-ethanolic and ethanolic extracts was evaluated by the carrageenan-induced rat paw oedema test and the analgesic effect by the Randall-Selitto test. Antioxidant activity of the extracts was evaluated spectrophotometrically using the DPPH radical scavenging assay and the polyphenolic profile, by an HPLC-MS method. All extracts of H. crinita and T. alnifolia (500 mg/kg) showed significant anti-inflammatory and analgesic effects. The extract of T. alnifolia has shown an antioxidant effect greater than that of H. crinita . Gallic acid (33.31 μg/mL) and rutin (34.70 μg/mL) are the major polyphenolic compounds of T. alnifolia and H. crinita , respectively. This study justifies the use in the traditional medicine of T. alnifolia and H. crinita . The obtained results are promising for the use of these extract in the management of inflammatory disease