High-fat diet (HFD) is a major problem causing neuronal damage. However, the mechanisms and potential therapeutic targets have not been evaluated yet. Thymoquinone (TQ) could regulate oxidative stress and inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation as well as morphological changes in the cerebellum of rats with HFD. The present study establishes the role of TQ on oxidative stress, anti-inflammatory process and morphological changes in the cerebellum following high-fat diet supplementation in rats. Rats were divided into three groups as (1) Control, (2) HFD (6 mg/day) for eight weeks and (3) HFD supplementation (4 weeks) followed TQ 300 mg/kg/day treated (4 weeks). After treatment, body weight and serum cholesterol profile were measured. Also, blood samples were collected to measure oxidative stress markers glutathione (GSH), superoxide dismutase (SOD) and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher in body weight as compared with the control group. TQ treatment significantly (p<0.05) lowers the body weight with significant (p<0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). The anti-oxidative enzymes significantly reduced in HFD rats as compared with the control group. Surprisingly, treatment with TQ could improve the level of GSH and SOD. TQ treatment significantly (p<0.05) reduced the inflammatory markers as compared with HFD alone. The histological study revealed that neuronal damage was prevented in the cerebellum following treatment of TQ. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves anti-oxidant enzymes.

The use of herbal products for the treatment, prevention and cure of diseases is one of the oldest human medicinal practices. In fact, the majority of the population in developing countries depend on ancestral plant knowledge for healthcare. However, there is still a gap between progress observed in clinical pharmacy and in the field of herbal and traditional medicine, remaining many natural products with biological activity to be identified.

Plectranthus species (Lamiaceae family) have a widespread ethnobotanical use and are often cited by its medicinal properties and application, particularly in folk medicine. They contain many antioxidant compounds and exhibit several effects (anti-inflammatory, antimicrobial and antifungal) which suggest that Plectranthus may be a promising genus for the discovery of medicinal compounds.

Thus, the isolation of secondary metabolite compounds from the Plectranthus spp. is important to validate scientifically the popular uses of these plants and also to find new sources of potentially economically important products or compounds which can be transformed into active pharmaceutical ingredients. Besides, the cytotoxicity evaluation of the plant extracts and their active ingredients are required for their effective and safe therapeutic use.

This work enumerates the compounds isolated to date from Plectranthus ecklonii Benth., extracts and their biological activities. The HPLC analysis presented is part of an ongoing project at CBIOS of identification, quantification and evaluation of the bioactive components (in particular, diterpenes and hydrocinnamic acids) in different species of Plectranthus.

Essential oils (EOs), which are complex biomolecules composed of volatile compounds, have emerged as a new strategy to deal with bacterial infections and as a valid alternative to synthetic drugs. Here, we report the modification of biodegradable wet-spun microfibers composed of cellulose acetate (CA) and polycaprolactone (PCL) with EOs, aiming at their localized, controlled release. Cinnamon leaf oil (CLO), cajeput oil (CJO), and clove oil (CO) were selected from a group of 20 EOs according to their minimal inhibitory concentration (MIC) against Staphylococcus aureus (<22.4 mg/mL) and Escherichia coli (<11.2 mg/mL). CA/PCL prepared at 10% and 14%wt in a 3/1 ratio in acetic acid and acetone were processed in the form of microfibers by wet-spinning at an extrusion rate of 0.5 mL/h directly into an ethanol coagulation bath. Microfibers were modified by immersion in ethanol solutions containing EOs at 2xMIC and ampicillin (control antibiotic). Incorporation was confirmed by UV-VIS, FTIR and TGA. After 72h, fibers contained ampicillin at MIC but only 14%, 66% and 76% of MIC for CLO, CO and CJO, respectively. Unloaded and loaded microfibers were characterized as uniform and homogeneous. Data showed that even at small amounts the EO-modified microfibers were effective against the tested bacteria. Considering the amount immobilized, CLO-containing fibers were deemed the most effective from the group, suggesting a superior affinity of the EOs active groups towards the CA/PCL matrix. These results indicate that CA/PCL microfibers loaded with EOs can be easily produced and applied in scaffolds for biomedical applications.

Cyclic ADP-ribose (cADPR) is a natural occurring metabolite of NAD⁺ capable of mobilizing Ca²⁺ ions from intracellular stores. It was firstly isolated from sea urchin eggs extract, but it was later established that it is also produced in many other mammalian cells, including pancreatic β-cells, T-lymphocytes, smooth and cardiac muscle cells and cerebellar neurons, acting as a Ca²⁺-mobilizing agent. For this activity, cADPR has been classified as a second messenger that, activating the ryanodine receptors of the sarcoplasmatic reticulum, is able to mobilize the calcium ions from intracellular stores. cADPR is involved in many physiological processes related to the variation of the Ca²⁺ concentration, such as the synaptic homeostasis in neurons, as well as fertilization and cellular proliferation. This cyclic nucleotide, characterized by a very labile glycosidic bond at the N1, is rapidly hydrolysed also in neutral aqueous solutions to the inactive ADP-ribose. Matsuda and co-workers were the first who synthesized new analogues of the cADPR in which the adenine base was replaced by a hypoxanthine ring. This kind of modification produced the cyclic inosine diphosphate ribose (cIDPR) which proved to be stable in hydrolytic physiological conditions and showed significant Ca²⁺ mobilizing activity. A lot of modifications regarding the northern and southern ribose, as well as the purine base of cADPR, have been proposed so far. In our laboratories we have synthesized several analogues of cIDPR. In particular, the analogue with the northern ribose replaced by a pentyl chain (cpIDP) showed interesting Ca²⁺ mobilizing activity on the neuronal PC12 cell line. Starting from these results, we report here the synthesis of a novel analogue , in which the “northern” ribose of cIDPR was replaced by a 2”,3”-dihydroxy pentyl chain.

Since the last few decades, proteins have emerged as the major class of pharmaceuticals with more than 200 protein-based products currently available in the market, of which 90% are used as therapeutics. The protein engineering market is bolstered by the need for drugs with improved efficiency, specificity, technological capabilities, rise of antibody based drugs and steady growth in the therapeutic market. Monoclonal antibodies (mAbs) is the fastest growing segment in the therapeutic market, though the other segments comprising non-mAb recombinant proteins like Insulin, Erythropoetin (EPO), Interferons (INF),Interleukins (ILs) and Somatotropin (hGH) are also in great demand for therapy.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target.

By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding.

In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.