Inhibition of TNF-α has become a feasible target for alleviating inflammation-mediated diseases. Currently, techniques developed, such as anti-TNF antibody therapies, prove not to be nearly as beneficial enough to effectively treat inflammation-mediated syndromes because of the increased risk for severe infections and malignancies. Our study has undertaken the attempt of identifying small molecules to inhibit TNF-α. This study manually selected 37 plant-derived compounds based on IC50 value from various literature, which showed inhibitory activity against TNF-α. By employing an in silico pipe-line, we have aimed to explore the binding modes, to discover the most possible mechanism of inhibition, as well as, for a deeper understanding of structural changes, which is necessary for rationalization of the targeted inhibition by our proposed bioactive compounds. Therefore, this study has identified two potential compounds through advanced induced fit docking and simulation study. The stability of protein-ligand complex and structural changes was studied by performing 100ns molecular dynamics simulation with its binding energy estimated through MM-PBSA analysis.

Olea europea is among the top potential plants of the Arabian Peninsula. It is commonly known as Zaytoun in Arabic. The therapeutic qualities of the olive tree are mostly associated with the leaves utilised in infusion or decoction. Olive leaves possessed wide area of pharmacological and medicinal attributes. Currently, process optimization for extraction parameters in herbal infusions to maximize antioxidant phenolic compounds has drawn consideration. There are many reported studies on the health influences of olive leaves; still, there is limited research on the efficient extraction method. This study is intended to examine the optimum microwave-assisted extraction conditions by using response surface methodology with Box–Behnken design for the better extraction output of total phenolic content from olive leaves. Results showed that the obtained % yield ranges from 16 to 48 %, while the range of TPC was found to be from 28.76 to 221.43 mg GAE/g DW. The significance of regression coefficients was statistically examined by analysis of variance (ANOVA). It was analyzed that the lack of fit value of the quadratic model was insignificant, but the model was significantly fitted. So the second-order polynomial model could be used to optimize the extraction of phenolic compounds from olive leaves. This study provides ideas with the scientific basis of utilization of olive leaves as a rich source of phenolic compounds to be extracted using MAE.

The multidrug-resistant Pseudomonas aeruginosa is considered a public threat, with antibiotics increasing its resistance. Essential oils (EOs) have demonstrated significant effects against several microorganisms. However, due to their volatile nature they cannot be delivered to the bacteria infected site in their free-state. Therefore, biodegradable polymeric delivery platforms are being engineered. Here, hydrogel-like films were produced from a combination of sodium alginate (SA) and gelatin (GN) to serve as delivery platforms for the controlled release of cinnamon leaf oil (CLO) entrapped within chitosan microcapsules. The minimum inhibitory concentration (MIC) of CLO was established at 39.3 mg/mL against P. aeruginosa. Chitosan microcapsules were prepared via ionotropic gelation with tripolyphosphate, containing at the core the CLO at MIC. Successful production was confirmed by fluorescent microscopy using Nile red as detection agent. The encapsulation efficiency and controlled release of the oil were monitored in basic and physiological pH for 24 h. Microcapsules were then embedded within a biodegradable SA/GN polymeric matrix processed via a solvent casting/phase inversion methodology with SA/GN used at 70/30 polymer ratio and 2 wt% SA concentration in distilled water. The coagulation bath was composed of a 2 wt% CaCl₂ aqueous solution. The CLO-containing chitosan microcapsules homogeneous distribution was guaranteed by successive vortex and blending processes applied prior to casting. Flexible, highly hydrated films were obtained, with the presence of loaded chitosan capsules being confirmed by FTIR. Qualitative and quantitative antimicrobial examinations validated the modified film potential to fight infections caused by P. aeruginosa bacteria.

Problems associated with microbial resistance to antibiotics are growing due to their overuse. In this scenario, plant extracts have been considered as potential alternatives to antibiotics, since they can inhibit the action of the most common bacteria found colonizing infected wounds. The propolis extract (PE) has been used for centuries in folk medicine due to its antimicrobial, antioxidant, and anti-inflammatory properties as well as to its ability to induce tissue regeneration. Also known as “bee glue”, propolis is a complex mixture of chemical constituents (such as resin, waxes, pollen, essential oil and organic compounds) with a high polyphenol content. To improve the stability and long-term effectiveness of PE in wound healing, polymeric films composed of biodegradable and biocompatible polymers are being engineered as delivery vehicles. Here, sodium alginate/gelatin (SA/GN) films (2 wt% SA concentration, polymer ratio 70/30 v/v), containing PE, were prepared via a simple, green process of solvent casting/phase inversion technique, followed by crosslinking with calcium chloride (2 wt%) solutions. The minimum inhibitory concentration (MIC) of PE was established as 0.338 mg/mL for Staphylococcus aureus and 1.353 mg/mL for Pseudomonas aeruginosa, the most prevalent bacteria in infected wounds. The extract was incorporated at P. aeruginosa MIC (a value effective against both bacteria) within the polymeric films before (blended with the polymeric solution) and after (immobilization via physisorption) film production. Flexible, highly hydrated films were obtained. Successful incorporation of PE was confirmed via Fourier-transformed infrared spectroscopy (FTIR). The antibacterial activity of the films was assessed via agar diffusion (qualitative) and killing time kinetics (quantitative) examinations. Data confirmed the modified films effectiveness to fight bacteria infections caused by S. aureus and P. aeruginosa and their ability to be applied in the treatment of infected wounds.

Seaweeds are an important source of bioactive metabolites in the development of drugs and nutraceuticals. This study aimed to analyze the anti-proliferative and apoptotic activity of methanol extract (ME) of G.edulis on human Rhabdomyosarcoma (RD) and breast adenocarcinoma (MCF-7) cell lines. De-polysaccharide ME of G.edulis was extracted to determine the anti-proliferative and apoptotic activity. The cytotoxic activity was evaluated by MTT and neutral red uptake assay, while apoptotic activity was characterized by cellular morphology, DNA fragmentation and Caspase 3/7 assay. The results of cytotoxicity assay showed that the decrease of the percentage of cell viability in a dose-dependent manner as signified by cell death. The ME of G.edulis exhibited potent cytotoxicity activity against RD (IC_50METHANOL:50.31μg/ml) and MCF-7 (IC_50METHANOL:32.05μg/ml) cells compared to the standard cycloheximide (IC_50RD:36.26 μg/ml; IC_50MCF-7: 28.87 μg/ml) as confirmed by MTT assay. Further, potential cytotoxic activity of ME (IC_50RD: 45.95 μg/ml; IC_50MCF-7:35.13 μg/ml) against RD and MCF-7 were confirmed by neutral red assay compared to the standard cycloheximide (IC_50RD: 31.80 μg/ml; IC_50MCF-7: 27.84 μg/ml). The apoptosis was induced by activating the Caspase 3/7 pathway both in RD and MCF-7 cells treated with ME after 24 hours. Highest Caspase 3/7 activity was observed after 4 hours in RD cells, whereas in MCF-7 high Caspase activity was observed after 3 hours of the treatment. Further, the DNA ladder pattern was observed in MCF-7 cells treated with ME of. G.edulis whereas RD cells did not show any typical ladder pattern. Besides, the morphological changes of apoptosis were examined using two concentrations which produce 50% cell inhibition (IC₅₀) and its half (IC_50/2). Most of the apoptosis morphological features were observed under the inverted microscope and when stained with fluorescence dye Hoechst stain. Thus, it can be concluded that the ME of G.edulis possesses anticancer activity via activating the Caspases pathway.

Since ancient times, plants have been used as preservatives, spices, flavorings and as natural remedies to prevent or treat diseases, thanks to the biological activity correlated with the bioactive compounds they contain. The avocado fruit (Persea americana), native to Mexico and Guatemala, has been traditionally used for its pleasant organoleptic characteristics, high nutritional value and health benefits, but its residual biomass (seed, skin and tree leaves) is also valuable in therapeutic terms. For this reason, the present investigation reviews the pharmacological potential of avocado waste. It can serve as a source of antioxidants, hypotensive, anti-analgesic, photoprotective, and anti-inflammatory agents, and to treat skin disorders. These properties are generally attributed to the phenolic composition. The content of phenolic compounds in avocado waste extracts varied between 16 and 307 g/kg dry weight, depending on the waste type and extraction conditions, among others. In particular, our results suggested that using water as solvent, high amount of phenolic compounds can be obtained from the peel (266 g/kg dry weight) and it was correlated with a major antioxidant activity. Thereby the peels can be applied to obtain antioxidants and water can be used as an environmentally friendly extraction solvent for food and pharmacological applications.

Introduction. Lentinan is a polysaccharide isolated from Lentinula edodes, a mushroom traditionally used in Asian medicine for the treatment of various ailments, including oncologic diseases. The aim of this umbrella review is to understand whether lentinan can be a useful integrative remedy for cancer patients.

Methods. PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were systematically searched for relevant meta-analyses from inception to September 29th, 2020. The quality of included studies was assessed with a dedicated NIH (National Institutes of Health) tool.

Results. After database search, 8 meta-analyses met inclusion criteria, all characterized by a fair-to-good methodological quality. Retrieved evidence reported that lentinan can be useful to improve response rate, 1-year survival, performance status, quality of life, and radio/chemotherapy toxicity when administered in adjunct to standard care for some lung and gastrointestinal cancers. In particular, lentinan integrative therapy was able to ameliorate performance status and radio/chemotherapy toxicity in patients with esophageal, gastric, and colorectal cancer, whereas it was capable of improving response rate and adverse effects of standard therapy in subjects with lung malignancies. Individuals with advanced-stage solid tumors also benefited from lentinan integrative supplementation in terms of 1-year survival rate and health-related quality of life.

Discussion. Lentinan may be a valid integrative therapeutic option to administer in adjunct to radio/chemotherapy for selected patients with some solid tumors. Further studies are advised to better understand all potential interactions, side effects, long-term outcomes, disease- and patient-related predictors of efficacy of this complementary therapy.

2,5-diketopiperazines (DKP) are the simplest cyclo-peptides in nature and probably could play a key role in the origin (chemical evolution) of life [1]. They are ubiquitous in the environment: either in microorganisms (bacteria, fungi) or higher species (algae, lichens, marine sponges, gorgonians, tunicates, plants, animals venom), but also in food and beverages [2]. These natural dipeptides have been known since the beginning of the 20^th century [3] but they have been neglected for a long time. Only recently, DKPs, especially proline-containing cyclo-dipeptides, have been enjoyed greater and greater significant interest due to their unique rigid heterocyclic structure, with diverse substituted functional groups, and a wide range of bioactivities, such as anticancer, antiviral, neuroprotective in neurodegenerative diseases, cytotoxic, antioxidant, antibacterial, antifungal, antimutagenic, anti-inflammatory or antihyperglycemic. They have relevance in ion-transport, quorum sensing, cell-cell signaling, as a system of the brain delivery of drugs with low permeability to cross the blood-brain barrier [4] and have a high affinity to a large number of receptors [2]. Short cyclic peptides have numerous favorable features, such as inter alia low toxicity, increased cell permeability, good bioavailability, binding affinity, or target selectivity [5]. Proline-containing peptides are more resistant to degradation by enzymes.

This presentation is focused on the survey of the high potential of proline-containing DKPs in medicinal use in the nearest future, in light of the newest scientific literature.

References

1. Ying J.; Lin, R.; Xu, P.; Wu, Y.; Zhao, Y. Scientific Reports. 2018, 8, 936.

2. Borthwick, A.D. Chem. Rev. 2012, 112, 3641.

3. Corey, R. J.Am.Chem.Soc. 1938, 60(7), 1598.

4. Cornacchia, C.; Cacciatore, I.; Baldassarre, L.; Mollica, A.; Feliciani, F.; Pinnen, F. Mini Reviews in Medicinal Chemistry. 2012.

5. Feni, L.; Jutten, L.; Parente, S.; Piarulli, U.; Neundorf, I.; Dia, D. Chem. Commun. 2020, 56, 5685.

Diabetes mellitus is an endocrine disorder, characterized by hyperglycemia with abnormal carbohydrate, protein and lipid metabolism. There has been an increase in prevalence of diabetes mellitus, with an estimate of around 171 million people worldwide. Currently available synthetic treatments are associated with toxic side effects, therefore plant sources are considered as an alternative for effective management of diabetes mellitus and its associated complications. Mehon, an antidiabetic polyherbal formulation is available commercially with proven antidiabetic activities however, lack studies on systematic mechanism of action. Therefore, in the present study Hydro-alcoholic(HAE) and aqueous(AQE) extracts of Mehon were analyzed for its Total phenolic, Total flavonoid contents, effects on a-amylase and a-glucosidase inhibitory activities, followed by glucose adsorption, diffusion and transport across membrane of yeast cells. Our results revealed that HAE exhibited higher Total Phenolic content ( 95.44±0.22GAE/mg) and Total flavonoid content (86±0.15QE/mg) compared to AQE and (TPC 47.87±0.29GAE/mg, TFC 38.82±0.15QE/mg).Glucose Adsorption increased remarkably with an increment in glucose concentration (5mM/L-100mM/L), highest glucose binding capacity was observed to be 74.56 ±1.02 mM and 73.86±1.09mM at 100mM concentration for HAE and AQE respectively. Rate of glucose uptake into yeast cells was linear in all the 5 glucose concentrations (5mM to 25 mM). In both the extracts, diffusion of glucose was directly proportional to the time from 30 to 120 min. The GRDI was calculated to be 27.44% and 17.43% at 30 min which gradually reduced to 14.63% and 7.00% at 120 min for HAE and AQE respectively. Among both the extract HAE showed alpha-amylase (71.87%) and alpha-glucosidase (70.12%) inhibitory activities in comparison to standard drugs Acarbose These mechanisms might be accountable in lowering the concentration of postprandial serum glucose and thus confirms the antihyperglycemic propensities of commercial antidiabetic polyherbal formulations Mehon.

Obesity, a global health concern is associated with the dysbiosis of intestinal microbial composition. Previous in vitro and in vivo studies have reported the potentials of urolithins on reducing lipid accumulation. This study aims to investigate the potentials of urolithin A (Uro-A), a gut-derived metabolite of ellagitannins in reducing body weight gain through the modulation of the gut microbiota. To establish the induced obesity model in rats, animals were fed on a high-fat diet which were later administered with Uro-A. Serum biochemical parameters were quantified, and changes in the composition of the gut microbial community were analyzed using 16S rDNA gene sequencing. Our results showed that Uro-A significantly decreased the body weight gain in HFD-fed rats. Serum biochemical parameters analyses showed that this metabolite increased the level of the high-density lipoproteins while decreasing the serum levels of triglycerides, total cholesterol, and low-density lipoproteins. Furthermore, the taxonomic analysis revealed that urolithin A treatment changed the gut microbial composition. Besides, Uro-A elevated the abundance of Parabacteroides, reduced the abundances of Desulfovibrionacea, Lachnospiraceae, and Coriobacteriaceae. These modulated gut microbes are related to body weight gain, inflammation, impaired glucose, and dysfunctional lipid metabolism, which are all closely associated with obesity. Taken together, our results suggest that Uro-A possesses anti-obesity property, which may be related to the modulation of the gut microbial composition.