Bioavailability Of Compounds Research Articles

Pharmacokinetics of tolfenamic acid in ducks (Anas platyrhynchos domestica) after different administration routes

ABSTRACT 1. The objective of this research was to compare the pharmacokinetics and bioavailability of tolfenamic acid, analgesic, antipyretic and anti-inflammatory compound, after administration through different routes to Pekin ducks. The investigation was carried out over four time periods using a randomised cross-pharmacokinetic design. 2. Tolfenamic acid was administered to ducks intravenously, intramuscularly, subcutaneously and orally at a dose of 2 mg/kg. Tolfenamic acid analysis was performed using HPLC-UV and pharmacokinetic data were conducted by non-compartmental analysis. 3. The total clearance, volume of distribution at steady state and terminal elimination half‐life after intravenous administration were 0.14 l/h/kg, 0.29 l/kg and 1.80 h, respectively. The peak plasma concentration and bioavailability for intramuscular, subcutaneous and oral administration were 4.59, 3.55 and 2.23 μg/ml and 93.62, 74.30 and 43.43%, respectively. 4. Tolfenamic acid was absorbed rapidly, eliminated quickly and exhibited a small distribution volume in Pekin ducks. Pharmacokinetic parameters, including maximum concentration, area under the plasma concentration – time curve and bioavailability, were found to be different in ducks from other bird species.

Development and characterization of nanoemulsions containing Lippia origanoides Kunth essential oil and their antifungal potential against Candida albicans.

Nanoemulsions based on plant essential oils have shown promise as alternatives against fungal pathogens by increasing the solubility and bioavailability of the active compounds of essential oils, which can improve their efficacy and safety. In the present study, we aimed to prepare and characterize nanoemulsions of Lippia origanoides essential oil, and analyze their antifungal activity against C. albicans in planktonic and biofilm form. Additionally, we sought to verify their cytotoxicity. Alginate nanoemulsions were prepared with different concentrations of essential oil, sunflower oil and surfactant to investigate ideal formulations regarding stability and antifungal efficiency. The results showed the nanoemulsions remained stable for longer than 60 days, with acidic pH, particle sizes ranging from 180.17±6.86nm to 497.85±253.50nm, zeta potential from -60.47±2.25 to -43.63±12, and polydispersity index from 0.004 to 0.622. The photomicrographs revealed that the addition of sunflower oil influenced the formation of the particles, forming nanoemulsions. The antifungal results of the essential oil and nanoemulsions showed that the MIC ranged from 0.078 to 0.312mg mL-1. The nanoemulsions were more effective than the free essential oil in eradicating the biofilm, eliminating up to 89.7% of its mass. With regard to cytotoxicity, differences were found between the tests with VERO cells and red blood cells, and the nanoemulsions were less toxic to red blood cells than the free essential oil. These results show that nanoemulsions have antifungal potential against strains of C. albicans in planktonic and biofilm forms.

Comprehensive Study of Sustainable Pressurized Liquid Extractions to Obtain Bioavailable Antioxidant Phenolic Compounds from Grape Seed By-Products

Few investigations have been conducted to evaluate pressurized liquid extraction (PLE) technology as a sustainable method for the recovery of phenolic compounds of grape seed by-products. In this study, PLE combined with an experimental design was evaluated for optimizing the sustainable extraction of phenolic compounds from grape seed by-products. The solvent ethanol content (X1, 0–100%), temperature (X2, 20–100 °C) and time (X3, 1–11 min) were studied as independent experimental factors. Yield, TPC, antioxidant activity and phenolic composition were analyzed as optimized dependent variables. Two optimal extraction conditions at different temperatures (20 °C and 100 °C) were found, but thermal degradations at 100 °C allowed for selecting the optimal condition as 75% ethanol, 11 min and 20 °C. The optimal extracts showed high phenolic content (TPC = 350.80 ± 3.97 mg GAE/g extract) and antioxidant activity (ABTS, 9.31 ± 0.33 mmol Trolox/g extract), mainly composed of polymeric and mono-oligomeric flavan-3-ols. The digestion process reduced the TPC and antioxidant activity due to the low bioaccessibility of the flavan-3-ols, mainly as catechin, epicatechin and polymeric proanthocyanidin losses during the digestion process. However, increases in the antioxidant activity of the basolateral side (DDPH, 0.061 ± 0.000 mmol Trolox/g extract) were determined after in vitro transepithelial transport, which is a consequence of bioavailable catechin and epicatechin and reduced amounts of dimer B2, dimer B1, epicatechin gallate and gallic acid. Consequently, PLE combined with hydroalcoholic solvents at a low temperature resulted in a valuable methodology to obtain sustainable extracts from grape seed by-products (contributing to the circular economy), containing bioavailable phenolic compounds, which are able to increase the antioxidant status.

Evaluation of STK17B as a cancer immunotherapy target utilizing highly potent and selective small molecule inhibitors

IntroductionThe serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy.MethodsTo assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed into a flow cytometry-based pharmacodynamic readout of STK17B inhibition both in vitro and in vivo.ResultsIn a mouse T cell activation assay, STK17B inhibitors demonstrated the ability to enhance interleukin-2 (IL-2) production. Similarly, treatment with STK17B inhibitors resulted in stronger cytokine secretion in human T cells activated using a T cell bispecific antibody. Subsequent chemistry optimization led to the identification of a highly selective and orally bioavailable tool compound, BLU7482. In vivo, STK17B inhibition led to dose-dependent modulation of myosin light chain 2 phosphorylation and enhanced priming of naïve T cells, as determined by upregulation of CD69, IL-2 and interferon-γ secretion. In line with increased T cell activation, treatment with STK17B inhibitor enhanced antitumor activity of anti–PD-L1 antibody in the MCA205 model.ConclusionsIn summary, we successfully identified and optimized STK17B kinase inhibitors which led to increased T cell responses in vitro and in vivo. This allowed us to evaluate the potential of STK17B inhibition as an approach for cancer immunotherapy.

Determining the Consequences of Climate Change for Aquatic Ecosystems Using Bioassay Methods: a Review

The article describes the scientific and methodological possibilities of bioassay in the field of studying the effects of climate change on water bodies and aquatic organisms. In fish aquaculture, it was revealed that an increase in water temperature changes the biochemical parameters of the internal environments of organisms, affects their behavior and the number of offspring. A number of biogeochemical transformations of aquatic ecosystems are predicted: a decrease in the pH of water, mineralization of organic matter of bottom sediments, release and increase in bioavailability of compounds of potentially toxic elements. Bioassay methods using monocultures and laboratory microcosms have shown that maximum temperature values and a cascade of concomitant changes will lead to a restructuring of the aquatic life community, changes in the habitats of organisms, and the disappearance of stenothermic species. The realism of such scenarios is confirmed by paleodata and modern natural phenomena.

Defatted Flaxseed Flour as a New Ingredient for Foodstuffs: Comparative Analysis with Whole Flaxseeds and Updated Composition of Cold-Pressed Oil.

Flaxseeds are functional foods popular in current diets. Cold-pressing is a solvent-free method to extract flaxseed oil, resulting in a by-product-defatted flour. This study compared whole flaxseeds and defatted flour (proximate composition, fatty acids, vitamin E, total phenolics and flavonoids, antioxidant activity, amino acids, and protein quality) and updated the composition of cold-pressed oil (oxidative stability, peroxide value, UV absorbance, colour, fatty acids, vitamin E, total phenolics and flavonoids, and antioxidant activity) to assess the nutritional relevance and potential for food applications of these samples. The flour had higher ash (6% vs. 4%), fibre (36% vs. 34%), protein (28% vs. 16%), phenolics (205 vs. 143 mg gallic acid equivalents/100 g), and antioxidant activity than seeds (p < 0.05), so it should be valued as a novel high-fibre food ingredient with high-quality plant-based protein, as it contains all essential amino acids (106 mg/g) and a high essential amino acids index (112%), with L-tryptophan as the limiting amino acid. The oil, while low in oxidative stability (1.3 h), due to its high polyunsaturated fatty acids sum (75%), mostly α-linolenic acid (57%), contains a significant amount of vitamin E (444 mg/kg), making it a specialty oil best consumed raw. The exploration of the flour as a minimally processed food ingredient highlights its role in supporting food security, circular economy, and sustainability goals, aligning with consumer preferences for natural, low-fat foods. Future research should investigate the bioactivity and shelf-life of the samples, as well as the bioavailability of compounds after digestion.

Deciphering the importance of nanoencapsulation to improve the availability of bioactive molecules in food sources to the human body

Various bodily functions are maintained, and health benefits are provided by food-derived bioactive components. Fruits and vegetables contain numerous beneficial components, including vitamins, minerals, antioxidants, enzymes, and phytonutrients. However, the body's ability to absorb these substances at a given rate and degree frequently limits their bioavailability. If food-derived bio actives are used as therapeutic or dietary interventions, this limitation can result in low efficacy and suboptimal results. Recently, nanotechnology has been a useful method for increasing the bioavailability of bioactive compounds produced from food. Active ingredients can be delivered and absorbed more efficiently with the help of nanotechnology. By altering their size or surface properties, bioactive components can be made more soluble, permeable, and bioavailable through nanotechnology. The present review will provide an overview of the various bioactive components, the application of nanotechnology to improve the availability of bioactive molecules to humans and animals, and the challenges and safety concerns associated with nanotechnology in the production of food-derived bioactive molecules.

Low-melting mixture solvents as novel solubilizing agents: Improving tolvaptan formulation and therapeutic efficacy

Presently, a significant number of pharmaceutical drugs exhibit poor solubility in water and fall within categories II and IV of the biopharmaceutical classification system. This predicament has prompted the exploration for novel solvents or excipients to enhance the solubility and bioavailability of the active compounds in aqueous environments. Low-melting mixture solvents (LoMMSs) have gained recognition as potential solvents for active pharmaceutical ingredients to improve therapeutic efficacy and delivery. This study focuses on the preparation of a eutectic mixture composed of betaine, malic acid, proline, and water (BE-MA-PR-WA) to enhance the formulation options for tolvaptan, an FDA-approved medication used to treat acute congestive heart failure, which has limited solubility in aqueous solutions. The findings presented in this article represent the first reported results on the administration of LoMMS-solubilized tolvaptan. Furthermore, an examination of the solubility and bioavailability of tolvaptan utilizing this mixture was conducted, alongside an assessment of its toxicity. The solubility of tolvaptan in BE-MA-PR-WA (1:1:1:7) increased 483 times compared to solubility in water. Toxicity studies indicated that the LoMMS formulation BE-MA-PR-WA was safe for oral administration. The oral bioavailability of tolvaptan was significantly increased by 1.9-fold in the BE-MA-PR-WA than that in water. In addition, the 5-hour urine volume of rats indicated that BE-MA-PR-WA also enhanced the diuretic effects of tolvaptan in rats. The findings suggest that BE-MA-PR-WA enhance the solubility and bioavailability of tolvaptan, and are deemed non-toxic. Consequently, LoMMS may be deemed promising solubilizing agents, potentially facilitating the absorption of poorly bioavailable medications.

Synthesis, biological evaluation, docking and molecular dynamics studies of Biginelli-type tetrahydropyrimidine analogues: Antimicrobial, cytotoxicity and antioxidant activity

Tetrahydropyrimidines have a fascinating scaffold that has garnered substantial attention from pharmacists and medicinal chemists. They are heterocyclic compounds used in anti-cancer, anti-microbial, and antioxidants therapies. Herein, a group of tetrahydropyrimidines were provided by using urea, α-ketoacid/β-ketoester, and appropriate aromatic aldehydes. Then, the antioxidant properties of the derivatives were investigated by the DPPH assay. Besides, the cytotoxicity activity of derivatives was evaluated on two MCF-7 and HepG-2 cell lines. The anti-microbial activity of derivatives was also assessed on two positive gram strains, two negative gram strains, and a fungal strain. Derivatives 4a and 4e showed the strongest antioxidant properties, with IC50s of 0.83 and 0.07 mg/mL, respectively. Compounds 4a and 4d were the most potent compounds, with IC50s of 15.81 and 12.34 µM, respectively, on both cancer cell lines. Furthermore, compounds 4b, 4j, and 4i showed the highest anti-microbial activity on S. aureus (MIC = 7.31 µM), B. subtilis (MIC = 10.81 µM), and E. coli (MIC = 11.45 µM), P. aeruginosa (MIC = 8.12 µM), and C. albicans (MIC = 12.03 µM), respectively. Then, the oral bioavailability and pharmacokinetic properties of compounds were predicted. Moreover, the most possible sites of the molecules that are metabolized by the main cytochromes were estimated. Then, the in silico cardiotoxicity and Cyto-safe properties of the compounds were studied. Finally, to determine the stability of the analogues in the Eg5 active site, docking and molecular dynamics simulations were performed.

Purple maize arabinoxylan could protect antioxidant compounds during digestion

Purple maize is a pigmented variety rich in antioxidants. Arabinoxylans (AX) are prebiotic compounds also found in the grain wall that can form gels. Recently, antioxidants have extensively been studied for their beneficial effects. However, these bioactive compounds do not easily reach the intestine in a stable form. These gels can protect certain compounds during in vitro digestion. This work aimed to extract the AX and simultaneously obtain the antioxidant compounds present in the external walls of the purple maize grain to produce gels with 2% and 4% AX to apply an in vitro digestion method. Popcorn maize (unpigmented) was used as a control. The amount of ferulic acid, polyphenols, and anthocyanins, and their antioxidative activity, were measured at in vitro digestion of the gels. This work highlights the ability of AX gels to enhance the potential bioavailability of antioxidant compounds including anthocyanins from purple maize after digestion.

Chia gum-gelatin-based encapsulation of chia sprouts phenolic compounds enhanced storage stability, bioavailability, antioxidant, antidiabetic, and antibacterial properties

Chia seeds are currently gaining popularity as functional and healthy foods. The developed chia 7-day sprout phenolic extract (CSP) is an abundant supply of highly concentrated antioxidant phenolic compounds with health-promoting and antibacterial properties. The easy destruction against different environmental changes and low bioavailability of these phenolic compounds are the main limitations of their applications/utilization. This study aims to microencapsulate the phenolic compounds of developed CSP for use as valuable functional food additives. Three microcapsules were prepared using coating materials, chia gum (CG), gelatin (G), and their mixture (CG/G) via the freeze-drying technique. The prepared CG-, CG/G-, and G-microcapsules demonstrated high encapsulation efficiency percentages of 97.0, 98.1, and 94.5%, respectively. They retained most of the CSP-phenolics (91.4–97.2%) and increased total antioxidant activity (108–127.1%). The prepared microcapsules released more CSP-phenolic compounds into the simulated intestinal stage (70–82%) than the gastric stage (15–24%), demonstrating that the coating materials enhance protection during the gastric stage. The produced microcapsules exhibited higher storage stability at 40 °C for 60 days than the non-capsulated CSP, indicating that the encapsulation provided enhanced stability. The prepared microcapsules microstructures showed uniform, smoother surfaces, and hidden micropores compared to their coating material microstructures. In addition, the connection between the functional groups of coating materials and CSP-phenolic compounds was demonstrated by FTIR analysis. The prepared CG-, CG/G-, and G-microcapsules can perfectly inhibit the α-amylase and α-glucosidase activities by 65, 68, 60 and 74, 78, and 70%, respectively, compared to CSP (54, and 66%). The three prepared microcapsules displayed better antibacterial with low MBC values (0.36–0.68 mg ml−1) compared to CSP (0.53–0.74 mg ml−1). The prepared CSP microcapsules can be incorporated into various food products to enhance their antioxidant, antidiabetic, and antibacterial properties.

Implications for Clinical Practice, Mechanisms, and Efficacy of Ageratum conyzoides Leaf Extracts in Streptozotocin-Induced Diabetes Rats: An Investigation into Their Antidiabetic, Hypolipidemic, and Antiatherogenic Activities

Ageratum conyzoides, a perennial herb native to tropical and subtropical regions, has been utilized in traditional medicine for centuries due to its diverse therapeutic properties. This review consolidates current research on the antidiabetic, hypolipidemic, and antiatherogenic effects of Ageratum conyzoides leaf extracts, specifically in streptozotocin-induced diabetic rat models. The review explores the plant’s potential mechanisms of action, including enhancement of insulin sensitivity, improvement of lipid profiles, and reduction of atherosclerotic plaque formation. Ageratum conyzoides extracts have demonstrated significant antidiabetic effects by lowering blood glucose levels, enhancing insulin secretion, and improving insulin sensitivity. They also exhibit hypolipidemic effects by reducing total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol. Additionally, these extracts show antiatherogenic properties by inhibiting plaque formation and reducing oxidative stress, thereby supporting cardiovascular health. The review examines the pharmacokinetics and bioavailability of Ageratum conyzoides bioactive compounds, emphasizing the need for further research to optimize their therapeutic potential. Comparative studies highlight its efficacy relative to other natural remedies and pharmaceuticals, noting its favorable safety profile. The review underscores the importance of integrating Ageratum conyzoides into both traditional and modern medicine practices and explores its role in dietary supplements and functional foods. Ongoing translational research and clinical trials are essential to validate the efficacy and safety of these extracts for broader clinical application. Keywords: Ageratum conyzoides, Leaf Extracts, Streptozotocin, Diabetes, Rats

Application of Difluoromethyl Isosteres in the Design of Pesticide Active Molecules.

Difluoromethyl (CF2H) groups have been found in many listed pesticides due to their unique physical and chemical properties and outstanding biological activity. In pesticide molecules, compared with the drastic changes brought by trifluoromethyl, difluoromethyl usually moderately regulates the metabolic stability, lipophilicity, bioavailability, and binding affinity of compounds. Therefore, difluoromethylation has become an effective means to modify the biological activity of pesticide molecules. This paper reviews the representative literatures and patents containing difluoromethyl groups in the past 10 years, and introduces the research progress. The aim is to provide an effective reference value for the study of difluoromethyl in pesticides.

The bioavailability of polyphenols following acute consumption of pigmented barley and wheat.

Polyphenols from pigmented cereal grains exert health-promoting effects but data on their bioavailability are limited. This study investigated the acute bioavailability of polyphenols from the consumption of pigmented whole grain cereal porridges, including purple barley (PB), purple wheat (PW), and blue wheat (BW), compared to a non-pigmented regular wheat (RW). A secondary objective was to assess their effects on plasma antioxidant and inflammatory status postprandially. Phenolic characterisation and antioxidant profiling were performed on extracts from the cooked cereals. Three healthy individuals consumed 200 g of a cereal in a 4-way crossover trial with a one-week washout in between meals. Blood samples were collected at fasting baseline, 30 minutes, 1 hour, 2 hours and 4 hours postprandially. Urine samples were collected at fasting baseline and the 4-hour time point. Pigmented grains exhibited significantly higher phenolic content and antioxidant capacity (p < 0.001) compared to RW. This suggests that pigmented grains may be a better source of polyphenols and potentially offer greater health benefits. However, polyphenol bioavailability following pigmented grain consumption was reduced (less than 6%), suggesting that a substantial fraction remained unabsorbed. The bioavailable phenolic compounds detected included phenolic acids (protocatechuic and caffeic acid), hippuric acid and other phenolic metabolites. Interpersonal variability and the type of grain consumed had an impact on the absorption and excretion of phenolic acids. Only PW consumption resulted in significant (p < 0.01) increases in plasma antioxidant status but no short-term impact on the inflammatory status. This study provides valuable insights into the complex dynamics of polyphenol bioavailability from pigmented cereal consumption and warrants further investigation.

Unexplored Opportunities of Utilizing Food Waste in Food Product Development for Cardiovascular Health.

Global food production leads to substantial amounts of agricultural and food waste that contribute to climate change and hinder international efforts to end food insecurity and poverty. Food waste is a rich source of vitamins, minerals, fibers, phenolic compounds, lipids, and bioactive peptides. These compounds can be used to create food products that help reduce heart disease risk and promote sustainability. This review examines the potential cardiovascular benefits of nutrients found in different food waste categories (such as fruits and vegetables, cereal, dairy, meat and poultry, and seafood), focusing on animal and clinical evidence, and giving examples of functional food products in each category. Current evidence suggests that consuming fruit and vegetable pomace, cereal bran, and whey protein may lower the risk of cardiovascular disease, particularly in individuals who are at risk. This is due to improved lipid profile, reduced blood pressure and increased flow-mediated dilation, enhanced glucose and insulin regulation, decreased inflammation, as well as reduced platelet aggregation and improved endothelial function. However, the intervention studies are limited, including a low number of participants and of short duration. Food waste has great potential to be utilized as cardioprotective products. Longer-term intervention studies are necessary to substantiate the health claims of food by-products. Technological advances are needed to improve the stability and bioavailability of bioactive compounds. Implementing safety assessments and regulatory frameworks for functional food derived from food waste is crucial. This is essential for maximizing the potential of food waste, reducing carbon footprint, and improving human health.

The ABCG2 Transporter Affects Plasma Levels, Tissue Distribution and Milk Secretion of Lumichrome, a Natural Derivative of Riboflavin.

The ABCG2 membrane transporter affects bioavailability and milk secretion of xenobiotics and natural compounds, including vitamins such as riboflavin. We aimed to characterize the in vitro and in vivo interaction of ABCG2 with lumichrome, the main photodegradation product of riboflavin, which has proven in vitro anti-cancer activity and a therapeutical role in antibacterial photodynamic therapy as an efficient photosensitizer. Using MDCK-II polarized cells overexpressing murine Abcg2 and human ABCG2 we found that lumichrome was efficiently transported by both variants. After lumichrome administration to wild-type and Abcg2-/- mice, plasma AUC20-120 min was 1.8-fold higher in Abcg2-/- mice compared with wild-type mice. The liver and testis from Abcg2-/- mice showed significantly higher lumichrome levels compared with wild-type, whereas lumichrome accumulation in small intestine content of wild-type mice was 2.7-fold higher than in Abcg2-/- counterparts. Finally, a 4.1-fold-higher lumichrome accumulation in milk of wild-type versus Abcg2-/- mice was found. Globally, our results show that ABCG2 plays a crucial role in plasma levels, tissue distribution and milk secretion of lumichrome potentially conditioning its biological activity.

Nanoencapsulation of quinoa oil enhanced the antioxidant potential and inhibited digestive enzymes

Quinoa oil is rich in unsaturated fatty acids and vitamin E, but its instability limits its application in food, pharmaceutical, and cosmetic products. Nanoencapsulation emerges as a promising strategy to promote water dispersibility, preserve and enhance functional properties, and increase the bioavailability of bioactive compounds. This study encapsulated quinoa oil through O/W emulsification, using porcine gelatin (OG) and isolated whey protein (OWG) as encapsulating agents. The particles were characterized by different physical and chemical methods and evaluated in vitro for cytotoxicity using Chinese hamster ovary (CHO) cells, human hepatocarcinoma cells (HepG2) and epithelial cells, and bioactive potential through the determination of Total Antioxidant Capacity (CAT) (acidic and neutral media) and iron chelation, and inhibition of digestive enzymes (α-amylase and amyloglucosidase). OG and OWG particles presented smooth surfaces, with an average size between 161 ± 7 and 264 ± 6 nm, with a polydispersity index of 0.11 ± 0.03 and 0.130 ± 0.04, encapsulation efficiency of 74 ± 1.47 % and 83 ± 2.92 %, and water dispersibility >70 %, respectively. Free and nanoencapsulated quinoa oil did not show cytotoxic effects (cell viability >70 %). Nanoencapsulation promoted the enhancement of the antioxidant activity of quinoa oil in the range of 50–63 % in a neutral medium and 96–153 % in an acidic medium than free oil (p < 0.05). OG and OWG also enhanced the inhibition of the enzymes α-amylase (by 5–7 %) and amyloglucosidase (6–9 times more) than free oil (p < 0.05). The results showed that nanoencapsulation increased the potential for quinoa oil application, enabling the development of innovative products.

Unveiling the nutrient-wealth of black soybean: A holistic review of its bioactive compounds and health implications.

Legumes, an essential component of staple diets, hold a prominent place in global cuisines. Soybean stands out as a widely cultivated legume and is valued for its high protein content, dietary fiber, and rich micronutrients. Several varieties of soybean are available, of which black and yellow varieties show dominance in varied countries and cultures. Over time, the cultivation and consumption of black soybeans have markedly reduced compared to the yellow variety. Despite its rich nutritional and therapeutic indices, it has lost its usage over time. Traditionally, it was utilized in oriental medicine for detoxification and anti-inflammatory potential. However, the antinutrients present in black soybean limit its utilization in the food sector due to their interference with overall nutrient absorption. Several studies in the last few decades have focused on reducing the content of antinutritional factors. However, the information on the use of different processing techniques, both singly and in blends, to reduce antinutrients and enhance the bioaccessibility, bioavailability, and bioactivity of bioactive compounds and varied nutrients is limited and fragmented. Furthermore, studies have highlighted black soybeans' protective effects against various degenerative diseases. However, the studies on the effect of processing to enhance its antioxidative properties to make them a sought-after food commodity with nutraceutical potential and therapeutic efficacy are limited and widely scattered. The review aims to consolidate knowledge of diverse processing methods to improve their nutritional and bioactive profile for wider applications in the food and pharmaceutical industries. Further, it has also highlighted its nutraceutical properties for developing varied functional foods against degenerative diseases to have better therapeutic efficacy.

Tirbanibulin (KX2-391) analog KX2-361 inhibits botulinum neurotoxin serotype A mediated SNAP-25 cleavage in pre- and post-intoxication models in cells.

Botulinum neurotoxins (BoNT) inhibit neuroexocytosis, leading to the potentially lethal disease botulism. BoNTserotype A is responsible for most human botulism cases, and there are no approved therapeutics to treat already intoxicated patients. A growing body of research has demonstrated that BoNT/A can escape into the central nervous system, and therefore, identification of BoNT/A inhibitors that can penetrate BBB and neutralize the toxin within intoxicated neurons would be important. We previously identified an FDA-approved, orally bioavailable compound, KX2-391 (Tirbanibulin)that inhibits BoNT/A in motor neuron assays. Recently, a structural analog of KX2-391, KX2-361, has been shown to exhibit good oral bioavailability and cross BBB with high efficiency in mouse experiments. Therefore, in this work, we evaluated the inhibitory effects of KX2-361 against BoNT/A. Toward this goal, we first evaluated the compound for its effects on cell viability in PC12 cells, via MTT assay, and in mouse embryonic stem cell (mESC)-derived motor neurons, with imaging-based assays. Following, we tested KX2-361 in mESC-derived motor neurons intoxicated with BoNT/A holotoxin, and the compound exhibited activity against the toxin in both pre- and post-intoxication conditions. Excitingly, KX2-361 also inhibited BoNT/A enzymatic component (light chain; LC) in PC12 cells transfected with BoNT/A LC. Furthermore, our molecular docking analyses suggested that KX2-361 can directly bind to BoNT/A LC. Medicinal chemistry approaches to develop structural analogs of KX2-361 to increase its efficacy against BoNT/A may provide a critical lead compound with BBB penetration capacity for drug development efforts against BoNT/A intoxication.

Optimization of Polyphenol Extraction Conditions from Rhizomes of Curcuma zedoaria with Antioxidant, Anti-Inflammatory and Anti-Diabetic Activities In Vitro

The recovery of polyphenol compounds is seen as an arduous task because polyphenol compounds are available as free aglycones, as sugar or ester conjugates, or as polymers with several monomeric components. The response surface method (RSM) as a tool to optimize the factors that affect extraction efficacy as well as to obtain maximum recovery of the compounds of interest. This study optimizes ultrasound-assisted polyphenol extraction from Curcuma zedoaria rhizomes using response surface methodology (RSM). Three variables were considered: Ethanol concentration (70 - 90 %, v/v), temperature (60 - 80 °C), and ultrasound time (15 - 25 min). Data were analyzed by ANOVA, yielding an R2 of 0.9993, a significant interaction effect (p &lt; 0.0001), and an insignificant lack-of-fit test (p = 0.6684). Optimal conditions for maximum polyphenol content (TPC = 31.05 ± 0.53 mg GAE/g powder) were 80.02 % ethanol, 68 °C, 20.47 min ultrasound time, and 1/10 (w/v) raw material/solvent ratio. Experimental values matched RSM predictions, confirming successful extraction optimization from Curcuma zedoaria rhizomes. The polyphenol-rich optimum extract from Curcuma zedoaria rhizomes has been studied for its antioxidant, anti-inflammatory and anti-inflammatory properties in vitro. The results were found, the optimum extract of Curcuma zedoaria rhizomes could perform effective neutralization activities of free radicals performed in DPPH test (IC50 = 5.89 ± 0.23 µg/mL), NO· (IC50 = 5.89 ± 0.23 µg/mL) and ABTS·+ (IC50 = 8.28 ± 0.12 µg/mL). Besides, this optimum extract had the ability to protect red blood cell membranes and inhibit protein denaturation due to heat with IC50 times values ​​such as 29.06 ± 0.35 and 30.24 ± 0.32 µg/mL. In addition, it also significantly inhibited α-amylase, α-glucosidase enzyme activities with IC50 values ​​of 5.89 ± 0.23 and 9.62 ± 0.11 μg/mL, respectively. This investigation showed that the polyphenol-rich optimum extract from Curcuma zedoaria rhizomes was a promising antioxidant, anti-inflammatory and anti-diabetic agent. HIGHLIGHTS Using ultrasound and the Box-Behnken design to extract polyphenols from Curcuma zedoaria rhizomes can speed up and improve extraction efficiency. The goal of this study is to maximize the extraction parameters for polyphenols from the rhizomes of Curcuma zedoaria. There is strong agreement between the experimental data and the model that predicts the polyphenol content in the Box-Behnken design. In vitro biological activities such as anti-inflammatory, antidiabetic and antioxidant properties are significantly correlated with polyphenol concentration. The findings of our investigation show a noteworthy enhancement in the bioavailability of polyphenol compounds through increased extraction efficiency and bioactivity. GRAPHICAL ABSTRACT