Influence of maize genotypes and harvest stages on in-silo fermentation quality and nutritional value of corn silage during hot summer condition of the tropics.

The aim of the experiment was to evaluate the potential of promising summer maize genotypes and optimal stage of harvesting these genotypes for ensiling in terms of dry matter (DM), starch, and crude protein (CP) yields, silage fermentation quality, nutrients profile, total digestible nutrients, metabolizable energy (ME) content, Cornell Net Carbohydrate and Protein System (CNCPS) carbohydrate (CHO) subfractions composition, in vitro DM digestibility (DMD) and in situ starch degradation characteristics. Six maize genotypes were chosen for the study: DK9108 from Monsanto, P30Y87, P3939 from Pioneer, QPM-300 (quality protein maize) and W94 from the International Maize and Wheat Improvement Center (CIMMYT), and a local cultivar, Afgoii, from the Cereal Research Institute (Persabaq, KP). A total of 72 plots (8 m × 10 m) were blocked in three replicate fields, and within each field, each genotype was sown in four replicate plots according to a randomized complete block design. For the data analysis, the Proc-Mixed procedure of Statistical Analysis System with repeated measure analysis of variance was used. The DM yield was strongly influenced (P < 0.001) by maize genotypes, varying from 12.6 to 17.0 tons/ha. Except for total CHO and ammonia nitrogen (NH3-N), the contents of all measured chemical components varied (P < 0.001) among the genotypes. Further comparison revealed that, genotype P3939 had a higher (P < 0.05) content of CP (7.27 vs. 6.92%), starch (36.7 vs. 27.9%), DMD (65.4 vs. 60.0%), ME (2.51 vs. 2.30 Mcal/kg) and lactic acid (5.32 vs. 4.83%) and lowest content of NDF (37.3 vs. 43.1%), pH (3.7 vs. 4.10) compared to the local cultivar (Afgoii). Advancement of post-flowering maturity from 25 to 35% DM (23 to 41 days after flowering (DAF)) increased (P < 0.05) the DM yield (10.4 to 17.8 tons/ha), starch content (29.1 to 35.0%), DMD (65.3 to 67.3%) and ME (2.34 to 2.47 Mcal/kg), and decreased (P < 0.001) the contents of CP (7.42-6.73%), NDF (48.8-38.5%), pH (4.10 to 3.60), NH3-N (8.93-7.80%N) and effective degradability of starch (95.4 to 89.4). Results showed that for higher yields and silage nutritional and fermentation quality, maize crops should be harvested at whole crop DM content of 30-35% (34 to 41 DAF). It was further concluded that genotype P3939 is the most suitable summer maize genotype for silage production in terms of yields and silage nutritional and fermentation quality under the hot environmental conditions of the tropics.

Synthesis of 2-Ethylhexyl 5-Bromothiophene-2-Carboxylates; Antibacterial Activities against Salmonella Typhi, Validation via Docking Studies, Pharmacokinetics, and Structural Features Determination through DFT.

A new class of thiophene-based molecules of 5-bromothiophene-2-carboxylic acid (1) have been synthesized in current research work. All analogs 4A-4G were synthesized with optimized conditions by coupling reactions of 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) with various arylboronic acids. The results indicated that the majority of compounds showed promising effective in vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p-tolyl)thiophene-2-carboxylate (4F), in particular among the synthesized analogs, showed outstanding antibacterial action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. The intermolecular interaction was investigated by using a molecular docking study of thiophene derivatives 4A-4G against XDR S. Typhi. The values of the binding affinity of functionalized thiophene molecules and ciprofloxacin were compared against bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears to be a promising antibacterial agent and showed the highest potential value. Density functional theory (DFT) calculations were executed to examine the electronic, structural, and spectroscopic features of the newly synthesized molecules 4A-4G.

Apolipoprotein E Gene Variation in Pakistani Subjects with Type 2 Diabetes with and without Cardiovascular Complications.

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.

Treatment with Glyphosate Induces Tolerance of Citrus Pathogens to Glyphosate and Fungicides but Not to 1,8-Cineole.

During the postharvest period, citrus fruits are exposed to Penicillium italicum, Penicillium digitatum, and Geotrichum candidum. Pesticides such as imazalil (IMZ), thiabendazole (TBZ), orthophenylphenol (OPP), and guazatine (GUA) are commonly used as antifungals. Glyphosate (GP) is also used in citrus fields to eliminate weed growth. The sensitivity of fungal pathogens of citrus fruit to these pesticides and 1,8-cineole was evaluated, and the effect of GP on the development of cross-resistance to other chemicals was monitored over a period of 3 weeks. IMZ most effectively inhibited the mycelial growth and spore germination of P. digitatum and P. italicum, with minimum inhibitory concentrations (MICs) of 0.01 and 0.05 mg/mL, respectively, followed by 1,8-cineole, GP, and TBZ. 1,8-Cineole and GP more effectively inhibited the mycelial growth and spore germination of G. candidum, with minimum inhibitory concentrations (MICs) of 0.2 and 1.0 mg/mL, respectively, than OPP or GUA. For the spore germination assay, all substances tested showed a total inhibitory effect. Subculturing the fungal strains in culture media containing increasing concentrations of GP induced fungal tolerance to GP as well as to the fungicides. In soil, experiments confirmed that GP induced the tolerance of P. digitatum to TBZ and GP and the tolerance of P. italicum to IMZ, TBZ, and GP. However, no tolerance was recorded against 1,8-cineole. In conclusion, it can be said that 1,8-cineole may be recommended as an alternative to conventional fungicides. In addition, these results indicate that caution should be taken when using GP in citrus fields.

Antioxidant, Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC50 of 1.30 ± 0.05 mg/mL in the DPPH test and an EC50 equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC50) was 7.8 ± 0.3 µL EO/L, while the effective concentration in the ingestion test (LC50) was 15.0 ± 2.1 µL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.

Antioxidant and Antimicrobial Activities of Chemically-Characterized Essential Oil from Artemisia aragonensis Lam. against Drug-Resistant Microbes.

This study investigated the chemical composition, antioxidant and antimicrobial activity of essential oil extracted from Artemisia aragonensis Lam. (EOA). Hydrodistillation was employed to extract EOA. Gas chromatography with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry analyses (GC-MS) were used to determine the phytochemical composition of EOA. Antioxidant potential was examined in vitro by use of three tests: 2.2-diphenyl-1-picrilhidrazil (DPPH), ferric reducing activity power (FRAP) and total antioxidant capacity assay (TAC). Agar diffusion and microdilution bioassays were used to assess antimicrobial activity. GC/MS and GC-FID detected 34 constituents in the studied EOA. The major component was Camphor (24.97%) followed by Borneol (13.20%), 1,8 Cineol (10.88%), and Artemisia alcohol (10.20%). EOA exhibited significant antioxidant activity as measured by DPPH and FRAP assays, with IC50 and EC50 values of 0.034 ± 0.004 and 0.118 ± 0.008 mg/mL, respectively. EOA exhibited total antioxidant capacity of 7.299 ± 1.774 mg EAA/g. EOA exhibited potent antibacterial activity as judged by the low minimum inhibitory concentration (MIC) values against selected clinically-important pathogenic bacteria. MIC values of 6.568 ± 1.033, 5.971 ± 1.033, 7.164 ± 0.0 and 5.375 ± 0.0 µg/mL were observed against S. aureus, B. subtills, E. coli 97 and E. coli 57, respectively. EOA displayed significant antifungal activity against four strains of fungi: F. oxysporum, C. albicans, A. flavus and A. niger with values of 21.50 ± 0.43, 5.31 ± 0.10, 21.50 ± 0.46 and 5.30 ± 0.036 µg/mL, respectively. The results of the current study highlight the importance of EOA as an alternative source of natural antioxidant and antibacterial drugs to combat antibiotic-resistant microbes and free radicals implicated in the inflammatory responses accompanying microbial infection.

Solanum elaeagnifolium Var. Obtusifolium (Dunal) Dunal: Antioxidant, Antibacterial, and Antifungal Activities of Polyphenol-Rich Extracts Chemically Characterized by Use of In Vitro and In Silico Approaches.

The present work was designed to study the chemical composition and the antioxidant and antimicrobial properties of fruits (SFr) and leaf (SF) extracts from Solanum elaeagnifolium var. obtusifolium (Dunal) Dunal (S. elaeagnifolium). The chemical composition was determined using HPLC-DAD analysis. Colorimetric methods were used to determine polyphenols and flavonoids. Antioxidant capacity was assessed with DPPH, TAC, and FRAP assays. Antimicrobial activity was assessed using disk diffusion and microdilution assays against two Gram (+) bacteria (Staphylococcus aureus ATCC-6633 and Bacillus subtilis DSM-6333) and two Gram (-) bacteria (Escherichia coli K-12 and Proteus mirabilis ATCC-29906), while the antifungal effect was tested vs. Candida albicans ATCC-1023. By use of in silico studies, the antioxidant and antimicrobial properties of the studied extracts were also investigated. HPLC analysis showed that both fruits and leaf extracts from S. elaeagnifolium were rich in luteolin, quercetin, gallic acid, and naringenin. Both SFr and SF generated good antioxidant activity, with IC50 values of 35.15 ± 6.09 µg/mL and 132.46 ± 11.73 µg/mL, respectively. The EC50 of SFr and SF was 35.15 ± 6.09 µg/mL and 132.46 ± 11.73 µg/mL, respectively. SFr and SF also showed a good total antioxidant capacity of 939.66 ± 5.01 µg AAE/and 890.1 ± 7.76 µg AAE/g, respectively. SFr had important antibacterial activity vs. all tested strains-most notably B. subtilis DSM-6333 and E. coli, with MICs values of 2.5 ± 0.00 mg/mL and 2.50 ± 0.00 mg/mL, respectively. SFr demonstrated potent antifungal activity against C. albicans, with an inhibition diameter of 9.00 ± 0.50 mm and an MIC of 0.31 ± 0.00 mg/mL. The in silico approach showed that all compounds detected in SFr and SF had high activity (between -5.368 and 8.416 kcal/mol) against the receptors studied, including NADPH oxidase, human acetylcholinesterase, and beta-ketoacyl-[acyl carrier protein] synthase.

Relationship between the Chemical Composition and the Biological Functions of Coffee.

Coffee is a Rubiaceae coffee plant ranked as the first of the three most important beverages in the world, with effects including lowering blood sugar, protecting the liver, and protecting the nerves. Coffee contains many chemical components, including alkaloids, phenolic acids, flavonoids, terpenoids, and so on. Chemical components in coffee are the basis of its biological function and taste. The chemical components are the basis of biological activities and form the characteristic aroma of coffee. The main chemical components and biological activities of coffee have been extensively studied, which would provide a relevant basis and theoretical support for the further development of the coffee industry.

Buffalo Yogurt Fortified with Eucalyptus (Eucalyptus camaldulensis) and Myrrh (Commiphora Myrrha) Essential Oils: New Insights into the Functional Properties and Extended Shelf Life.

Eucalyptus (Eucalyptus camaldulensis) and Myrrh (Commiphora Myrrha) essential oils (EOs) stand out for their benefits in terms of health and functionality. Buffalo set yogurt enriched with different concentrations of EOs (0.3, 0.6, and 0.9%) were investigated. The effects of addition on sensory, syneresis, antibacterial activity, and bioactive properties (total phenol content and antioxidant activity) of yogurt were studied. The most acceptable organoleptic properties of treated yogurt were those samples treated with Eucalyptus oil. The levels of syneresis were decreased by increasing the concentration of EOs. Moreover, the antioxidant activity, antibacterial activity, and total phenolic content were enhanced by increasing the concentration of EOs. Yogurt with 0.9% Eucalyptus oil showed the highest antioxidant activity and total phenolic content. The same concentration of Eucalyptus oil showed the highest antibacterial activity against S. typhimurium (the inhibition zone was 20.63 mm) then E. coli (the inhibition zone was 19.43 mm). On the other hand, the highest antibacterial effect against L. monocytogene was for Myrrh oil-enriched yogurt by 0.9% and the inhibition zone was 19.21 mm. The obtained results showed that Eucalyptus and Myrrh oils can be applied to yogurt to improve its beneficial properties in terms of physical characteristics and for human health due to their antioxidant activity and phenolic materials.

Boiling Technique-Based Food Processing Effects on the Bioactive and Antimicrobial Properties of Basil and Rosemary.

Rosemary (Rosmarinus officinalis) and basil (Ocimum sanctum Linn) are mostly used as herbal teas, made by steeping whole or ground herbs in boiling water. Hence, it is important to know the effect of boiling time on the bioactivity of these herbs. The effect of different boiling times (5, 10, and 15 min) on the antioxidant and antimicrobial properties, and some selected phenolic compounds of these herbs was examined in this study. Experimental results revealed that basil displayed the highest total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity when it was boiled for 5 min, and the lowest TPC was obtained when it was boiled for 15 min. On the other hand, rosemary had the highest TPC, TFC, and antioxidant potential after being boiled for 15 min, while it had the lowest after being boiled for 5 min. There was no growth inhibition of rosemary extracts against gram-negative bacteria, whereas higher growth inhibition was observed against gram-positive bacteria. The MIC and MBC of rosemary ethanolic extract against Listeria monocytogenes were 5 and 5 mg/mL and against B. subtilis were 10 and 10 mg/mL, respectively. While MIC and MBC of methanolic extract against L. monocytogenes were 5 and 5 mg/mL and against Bacillus subtilis were and 5 and 5 mg/mL, respectively. Salicylic acid was the most abundant (324.7 mg/100 g dry weight (dw)) phenolic compound in the rosemary sample boiled for 5 min, and acetyl salicylic acid was the most abundant (122.61 mg/10 g dw) phenolic compound in the basil sample boiled for 15 min.

Assessment of Vitamin D Status in the Drâa-Tafilalet Population (Morocco) Based on Sociodemographic, Health, and Nutritional Factors.

The purpose of this study was to evaluate the vitamin D status and determine the factors influencing it in the Drâa-Tafilalet community (southeastern Morocco). Sociodemographic factors, health, cognitive status, sun exposure, and nutritional conditions were examined to help us understand their association with vitamin D status. Vitamin D data were gathered through laboratory testing, while demographic and health information was collected through interviews with participants in 2023. The study involved 100 participants aged 60 and above, most of whom were women (85%) rather than men (15%). The majority of participants were Arabs (90%), with a minority being Amazigh (10%). The average vitamin D level was 31.83 ± 10.55 ng/mL, varying based on participants' age, education, and gender. Sun-exposed individuals exhibited significantly higher mean vitamin D levels (33.56 ± 11.99 ng/mL) compared to those with limited sun exposure (28.97 ± 9.28 ng/mL). Moreover, the time spent outdoors, seasonal changes, and the duration of sun exposure affected the levels of vitamin D. These findings depict the vitamin D status of the elderly population of Drâa-Tafilalet, recognized as one of Morocco's poorest regions, shedding light on the significant influencers. Nonetheless, additional research is necessary to explore the correlation between dietary habits, sunlight exposure, and vitamin D levels in both young and elderly populations.

Pharmacotherapeutic potential of malvidin to cure imidacloprid induced hepatotoxicity via regulating PI3K/AKT, Nrf-2/Keap-1 and NF-κB pathway.

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine-aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions.

Polysaccharide-coated quercetin-loaded nanoliposomes mitigate bitterness: A comparison of carrageenan, pectin, and trehalose.

The intense bitterness of quercetin poses a challenge to its utilization in the food industry. To address this issue, three anionic polysaccharides (carrageenan, pectin, and trehalose) were individually incorporated to fabricate polysaccharide-coated liposome nanocarriers. Electronic tongue analysis revealed a significant decreasing bitterness value (10.34 ± 0.07 mV, sensory score 1.8 ± 0.2, taste weak bitter) in quercetin-loaded nanoliposomes, compared with the bitterness value of quercetin aqueous solution (14 ± 0.01 mV, sensory score 7.3 ± 0.3, taste strong bitter). Furthermore, the polysaccharide-coated nanoliposomes exhibited an even greater capacity to mask the bitterness of quercetin, with carrageenan coated nanoliposomes demonstrating the most pronounced effect. The superior bitter masking ability of carrageenan coated nanoliposomes can be attributed to its high charge and viscosity. In sensory evaluations, gummy incorporated with carrageenan-coated nanoliposomes received the highest ratings, exhibiting enhanced overall palatability and antioxidant activity. This study offers insights into expanding the use of bitter nutrients in food applications and paves the way for more appealing and healthful food products.

Molecular modeling and simulation approaches to characterize potential molecular targets for burdock inulin to instigate protection against autoimmune diseases.

In the current study, we utilized molecular modeling and simulation approaches to define putative potential molecular targets for Burdock Inulin, including inflammatory proteins such as iNOS, COX-2, TNF-alpha, IL-6, and IL-1ß. Molecular docking results revealed potential interactions and good binding affinity for these targets; however, IL-1ß, COX-2, and iNOS were identified as the best targets for Inulin. Molecular simulation-based stability assessment demonstrated that inulin could primarily target iNOS and may also supplementarily target COX-2 and IL-1ß during DSS-induced colitis to reduce the role of these inflammatory mechanisms. Furthermore, residual flexibility, hydrogen bonding, and structural packing were reported with uniform trajectories, showing no significant perturbation throughout the simulation. The protein motions within the simulation trajectories were clustered using principal component analysis (PCA). The IL-1ß-Inulin complex, approximately 70% of the total motion was attributed to the first three eigenvectors, while the remaining motion was contributed by the remaining eigenvectors. In contrast, for the COX2-Inulin complex, 75% of the total motion was attributed to the eigenvectors. Furthermore, in the iNOS-Inulin complex, the first three eigenvectors contributed to 60% of the total motion. Furthermore, the iNOS-Inulin complex contributed 60% to the total motion through the first three eigenvectors. To explore thermodynamically favorable changes upon mutation, motion mode analysis was carried out. The Free Energy Landscape (FEL) results demonstrated that the IL-1ß-Inulin achieved a single conformation with the lowest energy, while COX2-Inulin and iNOS-Inulin exhibited two lowest-energy conformations each. IL-1ß-Inulin and COX2-Inulin displayed total binding free energies of - 27.76 kcal/mol and - 37.78 kcal/mol, respectively, while iNOS-Inulin demonstrated the best binding free energy results at - 45.89 kcal/mol. This indicates a stronger pharmacological potential of iNOS than the other two complexes. Thus, further experiments are needed to use inulin to target iNOS and reduce DSS-induced colitis and other autoimmune diseases.

Design, Synthesis, Evaluation, and Molecular Docking Study of Ascorbic Acid Dual-Coated Omeprazole Pellets and the Antioxidative Effect of Ascorbic Acid on Omeprazole-Induced Renal Injury in an Animal Model.

The present study was carried out to investigate the antioxidant effect of ascorbic acid on omeprazole (O.P.)-induced acute kidney infection (AKI). Design of experiment (DoE) was employed to fabricate formulations (P1-P8) by the extrusion spheronization technique, and they were evaluated using various analytical techniques. P1-P8 formulations have % drug loading ranging from 56.34 ± 1.10 to 98.67 ± 1.05%, encapsulation efficiency from 70.98 ± 0.96 to 98.67 ± 1.05%, percentage drug release varying from 36.56 ± 1.34 to 93.45 ± 1.45%, Hausner's ratio ranging from 1.026 ± 0.05 to 1.065 ± 0.02%, and Carr's index varying from 2.3 ± 0.07 to 6.1 ± 0.06 g/mL. The optimized formulation (P6) was dual-coated with Eudragit L-100 (5% w/v) and ascorbic acid (2% w/v). A smooth uniform morphology was found after coating, and particle size nonsignificantly changed from 85.31 ± 77.43 to 101.99 ± 65.56 µm. IR spectra showed omeprazole characteristic peaks confirming drug loading, and peaks at 1747.40 and 1611.51 cm-1 confirmed ascorbic acid and Eudragit L-100 coating. X-ray diffraction (XRD) analysis confirmed the crystalline nature, and thermal degradation studies until 500 °C demonstrated increased stability after coating. Cytotoxicity analysis with 97% cell viability revealed the nontoxic behavior of pellets. In vitro dissolution studies of coated pellets showed <20% drug release at pH 1.2 and 99.54% at pH 6.8. Animal studies showed that pure omeprazole showed a nonsignificant decrease in weight, urine output, and fecal output compared to rodents on ascorbic acid pellets. Increased uric acid and creatinine levels in the group on pure omeprazole indicated AKI. Histopathological studies of renal cells also supported these results. The integration of experimental pellet formulation with molecular docking simulations has unveiled the potential of ascorbic acid and omeprazole as highly promising therapeutic agents for addressing oxidative stress and inflammation.

Exploring Citrus sinensis Phytochemicals as Potential Inhibitors for Breast Cancer Genes BRCA1 and BRCA2 Using Pharmacophore Modeling, Molecular Docking, MD Simulations, and DFT Analysis.

BACKGROUND: Structure-activity relationship (SAR) is considered to be an effective in silico approach when discovering potential antagonists for breast cancer due to gene mutation. Major challenges are faced by conventional SAR in predicting novel antagonists due to the discovery of diverse antagonistic compounds. Methodologyand Results: In predicting breast cancer antagonists, a multistep screening of phytochemicals isolated from the seeds of the Citrus sinensis plant was applied using feasible complementary methodologies. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed through the Flare project, in which conformational analysis, pharmacophore generation, and compound alignment were done. Ten hit compounds were obtained through the development of the 3D-QSAR model. For exploring the mechanism of action of active compounds against cocrystal inhibitors, molecular docking analysis was done through Molegro software (MVD) to identify lead compounds. Three new proteins, namely, 1T15, 3EU7, and 1T29, displayed the best Moldock scores. The quality of the docking study was assessed by a molecular dynamics simulation. Based on binding affinities to the receptor in the docking studies, three lead compounds (stigmasterol P8, epoxybergamottin P28, and nobiletin P29) were obtained, and they passed through absorption, distribution, metabolism, and excretion (ADME) studies via the SwissADME online service, which proved that P28 and P29 were the most active allosteric inhibitors with the lowest toxicity level against breast cancer. Then, density functional theory (DFT) studies were performed to measure the active compound's reactivity, hardness, and softness with the help of Gaussian 09 software. CONCLUSIONS: This multistep screening of phytochemicals revealed high-reliability antagonists of breast cancer by 3D-QSAR using flare, docking analysis, and DFT studies. The present study helps in providing a proper guideline for the development of novel inhibitors of BRCA1 and BRCA2.

Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells.

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-ß1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects.

Comprehensive analysis of bioactive compounds in Crocus sativus stamens extracts by HPLC-DAD: investigating antidiabetic activity via in vitro, in vivo, and molecular docking simulation.

Introduction: Medicinal herbs used in traditional diabetes treatment are a rich source of anti-diabetic compounds. Pancreatic α-amylase inhibitors offer an effective strategy to reduce postprandial hyperglycemic levels via control of starch degradation. In this context, our study for the first time investigates the effect of Crocus sativus stamens extracts on α-amylase inhibition. Material and methods: The hydromethanolic and hydroethanolic extracts were obtained by macerating the dried stamen powder with methanol/water or ethanol/water, respectively. The total phenolic content of the stamen extracts was assessed using the Folin-Ciocalteu reagent method, while the total flavonoid content was determined using the Aluminum Chloride method. Phytochemicals were further quantified and identified using HPLC-DAD. For evaluation of hypoglycemic activity, in vitro α-amylase enzyme inhibition was calculated. The results were confirmed in vivo using an oral starch tolerance test in both normal and diabetic rats. Results: Our findings demonstrated a higher level of polyphenols and flavonoids in the hydroethanolic extract. Important flavonoids found were kaempferol, rutin, and vanillic acid, while prominent carotenoids contained trans- and cis-crocins. The in vitro study showed that both hydromethanolic and hydroethanolic extracts had considerable inhibitory effects, with maximum inhibitions of approximately 83% and 89%, respectively. In vivo tests indicated that both extracts effectively lowered peak blood glucose and area under the curve in both normal and diabetic rats following oral starch treatment. The obtained results are also supported by a docking study. Conclusion: These findings imply that C. sativus stamens possess a distinctive capability to reduce postprandial blood glucose levels. This effect is likely mediated through the inhibition of α-amylase, presenting a novel dietary avenue for managing diabetes.

Exploring the multifaceted bioactivities of Lavandula pinnata L. essential oil: promising pharmacological activities.

Introduction: This study investigates the biological activities of Lavandula pinnata essential oil (LPEO), an endemic lavender species from the Canary Islands, traditionally used in treating various ailments. Methods: LPEO was extracted by hydrodistillation and analyzed using GC-MS. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Antimicrobial activity was evaluated by disc diffusion, MIC, MBC, and MFC determination against bacterial (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa) and fungal (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, Penicillium digitatum) strains. Antidiabetic and anti-gout potential were investigated through α-amylase, α-glucosidase, and xanthine oxidase inhibition assays. Antityrosinase activity was determined using a modified dopachrome method. Cytotoxicity was assessed by MTT assay against breast (MCF-7, MDA-MB-468), liver (HepG2), colon (HCT-15) cancer cells, and normal cells (PBMCs). Results and discussion: LPEO exhibits potent antiradical activity (IC50 = 148.33 ± 2.48 µg/mL) and significant antioxidant capacity (TAC = 171.56 ± 2.34 µg AA/mg of EO). It demonstrates notable antibacterial activity against four strains (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa) with inhibition zones ranging from 18.70 ± 0.30 mm to 29.20 ± 0.30 mm, along with relatively low MIC and MBC values. LPEO displays significant antifungal activity against four strains (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, and Penicillium digitatum) with a fungicidal effect at 1 mg/mL, surpassing the positive control (cycloheximide), and MIC and MFC values indicating a fungicidal effect. It exhibits substantial inhibition of xanthine oxidase enzyme (IC50 = 26.48 ± 0.90 µg/mL), comparable to allopurinol, and marked inhibitory effects on α-amylase (IC50 = 31.56 ± 0.46 µg/mL) and α-glucosidase (IC50 = 58.47 ± 2.35 µg/mL) enzymes.The enzyme tyrosinase is inhibited by LPEO (IC50 = 29.11 ± 0.08 mg/mL). LPEO displays moderate cytotoxic activity against breast, liver, and colon cancer cells, with low toxicity towards normal cells (PBMC). LPEO exhibits greater selectivity than cisplatin for breast (MCF-7) and colon (HCT-15) cancer cells but lower selectivity for liver (HepG2) and metastatic breast (MDA-MB-468) cancer cells. These findings suggest the potential of LPEO as an antioxidant, antimicrobial, anti-gout, antidiabetic, and anticancer agent.

Phytochemical characterization and multifaceted bioactivity assessment of essential oil from Ptychotis verticillata Duby: Anti-diabetic, anti-tyrosinase, and anti-inflammatory activity.

The aim of this study is to explore the pharmacological properties of the essential oil derived from Ptychotis verticillata Duby (PVEO), a medicinal plant native to Morocco, focusing on its antidiabetic, anti-tyrosinase, and anti-inflammatory effects. Additionally, the study aims to characterize the phytochemical composition of PVEO and evaluate its potential as a natural therapeutic alternative for various health conditions. To achieve this, phytochemical analysis was conducted using gas chromatography-mass spectrometry (GC-MS). Furthermore, in vitro assessments were conducted to investigate PVEO's antidiabetic activity by inhibiting α-amylase, xanthine oxidase, and α-glucosidase. Tests were also undertaken to evaluate the anti-inflammatory effect of PVEO on RAW 264.7 cells stimulated by lipopolysaccharide (LPS), as well as its efficacy as an anti-tyrosinase agent and its lipoxygenase inhibition activity. The results of the phytochemical analysis revealed that PVEO is rich in terpene compounds, with percentages of 40.35 % γ-terpinene, 22.40 % carvacrol, and 19.77 % ß-cymene. Moreover, in vitro evaluations demonstrated that PVEO exhibits significant inhibitory activity against α-amylase, xanthine oxidase, and α-glucosidase, indicating promising antidiabetic, and anti-gout potential. Furthermore, PVEO showed significant anti-tyrosinase activity, with an IC50 of 27.39 ± 0.44 µg/mL, and remarkable lipoxygenase inhibition (87.33 ± 2.6 %), suggesting its candidacy for dermatoprotection. Additionally, PVEO displayed a dose-dependent capacity to attenuate the production of NO and PGE2, two inflammatory mediators implicated in various pathologies, without compromising cellular viability. The findings of this study provide a solid foundation for future research on natural therapies and the development of new drugs, highlighting the therapeutic potential of PVEO in the treatment of gout, diabetes, pigmentation disorders, and inflammation.