Co-Delivery of Dragon's Blood and Alkanna tinctoria Extracts Using Electrospun Nanofibers: In Vitro and In Vivo Wound Healing Evaluation in Diabetic Rat Model.

The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. Dragon's blood (DB) and Alkanna tinctoria (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25-38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Along with that, the DB-AT NFs showed effective growth inhibition for both P. aeruginosa and S. aureus compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.

Diabetes-related lower limb wounds: Antibiotic susceptibility pattern and biofilm formation.

The expeditious incidence of diabetes mellitus in Riyadh, Saudi Arabia, there is a significant increase in the total number of people with diabetic foot ulcers. For diabetic lower limb wound infections (DLWs) to be effectively treated, information on the prevalence of bacteria that cause in this region as well as their patterns of antibiotic resistance is significant. Growing evidence indicates that biofilm formers are present in chronic DFU and that these biofilm formers promote the emergence of multi-drug antibiotic resistant (MDR) strains and therapeutic rejection. The current study targeted to isolate bacteria from wounds caused by diabetes specifically at hospitals in Riyadh and assess the bacterium's resistance to antibiotics and propensity to develop biofilms. Totally 63 pathogenic microbes were identified from 70 patients suffering from DFU. Sixteen (25.4%) of the 63 bacterial strains were gram-positive, and 47 (74.6%) were gram-negative. Most of the gram-negative bacteria were resistant to tigecycline, nitrofurantoin, ampicillin, amoxicillin, cefalotin, and cefoxitin. Several gram-negative bacteria are susceptible to piperacillin, meropenem, amikacin, gentamicin, imipenem, ciprofloxacin, and trimethoprim. The most significant antibiotic that demonstrated 100% susceptibility to all pathogens was meropenem. Serratia marcescens and Staphylococcus aureus were shown to have significant biofilm formers. MDR bacterial strains comprised about 87.5% of the biofilm former strains. To the best of our knowledge, Riyadh, Saudi Arabia is the first region where Serratia marcescens was the most common bacteria from DFU infections. Our research findings would deliver information on evidence-based alternative strategies to develop effective treatment approaches for DFU treatment.

Optimization of cationic nanoparticles stabilized by poloxamer 188: A potential approach for improving the biological activity of Aloeperryi.

Aloe perryi (AP) has gained considerable interest as a medicinal herb in various biological applications due to its rich phytochemical composition. However, the therapeutic benefits of AP could be potentiated by utilizing nanotechnology. Moreover, cationic solid lipid nanoparticles (CSLNs) possess remarkable characteristics that can greatly enrich a variety of biological uses. An optimization approach was used to achieve high-quality CSLNs to maximize the therapeutic efficacy of AP. Therefore, a factorial design was used to investigate the influence of various variables on the attributes of CSLNs quality. In this study, the factors under investigation were compritol 888 ATO (C-888, X1), poloxamer 188 (PL188, X2), and chitosan (CS, X3), which served as independent variables. The parameters measured as dependent variables included particle size (Y1), zeta potential (Y2), and encapsulation efficiency EE (Y3). The relationship among these variables was determined by Analysis of Variance (ANOVA) and response surface plots. The results revealed that PL188 played a significant role in reducing the particle size of CSLNS (ranging from 207 to 261 nm with 1 % PL188 to 167-229 nm with 3 % PL188). Conversely, an increase in the concentration of CS led to a rise in the particle size. The magnitude of positive zeta potential values was dependent on the increased concentration of CS. Moreover, the higher amounts of C-888 and PL188 improved the EE% of the CSLNs from 42 % to 86 %. Furthermore, a concentration-dependent antioxidant effect of the optimized AP-CSLNs was observed. The antioxidant activity of the optimized AP-CSLNs at 100 µg/mL was 75 % compared to 62 % and 60 % for AP-SLNs and AP solution, respectively. A similar pattern of improvement was also observed with antimicrobial, and anticancer activities of the optimized AP-CSLNs. These findings demonstrated the potential of AP-CSLNs as a carrier system, enhancing the biological activities of AP, opening new possibilities in herbal medicines.

Chitosan-Coated Solid Lipid Nanoparticles as an Efficient Avenue for Boosted Biological Activities of Aloe perryi: Antioxidant, Antibacterial, and Anticancer Potential.

Aloe perryi (ALP) is an herb that has several biological activities such as antioxidant, antibacterial, and antitumor effects and is frequently used to treat a wide range of illnesses. The activity of many compounds is augmented by loading them in nanocarriers. In this study, ALP-loaded nanosystems were developed to improve their biological activity. Among different nanocarriers, solid lipid nanoparticles (ALP-SLNs), chitosan nanoparticles (ALP-CSNPs), and CS-coated SLNs (C-ALP-SLNs) were explored. The particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and release profile were evaluated. Scanning electron microscopy was used to see the nanoparticles' morphology. Moreover, the possible biological properties of ALP were assessed and evaluated. ALP extract contained 187 mg GAE/g extract and 33 mg QE/g extract in terms of total phenolic and flavonoid content, respectively. The ALP-SLNs-F1 and ALP-SLNs-F2 showed particle sizes of 168.7 ± 3.1 and 138.4 ± 9.5 nm and the zeta potential values of -12.4 ± 0.6, and -15.8 ± 2.4 mV, respectively. However, C-ALP-SLNs-F1 and C-ALP-SLNs-F2 had particle sizes of 185.3 ± 5.5 and 173.6 ± 11.3 nm with zeta potential values of 11.3 ± 1.4 and 13.6 ± 1.1 mV, respectively. The particle size and zeta potential of ALP-CSNPs were 214.8 ± 6.6 nm and 27.8 ± 3.4 mV, respectively. All nanoparticles exhibited PDI < 0.3, indicating homogenous dispersions. The obtained formulations had EE% and DL% in the ranges of 65-82% and 2.8-5.2%, respectively. After 48 h, the in vitro ALP release rates from ALP-SLNs-F1, ALP-SLNs-F2, C-ALP-SLNs-F1, C-ALP-SLNs-F2, and ALP-CSNPs were 86%, 91%, 78%, 84%, and 74%, respectively. They were relatively stable with a minor particle size increase after one month of storage. C-ALP-SLNs-F2 exhibited the greatest antioxidant activity against DPPH radicals at 73.27%. C-ALP-SLNs-F2 demonstrated higher antibacterial activity based on MIC values of 25, 50, and 50 µg/mL for P. aeruginosa, S. aureus, and E. coli, respectively. In addition, C-ALP-SLNs-F2 showed potential anticancer activity against A549, LoVo, and MCF-7 cell lines with IC50 values of 11.42 ± 1.16, 16.97 ± 1.93, and 8.25 ± 0.44, respectively. The results indicate that C-ALP-SLNs-F2 may be promising nanocarriers for enhancing ALP-based medicines.

Green Synthesis and Investigation of Surface Effects of α-Fe2O3@TiO2 Nanocomposites by Impedance Spectroscopy.

Nanocomposites based on iron oxide/titanium oxide nanoparticles were prepared by employing green synthesis, which involved phytochemical-mediated reduction using ginger extract. XRD confirmed the composite formation, while scanning electron microscopy (SEM), dynamic light scattering (DLS), and energy-dispersive X-ray spectroscopy (EDX) was employed to investigate the particle size, particle morphology, and elemental analysis. SEM indicated the formation of particles with non-uniform shape and size distribution, while EDX confirmed the presence of Fe, Ti and oxygen in their elemental state. The surface effects were investigated by Fourier transform infrared radiation (FTIR) and impedance spectroscopy (IS) at room temperature. IS confirmed the co-existence of grains and grain boundaries. Thus, FTIR and IS analysis helped establish a correlation between enhanced surface activity and the synthesis route adopted. It was established that the surface activity was sensitive to the synthesis route adopted. The sample density, variation in grain size, and electrical resistivity were linked with surface defects, and these defects were related to temperature. The disorder and defects created trap centers at the sample's surface, leading to adsorption of CO2 from the environment.

Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study.

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is ß-Lactam antibiotics. However, most bacteria have developed resistance against ß-Lactams by producing enzymes ß-Lactamase or penicillinase. The discovery of new ß-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1-5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8-5.3 µg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to ß-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.

Biodiesel Production from Alkali-Catalyzed Transesterification of Tamarindus indica Seed Oil and Optimization of Process Conditions.

Biodiesel is considered a sustainable alternative to petro-diesel owing to several favorable characteristics. However, higher production costs, primarily due to the use of costly edible oils as raw materials, are a chief impediment to its pecuniary feasibility. Exploring non-edible oils as raw material for biodiesel is an attractive strategy that would address the economic constraints associated with biodiesel production. This research aims to optimize the reaction conditions for the production of biodiesel through an alkali-catalyzed transesterification of Tamarindus indica seed oil. The Taguchi method was applied to optimize performance parameters such as alcohol-to-oil molar ratio, catalyst amount, and reaction time. The fatty acid content of both oil and biodiesel was determined using gas chromatography. The optimized conditions of alcohol-to-oil molar ratio (6:1), catalyst (1.5% w/w), and reaction time 1 h afforded biodiesel with 93.5% yield. The most considerable contribution came from the molar ratio of alcohol to oil (75.9%) followed by the amount of catalyst (20.7%). In another case, alcohol to oil molar ratio (9:1), catalyst (1.5% w/w) and reaction time 1.5 h afforded biodiesel 82.5% yield. The fuel properties of Tamarindus indica methyl esters produced under ideal conditions were within ASTM D6751 biodiesel specified limits. Findings of the study indicate that Tamarindus indica may be chosen as a prospective and viable option for large-scale production of biodiesel, making it a substitute for petro-diesel.

Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway.

Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases.

Clove and Its Active Compound Attenuate Free Fatty Acid-Mediated Insulin Resistance in Skeletal Muscle Cells and in Mice.

Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation. NGC and SAM treatments enhanced proximal insulin signaling by decreasing serine phosphorylation of insulin receptor substrate-1 (IRS-1) and increasing its tyrosine phosphorylation. SAM and NGC treatments also modified distal insulin signaling by enhancing protein kinase B (PKB) and glycogen synthase kinase-3-beta (GSK-3 beta) phosphorylation in muscle cells. Glucose uptake was enhanced in muscle cells after treatment with SAM and NGC. We observed increased glucose tolerance, glucose-stimulated insulin secretion, decreased insulin resistance, and increased beta cell function in diabetic mice treated with NGC. The results of our study demonstrate that clove extract and its active agent NGC can be potential therapeutic agents for alleviating insulin resistance.

A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells.

Glycotoxins/Advanced glycation end products (AGEs) have implications in development of diabetes and related diseases. In the present study we deciphered the mechanisms of action of URM-II-81, a new derivative of isatin, in alleviation of insulin resistance in human hepatocytes and murine adipocytes. URM-II-81 reduced AGEs formation and receptor for advanced glycation end products (RAGE) expression in both cell types. We also observed suppression of methylglyoxal (MGO) mediated ROS production and deactivation of PKC-α. URM-II-81 restored proximal insulin signaling by modulating IRS-1 phosphorylation. URM-II-81 also alleviated MGO mediated diminished distal insulin signaling by increasing protein kinase B (PKB) and glycogen synthase kinase 3-beta (GSK-3-beta) phosphorylation. Glycogen synthesis was also increased in hepatocytes after treatment with URM-II-81. In adipocytes URM-II-81 prevented MGO induced reduced glucose uptake. We conclude that URM-II-81 can be a possible treatment target to address glycotoxins induced insulin resistance.

Attenuation of palmitate induced insulin resistance in muscle cells by harmala, clove and river red gum.

The present study aimed to decipher the mechanism of action of selected anti-diabetic plants extracts on palmitic acid mediated insulin resistance in muscle cells. Our results showed that extract from Peganum harmala seeds, Eucalyptus camaldulensis and Syzygium aromaticum leaves, showed significant antioxidant activity. We found that these extracts were able to affect stress signalling by reducing p-38 MAP kinase phosphorylation. They also reduced phosphorylation of substrate for insulin receptor (IRS) at serine residues and increased its phosphorylation at tyrosine residues and also enhanced PKB phosphorylation. Glucose uptake was also enhanced in muscle cells after treatment with these extracts. Extracts from Lantana camara, Psidium gujava fruit and different parts of Cassia alata did not affect FFA mediated down-regulation of insulin signalling. The study conclude that seeds of Peganum harmala and leaves of Eucalyptus camaldulensis and Syzygium aromaticum enhanced insulin signal transduction and glucose uptake in muscle cells via reducing oxidative stress. As a result, these herbal extracts may be considered useful to protect from insulin resistance.

A bis-Schiff base of isatin improves methylglyoxal mediated insulin resistance in skeletal muscle cells.

Methylglyoxal (MGO) is a highly reactive advanced glycation end products (AGEs) precursor and its abnormal accumulation causes damage to various tissues and organs. In our previous study, we synthesized a novel MGO inhibitor, MK-I-81, a bis-Schiff base derivative of isatin. In this study we demonstrate the mechanism of action of MK-I-81, on insulin resistance in skeletal muscle cells. MK-I-81 reduced AGEs formation and restored proximal insulin signaling by modulating IRS-1 phosphorylation. MK-I-81 also alleviated MGO mediated diminished distal insulin signaling by increasing protein kinase B and glycogen synthase kinase 3-beta phosphorylation. We also observed that MK-I-81 prevented reduced glucose uptake and glycogen synthesis induced by MGO in muscle cells. We found that the mechanism of action by which MK-I-81 reduced insulin resistance was suppression of production of MGO mediated ROS production in C2C12 cells. We evaluated deactivation of PKC-α and receptor for advanced glycation end products (RAGE) after treatment of cells with MK-I-81. MK-I-81 also reduced MGO mediated IRS-1, PKC-α and RAGE interaction in muscle cells. MK-I-81 also promoted nuclear factor erythroid 2-related factor-2 phosphorylation, heme oxygenase-1 and glyoxalase expression levels. We conclude that MK-I-81 can be a potential therapeutic target to address AGEs mediated insulin resistance. A novel Advanced Glycation End products (AGEs) inhibitor, MK-I-81 (a bis Schiff base of isatin), restored AGEs mediated down regulation of insulin signaling via modulating key molecules of proximal and distal insulin signaling. MK-I-81 also increased glucose uptake and glycogen synthesis in muscle cells. Novel bis-Schiff base of isatin showed significant antioxidant activity and also reduced receptor for AGEs (RAGE) expression and PKC-alpha activation therefore; MK-I-81 reduces AGEs induced insulin resistance.