Elucidation of anti-hyperglycemic activity of Psidium guajava L. leaves extract on streptozotocin induced neonatal diabetic Long-Evans rats.

BACKGROUND: Psidium guajava L (Guava) belongs to the Myrtaceae family and has been claimed to possess several pharmacological properties including antidiabetic. OBJECTIVE: This study was designed to evaluate the anti-hyperglycemic activity of P guajava L leaves aqueous extract on neonatal streptozotocin-induced type 2 diabetic model rats. METHODS: Streptozotocin was induced (90 mg/kg) intraperitoneally to 48 h old Long Evans rat pups. After three months, 18 male type-2 diabetic model rats were confirmed by OGTT (FG > 7 mmol/L). Therefore, experimental rats were divided into three groups 2) Diabetic water control (10 ml/kg), 3) Gliclazide treated (20 mg/kg), and 4) Extract treated group (1.25g/kg)] Six normal female rats comprised group 1 [Non-diabetic water control (10 ml/kg)]. All rats were treated orally with their respective treatment for 28 consecutive days. Blood samples were collected on 0 days (by tail cut method) and the end day (by cardiac puncture) of the experiment. The anti-hyperglycemic activity was evaluated by measuring fasting glucose, serum insulin, lipid profile, hepatic glycogen content, and intestinal glucose absorption by standard methods. RESULTS: The serum glucose level of extract treated group was decreased by 16% as well as significantly (p<0.05) increased the serum insulin level (M±SD, 0 day vs 28thday; 0.319 ± 0.110 vs 0.600 ± 0.348, µg/L). Moreover, the extract-treated group also significantly (p<0.05) enhanced liver glycogen content and inhibited glucose absorption from the upper intestine. Besides, a significant (p < 0.05) reduction of LDL-cholesterol level was found in the extract-treated group (M±SD, 55 ± 33 vs 14 ± 9, mg/dl) compared with baseline values where other groups did not show any statistically remarkable changes. CONCLUSION: Current study concludes that P guajava leaves aqueous extract enhances insulin secretion from pancreatic beta-cells and promotes glycogen synthesis in the liver. The extract also inhibits glucose absorption from the upper intestine and improves dyslipidemia to some extent. Therefore, possesses the potential for drug development against T2DM.

Chemico-biological interaction unraveled the potential mechanistic pathway of Ixeridium dentatum compounds against atopic dermatitis.

This study aims to investigate the potential therapeutic application of Ixeridium dentatum (ID) in treating atopic dermatitis (AD) through network pharmacology, molecular docking, and molecular dynamic simulation. We employed GC-MS techniques and identified 40 bioactive compounds present in the ID and determined their targets by accessing public databases. The convergence of compounds and dermatitis related targets led to the identification of 32 common genes. Among them, IL1B, PTGS2, IL6, IL2, and RELA, were found to be significant targets which were analyzed using Cytoscape network topology. The KEGG pathway evaluation revealed that these targets were significantly enriched in the C-type lectin receptor signaling pathway. The therapeutic efficacy of Stigmasta-5,22-dien-3-ol, Urea, n-Heptyl-, and 3-Epimoretenol was demonstrated in molecular docking assay, as evidenced by their presence in the core compounds of the compound-target network. Furthermore, these compounds exhibited significant kinetic stability and chemical reactivity in DFT quantum analysis when compared to their co-crystallized ligands and reference drug, indicating their potential as key targets for future research. Among the top three docking complexes, namely IL6-3-Epimoretenol, and IL2- Stigmasta-5,22-dien-3-ol, both demonstrated exceptional dynamic characteristics in molecular dynamics simulations at 100 ns. The feasibility of these compounds could be attributed to the prior traditional interrelationship between ID and AD. Overall, this research elucidates the interplay between AD-associated signaling pathways and target receptors with the bioactive ID. The proposal posits the utilization of antecedent compounds as a substitute for the customary pharmaceutical intervention that obstructs the discharge of cytokines, which incite dermal inflammation in the C-type lectin receptor signaling pathway of atopic dermatitis.

Verbal and Social Autopsy of Adult Deaths and Adult Care-Seeking Pattern in Mozambique, 2019-2020.

In sub-Saharan Africa, recent data about causes of adult death and care-seeking during illnesses are limited. This analysis examines adult deaths using verbal and social autopsy data from a nationally and provincially representative sample registration system in Mozambique. Causes of death among those 18 years and older were assigned using the InSilicoVA algorithm, and underlying social causes were examined using the pathway to survival model. Care-seeking was analyzed in different groups to determine if care was sought from formal providers (doctor, nurse/midwife, and trained community health worker) or other providers (traditional provider, family member, and pharmacist), using χ2 tests and multinomial regression models. Among the 4,040 adult deaths reported during 2019-2020, the major causes were HIV (17%), cancer (13%), injury (10%), cardiovascular diseases (9%), pneumonia (7%), tuberculosis (5%), and maternal causes (3%). Formal care-seeking was more likely among adults who had primary or higher level education (relative risk ratio [RRR]: 1.6, P < 0.001; RRR: 1.7, P < 0.01), were married (RRR: 1.3, P < 0.01), and had highest household wealth (RRR: 3.1, P < 0.001). Formal care-seeking was less likely among adults who were male (RRR: 0.7, P < 0.001), had social capital (RRR: 0.7, P < 0.05), or resided in the southern region (RRR: 0.4, P < 0.001). Information about adult causes of death is useful for formulating policy and for developing, monitoring, and evaluating programs to improve adult health in Mozambique. Care-seeking-related information helps identify barriers for seeking care from formal health providers while emphasizing the need for generating local resources and strengthening outreach health systems service delivery.

Effect of sucrose, trehalose, maltose and xylose on rheology, water mobility and microstructure of gluten-free model dough based on high hydrostatic pressure treated starches.

Due to functional and physicochemical properties, starch in its native state has limited range of applications. Simultaneously, information on effects of different sugars and their interactions with modified starch on gluten-free model dough is also limited. To better overcome these restrictions, the effects of sucrose, trehalose, maltose and xylose on rheology, water mobility and microstructure of gluten-free dough prepared with high hydrostatic pressure (HHP) treated maize (MS), potato (PS) and sweet potato starch (SS) were investigated. MS, PS and SS dough with trehalose exhibited a lower degree of dependence of G' on frequency sweep (z'), higher strength (K) and relative elastic part of maximum creep compliance (Je/Jmax), suggesting stable network structure formation. Total gas production (VT) of MS dough with maltose, PS dough with sucrose and SS dough with trehalose was increased from 588 to 1454 mL, 537 to 1498 mL and 637 to 1455 mL respectively. Higher weakly bound water (T22) was found in the dough with trehalose at 60 min of fermentation, suggesting more hydrogen bonds and stable network. Thus, trehalose might be a potential improver in HHP treated starch-based gluten-free products.

Comparative study of thermo-mechanical, rheological, and structural properties of gluten-free model doughs from high hydrostatic pressure treated maize, potato, and sweet potato starches.

Effects of high hydrostatic pressure (HHP, 100, 300 and 500 MPa for 30 min at 25 °C) treated maize (MS), potato (PS), and sweet potato (SS) starches on thermo-mechanical, rheological, microstructural properties and water distribution of gluten-free model doughs were investigated. Significant differences were found among starch model doughs in terms of water absorption, dough development time, and dough stability at 500 MPa. Total gas production of MS, PS and SS doughs was significantly increased from 541 to 605 mL (300 MPa), 527 to 568 mL (500 MPa) and 551 to 620 mL (500 MPa) respectively as HHP increased. HHP increased storage (G') and loss (G″) modulus in terms of rheological properties suggesting, the higher viscoelastic behavior of starch model doughs. The dough after 500 MPa treatment showed lower degree of dependence of G' on frequency sweep suggesting, the formation of a stable network structure. In addition, continuous abundant water distribution and uniform microstructure were found in MS (300 MPa), PS (500 MPa) and SS (500 MPa) doughs for 60 min fermentation. Thus, the starches after HHP show great application potential in gluten-free doughs with improved characteristics.

Reversible Proton-Coupled Reduction of an Iron Nitrosyl Porphyrin within [DBU-H]+-Based Protic Ionic Liquid Nanodomains.

The reduction of [Fe(OEP)(NO)] has been studied in the presence of aprotic room-temperature ionic liquids (RTIL) and protic (PIL) ionic liquids dissolved within a molecular solvent (MS). The cyclic voltammetric results showed the formation of RTIL nanodomains at low concentrations of the RTIL/PIL solutions. The pKa values of the two PILs studied (i.e., trialkylammonium and [DBU-H]+-based ionic liquids) differed by four units in THF. While voltammetry in solutions containing all three RTILs showed similar potential shifts of the first reduction of [Fe(OEP)(NO)] to [Fe(OEP)(NO)]- at low concentrations, significant differences were observed at higher concentrations for the ammonium PIL. The trialkylammonium cation had previously been shown to protonate the {FeNO}8 species at room temperature. Visible and infrared spectroelectrochemistry revealed that the [DBU-H]+-based PIL formed hydrogen bonds with [Fe(OEP)(NO)]- rather than formally protonating it. Despite these differences, both PILs were able to efficiently reduce the nitrosyl species to the hydroxylamine complex, which could be further reduced to ammonia. On the voltammetric time scale and when the switching potential was positive of the Fe(II)/Fe(I) potential, the hydroxylamine complex was re-oxidized back to the NO complex via direct oxidation of the coordinated hydroxylamine at low scan rates or initial oxidation of the ferrous porphyrin at high scan rates. The results of this work show that, while [DBU-H]+ does not protonate electrochemically generated [Fe(OEP)(NO)]-, it still plays an important role in efficiently reducing the nitroxyl ligand via a series of proton-coupled electron transfer steps to generate hydroxylamine and eventually ammonia. The overall reaction rates were independent of the PIL concentration, consistent with the nanodomain formation being important to the reduction process.

Infrared Spectroelectrochemistry of Iron-Nitrosyl Triarylcorroles. Implications for Ligand Noninnocence.

Recent DFT calculations have suggested that iron nitrosyl triarylcorrole complexes have substantial {FeNO}7-corrole•2- character. With this formulation, reduction of Fe(C)(NO) complexes, where C = triarylcorrole, should be centered on the corrole macrocycle rather than on the {FeNO}7 moiety. To verify this proposition, visible and infrared spectroelectrochemical studies of Fe(C)(NO) were carried out and the results were interpreted using DFT (B3LYP/STO-TZP) calculations. The first reduction of Fe(C)(NO) led to significant changes in the Soret and Q-band regions of the visible spectrum as well as to a significant downshift in the νNO and changes in the corrole vibrational frequencies. DFT calculations, which showed that the electron was mostly added to the corrole ligand (85%), were also able to predict the observed shifts in the νNO and corrole bands upon reduction. These results underscore the importance of monitoring both the corrole and nitrosyl vibrations in ascertaining the site of reduction. By contrast, the visible spectroelectrochemistry of the second reduction revealed only minor changes in the Soret band upon reduction, consistent with the reduction of the FeNO moiety.

Proton Transfer versus Hydrogen Bonding in a Reduced Iron Porphyrin Nitrosyl Complex.

The 1H NMR spectra of Fe(OEP)(HNO), which was formed from Fe(OEP)(NO)- in the presence of 3,5-dichlorophenol, were studied as a function of temperature. The chemical shift of the HNO proton showed a unique behavior which could be explained based on the equilibrium between the protonated complex, Fe(OEP)(HNO), and the hydrogen-bonded complex, Fe(OEP)(NO)-···HOPh. This equilibrium was consistent with UV/visible spectroscopy and the voltammetric data. UV/visible stopped-flow experiments showed that the hydrogen-bonded complex, which was formed when weak acids such as phenol were added, and the Fe(OEP)(HNO) complex were quite similar. In addition to the HNO proton resonance, the meso-resonances were consistent with the proposed equilibrium. Density functional theory calculations of various Fe(OEP)(NO)-/Fe(OEP)(HNO) species were calculated, and the results were consistent with experimental data.

Redox and Spectroscopic Properties of Iron Porphyrin Nitroxyl in the Presence of Weak Acids.

The spectroelectrochemistry and voltammetry of Fe(OEP) (NO) in the presence of substituted phenols was studied. Cyclic voltammetry showed that two closely spaced waves were observed for the reduction of Fe(OEP) (NO) in the presence of substituted phenols. The first wave was a single electron reduction under voltammetric conditions. The second wave was kinetically controlled, multielectron process. Visible spectroelectrochemistry of Fe(OEP) (NO) in the presence of substituted phenols showed that three species were present during the electrolysis. Additional spectroscopic studies indicated that the two reduction species were Fe(OEP) (HNO) and Fe(OEP)(H2NOH). The Fe(OEP) (HNO) species, which can be generated chemically, was stable over a period of hours. Additional acid did not lead to further protonation. Proton NMR spectroscopy confirmed the Fe(OEP) (HNO) species could be deprotonated under basic conditions. The third species, Fe(OEP)(H2NOH), was generated by the further reduction of the chemically generated Fe(OEP) (HNO) complex. Both the Fe(OEP) (HNO) and Fe(OEP)(H2NOH) complexes could be slowly oxidized back to Fe(OEP) (NO). At millimolar concentrations of Fe(OEP) (HNO), there was no evidence for the disproportionation of Fe(OEP) (HNO) to Fe(OEP) (NO) and H2 in the presence of substituted phenols. Nor was there evidence for the generation of N2O. The FTIR spectroelectrochemistry showed changes in the infrared spectra in the presence of substituted phenols, but no isotopic sensitive bands were observed for the reduced species between 1450 and 1200 cm-1. This may be because the νNO band shifted into a region (1500-1450 cm-1) where it would be difficult to observe.