ABSTRACT Type 2 diabetes mellitus is one of the most debilitating and burdensome global chronic diseases especially in developing countries. Although pharmaceutical treatments for diabetes are now widely available, their long‐term side effects and economical costs have driven consumers into adopting a more environmentally friendly solution. Medicines derived from natural products have gained stronger traction recently due to the emphasis on more natural solutions for diseases. Alpha‐mangostin is a xanthone compound mainly found in Garcinia mangostana rind and has been consistently studied for its beneficial health effects and biological properties such as cardiovascular, cancer, obesity and several other chronic diseases. This article aims to review the current evidence on the antidiabetic effects of alpha‐mangostin by synthesizing findings from in vitro, in vivo and clinical studies. Based on our analysis, alpha‐mangostin has been shown to have promising antidiabetic properties including enhancing insulin secretion, improving glucose uptake through upregulation of GLUT4 receptors, reducing oxidative stress, modulating inflammatory responses, promoting wound healing, protecting the structure of key organs such as the liver, kidney and eye with corresponding changes in their associated biomarkers, reduces HbA1c levels and maintain normal hemoglobin population, reduces atherogenic index, reduces HOMA‐IR index, decreases mRNA expressions of genes associated with carbohydrate and fat metabolism and decreases ER‐stress related protein expressions. In clinical settings, the intervention with alpha‐mangostin‐containing products has been associated with a decrease in insulin level in obese subjects with associated weight loss, reduction of inflammatory markers and a reduction in markers of dyslipidemia. Further studies should focus on more rigorous clinical trials along with more convincing formulations or functional food products containing alpha‐mangostin.

Hyperhomocysteinemia causes endoplasmic reticulum (ER) stress, which elevates reactive oxygen species (ROS) and induces endothelial dysfunction, the hallmark of cardiovascular diseases. Nigella sativa seeds contain thymoquinone (TQ), a cardioprotective bioactive component. Nevertheless, research on investigating the effectiveness of TQ in preventing endothelial dysfunction caused by homocysteine (Hcy) is scarce. Therefore, the purpose of this work was to examine the role of TQ in restoring Hcy-induced endothelial dysfunction as well as the mechanisms behind this role. Male Sprague-Dawley (SD) rat aortas were isolated and then co-treated in an organ bath with Hcy and TQ, tauroursodeoxycholic acid (TUDCA), apocynin, or Tempol to examine vascular function. Furthermore, human umbilical vein endothelial cells (HUVECs) were treated with Hcy and TQ, Tempol, apocynin, TUDCA or H2O2 to determine the cell viability via a phase contrast microscope and dye exclusion test. ER stress pathway involvement, ROS and NO bioavailability were investigated using immunoassays and fluorescence staining, respectively. The binding affinity of TQ to GRP78 has been identified using molecular docking. According to our findings, Hcy hindered endothelium-dependent relaxation in an isolated aorta and caused apoptosis in HUVECs. TQ, TUDCA, Tempol, and apocynin were able to counteract these negative effects. In HUVECs, treatment with TQ decreased ROS levels, increased NO bioavailability, and decreased GRP78 and NOX4 protein. According to the molecular docking study outcomes, TQ could attach to GRP78 effectively via a hydrogen bond and a hydrophobic connection to the amino acid at GRP78 ATP binding pocket. Taken together, the findings show that TQ protected endothelial function caused by Hcy via inhibiting ER stress-mediated ROS and eNOS uncoupling.

Diabetic wounds are particularly difficult to treat medically because they heal at a slower pace than regular wounds. Macrophages are essential in all stages of normal wound healing, including inflammation, proliferation and rem odelling. When wound healing is affected, macrophages can reduce the level of growth factor and increase the level of interleukin-6 (IL-6), disrupt the balance between tissue inhibitors of metalloproteinase (TIMPs) and matrix metalloproteinase (MMPs), which can slow down healing. Alpha(α)-mangostin, a natural xanthone derived from the pericarp of the mangosteen, has gained considerable attention due to its anti-inflammatory properties, suggesting its potential to promote wound healing. However, its exact role in healing diabetic foot ulcers, common in diabetes, remains unclear. Hence, this study aims to explore how α-mangostin might affect diabetic wound healing by evaluating its impact on PDGF, CTGF, BFGF, VEGF, TGF-β, MMP-9, TIMP-2 and IL-6 secretion in macrophage cells. Human monocytic macrophages (THP-1) were incubated with a 35 mM glucose solution for 72 h to create a glucose-enriched medium. The cells were then incubated with α-mangostin (0.15, 2.5 and 5 µg/mL) together with 35 mM glucose. Carboxymethyl cellulose (CMC) served as positive controls; glucose-enriched media and media-alone served as negative controls. Protein expression was measured using ELISA. α-mangostin (2.5 µg/mL) increased the levels of PDGF and VEGF and decreased the level of MMP-9 compared to glucose controls. There was no significant difference in other growth factors, TIMP-2 and IL-6 protein levels across any of the treatment groups compared to glucose controls. In conclusion, α-mangostin particularly at 2.5 µg/mL demonstrated a significant increase in PDGF and VEGF levels while simultaneously reducing MMP-9 in macrophage cells under glucose-induced conditions. These findings suggest that α-mangostin holds the potential for enhancing the healing of chronic wounds in diabetic conditions. HIGHLIGHTS Treatment of macrophages (THP-1 cells) with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant increase in PDGF and VEGF secretion compared to glucose control. Treatment of the cells with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant reduction of MMP-9 secretion compared to glucose control. There is no significant effects of Alpha (α)-mangostin on IL-6 and TIMP secretion compared to controls This study suggests that Alpha (α)-mangostin may be beneficial in promoting diabetic wound healing via stimulation of PDGF and VEGF secretion and reducing MMP-9 levels. GRAPHICAL ABSTRACT

The interaction of green zinc oxide nanoparticles (ZnO NPs) with bacterial strains are still scarcely reported. This work was conducted to study the green-one-pot-synthesized ZnO NPs from the Aloe Vulgarize (AV) leaf peel extract assisted with different sonication techniques followed by the physicochemical, biological activities and molecular docking studies. The NPs structure was analyzed using FTIR, UV -vis and EDX. The morphology, particle size and crystallinity of ZnO NPs were identified using FESEM and XRD. It was found that the formed flower-like structure with sharp edge and fine size of particulates in ZnO NPs/AV could enhance the bacterial inhibition. The minimum inhibitory concentration (MIC) for all the tested bacterial strains is at 3.125 mu g/ml and the bacterial growth curve are dependent on the ZnO NPs dosage. The results of disc diffusion revealed that the ZnO NPs/AV possess better antibacterial effect with bigger ZOI due to the presence of AV active ingredient. The molecular docking between active ingredients of AV in the NPs with the protein of IFCM and 1MWU revealed that low binding energy (E bind = -6.56 kcal/mol and -8.99 kcal/mol, respectively) attributes to the excessive hydrogen bond from AV that highly influenced their interaction with the amino acid of the selected proteins. Finally, the cytotoxicity test on the biosynthesized ZnO NPs with concentration below 20 mu g/ml are found nontoxic on the HDF cell. Overall, ZnO NPs/20 % AV (probe sonication) is considered as the best synthesis option due to its efficient one -pot method, short sonication time but own the best antibacterial effect.

Abstract Poor wound healing is a common manifestation of diabetes mellitus, culminating in chronic, non-healing ulcer. Alpha(α)-mangostin, one of the most active xanthones found in mangosteen pericarp, has been reported to promote wound healing. However, its effectiveness and mechanism in expediting diabetic wound healing is unknown. The aim of this study was to investigate the effect of alpha-mangostin on wound cell migration and growth factor expressions in a diabetic wound healing model. Human coronary artery endothelial cells (HCAEC) and human dermal fibroblast (HDF) cells were used in this laboratory study. Alpha-mangostin of different concentrations and carboxymethyl cellulose (used as positive control) were introduced to the cell culture plates. Scratch assay was performed for each plate and the rate of cell migration was calculated. Growth factors released by the cells were measured using the ELISA method. Treatment with alpha-mangostin at 0.15 ug/ml concentration showed the fastest rate of endothelial and fibroblast cell migration compared to negative controls. Alpha-mangostin treatment increased PDGF, TGF-β, FGF, TIMP, and reduced MMP-9 levels compared to glucose controls. The findings indicate that in an in vitro diabetic wound healing model, alpha-mangostin stimulates endothelial and fibroblast cell migration, increased the release of growth factors, and lowered the MMP-9 secretion.

Many aspects govern the nature of the resulting phase of a self-assembly of glycolipid, including its detailed stereochemical structure, solvent type, and state condition. Glycolipid has attracted considerable attention due to its extensive lyotropic applications in surfactant industry and material science. However, its application as thermotropic liquid crystal is unknown and rarely investigated. Herein, the thermotropic properties of a series of glycolipids, namely Guerbet branched chain alpha-D-mannosides (C8 to C24 total carbons) were studied by X-ray scattering, dielectric spectroscopy, and rheology. The shortest chain alpha ManC6C2 exhibited lamellar phase over the entire temperature range whereas both alpha ManC8C4 and alpha ManC10C6 only at elevated temperatures since these have larger hydrophobic volumes. Interestingly, at the room temperature, both anhydrous alpha ManC8C4 and alpha ManC10C6 showed formation of rippled structures. Prior to transforming into the fluid lamellar phase, these complex structures possess greater viscosity than the former. The longer chain mannosides (alpha ManC12C8 and alpha ManC14C10) adopted an inverse bicontinuous Ia3d cubic and inverse hexagonal phases, respectively. The temperature-dependent evolution of dielectric relaxation times, tau(T) of primary relaxation within the lamellar, hexagonal, and isotropic phases is explored. Distortion-sensitive tests, enabled by derivative-based analysis, evaluate the suitability of tau(T) parametrisation using the Vogel-Fulcher-Tammann (VFT) and critical-like equations. According to the dielectric and rheological analyses, as the temperature increases, both epsilon|| and epsilon perpendicular to increased, while the viscosity decreased. The findings suggest that higher temperatures are accountable for higher molecular mobility and fluidisation of the phase structure. These fundamental investigations are important to the bottom-up approach development of regulated and specially designed nanoscale material (e.g., a cryoprotective agent).

Wound healing is a complex and dynamic cellular process to restore tissue function. Current treatments for chronic wounds especially diabetic ulcers are expensive, with adverse effects. Recently, numerous researchers have focused on the potential effect of natural products on wound healing. One of them is mangosteen (Garcinia mangostana Linn). It is a well-known tropical fruit that is native to Southeast Asia. The active ingredient of mangosteen pericarp contains xanthones that exhibit a wide range of pharmacological activities, including anti-inflammatory and anti-bacterial properties which are the core elements needed in wound healing. Firstly, this review discusses the concepts of abnormal and normal wound healing mechanisms. Then an in depth observation of the pharmacological activities of mangosteen and its derivatives was presented to study their potentially beneficial applications in the treatment of chronic wound healing which is a contemporary medical issue.

The lyotropic phase behavior of four common and easily accessible glycosides, n-octyl α-d-glycosides, namely, α-Glc-OC8, α-Man-OC8, α-Gal-OC8, and α-Xyl-OC8, was investigated. The presence of normal hexagonal (HI), bicontinuous cubic (VI), and lamellar (Lα) phases in α-Glc-OC8 and α-Man-OC8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance (2H NMR), via monitoring the D2O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC8 and α-Xyl-OC8 in D2O were constructed and confirmed using small- and wide-angle X-ray scattering and 2H NMR. The average number of bound water molecules (nb) per headgroup in the Lα phase was determined by the systematic measurement of the quadrupolar splitting of D2O over a wide range of molar ratio values (glycoside/D2O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5-2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n-octyl α-d-glycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.

Using mannose as the sugar head, five Guerbet glycolipids with chain ranges from C-8 to C-24 were synthesised and studied for their liquid crystal behaviour. Differential scanning calorimetry, optical polarising microscopy and small-angle X-ray scattering were employed to determine the thermal, phase and structure properties. Unlike monoalkylated glycolipids, these Guerbet mannosides showed a glass transition below 0 degrees C, except for alpha-Man-OC14C10. In the dry state, lamellar was observed for alpha-Man-OC6C2 and alpha-Man-OC8C4, while alpha-Man-OC12C8 and alpha-Man-OC14C10 formed non-lamellar phases, including inverse bicontinuous cubic phase of space group Ia3d and inverse hexagonal phase, respectively. The phase for middle-chain mannoside (alpha-ManOC10C6) could not be assigned conclusively at room temperature, but this metastable phase forms lamellar above 37 degrees C. The partial binary phase diagrams in water were also determined. Under excess water conditions at room and physiological temperatures, these materials form normal micellar solution, lamellar, inverse bicontinuous cubic of space group Pn3m and inverse hexagonal phases. The results were compared with those from other monosaccharide glycolipids from the same sugar Guerbet family. Although these compounds are obvious candidate material for lyotropic applications such as drug carrier and protein crystallisation medium, possible thermotropic application is now being explored. [GRAPHICS] .

Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An Ia3d bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-β-d-glucopyranoside (β-Glc-OC6C10) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of β-Glc-OC6C10 which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-β-d-glucopyranoside (β-Glc-OC8) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 Å, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-β-d-maltopyranoside (β-Mal-OC8). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly.