Background: Allergic diseases represent a significant global health burden, and current pharmacological treatments primarily offer symptomatic relief without addressing the underlying immune dysregulation. Allergen-specific immunotherapy (AIT) is the only disease-modifying approach capable of inducing long-term remission by targeting the immunological mechanisms that drive the allergic response. Sublingual immunotherapy (SLIT) is a noninvasive alternative to subcutaneous immunotherapy, leveraging the rich vascularisation and antigen-presenting cell population of the oral mucosa. Objective: SLIT tablets were formulated using Indonesian house dust mite (IHDM) allergenic extracts, with the aim of optimising tablet properties by modulating the disintegrant concentration and croscarmellose-to-crospovidone ratios. Methods: Six formulations, each with three batches, were prepared via direct compression, varying the total disintegrant content (5.25 and 10.5% w/w) and excipient ratios. The tablets were evaluated for hardness, disintegration time, friability, and dissolution, and specific allergenic protein release (Der p 1 as a marker) was quantified using ELISA. A 2 × 3 factorial experimental design was used in the DoE approach, with data analysed using GraphPad Prism and Minitab, and response surface methodology (RSM) applied via Stat-Ease 360. Results: Higher disintegrant concentrations reduced tablet hardness but increased friability and disintegration rates. Pareto analysis revealed that both the total disintegrant content and disintegrant ratio significantly influenced tablet performance. All formulations demonstrated favourable dissolution profiles. The optimised formulation (F2), containing 5.25% (w/w) total disintegrants with a croscarmellose-to-crospovidone ratio of 1.5:2, achieved a disintegration time of 4.33 ± 0.88 s, hardness of 89.20 ± 6.12 N, and friability of 0.00 ± 0.01 %. Conclusion: These findings support the potential of IHDM-based SLIT tablets as an effective and mechanistically rational platform for allergen immunotherapy, contributing not only to symptoms but also to long-term modification of allergic diseases
BACKGROUND:Aloe vera is widely used for dermatological applications due to its bioactive phenolic compounds, including aloin, aloesin, aloe-emodin, and tannins. Gold nanoparticles (AuNPs) have pharmacological properties such as antioxidant and antibacterial activities and may enhance skin elasticity. OBJECTIVE:This study developed polyvinyl alcohol (PVA) stabilized gold nanoparticles from Aloe vera extract and evaluated their physicochemical properties, preliminary stability, and in vitro biocompatibility under mild UV exposure. METHODS:Gold nanoparticles were biosynthesized by reacting Aloe vera extract with 1 mM chloroauric acid (HAuCl4) in the presence of PVA. The formulations were characterized by UV-Vis spectroscopy, particle size and polydispersity index (PDI), TEM, SEM-EDS, and FTIR. The optimized formulation was further evaluated in a preliminary accelerated stability study and tested for cytotoxicity in B16F10 melanoma cells using the MTT assay under mild UVA and UVB exposure. RESULTS:Formula 4 was selected as the optimized formulation after preliminary screening, showing stable dispersion without visible aggregation, a particle size of 101.40 ± 1.51 nm, and a PDI of 0.24 ± 0.06. After optimization, this formulation was subjected to accelerated stability testing, with Day-1 particle size and PDI values of 107.00 ± 1.11 nm and 0.25 ± 0.04, respectively. During accelerated storage, the particle size remained within the nanoscale range. Cytotoxicity testing showed that NGA was non-cytotoxic toward B16F10 melanoma cells, with an IC50 value of 2873.20 μg/mL. Under the mild UVA and UVB conditions used in this study, treated cells also maintained high viability. CONCLUSION:PVA-stabilized gold nanoparticles synthesized from Aloe vera showed favorable physicochemical properties, preliminary storage stability, and low in vitro cytotoxicity. Under the mild UV exposure conditions applied in this study, NGA remained biocompatible; however, the present findings do not yet establish a definitive photoprotective effect. Further studies using stronger irradiation settings and appropriate positive controls are required.
This study evaluated the effects of an alkaloid-rich leaf extract of Dalbergiella welwitschii (Baker) Baker f. on hepatic carbohydrate metabolism in streptozotocin-induced diabetic rats. Diabetes was induced in rats, which were then treated with low (50 mg/kg) and high (100 mg/kg) doses of the extract, or metformin (200 mg/kg), for 20 days. Key hepatic enzymes-glycogen phosphorylase, glucose-6-phosphatase, lactate dehydrogenase, fructose-1,6-bisphosphatase, glycogen synthase, and hexokinase-along with hepatic glycogen and insulin levels were measured. Treatment with the extract significantly restored enzyme activities, increased insulin levels, and enhanced glycogen content. These results indicate that D. welwitschii extract can modulate hepatic carbohydrate metabolism and may have potential therapeutic benefits for diabetes management.
Introduction: Chronic wounds are a major global health concern because their slow healing increases the risk of infection. Conventional dressings often fail to provide both effective antibacterial protection and optimal moisture control. Electrospun nanofibre membranes, with porous structures that resemble the extracellular matrix, offer a promising alternative. Curcuma xanthorrhiza, a traditional Southeast Asian rhizome, is rich in bioactive compounds such as curcumin and xanthorrhizol, which are known for their anti-inflammatory, antioxidant, and antibacterial properties. Methods: In this study, coaxial electrospinning was used to create core–shell nanofibre membranes, featuring polycaprolactone as the core and a gelatine/chitosan blend as the shell. Curcuma extract was incorporated at 1% (w/w) into the core. The resulting fibres were examined for their morphology, chemical composition, and thermal stability using scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Antibacterial activity was tested against Staphylococcus aureus and Escherichia coli using the disc diffusion method. Results and Discussion: Nanofibres loaded with Curcuma extract were smooth, continuous, and nanoscale in diameter, while fibres without extract were thicker due to a higher polymer concentration. The average fibre diameter ranged from 120.3 to 284.2 nm. Chemical analysis confirmed successful incorporation of the extract, with characteristic functional groups preserved and clear interactions between the polymers and bioactive compounds. Thermal analysis showed the fibres were stable up to 300°C. Antibacterial testing of C. xanthorrhiza-loaded nanofibres demonstrated no activity against S. aureus (0 mm) and E. coli (0 mm). Conclusion: In this study, C. xanthorrhiza-loaded nanofibres exhibit promising physical and chemical properties in their formulation. While the antibacterial activity was limited at the current tested concentration, it is suggested that the loading capacity of the extract be increased.
This article reports a green synthesis of silver nanoparticles (AgNPs) by a hydroalcoholic extract obtained from aerial parts of Quercus suber L. collected from the Beni Ali region, northern Algeria. By varying sonication time, ultrasonic amplitude, and extract concentration using response surface methodology with central composite design, we optimized the biosynthesis process for maximum nanoparticle formation efficiency. AgNPs were fully characterized using ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) analysis, thermogravimetric analysis (TGA), and zeta potential measurements to confirm their preliminary physical composition. The analyses confirmed that crystalline and functionalized nanoparticles with the average size of 64.34 nm demonstrated thermal stability throughout the synthesis procedure. AgNPs capped with Q. suber extract showed significant activities in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays, which indicated that they had potent free radical scavenging and ferric-reducing abilities. Antimicrobial assays showed AgNPs’ inhibition zones were larger than those of plant extract and silver nitrate samples against gram-positive and gram-negative bacteria and fungal strains. A dose-dependent cytotoxic effect was observed on the MCF-7 human breast adenocarcinoma cells, with a half maximal inhibitory concentration IC50 of 122.25 μg/mL, suggesting moderate toxicity and potential therapeutic application. Q. suber-mediated green synthesis of AgNPs has shown potential as an environmentally friendly and easy method. This study sets the stage for in vivo exploration of these biogenic nanoparticles for both therapeutic and environmental applications.
Hepatocellular carcinoma (HCC) is a critical public health concern due to its rising incidence and mortality. Early diagnosis is challenging due to nonspecific symptoms and limitations of traditional methods. This study explores the potential of three key biomarkers, serum alpha-fetoprotein (AFP), des-γ-carboxyprothrombin (DCP), and glypican-3 (GPC3), in advancing personalized medicine for HCC, focusing on their roles in diagnostics and therapeutics. We conducted a literature review using specific keywords to narrow our search. Our findings indicate that AFP and DCP are primarily used for diagnostics, while GPC3 serves both diagnostic and therapeutic purposes. AFP is commonly used in late-stage detection due to its limited sensitivity and specificity in early stages, which can lead to false diagnoses. DCP plays a significant role as both a diagnostic tool and therapeutic target, while GPC3 is used to differentiate malignant from non-cancerous liver tissues. The review highlights the mechanisms, roles, and personalised treatments associated with these biomarkers, while also addressing challenges such as biopsy issues and funding limitations. In conclusion, the development and improvement of AFP, DCP, and GPC3 as biomarkers for the diagnostics and treatment of HCC are important. Thus, their limitations should be addressed as these biomarkers play a crucial role in modern cancer therapy and are critical for increasing the survival rates of HCC patients.
Introduction: Palm olein has been used as an excipient in the formulation of topical emulsions due to its rich source of natural antioxidants that can lead to better skin health and higher stability upon storage. Despite its potential as a topical drug delivery vehicle, the practical implementation of manufacturing 20% (w/w) palm olein-in-water emulsions for commercial purposes has not been explored extensively, and obtaining experimental data on scale-up studies would be helpful in facilitating this realisation. Methods: This research work established and optimised the manufacturing process parameters for the production of cream and lotion formulations containing betamethasone 17-valerate, utilising palm olein as the vehicle, with scale-up from lab-scale 5 kg batches to pilot-scale 80 kg batches. Design of experiments (DoE) where response surface methodology as well as three-level, two-factors (32) full factorial design were used to develop statistical models for representing the possible relationships between factors: homogenisation time and speed, and responses: particle size and phase separation. Results: The findings established that the quadratic model was the most suitable model as it could predict the interactions between factors and responses in an accurate manner as well as suggest the optimum operating conditions. The optimum homogenisation time and speed were found to be 40 minutes and 3400 rpm, respectively. These conditions produced emulsions with the smallest particle size (3.2 µm ± 0.03) and the least phase separation value (29.7% ± 0.35). Conclusion: The study successfully demonstrated the potential to scale up the manufacturing of 20% (w/w) palm olein-in-water emulsions for commercial purposes. The optimised parameters, obtained through DoE, facilitate the large-scale production of stable emulsions containing betamethasone 17-valerate.
The therapeutic efficacy of natural extracts such as propolis, sea cucumber or gamat (Stichopus hermanii), and pegagan (Centella asiatica) is supported by their anti-inflammatory, antioxidant, and regenerative properties. However, their pharmaceutical application is limited due to poor solubility and low bioavailability. This study aimed to develop and characterize a Self-Nanoemulsifying Drug Delivery System (SNEDDS) using Labrasol to enhance the delivery and stability of a combination of these three extracts, that exhibit synergistic effects as tissue regeneration, antimicrobial, anti-inflammatory, and antioxidant properties. SNEDDS formulations were prepared by a high energy method with Labrasol, Tween 80, and propylene glycol. The formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential, and thermodynamic stability test. The optimized SNEDDS exhibited nano-sized droplets (151.13 nm ± 17.26) with low PDI (0.39 ± 0.01) and zeta potential (-50.30 ± 1.04) within the stable range, indicating a uniform, physically stable nanoemulsion, and passed the thermodynamic stability test. In conclusion, the optimized SNEDDS formulation demonstrated nano-sized droplets with low PDI and stable zeta potential, indicating good physical stability.
Over the past decade, the occurrence of bone defects has seen a notable rise. In both developed and developing nations, their prevalence tends to increase in parallel with population density and levels of physical activity. Various therapeutic approaches have been implemented to address bone fractures, focusing on preventing infections, promoting faster healing, and restoring normal bone function. Among these, bone grafting—a surgical technique involving the use of biomaterials—remains a widely utilized method for bone replacement. This review aims to identify biomaterials that have biocompatibility with bone, osteoinductive, and osteoconductive properties so that they can trigger good osteogenesis. This review is based on a compilation of publications from various databases related to factors affecting the process of bone ossification. This study also evaluates the characteristics of hydroxyapatite biomaterials that play a role in inducing osteogenesis. The phosphate/calcium ratio close to 1.67, porosity in the range of 40 to 60%, pore diameter of 200 to 900 nm, and crystallinity of 40 to 60% will help the osteogenesis to perform well. The results of this study highlight the advantages of hydroxyapatite in terms of its osteoconductive, osteoinductive, and osteointegrative properties, which can trigger osteogenesis.
Introduction: An allergy is a hypersensitivity reaction generally mediated by the immune system, which is usually followed by an increase in IgE levels. The early phase of the molecular pathogenesis of allergies begins with the binding activation of the allergen and protease-activated receptor, followed by the phosphorylation of the three protein kinases. The role of p38 MAPK, ERK1/2, and JNK are integral to the pathophysiology of allergic asthma. Curcuma longa has been known as an anti-inflammatory herbal medicine that has a potential to be an asthma allergy drug. The in silico and absorption, distribution, metabolism, excretion, and toxicology (ADMET) prediction studies were conducted to identify the C. longa secondary metabolites as a potential asthma allergy drug. Those compounds suggest the molecular activity inhibition in the inflammatory pathways underlying allergic manifestations. Methods: Candidate compounds that fulfilled Lipinski’s theoretical requirements were docked to three protein kinases using Molegro Virtual Docker Version 5.5. The rerank score of each compound was compared with those of the standard ligand and existing drug. Results: At least two compounds with rerank scores consistently lower or comparable to the existing ligands and drugs, namely compound A (1,5-dihydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-4,6-heptadien-3-one) and compound B (Bisdesmethoxycurcumin), were identified. The ADMET profile gave an outstanding result to be developed as a drug candidate. Conclusion: The secondary metabolites derived from C. longa exhibit potent inhibitory effects on those three kinases. This strategy seems to hold a significant potential for developing novel therapeutics targeting inhalant-induced allergies.
Context: Bone defects associated with fractures exceeding 2 cm in circumference present significant clinical challenges due to the high risk of nonunion or malunion. Scaffold implantation offers a non-toxic, effective strategy to support bone regeneration and restore structural integrity. Aims: To evaluate and compare the regenerative effects of bovine hydroxyapatite-calcium sulfate-gelatin (BHA-CS-gelatin) and nano-BHA-CS-gelatin scaffolds. Focus was placed on cellular morphology, including osteoblasts, osteocytes, and osteoclasts, cell migration, and the expression of osteogenic markers: collagen type I (COL1), Runx2, osteocalcin, and osteoprotegerin (OPG). Methods: In vivo experiments used New Zealand White rabbits with surgically induced bone defects treated with either BHA-CS-gelatin or nano-BHA-CS-gelatin scaffolds. Bone regeneration was assessed by histological, immunohistochemical, and ELISA analyses. Rabbits were sacrificed on days 7 and 28 for histology and immunohistochemistry evaluations. OPG levels were measured by ELISA on days 0, 1, 3, 5, 7, 14, and 28. Results: Histological analysis showed enhanced migration of osteoblasts, osteocytes, and osteoclasts in the nano-BHA-CS-gelatin group. Immunohistochemistry revealed significantly higher expression of COL1, Runx2, and osteocalcin in this group at day 28 (p<0.05). ELISA demonstrated a significant increase in OPG levels on day 14 compared with the conventional BHA-CS-gelatin scaffold group (p<0.05). Conclusions: Nano-BHA-CS-gelatin scaffolds significantly accelerate bone defect closure and enhance osteogenic marker expression more effectively than conventional scaffolds. These results support their preclinical potential application in bone repair and regenerative medicine.
Extracts from plants are rich in phytochemicals that can be used as biogenic reducing agents for the synthesis of Ag (silver) nanoparticles (AgNPs). In this research, we synthesized AgNPs using Dicranopteris linearis leaves extract and assessed their cytotoxicity and antimicrobial activities. The aqueous extract of D. linearis (DL) leaves was analyzed using liquid chromatography-mass spectrometry (LC-MS). The extracts served as reducing agents for silver nitrate, producing AgNPs-DL. The nanoparticles were characterized by UV-visible spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS), and cytotoxicity was assessed against human breast adenocarcinoma cells line (MCF-7) using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Antimicrobial activity was tested against four bacteria, such as Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus, using the dac diffusion method. AgNPs-DL were successfully synthesized from D. linearis leaves extract. LC-MS/QTOF analysis revealed a diverse phytochemical profile, supporting the extract's role in nanoparticle synthesis. SEM analysis showed predominantly spherical formation of AgNPs with size of 279.3 nm in average. Cytotoxicity assay indicated low toxicity against MCF-7 cells. AgNPs-DL also demonstrated inhibitory activity against E. coli, P. deruginosa, B. subtilis, and S. aureus. Phytochemicals in D. linearis leaves extract contribute to stabilization and reduction of silver ions, resulting in AgNPs with distinct physicochemical properties and notable bioactivity
Sickle cell disease (SCD) is an inherited blood disorder marked by the production of abnormal hemoglobin, leading to the distortion—or sickling—of red blood cells. The SCD arises from a single-point mutation that substitutes glutamic acid with valine at the sixth codon of the β-globin chain in hemoglobin. This substitution promotes deoxyhemoglobin aggregation, elevating red blood cell stiffness, and triggering vaso-occlusive and hemolytic repercussions. To explore therapeutic advances in tackling this disease, this review analyzed articles published from January 2015 to January 2025 using the three databases using relevant keywords focusing on SCD and advancement in therapy. It was found that allogeneic hematopoietic stem cell (HSC) transplantation can alleviate symptoms but is limited by a shortage of well-matched donors and immunological challenges. In contrast, autologous gene-modified HSC transplantation via gene therapy offers comparable therapeutic benefits without associated immunological complications. Clinical trials utilizing lentiviral vector-mediated gene insertion have demonstrated promising therapeutic outcomes by preventing hemoglobin aggregation. Emerging gene editing approaches such as CRISPR/Cas9 are expanding treatment options, marking the transition of SCD gene therapy from theoretical concept to clinical application.
Introduction: Plant-mediated green synthesis of nanoparticles has become a promising option in green nanotechnology because it is simple, cost-effective, eco-friendly, and biologically effective. This study focused on the synthesis and characterisation of silver nanoparticles (AgNPs) using Aidia densiflora leaf extract, as well as the evaluation of their antimicrobial and cytotoxic activities. Methods: AgNPs were synthesised with A. densiflora leaf extract and their formation was confirmed using an ultraviolet–visible (UV–Vis) spectrophotometer. Liquid chromatography-mass spectrometry quadrupole time-of-flight was utilised for phytochemical profiling. The synthesised AgNPs were characterised using a zetasizer and zeta potential analyser, scanning electron microscopy-energy dispersive X-ray, Fourier Transform Infrared, X-ray diffraction (XRD), and thermogravimetric analysis. Antimicrobial activity of AD-AgNPs was tested against six microorganisms using the disc diffusion method, while cytotoxicity against MCF-7 human breast cancer cells was evaluated via MTT assay. Results: AgNP formation was confirmed by XRD and UV–Vis analysis, with absorbance peaks at 399–424 nm. Optimal synthesis was achieved using 10 mM AgNO? at 60°C and pH 7. SEM showed spherical-like nanoparticles averaging 96.06 nm with significant aggregation. The zeta potential was –35.6 mV, and XRD indicated a face-centred cubic structure with a crystalline size of 6.94 nm. AD-AgNPs showed no antimicrobial activity and low cytotoxicity. Conclusion: A. densiflora leaf extract can be used to synthesise AgNPs, however, further optimisation is required for better nanoparticle stabilisation and improvement of bioactivities.
Alpha-mangostin (AM) is a naturally occurring xanthone with remarkable pharmacological properties, including anti-inflammatory, anti-bacterial, and antioxidant effects. The compound is commonly extracted from the pericarps of Garcinia mangostana L. fruits, but its seasonal availability is limited. Investigating the potential of using various organs of the tree for AM extraction can help mitigate limitations imposed by the seasonal availability of fruits. This study employs the Soxhlet extraction method and gravitational column chromatography for the preparation of AM from various plant organs. The purity of the compound in the extract was quantitatively determined using high-performance liquid chromatography analysis. The stem barks demonstrated the highest yield at 1.3%, with a concentration of 324.593 µg/mL and a purity of 95.215% for AM. The finding is expected to assist in uncovering alternative sources of AM and contribute to sustainable utilisation of the tree, as various plant organs could be employed in AM extraction.
Curcuma xanthorrhiza has an active component xanthorrhizol that is poorly soluble in water, resulting in limited absorption and bioavailability. Liquid Self Nano Emulsifying Drug Delivery System (SNEDDS) dosage formulations can improve its solubility and absorption due to its small particle size. Solid SNEDDS technology significantly overcomes some of problems in liquid SNEDDS preparations to improve the stability of liquid formulations. This study aims to formulate and characterize Curcuma xanthorrhiza S-SNEDDS preparation. SNEDDS was characterized by particle size and thermodynamic tests. Method of making S-SNEDDS uses two ways, absorption of porous compounds and spray drying. S-SNEDDS were characterized by testing infrared spectra, X-ray diffraction, scanning electron microscopy, microbial contamination and particle flow properties. Optimal S-SNEDDS formulation with 2 formulas namely F7 and F11 mannitol carrier. FTIR testing showed no interacting compounds. SEM and X-ray diffraction testing of F7 showed that the preparation was semicrystalline. While F11 described the preparation as much more crystalline due to the high content of mannitol. The microbial contamination test detected no microorganism compounds. In addition, the particle flow properties obtained a result of 02.53 seconds with a height of 24.95 mm. It is concluded that the S-SNEDDS formula F7 of Curcuma xanthorrhiza has semicrystalline preparation criteria.
A chronic inflammatory dermatosis, eczema, affects more than 12% of the pediatric population and 7.2% of adults. Clinically, it presents with erythematous, scaly, and intensely pruritic lesions. Severe forms of the disease frequently exhibit poor responsiveness to treatments aimed at a single inflammatory pathway. Curcuma xanthorrhiza Roxb. rhizomes possess antioxidant, anti-inflammatory, and anti-allergic activities through a multi-target mechanism. This study aimed to evaluate the secondary metabolites of C. xanthorrhiza Roxb. rhizomes that can be developed into eczema drugs using virtual screening in silico. Secondary metabolite compounds from C. xanthorrhiza rhizomes were evaluated for their drug-likeness properties Subsequently, the similarity of their physicochemical properties was assessed using the principal component analysis. A target search of drug candidates was performed using the Swiss Target Prediction and Gene Expression Omnibus (GEO) Omnibus. Docking was performed using Molegro by comparing the rerank scores of the drug candidates with those of the original ligands. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was performed using the pkCSM. Carbonic anhydrase II, epidermal growth factor receptor, and the mammalian target of rapamycin came as the protein target for eczema disease. For the docking result, demethoxycurcumin (C00037023), 1,5-dihydroxy-1,7-bis (4-hydroxy-3-methoxyphenyl)-4,6-heptadien-3-one (C00055412), 1,7-bis (4-hydroxy-3-methoxyphenyl)-3,5-heptanediol (C00055175), and 3’-demethoxycyclocurcumin (C00054761) had both better rerank score than the native ligand and good ADMET profiles. Four compounds derived from C. xanthorrhiza Roxb. rhizomes can be developed as an eczema potential treatment.