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Allantoin (ALL) is a phytochemical possessing an impressive array of biological activities. Nonetheless, developing a nanostructured delivery system targeted to augment the gastric antiulcerogenic activity of ALL has not been so far investigated. Consequently, in this survey, ALL-loaded chitosan/sodium tripolyphosphate nanoparticles (ALL-loaded CS/STPP NPs) were prepared by ionotropic gelation technique and thoroughly characterized. A full 2 4 factorial design was adopted using four independently controlled parameters (ICPs). Comprehensive characterization, in vitro evaluations as well as antiulcerogenic activity study against ethanol-induced gastric ulcer in rats of the optimized NPs formula were conducted. The optimized NPs formula, (CS (1.5% w/v), STPP (0.3% w/v), CS:STPP volume ratio (5:1), ALL amount (13 mg)), was the most convenient one with drug content of 6.26 mg, drug entrapment efficiency % of 48.12%, particle size of 508.3 nm, polydispersity index 0.29 and ζ-potential of + 35.70 mV. It displayed a sustained in vitro release profile and mucoadhesive strength of 45.55%. ALL-loaded CS/STPP NPs (F-9) provoked remarkable antiulcerogenic activity against ethanol-induced gastric ulceration in rats, which was accentuated by histopathological, immunohistochemical (IHC) and biochemical studies. In conclusion, the prepared ALL-loaded CS/STPP NPs could be presented to the phytomedicine field as an auspicious oral delivery system for gastric ulceration management.

Background The management of papulopustular rosacea presents a significant clinical challenge. Anti‐inflammatory and vasoconstrictive treatments are ineffective in the rapid amelioration of the dryness, burning, and itching caused by skin barrier damage in patients with papulopustular rosacea. Aims To assess the efficacy and safety of the topical application of compound heparin sodium allantoin gel to treat rosacea. Methods Eighty‐two patients participated in this randomized, prospective, single‐center, and controlled trial. The Clinician Erythema Assessment score, Investigator Global Assessment score, transepidermal water loss, and skin hydration were evaluated at 0, 2, 4, 8, and 12 weeks. Rosacea‐specific quality of life score, itching, dryness, burning, Global Aesthetic Improvement Scale, and Patient Self‐Assessment grades were also assessed. Results Compared with the traditional therapy group, the 8‐week and 12‐week topical application of compound heparin sodium allantoin gel to treat rosacea significantly decreased Clinician Erythema Assessment/Investigator Global Assessment grades, burning and itching grades, and rosacea‐specific quality of life scores. Compound heparin sodium allantoin gel significantly improved the skin barrier with hydration and significantly decreased trans‐epidermal water loss. For patients with Demodex infestation, externally applied compound heparin sodium allantoin gel was associated with better rosacea treatment outcomes and improved skin barrier function than externally applied hyaluronic acid. This may be attributable to the inhibition of abnormal demodex, improved skin barrier, and repair of minor skin wounds. Conclusions Compound heparin sodium allantoin gel effectively improved facial erythema, alleviated ithching and burning sensations, and improved patients' quality of life. Trail Registration ClinicalTrials.gov identifier: ChiCTR2400087948

Snail mucus is a mixture of active substances commonly thought to have healthy properties for the treatment of skin disorders. Although snail mucus is an ingredient of several cosmetic and para-pharmaceutic products, a comprehensive characterization of chemical composition and biological effects is still missing. Crude purified extracts from Helix aspersa muller mucus (HelixComplex) were prepared and, after chemical characterization, tested on in vitro experimental models. Differently from what expected, HelixComplex was characterized by the presence of small amounts of glycolic acid and allantoin. By using different in vitro assays on fibroblast cultures, we found that HelixComplex lacked of cytotoxicity, protected cells from apoptosis (p < 0.05) and, importantly, was able to significantly induce cell proliferation and migration through direct and indirect mechanisms. These effects were associated to morphological changes, cytoskeleton re-organization and release of cytokines. In conclusion, our findings suggest that snail mucus biological effects are attributable to cell proliferation and migration, and pave the way for further investigating snail mucus potential as therapeutic agent.

Using the skin tissue engineering approach is a way to help the body to recover its lost skin in cases that the spontaneous healing process is either impossible or inadequate, such as severe wounds or burns. In the present study, chitosan/gelatin-based scaffolds containing 0.25, 0.5, 0.75, and 1% allantoin were created to improve the wounds’ healing process. EDC and NHS were used to cross-link the samples, which were further freeze-dried. Different in-vitro methods were utilized to characterize the specimens, including SEM imaging, PBS absorption and degradation tests, mechanical experiments, allantoin release profile assessment, antibacterial assay, and cell viability and adhesion tests. The results indicated that the scaffolds’ average pore sizes were approximately in the range of 390–440 µm, and their PBS uptake amounts were about 1000% to 1250% after being soaked in PBS for 24 h. Around 70% of the specimens were degraded in 6 days, but they were not fully degraded after 21 days. Besides, the samples showed antibacterial activity against S. aureus and E. coli bacteria. In general, the MTT cell viability test indicated that the cells’ density increased slightly or remained the same during the experiment. SEM images of cells seeded on the scaffolds indicated appropriate properties of the scaffolds for cell adhesion.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by 1 H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN. Graphical Abstract In this study, we performed 1 H NMR-based metabonomic to analyze the serum, urine, and renal extracts in a rat model of diabetic nephropathy (DN), and identified the disturbed purine metabolism and its underlying xanthine oxidase induced oxidative stress and inflammation was involved in the pathogenesis of DN

Introduction. In our days, several approaches reported the use of natural compounds in medical applications. Among them, pectin and allantoin are nontoxic, biocompatible, and biodegradable; however, its use for possible wound healing therapeutics is still limited. Pectin and allantoin have been applied in pharmaceutical industry and beauty cosmetic and could be also applied as scaffolds for tissue regeneration, wound healing, and so on. The aim of this study was to combine by the first time two natural ingredients to develop a new biomaterial to treat skin injuries in a rat model. Methods. For the hydrogel development, new synthesis parameters were established for the obtaining of the film such as temperature, mixing velocity and time, and drying temperatures as well. To enrich the film, the allantoin concentrations were set at 90 wt% and 100 wt% of pectin used. By in vivo assay, films were tested in wound healing in female Wistar rats, 190±10 g in weight and 2 months aged. Results. The obtained films comprise 2 well-differentiated layers, one layer rich in allantoin, which will be the regenerative layer, and one rich in pectin, which will work as an antimicrobial and protective layer to the wound. These were characterized by swelling kinetics, Fourier transform of the infrared spectrum of absorption (FTIR) spectroscopy, and contact angle. The morphology and topography were determined by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo assay showed remarkable reduce in a time period in a wound healing process when the film was used. The results show that the use of PA (Pectin-Allantoin) hydrogel reduces the total healing time by 25% approximately. Conclusions. Pectin-Allantoin (PA) film has potential use in medical applications as wound healing material promoting healthy tissue renewal.

Key messageDegradation of nitrogen-rich purines is tightly and oppositely regulated under drought and low nitrogen supply in bread wheat. Allantoin is a key target metabolite for improving nitrogen homeostasis under stress.The metabolite allantoin is an intermediate of the catabolism of purines (components of nucleotides) and is known for its housekeeping role in nitrogen (N) recycling and also for its function in N transport and storage in nodulated legumes. Allantoin was also shown to differentially accumulate upon abiotic stress in a range of plant species but little is known about its role in cereals. To address this, purine catabolic pathway genes were identified in hexaploid bread wheat and their chromosomal location was experimentally validated. A comparative study of two Australian bread wheat genotypes revealed a highly significant increase of allantoin (up to 29-fold) under drought. In contrast, allantoin significantly decreased (up to 22-fold) in response to N deficiency. The observed changes were accompanied by transcriptional adjustment of key purine catabolic genes, suggesting that the recycling of purine-derived N is tightly regulated under stress. We propose opposite fates of allantoin in plants under stress: the accumulation of allantoin under drought circumvents its degradation to ammonium (NH4+) thereby preventing N losses. On the other hand, under N deficiency, increasing the NH4+ liberated via allantoin catabolism contributes towards the maintenance of N homeostasis.

Drought is a misfortune for agriculture and human beings. The annual crop yield reduction caused by drought exceeds the sum of all pathogens. As one of the gatekeepers of China’s “granary”, rice is the most important to reveal the key drought tolerance factors in rice. Rice seedlings of Nipponbare (Oryza sativa L. ssp. Japonica) were subjected to simulated drought stress, and their root systems were analyzed for the non-targeted metabolome and strand-specific transcriptome. We found that both DEGs and metabolites were enriched in purine metabolism, and allantoin accumulated significantly in roots under drought stress. However, few studies on drought tolerance of exogenous allantoin in rice have been reported. We aimed to further determine whether allantoin can improve the drought tolerance of rice. Under the treatment of exogenous allantoin at different concentrations, the drought resistant metabolites of plants accumulated significantly, including proline and soluble sugar, and reactive oxygen species (ROS) decreased and reached a significant level in 100 μmol L−1. To this end, a follow-up study was identified in 100 μmol L−1 exogenous allantoin and found that exogenous allantoin improved the drought resistance of rice. At the gene level, under allantoin drought treatment, we found that genes of scavenge reactive oxygen species were significantly expressed, including peroxidase (POD), catalase (CATA), ascorbate peroxidase 8 (APX8) and respiratory burst oxidase homolog protein F (RbohF). This indicates that plants treated by allantoin have better ability to scavenge reactive oxygen species to resist drought. Alternative splicing analysis revealed a total of 427 differentially expressed alternative splicing events across 320 genes. The analysis of splicing factors showed that gene alternative splicing could be divided into many different subgroups and play a regulatory role in many aspects. Through further analysis, we restated the key genes and enzymes in the allantoin synthesis and catabolism pathway, and found that the expression of synthetase and hydrolase showed a downward trend. The pathway of uric acid to allantoin is completed by uric acid oxidase (UOX). To find out the key transcription factors that regulate the expression of this gene, we identified two highly related transcription factors OsERF059 and ONAC007 through correlation analysis. They may be the key for allantoin to enhance the drought resistance of rice.

Salinity stress severely limits cucumber ( Cucumis sativus L.) productivity by disrupting growth, photosynthesis, and ion homeostasis. This study investigated the potential of foliar-applied allantoin (1 mM) and citrulline (1 mM) to enhance salinity tolerance in hairy cucumber, a salt-sensitive Iranian landrace. A completely randomized design factorial experiment with three replications tested salinity levels (0, 50, 100 mM NaCl) and foliar treatments (control, allantoin, citrulline, and their combination). The results showed that salinity reduced plant height, dry weight, chlorophyll content (SPAD, Fv/Fm), and relative water content (RWC) while increasing electrolyte leakage (EL), oxidative markers (MDA, H 2 O₂), and Na⁺ accumulation. Allantoin mitigated these effects by enhancing nitrogen (N) metabolism, improving K⁺/Na + homeostasis, and upregulating osmolyte (proline, sugars) and antioxidant (phenolics, ascorbic acid) accumulation. Citrulline boosted nitric oxide (NO) production, which reduced Na⁺ toxicity, improved stomatal conductance, and activated enzymatic antioxidants (SOD, APX). Their combined application synergistically improved growth (44.24% in yield), photosynthesis (5.12% in Fv/Fm), and RWC (6.45%) while reducing H 2 O 2 (61.53%) and oxidative stress (43.74% MDA). Notably, salt-stressed plants treated with both compounds exhibited elevated fruit levels of health-promoting metabolites (cucurbitacin, citrulline). Moreover, allantoin enhanced N assimilation and polyamine-mediated membrane stability, while citrulline-derived NO optimized ion transport and ROS scavenging. These findings highlight the dual role of allantoin (N metabolism) and citrulline (NO signaling) in conferring salt tolerance and propose their combined foliar application as a sustainable strategy for improving cucumber resilience in saline agriculture. Highlights - Allantoin+citrulline application improved cucumber biomass under 100 mM NaCl stress conditions - Allantoin improved K + /Ca +2 homeostasis, counteracting Na⁺ toxicity effects - Citrulline application enhanced stomatal conductance and CO₂ assimilation under stress - ROS-scavenging enzymes activity significantly enhanced by combined application - Combined treatment increased proline and soluble sugars for better osmotic adjustment

The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose levels.