Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK signaling pathways.

Objective: The current study aimed to investigate the potential therapeutic impact of allantoin on diabetes produced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Subjects and methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests were performed. Histopathological studies were performed in the liver, kidney and pancreas. Next, the expressions of the MAPK and insulin signaling pathway were measured by Western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. Results: The administration of allantoin resulted in a significant decrease in fasting blood glucose (FBG) levels, glycogen levels, and glycosylated hemoglobin levels in diabetic rats. Additionally, allantoin therapy led to a dose-dependent increase in body weight growth and serum insulin levels. In addition, the administration of allantoin resulted in a considerable reduction in lipid profile levels and amelioration of histological alterations in rats with diabetes. The administration of allantoin to diabetic rats resulted in a notable decrease in Malondialdehyde (MDA) levels, accompanied by an increase in the activity of antioxidant enzymes in the serum, liver, and kidney. The findings of oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests demonstrated a significant rise in insulin resistance following the administration of allantoin. The upregulation of IRS-2/PI3K/p-Akt/GLUT expression by allantoin suggests a mechanistic relationship between the PI3K/Akt signaling pathway and the antihyperglycemic activity of allantoin. Furthermore, it resulted in a reduction in the levels of TGF-ß1/p38MAPK/Caspase-3 expression in the aforementioned rat tissues affected by diabetes. Conclusions: This study implies that allantoin treats type 2 diabetes by activating PI3K. Additionally, it reduces liver, kidney, and pancreatic apoptosis and inflammation-induced insulin resistance.re.

Oleogels for the Promotion of Healthy Skin Care Products: Synthesis and Characterization of Allantoin Containing Moringa-based Oleogel.

BACKGROUND: Oleogelation is an efficient and emerging approach for obtaining biocompatible and biodegradable elastic semisolid crystals to be used in various cosmetic and pharmaceutical formulations. Recently, drug incorporation in oil structuring has been a promising strategy under consideration due to the effectiveness of this method. Plant oils have very beneficial characteristics for skin care and wound healing due to the presence of certain antioxidants. METHODS: In this study, the oleogels of Moringa oleifera seed oil with natural polysaccharides, including pectin, chitosan, and xanthan gum, were prepared using the emulsion template method. Moringa oil was selected because it can hydrate and moisturize the skin and has great antioxidant activity. Also, the natural polysaccharides, i.e., pectin and chitosan, exhibited good gelling properties. Allantoin, which is a wound healer and eucalyptus leaf oil with antioxidant potential, was incorporated into the emulsion-based-oleogels to enhance the antioxidant and antimicrobial activity of the oleogels. RESULTS: Allantoin and eucalyptus-loaded oleogels exhibited good antibacterial activity against E. coli. The FTIR spectra of moringa-based oleogels in the range between 3226-3422 cm-1 indicate the presence of hydrogen bonding in oleogels. CONCLUSION: The antioxidant potential of allantoin and eucalyptus-containing oleogel was maximized, and an IC50 value of 0.9719 µM was found. Maximum release of allantoin from oleogel was observed in the first hour.

The Influence of Oxidized Imino-Allantoin in the Presence of OXOG on Double Helix Charge Transfer: A Theoretical Approach.

The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin (OXIa) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A1OXIa2A3OXOG4A5]*d[T5C4T3C2T1] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the OXOG moiety, irrespective of the presence of OXIa in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the OXOG:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for OXIaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus' theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the OXOGC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards OXIa2C4 located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of OXIa can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of OXIa in the structure of clustered DNA damage can result in improved cancer treatment outcomes.

Oxamic transcarbamylase of Escherichia coli is encoded by the three genes allFGH (formerly fdrA, ylbE, and ylbF).

Escherichia coli uses allantoin as the sole nitrogen source during anaerobic growth. In the final step of allantoin degradation, oxamic transcarbamylase (OXTCase) converts oxalurate to carbamoyl phosphate (CP) and oxamate. The activity of this enzyme was first measured in Streptococcus allantoicus in the 1960s, but no OXTCase enzyme or the encoding gene(s) have been found in any strain. This study discovered that allFGH (fdrA, ylbE, and ylbF) are the genes that encode the global orphan enzyme OXTCase. The three genes form an operon together with allK (ybcF), encoding catabolic carbamate kinase. The allFGHK operon is located directly downstream of the allECD operon that encodes enzymes for the preceding steps of OXTCase. The OXTCase kinetic parameters were analyzed using the purified protein composed of AllF-AllG-AllH (FdrA-YlbE-YlbF); for the substrate CP, KM and Vmax were 1.3 mM and 15.4 U/mg OXTCase, respectively, and for the substrate oxamate, they were 36.9 mM and 27.0 U/mg OXTCase. In addition, the OXTCase encoded by the three genes is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase, ornithine transcarbamylase, and YgeW transcarbamylase. The present study elucidated the anaerobic allantoin degradation pathway of E. coli. Therefore, we suggest that the genes fdrA, ylbE, and ylbF are renamed allF, allG, and allH, respectively.IMPORTANCEThe anaerobic allantoin degradation pathway of Escherichia coli includes a global orphan enzyme, oxamic transcarbamylase (OXTCase), which converts oxalurate to carbamoyl phosphate and oxamate. This study found that the allFGH (fdrA, ylbE, and ylbF) genes encode OXTCase. The OXTCase activity and kinetics were successfully determined with purified recombinant AllF-AllG-AllH (FdrA-YlbE-YlbF). This OXTCase is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase (ATCase), ornithine transcarbamylase (OTCase), and YgeW transcarbamylase (YTCase). In addition, OXTCase activity requires three genes, whereas ATCase is encoded by two genes, and OTCase and YTCase are encoded by a single gene. The current study discovered OXTCase, the last unknown step in allantoin degradation, and this enzyme is a new member of the transcarbamylase group that was previously unknown.

Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO2 Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform.

This study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO2) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of the wound healing process. These scaffolds provide the simultaneous release of bioactive agents and concurrently support cell/tissue repair through the replicated structure of a native extracellular matrix. The hydrogel scaffolds were synthesized via a crosslinking reaction using EDC as a crosslinker for gelatin. Synthesized hydrogel scaffolds and the effect of TiO2 on their properties were characterized by structural, mechanical, morphological, and swelling properties, and the porosity, wettability, adhesion to skin tissue, and simultaneous release features. The biocompatibility of the scaffolds was tested in vitro on fibroblasts (MRC5 cells) and in vivo (Caenorhabditis elegans) in a survival probe. The scaffolds revealed porous interconnected morphology, porosity of 88.33 to 96.76%, elastic modulus of 1.53 to 4.29 MPa, full hydrophilicity, favorable skin adhesivity, and biocompatibility. The simultaneous release was investigated in vitro indicating dependence on the scaffold's composition and type of bioactive agents. The novel scaffolds designed as multi-target therapy have significant promise for improved wound healing in a beneficial and non-invasive manner.

Chitosan and neem gum-based polyelectrolyte complex for design of allantoin loaded biocomposite film: In-vitro, ex-vivo, and in-vivo characterization.

Presently, the preference for chitosan (CS) and gum polysaccharides in biomedical applications including drug delivery and wound healing has been extensively documented. Despite this, the demerits of CS and gum polysaccharides such as poor mechanical properties, degradation rate, swelling, etc., limit their applications for designing biocomposite films for drug delivery. Therefore, the anticipated work aims to design a CS and neem gum polysaccharides (NGP) polyelectrolyte complex-based allantoin (AT)-loaded (CS/NGP-AT) biocomposite film for improved wound healing. In brief, CS, NGP, and CS/NGP-AT-based biocomposite films were prepared using the solvent-casting method, and in-vitro, ex-vivo, and in-vivo characterizations were performed to assess the performance of these biocomposite films compared to their counterparts. In this, diffractogram and thermogram analysis assured the conversion of crystalline AT into an amorphous form. The optimized CS/NGP/AT-3 formulation exhibited controlled water absorption, appropriate water uptake capacity, good water retention ability, excellent water vapor transmission rate, controlled degradation rate, enhanced mechanical properties, cell and blood biocompatibility, etc. Furthermore, it offered improved antimicrobial, anti-inflammatory, and antioxidant potential. The optimized film provided a modified release (88.3 ± 0.3 %) of AT from the film for up to 48 h. Wound healing experiments on rats and their histopathology studies confirmed a significantly higher rate of wound recovery within 14 days compared to the control and CS/NGP film, attributable to the combined effects of CS, NGP, and AT. In conclusion, the fabricated CS/NGP-based biocomposite film presents promising prospects as an excellent candidate for wound healing applications.

Automated sepsis detection with vancomycin- and allantoin-polydopamine magnetic nanoparticles.

Rapid and accurate identification of the bacteria responsible for sepsis is paramount for effective patient care. Molecular diagnostic methods, such as polymerase chain reaction (PCR), encounter challenges in sepsis due to inhibitory compounds in the blood, necessitating their removal for precise analysis. In this study we present an innovative approach that utilizes vancomycin (Van) and allantoin (Al)-conjugated polydopamine (PDA)-coated magnetic nanoparticles (MNPs) for the rapid and automated enrichment of bacteria and their DNA extraction from blood without inducing clumping and aggregation of blood. Al/Van-PDA-MNPs, facilitated by IMS, eliminate the need for preliminary sample treatments, providing a swift and efficient method for bacterial concentration and DNA extraction within an hour. Employing Al/Van-PDA-MNPs within an automated framework has markedly improved our ability to pre-concentrate various Gram-negative and Gram-positive bacteria directly from blood samples. This advancement has effectively reduced the detection threshold to 102 colony-forming unit/mL by both PCR and quantitative PCR. The method's expedited processing time, combined with its precision, positions it as a feasible diagnostic tool for diverse healthcare settings, ranging from small clinics to large hospitals. Furthermore, the innovative application of nanoparticles for DNA extraction holds promising potential for advancing sepsis diagnostics, enabling earlier interventions and improving patient outcomes.

Impact of the Preparation Method on the Formulation Properties of Allantoin Hydrogels: Evaluation Using Semi-Solid Control Diagram (SSCD) Principles.

Allantoin possesses numerous beneficial properties for the skin, like anti-irritant effects, wound healing, skin hydration, and epithelization. In this paper, we investigated a suitable preparation method for an allantoin hydrogel using the Semi-Solid Control Diagram (SSCD) method and characterized its rheological and consistency behavior. To accomplish this, xanthan gum (XG) was selected as a model gelling agent. Briefly, four hydrogels were prepared, two without allantoin (coded M01 and M02) and two with allantoin (M1 and M2). Similarly, the formulations were either prepared through magnetic stirring (M01 and M1) or homogenization in a mortar (M02 and M2). The prepared hydrogels were evaluated using the SSCD for specific parameters and indexes. The Good Quality Index (GQI) shows a higher value for the formulation, M1 = 6.27, compared to M2 = 5.45. This result is also underlined by the value of M01 = 6.45, which is higher than M02 = 6.38. Considering the consistency, the formulation M01 possessed the highest spreadability, followed by M02 and then the allantoin hydrogels M1 and M2. The rheological behavior had a thixotropic pseudoplastic flow for all the formulations. The use of SSCD pictographs outlined the rheological properties that need improvement, the method that is suitable to prepare the allantoin hydrogels, and the influence of the allantoin suspended in the XG hydrogel.

Allantoin Derived From Dioscorea opposita Thunb Ameliorates Cyclophosphamide-Induced Premature Ovarian Failure in Female Rats by Attenuating Apoptosis, Autophagy and Pyroptosis.

Background and objectives Cyclophosphamide (CP) is widely used as a chemotherapy drug for the treatment of malignant tumors and autoimmune diseases, but it has strong toxic and side effects and can cause permanent damage to the ovaries, which affects women's quality of life. This study aimed to investigate the anti-premature ovarian failure protective effect of allantoin isolated from Dioscorea opposita Thunb. Methods Firstly, 75 mg/kg CP was injected into rats to establish an in vivo model of premature ovarian failure (POF). The POF rats were divided into the normal control group (NC), premature ovarian failure group (POF), and POF group treated with allantoin (ALL I 140 mg/kg and ALL II 70 mg/kg, daily 21 days). It investigated the estrous cycles, hormone levels, apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitophagy, and protein marker (Bax, Bcl2, LC3B, L-1ß, caspase-1 and NLRP3). Results The results indicated that allantoin alleviated cyclophosphamide-induced premature ovarian failure in female rats, decreased the anoestrum, increased the level of estradiol (E2), and decreased the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), decreased apoptosis rate, MMP, mitophagy and ROS in ovarian granulosa cells of POF rats, down-regulated L-1ß, caspase-1, LC3B-II/LC3B-I in ovarian tissue, and up-regulated the Bcl2 and NLRP3. Conclusions Our study revealed the ovarian-protective effect of allantoin in CP-induced premature ovarian failure for the first time, the effect was achieved through attenuation of the apoptosis, autophagy, and pyroptosis. The study underlines the potential clinical application of allantoin as a protectant agent for premature ovarian failure.

Biopolymer- and Natural Fiber-Based Biomimetic Tissues to Realize Smart Cosmeceuticals and Nutraceuticals Using an Innovative Approach.

More sustainable and smart cosmeceuticals and nutraceuticals are necessary due to the ecological transition. In this study, a pullulan-based water solution containing chitin nanofibril-nano-lignin (CN-LG) complexes that encapsulate fish collagen polypeptide, allantoin and nicotinamide was electrospun onto a nonwoven substrate made of bamboo fibers to obtain a smart nanostructured bilayer system for releasing active molecules onto the skin or other body tissues. Infrared spectroscopy was used to characterize the composition of the bilayer system before and after rapid washing of the sample with distilled water and liquids mimicking physiological fluids. The viability of keratinocytes was studied as well as the antioxidant activity, protective activity towards UV light, metalloproteinase release of aged fibroblasts and the inhibitor activity against collagen degradation. Immunomodulatory tests were performed to investigate the anti-inflammatory activity of the bilayer system as well as its indirect antimicrobial activity. The results indicate that the bilayer system can be used in the production of innovative sustainable cosmeceuticals. In general, the adopted strategy can be extended to several smart treatments for fast release that can be commercialized as solid products, thus avoiding the use of preservatives and water.

Development of Ag NPs/allantoin loaded PCL/GEL electrospun nanofibers for topical wound treatment.

In the present study, the allantoin and silver nanoparticle (Ag NPs) loaded poly caprolactone/gelatin (PCL/GEL) nanofibers produced using electrospinning technique and their cyto-compatibility and wound healing activity were evaluated in vitro and in vivo. The SEM imaging revealed diameters of 278.8 ± 10 and 240.6 ± 12 nm for PCL/GEL/Ag NPs and PCL/GEL/Ag NPs/allantoin scaffolds. The Ag NPs entrapment into scaffolds was evaluated by FTIR analysis and EDX mapping. Both scaffolds containing Ag NPs and Ag NPs/allantoin exhibited valuable wound healing activity in Wistar rat animal model. The profound granulation tissue formation, high collagen deposition in coordination with low level of edema and inflammatory cells in Ag NPs/allantoin loaded scaffolds resulted in complete and mature re-epithelialization in giving the healing score (12 out of 12) equal to positive control group to the wounds treated with these scaffolds. It was concluded that the Ag NPs/allantoin loaded scaffolds regarding to their good antibacterial activity and excellent wound healing activity could be introduced as new effective wound dressing materials.

Allantoin: A Potential Compound for the Mitigation of Adverse Effects of Abiotic Stresses in Plants.

Stress-induced alterations vary with the species of plants, the intensity and duration of the exposure, and stressors availability in nature or soil. Purine catabolism acts as an inherent defensive mechanism against various abiotic stresses and plays a pivotal role in the stress acclimatisation of plants. The intermediate metabolite of purine catabolism, allantoin, compensates for soil nitrogen deficiency due to the low carbon/nitrogen ratio, thereby maintaining nitrogen homeostasis and supporting plant growth and development. Allantoin accounts for 90% of the total nitrogenous compound in legumes, while it contributes only 15% in non-leguminous plants. Moreover, studies on a variety of plant species have reported the differential accumulation of allantoin in response to abiotic stresses, endowing allantoin as a stress modulator. Allantoin functions as signalling molecule to stimulate stress-responsive genes (P5CS; pyrroline-5-carboxylase synthase) and ROS (reactive oxygen species) scavenging enzymes (antioxidant). Moreover, it regulates cross-talk between the abscisic acid and jasmonic acid pathway, and maintains ion homeostasis by increasing the accumulation of putrescine and/or spermine, consequently enhancing the tolerance against stress conditions. Further, key enzymes of purine catabolism (xanthine dehydrogenase and allantoinase) have also been explored by constructing various knockdown/knockout mutant lines to decipher their impact on ROS-mediated oxidative injury in plants. Thus, it is established that allantoin serves as a regulatory signalling metabolite in stress protection, and therefore a lower accumulation of allantoin also reduces plant stress tolerance mechanisms. This review gives an account of metabolic regulation and the possible contribution of allantoin as a photo protectant, osmoprotectant, and nitrogen recycler to reduce abiotic-stress-induced impacts on plants.

Fabrication and characterization of an antibacterial chitosan-coated allantoin-loaded NaCMC/SA skin scaffold for wound healing applications.

The field of tissue engineering has recently emerged as one of the most promising approaches to address the limitations of conventional tissue replacements for severe injuries. This study introduces a chitosan-coated porous skin scaffold based on sodium carboxymethyl cellulose (NaCMC) and sodium alginate (SA) hydrogels, incorporating allantoin (AL) as an antibacterial agent. The NaCMC/SA hydrogel was cross-linked with epichlorohydrin (ECH) and freeze-dried to obtain a three-dimensional porous structure. The coated and non-coated scaffolds underwent comprehensive evaluation and characterization through various in-vitro analyses, including SEM imaging, swelling, degradation, and mechanical assessments. Furthermore, the scaffolds were studied regarding their allantoin (AL) release profiles, antibacterial properties, cell viability, and cell adhesion. The in-vitro analyses revealed that adding a chitosan (CS) coating and allantoin (AL) to the NaCMC/SA hydrogel significantly improved the scaffolds' antibacterial properties and cell viability. It was observed that the NaCMC:SA ratio and ECH concentration influenced the swelling capacity, biodegradation, drug release profile, and mechanical properties of the scaffolds. Samples with higher NaCMC content exhibited enhanced swelling capacity, more controlled allantoin (AL) release, and improved mechanical strength. Furthermore, the in-vivo results demonstrated that the proposed skin scaffold exhibited satisfactory biocompatibility and supported cell viability during wound healing in Wistar rats, highlighting its potential for clinical applications.

A Systematic Review and Meta-Analysis of the Association between Uric Acid and Allantoin and Rheumatoid Arthritis.

Alterations in the circulating concentrations of uric acid and its degradation product, allantoin, might account for the systemic pro-oxidant state and the increased cardiovascular risk in rheumatoid arthritis (RA). We sought to address this issue by conducting a systematic review and meta-analysis of the association between the plasma/serum concentrations of uric acid and allantoin and RA. We searched PubMed, Scopus, and Web of Science from inception to 20 June 2023 for studies comparing plasma/serum concentrations of uric acid and allantoin between RA patients and healthy controls. We assessed the risk of bias with the JBI Critical Appraisal Checklist for analytical studies and the certainty of evidence with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system. In the 19 studies selected for analysis, there were non-significant differences in uric acid concentrations between RA patients and controls (standard mean difference, SMD = 0.11, 95% CI -0.07 to 0.30, p = 0.22; I2 = 87.9%, p < 0.001; low certainty of evidence). By contrast, the concentrations of allantoin were significantly higher in RA patients (SMD = 1.10, 95% CI 0.66 to 1.55, p < 0.001; I2 = 55.6%, p = 0.08; extremely low certainty of evidence). In meta-regression, a significant association was observed between the SMD of uric acid concentrations and body mass index, a risk factor for atherosclerosis and cardiovascular disease (t = 3.35, p = 0.007). Our study has shown a significant increase in the concentrations of the oxidative stress biomarker allantoin in patients with RA. Further research is warranted to investigate the interplay between uric acid, allantoin, redox balance, and cardiovascular disease in this group. (PROSPERO registration number: CRD42023441127).

Multi-scale analysis provides insights into the roles of ureide permeases in wheat nitrogen use efficiency.

The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.

Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.

Metabolic disorders represent a major therapeutic challenge to public health worldwide due to their dramatically increasing prevalence. Acupuncture is widely used as adjuvant therapy for multiple metabolic diseases. However, detailed biological interpretation of the acupuncture stimulations is still limited. The gut and the liver are intrinsically connected and related to metabolic function. Microbial metabolites might affect the gut-liver axis through multiple mechanisms. Liver metabolomics and 16S rRNA sequencing were used to explore the specific mechanism of electroacupuncture in treating ZDF rats in this study. Electroacupuncture effectively improved glycolipid metabolism disorders of the ZDF rats. Histopathology confirmed that electroacupuncture improved diffuse hepatic steatosis and hepatocyte vacuolation, and promoted glycogen accumulation in the liver. The treatment significantly improved microbial diversity and richness and upregulated beneficial bacteria that maintain intestinal epithelial homeostasis and decreased bacteria with detrimental metabolic features on host metabolism. Liver metabolomics showed that the main effects of electroacupuncture include reducing the carbon flow and intermediate products in the TCA cycle, regulating the metabolism of various amino acids, and inhibiting hepatic glucose output and de novo lipogenesis. The gut-liver axis correlation analysis showed a strong correlation between the liver metabolites and the gut microbiota, especially allantoin and Adlercreutzia. Electroacupuncture treatment can improve abnormal energy metabolism by reducing oxidative stress, ectopic fat deposition, and altering metabolic fluxes. Our results will help us to further understand the specific mechanism of electroacupuncture in the treatment of metabolic diseases.

Allantoin improves salinity tolerance in Arabidopsis and rice through synergid activation of abscisic acid and brassinosteroid biosynthesis.

Soil salinity stress is one of the major bottlenecks for crop production. Although, allantoin is known to be involved in nitrogen metabolism in plants, yet several reports in recent time indicate its involvement in various abiotic stress responses including salinity stress. However, the detail mechanism of allantoin involvement in salinity stress tolerance in plants is not studied well. Moreover, we demonstrated the role of exogenous application of allantoin as well as increased concentration of endogenous allantoin in rendering salinity tolerance in rice and Arabidopsis respectively, via., induction of abscisic acid (ABA) and brassinosteroid (BR) biosynthesis pathways. Exogenous application of allantoin (10 µM) provides  salt-tolerance to salt-sensitive rice genotype (IR-29). Transcriptomic data after exogenous supplementation of allantoin under salinity stress showed induction of ABA (OsNCED1) and BR (Oscytochrome P450) biosynthesis genes in IR-29. Further, the key gene of allantoin biosynthesis pathway i.e., urate oxidase of the halophytic species Oryza coarctata was also found to induce ABA and BR biosynthesis genes when over-expressed in transgenic Arabidopsis. Thus, indicating that ABA and BR biosynthesis pathways were involved in allantoin mediated salinity tolerance in both rice and Arabidopsis. Additionally, it has been found that several physio-chemical parameters such as biomass, Na+/K+ ratio, MDA, soluble sugar, proline, allantoin and chlorophyll contents were also associated with the allantoin-mediated salinity tolerance in urate oxidase overexpressed lines of Arabidopsis. These findings depicted the functional conservation of allantoin for salinity tolerance in both plant clades.

Quantification of Allantoin in Yams (Dioscorea sp.) Using a 1H NMR Spectroscopic Method.

Allantoin is an abundant component of yams and has been known as a skin protectant due to its pharmacological activities. In previous methods for allantoin determination using high-performance liquid chromatography (HPLC), the separation was unsatisfactory. We herein developed a 1H quantitative nuclear magnetic resonance (qNMR) method for quantification of allantoin in the flesh and peel of yams. The method was carried out based on the relative ratio of signals integration of allantoin to a certain amount of the internal standard dimethyl sulfone (DMSO2) and validated in terms of specificity, linearity (range 62.5-2000 µg/ml), sensitivity (limit of detection (LOD) and quantification (LOQ) 4.63 and 14.03 µg/ml, respectively), precision (RSD% 0.02-0.26), and recovery (86.35-92.11%). The method was then applied for the evaluation of allantoin in flesh and peel extracts of four different yams cultivated in Korea.

Characterization and In Vivo Assay of Allantoin-Enriched Pectin Hydrogel for the Treatment of Skin Wounds.

This work describes a liquid allantoin-enriched pectin hydrogel with hydrophilic behavior that is supported by the presence of functional groups related to healing efficacy. A topical study shows the effect of the hydrogel application on surgically induced skin wound healing in a rat model. Contact angle measurements confirm hydrophilic behavior (11.37°), while Fourier-transform infrared spectroscopy indicates the presence of functional groups related to the healing effectiveness (carboxylic acid and amine groups). Allantoin is distributed on the surface and inside the amorphous pectin hydrogel surrounded by a heterogeneous distribution of pores. This promotes wound drying with better interaction between the hydrogel and cells involved in the wound healing process. An experimental study with female Wistar rats indicates that the hydrogel improves wound contraction, reducing around 71.43% of the total healing time and reaching total wound closure in 15 days.