MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

Combination of Dasatinib and Quercetin alleviates heat stress-induced cognitive deficits in aged and young adult male mice.

OBJECTIVE: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. METHODS: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. RESULTS: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. CONCLUSIONS: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.

Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin-Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions.

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin-angiotensin and dopaminergic systems influence intestinal Na+/K+-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of B0AT1 and ACE2 indicates the direct role of the renin-angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin-angiotensin and dopaminergic systems.

Preparation of Steamed Purple Sweet Potato-Based Films Containing Mandarin Essential Oil for Smart Packaging.

Anthocyanin-rich steamed purple sweet potato (SPSP) is a suitable raw material to produce smart packaging films. However, the application of SPSP-based films is restricted by the low antimicrobial activity of anthocyanins. In this study, SPSP-based smart packaging films were produced by adding mandarin essential oil (MEO) as an antimicrobial agent. The impact of MEO content (3%, 6%, and 9%) on the structures, properties, and application of SPSP-based films was measured. The results showed that MEO created several pores within films and reduced the hydrogen bonding system and crystallinity of films. The dark purple color of the SPSP films was almost unchanged by MEO. MEO significantly decreased the light transmittance, water vapor permeability, and tensile strength of the films, but remarkably increased the oxygen permeability, thermal stability, and antioxidant and antimicrobial properties of the films. The SPSP-MEO films showed intuitive color changes at different acid-base conditions. The purple-colored SPSP-MEO films turned blue when chilled shrimp and pork were not fresh. The MEO content greatly influenced the structures, physical properties, and antioxidant and antimicrobial activities of the films. However, the MEO content had no impact on the color change ability of the films. The results suggested that SPSP-MEO films have potential in the smart packaging of protein-rich foods.

A Comparative Study and Prediction of the Ex Vivo Permeation of Six Vaginally Administered Drugs across Five Artificial Membranes and Vaginal Tissue.

The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (Papp), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the Papp values (|Papp-predPapp| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model.

Efficacy of Laurus nobilis L. for Tight Junction Protein Imbalance in Leaky Gut Syndrome.

Laurus nobilis L. (LNL) belongs to the evergreen Lauraceae family. It is native to the Mediterranean and widely distributed in the southern United States, Europe, and the Middle East. LNL is rich in active ingredients of the sesquiterpene lactone series and has been reported to have antioxidant, anti-inflammatory, and anticancer effects. And parthenolide, known as a sesquiterpene lactone-based compound, inhibits the activation of lipopolysaccharide-binding protein (LBP), which is a major trigger for leaky gut syndrome. However, the effectiveness of LNL in improving the state of increased intestinal permeability has not yet been reported. Therefore, we demonstrated the efficacy of LNL, which is known to be rich in parthenolide, in improving intestinal permeability induced by IL-13. We investigated the improvement in permeability and analyzed major tight junction proteins (TJs), permeability-related mechanisms, weight and disease activity indices, and corresponding cytokine mechanisms. LNL maintained TJs homeostasis and clinical improvement by reducing increased claudin-2 through the inhibition of IL-13/STAT6 activation in TJ-damaged conditions. These results are expected to be effective in preventing leaky gut syndrome through the TJ balance and to further improve intestinal-related diseases, such as inflammatory bowel disease.

Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.

A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans.

Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPRER) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPRER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch.

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

Nanomedicines for intranasal delivery: understanding the nano-bio interactions at the nasal mucus-mucosal barrier.

INTRODUCTION: Intranasal administration is an effective drug delivery routes in modern pharmaceutics. However, unlike other in vivo biological barriers, the nasal mucosal barrier is characterized by high turnover and selective permeability, hindering the diffusion of both particulate drug delivery systems and drug molecules. The in vivo fate of administrated nanomedicines is often significantly affected by nano-biointeractions. AREAS COVERED: The biological barriers that nanomedicines encounter when administered intranasally are introduced, with a discussion on the factors influencing the interaction between nanomedicines and the mucus layer/mucosal barriers. General design strategies for nanomedicines administered via the nasal route are further proposed. Furthermore, the most common methods to investigate the characteristics and the interactions of nanomedicines when in presence of the mucus layer/mucosal barrier are briefly summarized. EXPERT OPINION: Detailed investigation of nanomedicine-mucus/mucosal interactions and exploration of their mechanisms provide solutions for designing better intranasal nanomedicines. Designing and applying nanomedicines with mucus interaction properties or non-mucosal interactions should be customized according to the therapeutic need, considering the target of the drug, i.e. brain, lung or nose. Then how to improve the precise targeting efficiency of nanomedicines becomes a difficult task for further research.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Modulation of Paracellular Permeability in SARS-CoV-2 Blood-to-Brain Transcytosis.

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors.

Breaking the Barriers: Machine-Learning-Based c-RASAR Approach for Accurate Blood-Brain Barrier Permeability Prediction.

The intricate nature of the blood-brain barrier (BBB) poses a significant challenge in predicting drug permeability, which is crucial for assessing central nervous system (CNS) drug efficacy and safety. This research utilizes an innovative approach, the classification read-across structure-activity relationship (c-RASAR) framework, that leverages machine learning (ML) to enhance the accuracy of BBB permeability predictions. The c-RASAR framework seamlessly integrates principles from both read-across and QSAR methodologies, underscoring the need to consider similarity-related aspects during the development of the c-RASAR model. It is crucial to note that the primary goal of this research is not to introduce yet another model for predicting BBB permeability but rather to showcase the refinement in predicting the BBB permeability of organic compounds through the introduction of a c-RASAR approach. This groundbreaking methodology aims to elevate the accuracy of assessing neuropharmacological implications and streamline the process of drug development. In this study, an ML-based c-RASAR linear discriminant analysis (LDA) model was developed using a dataset of 7807 compounds, encompassing both BBB-permeable and -nonpermeable substances sourced from the B3DB database (freely accessible from https://github.com/theochem/B3DB), for predicting BBB permeability in lead discovery for CNS drugs. The model's predictive capability was then validated using three external sets: one containing 276,518 natural products (NPs) from the LOTUS database (accessible from https://lotus.naturalproducts.net/download) for data gap filling, another comprising 13,002 drug-like/drug compounds from the DrugBank database (available from https://go.drugbank.com/), and a third set of 56 FDA-approved drugs to assess the model's reliability. Further diversifying the predictive arsenal, various other ML-based c-RASAR models were also developed for comparison purposes. The proposed c-RASAR framework emerged as a powerful tool for predicting BBB permeability. This research not only advances the understanding of molecular determinants influencing CNS drug permeability but also provides a versatile computational platform for the rapid assessment of diverse compounds, facilitating informed decision-making in drug development and design.

Permeable Bioelectronics toward Biointegrated Systems.

Bioelectronics integrates electronics with biological organs, sustaining the natural functions of the organs. Organs dynamically interact with the external environment, managing internal equilibrium and responding to external stimuli. These interactions are crucial for maintaining homeostasis. Additionally, biological organs possess a soft and stretchable nature; encountering objects with differing properties can disrupt their function. Therefore, when electronic devices come into contact with biological objects, the permeability of these devices, enabling interactions and substance exchanges with the external environment, and the mechanical compliance are crucial for maintaining the inherent functionality of biological organs. This review discusses recent advancements in soft and permeable bioelectronics, emphasizing materials, structures, and a wide range of applications. The review also addresses current challenges and potential solutions, providing insights into the integration of electronics with biological organs.

Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge.

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Influence of Surfactant on the Skin Permeation of Methylisothiazolinone and Methylchloroisothiazolinone.

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.

Curcumin-mediated alleviation of dextran-induced leaky gut in Drosophila melanogaster.

Aging is commonly characterized by a decline in the physiological functioning of the body organs, with one hallmark being the impairment of intestinal function, leading to increased intestinal permeability known as leaky gut. The aim of this study was to investigate the potential of curcumin to prevent the development of leaky gut in Drosophila melanogaster utilizing the smurf fly method. In this study, flies aged 3-5 days underwent a 10-day dextran sulfate sodium (DSS) treatment to induce intestinal permeability, followed by a smurf assay using brilliant blue dye and locomotor testing the next day. Flies displaying the smurf phenotype were divided into four groups: untreated control and curcumin-treated (10 µM, 50 µM, and 250 µM). After 21 days of treatment, flies were reassessed for the smurf phenotype and underwent locomotor testing. On day 23, flies were subjected to RT-qPCR analysis. By inducing increased intestinal permeability through the administration of DSS, a higher proportion of flies exhibiting the smurf phenotype and a reduced survival rate in the DSS-treated group were observed. Such phenotypes were reversed, decreased number of flies displaying the smurf phenotype and improved fly survival, upon the incorporation of curcumin in the fly food at concentrations of 10, 50, and 250 µM. Subsequent molecular analysis revealed upregulated expression of sod1, cat, and pepck genes, while no significant changes were observed in the expression of sod2, indy, and srl genes following treatment with curcumin at high concentration. Overall, our findings provide insight into the potential effect of curcumin to alleviate the phenotypical features associated with DSS-induced leaky gut, possibly via the selective regulation of aging-related genes.