搜索结果：Endocrine, metabolic & immune disorders drug targets

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone-mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies.

In Type 1 diabetes (T1D), pancreatic β cells are progressively lost, resulting in insulin insufficiency. Although exogenous insulin is essential for disease management, it is not a cure, and inadequate glycemic control continues to result in long-term complications. Thus, there is a need for therapies that address the underlying autoimmune response, a key component of T1D pathogenesis. This review examines a wide range of actionable immunomodulatory targets at the tissue, cellular, and molecular levels that form the basis of current and emerging therapies for T1D. Particular emphasis is placed on T cell populations, which play a central role; with other immune cell types contributing to varying degrees also discussed. Immune-modifying therapies aim to prevent or reverse the pathogenic functions of these cells, including their interactions with β cells. Many of these approaches are directed at specific immune cell populations, but not only the pathogenic ones. Recent advances have enabled more precise targeting, based on tissue relevance or antigen specificity. The immune system may also be indirectly modulated by targeting the microbiome, offering potential new strategies for early prevention of T1D. Many of these targets were identified from animal models and remain to be validated in humans, leaving numerous therapeutic avenues open for exploration.

We developed a novel FTY720 prodrug (pro-FTY) that specifically inhibits sphingosine-1-phosphate signaling in cancer cells using a novel drug delivery system that reacts with acrolein. Our objective was to evaluate the efficacy and safety of pro-FTY in preclinical experiments. Ten breast cancer cell lines, two multidrug-resistant cell lines, and one normal mammary cell line were used to compare the IC50 values of pro-FTY with those of other drugs. Patient-derived organoids (PDO) were established and utilized for IC50 value comparisons. Drug efficacy was tested in mice bearing either syngeneic 4T1 cell tumors or patient-derived xenograft tumors, and blood analysis (including mass spectrometry) was performed. FTY720 and pro-FTY inhibited the survival of all breast cancer cell lines, including multidrug-resistant cells resistant to paclitaxel or doxorubicin. Unlike pro-FTY, FTY720 inhibited the survival of normal breast cell lines, suggesting that pro-FTY does not affect normal breast cells. Pro-FTY showed reproducible activity against multidrug-resistant PDOs, whereas paclitaxel and doxorubicin did not. Mass spectrometric analysis of pro-FTY-treated mice showed that FTY720 accumulated in tumors but was barely detectable in blood. Importantly, lymphocytopenia occurred in FTY720-treated mice but not in pro-FTY-treated mice. Furthermore, intravenous pro-FTY treatment significantly suppressed tumor growth in mice bearing patient-derived xenograft tumors generated from multidrug-resistant PDOs. In conclusion, pro-FTY inhibited breast cancer, including multidrug-resistant breast cancer, while avoiding lymphocytopenia, highlighting its clinical potential. Pro-FTY selectively inhibits sphingosine-1-phosphate signaling in cancer cells using a novel acrolein-responsive drug delivery system that reacts with acrolein. Pro-FTY does not inhibit normal cell growth, thus avoiding lymphocytopenia. Pro-FTY is effective against multidrug-resistant breast cancer with a unique mechanism of action, highlighting its translational and therapeutic potential.

The microbiota-gut-brain axis represents a complex bidirectional communication network linking the gastrointestinal system and the central nervous system and has been increasingly recognized as a key contributor to neurological and psychiatric disorders. Growing evidence indicates that alterations in gut microbiota composition and function can influence brain development and function through neural, immune, endocrine, and metabolic pathways, thereby modulating neuroinflammation, neurotransmission, and blood-brain barrier integrity. Dysregulation of this axis has been implicated in a range of conditions, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism spectrum disorder, depression, anxiety, and stroke. Recent pharmacological advances have identified the microbiota-gut-brain axis as a promising therapeutic target. Current strategies focus on modulating shared pathophysiological mechanisms rather than disease-specific endpoints and include microbiota-directed interventions, immune-inflammatory modulators, neurotransmitter-targeting agents, and approaches aimed at restoring intestinal and blood-brain barrier function. In this review, we summarize the core mechanisms underlying microbiota-gut-brain axis dysfunction and organize existing pharmacological strategies according to their primary targets. By integrating evidence across multiple disorders, we provide a mechanism-oriented framework to support future drug development and precision therapeutic approaches for brain disorders.

This study investigates the potential mechanism of Xiezhuo Yishen Decoction (XYD) in the treatment of uric acid nephropathy (UAN). The active components and targets of XYD were determined via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins were chosen through the Uniprot database. GeneCards, Online Mendelian Inheritance in Man, and Drugbank were utilized to identify gene targets associated with UAN, whereas Venny 2.1.0 was employed to determine the common intersections between medication targets and disease targets. Cytoscape 3.7.1 was employed to map the network of active substances in Traditional Chinese medicine and their potential targets, while the protein-protein interaction network was constructed using the String database and Cytoscape software to identify critical target proteins. Gene ontology annotation analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed using R version 4.0.0 software . A total of 206 active components were identified from the XYD, of which 62 were recognized as possible therapeutic targets. We screened out 31 key targets by the protein-protein interaction network. Gene ontology enrichment analysis revealed 81 biological processes, 14 cellular components, and 96 molecular functions. Kyoto encyclopedia of genes and genomes enrichment analysis showed that 199 pathways were significantly enriched, whose functions were mainly involved in immune system, endocrine system, cell death and autophagy, and other biological processes. The molecular docking data indicated that the binding energy between the active components of XYD and the major targets exhibited significant binding affinity. The mechanism of XYD in treating UAN involves multiple components, multiple targets, and multiple pathways, including participating in lipid metabolism, inhibiting inflammation, regulating apoptosis and autophagy. The study also found that FOXO signal pathway may be a potential pathway for treating UAN. Additionally, a novel therapeutic approach for UAN has been established, targeting various signaling pathways.

Acetyl tributyl citrate (ATBC) and epoxidized soybean oil (ESBO) are widely used emerging plasticizers, but their potential to induce lipid metabolism disorders remains poorly understood. In this study, we explored their toxicological mechanisms using a network toxicology framework combined with molecular docking and molecular dynamics simulations. Potential targets of ATBC and ESBO were predicted from multiple databases and compared with genes associated with lipid metabolism disorders. Core targets were identified through protein-protein interaction network analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analyses were performed to infer relevant biological processes and pathways. Molecular docking and dynamics simulations were further applied to evaluate the binding affinity and stability between the compounds and key targets. Five core targets-epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), toll-like receptor 4 (TLR4), JUN proto-oncogene (JUN), and androgen receptor (AR)-were identified, mainly involved in immune regulation, hormone signaling, and the hypoxia-inducible factor 1 (HIF-1) pathway. Enrichment analyses suggested that the emerging plasticizers ATBC and ESBO may disturb lipid metabolism and contribute to diseases such as non-alcoholic fatty liver disease (NAFLD) and hormone-sensitive cancers. Docking results confirmed strong and specific interactions between the compounds and core targets. Overall, these findings support the hypothesis that ATBC and ESBO may disrupt hepatic lipid metabolism through HIF-1 activation and immune-endocrine pathway interference, providing insight into their potential health risks.

Corticosteroids have long been a standard-of-care treatment for chronic immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, corticosteroids are associated with potentially serious adverse effects and may be ineffective in cases of resistant or refractory disease. Acthar® Gel, a naturally sourced complex mixture of porcine pituitary peptides, is a noncorticosteroid alternative that is approved by the US Food and Drug Administration to treat a variety of IMIDs and autoimmune conditions. These include infantile spasms, systemic lupus erythematosus, exacerbations of multiple sclerosis and rheumatoid arthritis, and several ocular inflammatory disorders. Preclinical and clinical studies have shown that the immunomodulatory effects of Acthar Gel are distinct from those of corticosteroids and other adrenocorticotropic hormone (ACTH)-class therapeutics. For example, Acthar Gel stimulates both steroid-dependent and steroid-independent pathways that may mitigate inflammation. In this narrative review, we summarize the immunomodulatory effects of Acthar Gel, with a focus on its potential mechanisms in immune cells, such as B cells, T cells, and macrophages. These effects are thought to be mediated by binding and activation of transmembrane melanocortin receptors expressed on these immune cells. Receptor binding initiates an intracellular signal transduction cascade that ultimately regulates the expression of anti-inflammatory genes. Collectively, the experimental and clinical studies reviewed here suggest that Acthar Gel acts as an immunomodulator via melanocortin receptors and may be an effective anti-inflammatory therapeutic option for patients with IMIDs who are refractory or intolerant to corticosteroids.Graphical Abstract available for this article. Steroids, also known as corticosteroids, are medications that can help reduce inflammation and treat diseases where the body’s immune system mistakenly attacks its own healthy tissue, such as rheumatoid arthritis and multiple sclerosis. However, treatment with corticosteroids can cause harmful or unwanted side effects and may not work well for some patients. Acthar® Gel is an alternative to corticosteroids that is approved by the US Food and Drug Administration to treat diseases that affect the immune system, including infantile spasms, systemic lupus erythematosus, flare-ups of multiple sclerosis and rheumatoid arthritis, and certain eye inflammations. Research studies have shown that Acthar Gel’s mechanism of action is distinct from corticosteroids, with both direct activity on immune cells and induction of low levels of natural corticosteroids produced by the body. This review paper summarizes the effect of Acthar Gel on immune system cells, such as B cells, T cells, and macrophages, and how this treatment interacts with specific targets called melanocortin receptors on these immune cells. This interaction initiates a series of signals inside the cells that ultimately reduce inflammation. The research studies discussed in this review paper suggest that Acthar Gel helps regulate the immune system by acting on the melanocortin receptors. Acthar Gel may be an appropriate treatment option to help reduce inflammation for patients with immune system diseases who are unresponsive or unable to receive corticosteroids.

Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine-immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti-spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D3 related molecular targets were integrated with AIT-associated genes, followed by protein-protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D3 (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D3 to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine-immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance.

Neuroactive steroids, encompassing both peripherally derived hormones and neurosteroids synthesized de novo within the central nervous system, have emerged as pivotal modulators of brain physiology and pathology. This rapidly evolving field is transforming our understanding of how steroid signaling influences neural function, paving the way for novel biomarkers and targeted therapeutic strategies. Acting on specific neuronal receptors, these compounds finely regulate excitability, synaptic integration, and network dynamics, thereby linking endocrine and neural mechanisms in the maintenance of brain homeostasis. Over the past three decades, these mediators have been shown to exert broad influences on neurotransmitter systems, the hypothalamic-pituitary-adrenal (HPA) axis, and neuroinflammatory pathways. Mounting evidence implicates both neurosteroids and peripheral neuroactive steroids in the pathophysiology of numerous psychiatric and neurological disorders, including depression, bipolar disorder, anxiety disorders, PTSD, schizophrenia, autism spectrum disorder, substance use disorders, epilepsy, Alzheimer's disease, Parkinson's disease, tic disorders, and multiple sclerosis. This review synthesizes current evidence on how neurosteroids (and, more broadly, neuroactive steroids) contribute to the endogenous regulation of neural excitability, affective reactivity, and immune signaling, and explores how their dysregulation may represent a shared mechanism of vulnerability across diverse brain disorders. Finally, we highlight emerging therapeutic opportunities, underscored by recent advances such as zuranolone and ganaxolone, and discuss future challenges in optimizing delivery, enhancing receptor specificity, and refining clinical trial design to establish neurosteroid-based interventions as a versatile platform for treating and preventing complex neuropsychiatric disease.

Childhood obesity is a growing public health concern, with emerging evidence suggesting that environmental factors like bisphenol A (BPA) exposure may contribute to its development. This study aims to elucidate the genetic and molecular mechanisms linking BPA exposure to childhood obesity. We analyzed the publicly available dataset GSE9624 to identify differentially expressed genes (DEGs) associated with childhood obesity. We cross-referenced these DEGs with BPA-related toxicity targets obtained from the Comparative Toxicogenomics Database (CTD) and SwissTargetPrediction database. Network construction, molecular docking, enrichment analysis, Gene Set Variation Analysis (GSVA), and correlation analysis were performed to explore interactions between BPA exposure and childhood obesity. We identified 967 DEGs associated with childhood obesity, with 81 overlapping BPA-related toxicity targets. A heatmap revealed distinct expression patterns of these genes between obese and normal-weight children. Network analysis highlighted JUN, TOP2A, APOE, and LEP as hub genes. Molecular docking indicated strong binding affinities between BPA and these core targets. Enrichment analysis revealed disruptions in lipid metabolism, cell cycle, and oxidative stress pathways. GSVA demonstrated significant differences in oxidative stress, inflammatory response, and lipid metabolism between obese and normal-weight children. Correlation analysis further conformed BPA's impact on metabolic-immune pathways through core genes modulation. Our findings suggest that BPA exposure may drive childhood obesity by disrupting metabolic, inflammatory, and oxidative stress pathways. The identified core genes and pathways provide a molecular basis for further research and potential therapeutic targets in BPA-related metabolic disorders.

Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of insulin-producing β cells, which leads to chronic hyperglycaemia and lifelong insulin dependence. Despite advances in diabetes care, achieving optimal glucose control and preventing complications remains a challenge. Gene therapy has emerged as a transformative approach, targeting the underlying mechanisms of β-cell destruction and immune dysregulation. Studies have suggested the feasibility of using viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses, to deliver genes aimed at preserving pancreatic function and restoring immune balance. Innovative strategies, including CRISPR/Cas9-based genome editing and non-viral delivery systems, offer promise for addressing safety and efficacy challenges. This systematic review aims to evaluate the current state of gene therapy in T1D, focusing on findings from preclinical studies and ongoing clinical trials. It explores key approaches, such as β-cell regeneration, immune tolerance induction, and metabolic regulation, while critically assessing challenges related to delivery efficiency, long-term effects, and scalability. By synthesising existing evidence, this review provides a comprehensive overview of the progress and obstacles in translating gene therapy into a viable treatment for T1D, highlighting future directions to accelerate clinical application.

Verapamil, a calcium channel blocker, and low doses of anti-thymocyte globulin (ATG) have individually shown efficacy in preserving beta cell function in people with recent-onset symptomatic type 1 diabetes (stage 3). We hypothesised that combining interventions with complementary modes of action and different targets would increase their efficacy in arresting beta cell demise and promoting disease recovery. Continuous administration of verapamil via drinking water, combined with a short course of low-dose rabbit-anti-mouse ATG (mATG), was studied in female recent-onset diabetic NOD mice for its potential to induce disease remission and mechanism of action. Verapamil stably reversed diabetes in 3 out of 15 mice (20%) by day 56 after therapy start. Low-dose mATG reversed diabetes in 7 out of 18 mice (39%) by day 7 after therapy start, yet the effect waned to 3 out of 18 mice (17%) by day 56. The combination of verapamil with mATG induced durable diabetes reversal in 9 out of 20 mice (45%) by day 56, which was associated with preserved beta cell function, higher pancreatic insulin content and increased total beta cell volume with decreased severe insulitis. mATG, both alone and in combination, induced a temporary depletion of lymphocytes in peripheral blood on day 3 after therapy start, which largely recovered by day 14, when naive cells had shifted to a memory phenotype in both CD4+ and CD8+ T cells. Only in combination-treated mice was a higher CD4+ regulatory T cell to CD8+ effector memory T cell ratio observed in the pancreatic draining lymph nodes. The expression of the glucose-induced gene encoding thioredoxin-interacting protein (Txnip), a key regulator of beta cell apoptosis and dysfunction, was reduced in pancreatic beta cells in reversed mice, irrespective of whether they received verapamil or not. The combination of verapamil and low-dose mATG outperformed monotherapy in reversing recent-onset type 1 diabetes in NOD mice. This approach targets both the beta cell and immune axes, suggesting a promising strategy for disease reversal in human type 1 diabetes.

Background: Isorhamnetin (ISO), a dietary O-methylated flavonol, was evaluated for hypoglycemic activity and mechanism in a streptozotocin (STZ) model of type 1 diabetes. Methods: We conducted untargeted plasma metabolomics (ESI±), network integration and docking, and measured pancreatic PI3K, phosphorylated AKT, and COX-2; INS-1 β cells challenged with the PI3K inhibitor LY294002 were used to assess viability, intracellular ROS, and PI3K phosphorylation. Results: ISO lowered fasting glycemia, increased circulating insulin, improved dyslipidemia by reducing low-density lipoprotein cholesterol (LDL-C), and preserved islet architecture. Untargeted plasma metabolomics (ESI±) indicated broad remodeling with enrichment of arachidonic-, linoleic-, starch/sucrose- and glycerophospholipid pathways. Network integration and docking prioritized targets converging on PI3K/AKT and COX-2/eicosanoid signaling. Consistently, in pancreatic tissue, ISO increased PI3K, phosphorylated AKT, and reduced COX-2. In INS-1 beta cells challenged with the PI3K inhibitor LY294002, ISO improved viability, decreased intracellular ROS, and partially restored PI3K phosphorylation at 4 µM. Conclusions: Together, these data indicate that ISO exerts hypoglycemic effects while supporting β-cell integrity through activation of PI3K/AKT and tempering of COX-2-linked lipid-mediator pathways. ISO therefore emerges as a food-derived adjunct candidate for autoimmune diabetes, and the work motivates targeted lipidomics and in vivo pathway interrogation in future studies.

The cGAS-STING signaling pathway is a central component of the innate immune system. Skeletal muscle, the body's largest metabolic and endocrine organ, is essential for overall health, and maintaining its homeostasis is critically important. This review systematically elaborates on the central position and "double-edged sword" role of the cGAS-STING pathway in skeletal muscle pathophysiology. We detail how, under various pathological stimuli-such as metabolic stress, physical injury, aging, toxin exposure, and systemic diseases-cytoplasmic DNA accumulation aberrantly activates the cGAS-STING pathway. Excessive activation of this pathway drives chronic inflammation, metabolic disturbances, and induces various forms of programmed cell death and cellular senescence. These effects collectively lead to muscle atrophy, fibrosis, and impaired regeneration. Conversely, during physiological adaptation like exercise training, moderate activation of this pathway can facilitate beneficial metabolic remodeling and muscle fiber type transformation. This article critically assesses current research challenges and limitations, particularly regarding cell specificity, the distinction between physiological and pathological activation, disease heterogeneity, and model systems. It also explores potential therapeutic strategies, supported by molecular docking analyses that predict high-affinity interactions between key inhibitors and cGAS/STING proteins. These include small-molecule inhibitors, intervention with upstream activating signals, lifestyle management, and novel biologics with targeted delivery systems. Ultimately, we emphasize that a deeper understanding and precise modulation of cGAS-STING signaling will open new perspectives and offer a promising translational medicine outlook for preventing and treating a range of refractory muscle diseases.

Cervical cancer (CC) represents a leading malignant threat to women&#x2019;s health globally. Patients with advanced-stage CC frequently encounter limited therapeutic efficacy and prominent drug resistance, highlighting the urgent need for molecular-driven precision treatment strategies. Herein, we developed a proteomics-based molecular classification for CC. A total of 198 CC patients were classified into four distinct molecular subtypes: CC-I (n&#x2009;=&#x2009;55), CC-II (n&#x2009;=&#x2009;32), CC-III (n&#x2009;=&#x2009;43), and CC-IV (n&#x2009;=&#x2009;68). This classification system was further validated in an independent cohort, confirming its clinical reliability. Survival analysis indicated significant prognostic differences among the four subtypes (log-rank test, p&#x2009;<&#x2009;0.001). Functional analysis revealed distinct molecular characteristics: CC-I and CC-IV were characterized by enrichment of immune-related pathways, while CC-II and CC-III displayed upregulated metabolism-associated pathways. Notably, CC-IV overexpressed pathways associated with cell cycle regulation, p53 signaling, and DNA repair, potentially contributing to its aggressive phenotype. Meanwhile, CC-I and CC-IV had higher immune scores and were enriched with T cells and B cells, suggesting potential favorable responsiveness to immunotherapies. Focusing on the CC-IV, we observed that high CDK4/6 expression was correlated with poor clinical outcomes. Patient-derived organoid (PDO) models confirmed that CDK4/6 inhibitor (palbociclib) had significant growth-inhibitory effects on CC patients with high CDK4/6 expression. In conclusion, this study established the first validated proteome-based molecular subtyping system for CC, and identified actionable therapeutic targets, and provided a robust foundation for personalized treatment strategies in CC. The online version contains supplementary material available at 10.1186/s40364-026-00896-1.

Type 1 diabetes (T1D) results from a destructive dialog between stressed pancreatic beta-cells and immune system. While current disease-modifying approaches targeting these processes are being developed and tested, microRNAs have emerged as a molecular interface connecting both sides of islet autoimmunity. Specific miRNAs orchestrate beta-cell stress adaptation, immune activation, and intercellular communication, thus shaping disease trajectory and progression across stages. Recent discoveries identified distinct miRNA networks as ER-stress modulators and/or immune amplifiers and key regulators of beta-cell fate and circulating signals of ongoing inflammation. The clinical translation of these insights remains hindered by limited access to human tissues, inconsistent candidate validation, and lack of delivery systems capable of targeting pancreatic beta-cells. Bridging mechanistic understanding with advanced delivery systems may transform miRNAs both as biomarkers and active therapeutic agents, opening a path toward precision interventions in T1D.

Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, and endocrine systems, through antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms. Although previous reviews have addressed the pharmacological effects of vitexin and isovitexin, most are limited in scope-either focusing solely on vitexin or restricted to specific disease models such as cancer or diabetes. Moreover, some studies are outdated and do not reflect the recent advances in synthetic modification, green extraction technologies, and systems pharmacology. This review aims to provide a comprehensive evaluation of the pharmacological properties, pharmacokinetics, and clinical relevance of vitexin and isovitexin, highlighting their potential in disease prevention and treatment. A literature search was conducted using Web of Science, PubMed, and Google Scholar, with keywords including "vitexin", "isovitexin", "disease", and "mechanism". Here, we summarize the current research on the pharmacological effects of vitexin and isovitexin in metabolic disorders, inflammatory diseases, cancer, and neurodegenerative conditions, focusing on their molecular mechanisms and therapeutic targets. Furthermore, we discussed their toxicity, bioavailability, pharmacokinetics, and clinical research findings. Vitexin and isovitexin hold promise as therapeutic agents or adjuncts for multiple diseases with potential applications in modern medicine and healthcare. However, their pharmacological mechanisms, clinical efficacy, and potential synergistic effects with other therapeutic agents remain unclear. Further systematic research is needed to clarify molecular targets and optimize their therapeutic applications.

Hypertension affects over 1.39 billion people globally, causing 9.4 million deaths annually. This paper examines the intricate relationship between the immune system and hypertension, highlighting the contributions of both innate and adaptive immune responses. The innate response, involving natural killer (NK) cells, macrophages, toll-like receptors (TLRs), and dendritic cells, contributes to organ damage and inflammatory responses, exacerbating hypertension. Adaptive immunity, particularly T cells, further exacerbates vascular and renal dysfunction through the release of cytokines such as IFN-&#x3b3;, IL-17A, and TNF-&#x3b1;, ultimately leading to multisystem damage. Therapeutic strategies targeting these immune responses are being explored, including immunosuppressants such as mycophenolate mofetil (MMF) and methotrexate (MTX), as well as monoclonal antibodies against IL-1&#x3b2; and TNF-&#x3b1;. While these strategies show promise, further research is needed to evaluate their efficacy and safety. Furthermore, this paper highlights the potential benefits of immunological approaches in managing the root causes of hypertension, offering an alternative to conventional therapies focused on the renin-angiotensin-aldosterone system. In conclusion, this work highlights the immune mechanisms in the hypertension pathogenesis, identifying them as potential therapeutic targets for enhanced management and improved patient outcomes.

Functional constipation is the most common diagnosis of gastrointestinal disease in pediatric clinics. Food allergy has been shown to be associated with functional constipation in children. However, the causal relationship has not been well established. We observed food allergy-like intestinal immune responses and decreased intestinal motility in a mouse model that mimics the atopic march. Consequently, we utilized this model to investigate the role and regulatory mechanisms of the atopic march-induced food allergy on intestinal motility. Pathological features related to weakened intestinal motility were analyzed by RNA sequencing and metabolomics analyses. The role of metabolite deficiency on atopic march-induced constipation in mice was confirmed by supplementation in vivo. Elevated Th2/Th17 inflammation and decreased serotonin level were found in intestine of atopic march mice. Serotonin synthesis in enterochromaffin cells and enteric serotonergic neurons was found to be impaired. Clinical evidence further supports a reduction in serum serotonin in atopic dermatitis children with food allergies. Based on altered microbiota and disordered lipid metabolism, we identified insufficient isovaleric acid generation contributing to impaired serotonin synthesis in model mice. Isovaleric acid supplementation repaired serotonin synthesis in enteric serotonergic neurons and partially restored intestinal motility of atopic march-induced food allergy mouse model. Our study provided evidence for the regulatory mechanism of constipation related to atopic march-induced food allergy and suggested targets for its diagnosis and treatment. The atopic march murine model induces a food allergy-like intestinal immune response, characterized by diminished gastrointestinal motility. Enterogenic serotonin synthesis was impaired in atopic march model mice. Isovaleric acid supplementation repaired serotonin synthesis of enteric serotonergic neurons and restored intestinal motility of atopic march model mice.