Irritable bowel syndrome (IBS) is a widespread functional gastrointestinal disorder characterised by chronic abdominal discomfort and altered bowel habits. Despite its high impact on life quality and healthcare systems, the initial pathophysiology of IBS is not yet fully understood. The present narrative review aims to synthesise and integrate recent evidence regarding the multifactorial nature of IBS, focusing on the interplay between gut–brain interactions, microbiota, and immune responses, without proposing a novel model but rather reinforcing and updating existing conceptual frameworks. A comprehensive literature search of relevant studies published in English during the past two decades was conducted using Pub-Med, Scopus, and Google Scholar. The selected articles were thoroughly evaluated to provide a complete overview of IBS-related research. The review demonstrates that IBS is not only a multifactorial condition involving gut–brain axis dysregulation, altered gut motility, visceral hypersensitivity, and microbiome disturbances, but also a crucial psychosocial factor. Modern therapeutics targeting the microbiota and neurogastroenterology pathways show promising results but require further investigation. IBS represents a heterogeneous disorder with complex interrelated mechanisms. Improvements in understanding its multifaceted nature are of paramount importance in developing more effective diagnostic and therapeutic approaches. Continued research is essential to unravel the intricacies of IBS and improve patient outcomes.

Background: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with a complex pathogenesis that necessitates innovative therapeutic approaches for effective management. Among the commonly used treatments, mebeverine (MBH), an antispasmodic, is widely prescribed to alleviate IBS symptoms. However, challenges in delivering the drug precisely to the colonic region often hinder its therapeutic effectiveness. To address this limitation, silver nanoparticles (AgNPs) have emerged as promising drug delivery systems, offering unique physicochemical properties that can enhance the precision and efficacy of IBS treatments. Objectives: This study aimed to synthesize AgNPs as drug delivery vehicles for MBH and a previously reported analog. The research focused on evaluating the cytotoxic and genotoxic effects of the AgNPs and forecasting their possibly harmful effects on future sustainable development. Methods: AgNPs were synthesized using a rapid method and functionalized with MBH and its analog. The nanoparticles were characterized using different techniques. Cytotoxicity and genotoxicity were evaluated in vitro. Additionally, in silico docking analyses were performed to explore their safety profile further. Results: In vitro assays revealed concentration-dependent cytotoxic effects and a lack of genotoxic effects with MBH-loaded AgNPs. A molecular docking simulation was performed to confirm this effect. Conclusions: The study underscores the potential of AgNPs as advanced drug delivery systems for safe and significant therapeutic implications for IBS. Future in vivo and preclinical investigations are essential to validate the safe range of exposure doses and evaluation standards for assessing AgNPs’ safety in targeted and personalized medicine.

Background: Irritable bowel syndrome (IBS) has a major negative influence on quality of life, causing cramps, stomach pain, bloating, constipation, etc. Antispasmodics have varying degrees of efficacy. Mebeverine, for example, works by controlling bowel movements and relaxing the muscles of the intestines but has side effects. Therefore, more efficient medication is required. Methods: In the current study, we investigated the synthesis of novel mebeverine analogs and determined ex vivo their spasmolytic and in vitro and ex vivo anti-inflammatory properties. The ability to influence both contractility and inflammation provides a dual-action approach, offering a comprehensive solution for the prevention and treatment of both conditions. Results: The results showed that all the compounds have better spasmolytic activity than mebeverine and good anti-inflammatory potential. Among the tested compounds, 3, 4a, and 4b have been pointed out as the most active in all the studies conducted. To understand their mechanism of activity, molecular docking simulation was investigated. The docking analysis explained the biological activities with their calculated Gibbs energies and possibilities for binding both centers of albumin. Moreover, the calculations showed that molecules can bind also the two muscarinic receptors and interleukin-β, hence these structures would exert a positive therapeutic effect owed to interaction with these specific receptors/cytokine. Conclusions: Three of the tested compounds have emerged as the most active and effective in all the studies conducted. Future in vivo and preclinical experiments will contribute to the establishment of these novel mebeverine derivatives as potential drug candidates against inflammatory diseases in the gastrointestinal tract.

Human pathogenic fungi are the source of various illnesses, including invasive, cutaneous, and mucosal infections. One promising solution is using nanoparticles (NPs) as an antifungal agent. The current study aims to assess the antimicrobial and antifungal effects of drug-loaded silver nanoparticles (AgNPs) with previously reported mebeverine analogue (MA) as a potential drug candidate targeting gut microbiota and inflammation in the gastrointestinal tract. Density Functional Theory (DFT) calculations were conducted to identify possible mechanisms by which AgNPs could prevent microorganisms from growing. In vitro and ex vivo anti-inflammatory, in vitro antimicrobial, ex vivo spasmolytic activities, and in vitro hepatic cell morphology and proliferation of drug-loaded AgNPs were assessed. The drug-loaded AgNPs were considered to have promising antifungal activity against all tested fungal strains, Aspergillus niger, Penicillium chrysogenum, and Fusarium moniliforme, and yeasts, Candida albicans, Saccharomyces cerevisiae, and good antimicrobial activity against Gram-positive and Gram-negative bacterial strains. The results of in vitro and ex vivo determination of anti-inflammatory activity indicated that the drug-loaded AgNPs preserved MA’s anti-inflammatory activity and decreased inflammation. A similar effect was observed in spasmolytic activity measurements. Drug-loaded AgNPs also influenced the morphology and proliferation of hepatic cells, indicating a potential for improved gut and liver therapeutic efficacy. Each test was performed in triplicate, and the results were reported as mean values. Based on the results, drug-loaded AgNPs might be a promising antimicrobial agent, maintaining the MA’s potential as a spasmolytic and anti-inflammatory agent. Future in vivo and preclinical experiments will contribute to establishing the in vivo properties of drug-loaded AgNPs.

Background/Objectives: Mebeverine hydrochloride (MBH) is an antispasmodic agent used to regulate bowel movements and relax intestinal smooth muscle, but its application is limited by specific side effects; therefore, this study investigates the effects of previously synthesized MBH-loaded silver nanoparticles (AgNPs) on smooth muscle contractile activity and their anti-inflammatory potential as an alternative delivery system. Methods: The interactions of AgNPs with cholinergic inhibitors, selective antagonists, Ca²⁺ blockers, and key neurotransmitters were analyzed. In vitro, albumin denaturation suppression and ex vivo assays evaluated the anti-inflammatory effects of AgNPs-MBH, validated using a DFT in silico approach. To comprehensively assess the systemic impact and IBS treatment potential of AgNPs-MBH, we also examined in vitro their antimicrobial activity and hepatic cell responses, as the liver is a key organ in evaluating the overall safety and efficacy of nanoparticles. Additionally, the drug-release capabilities of Ag NPs were established. Results: Our findings indicate that AgNPs with MBH do not affect blocked cholinergic receptors, but their effects are more pronounced and distinct in amplitude and character than MBH. MBH-loaded AgNPs showed a lower anti-inflammatory effect than MBH but were still better than diclofenac. They also affected hepatic cell morphology and proliferation, suggesting potential for enhanced therapeutic efficacy. Drug-loaded AgNPs are considered not bactericidal. Conclusions: Based on our results, drug-loaded AgNPs might be a promising medication delivery system for MBH and a useful treatment option for IBS. Future in vivo and preclinical experiments will contribute to the establishment of drug-loaded AgNPs in IBS treatment.

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by abdominal pain or discomfort. Mebeverine is an antispasmodic that has been widely used in clinical practice to relieve the symptoms of IBS. However, its systemic use usually leads to side effects. Therefore, the current paper aimed to synthesize more effective medicines for IBS treatment. We used ring opening of isatoic anhydride for the synthesis in reaction with 2-phenylethylamine. In silico simulation predicted spasmolytic activity for 2-amino-N-phenethylbenzamides. The newly synthesized compounds demonstrated a relaxation effect similar to mebeverine but did not affect the serotonin or Ca²⁺-dependent signaling pathway of contractile activity (CA) in contrast. Having in mind the anti-inflammatory potential of antispasmodics, the synthesized molecules were tested in vitro and ex vivo for their anti-inflammatory effects. Four of the newly synthesized compounds demonstrated very good activity by preventing albumin denaturation compared to anti-inflammatory drugs/agents well-established in medicinal practice. The newly synthesized compounds also inhibited the expression of interleukin-1β and stimulated the expression of neuronal nitric oxide synthase (nNOS), and, consequently, nitric oxide (NO) synthesis by neurons of the myenteric plexus. This characterizes the newly synthesized compounds as biologically active relaxants, offering a cleaner and more precise application in pharmacological practice, thereby enhancing their potential therapeutic value.