Search Results (85)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended for the treatment of acute (low) back pain, despite modest effectiveness and well-known safety concerns, particularly in older patients. Pridinol is a centrally acting antispasmodic with a mechanism-oriented approach targeting muscle spasm, a key component of acute back pain. While a previous real-world analysis demonstrated a significantly better tolerability and effectiveness of pridinol compared with NSAIDs, age-dependent effects have not yet been systematically evaluated. Objective: To assess the age dependency of effectiveness, safety, and tolerability of pridinol versus NSAIDs in patients with acute (low) back pain under real-world conditions, based on already available data. Methods: This secondary analysis used propensity score-matched real-world data from the German Pain e-Registry (PROVIDENCE study; EUPAS identifier: 49718). A total of 934 patients with acute (low) back pain treated for four weeks with either pridinol (n = 467) or NSAIDs (n = 467) were stratified by age (<65 vs. ≥65 years). Outcomes included the incidence of adverse drug reactions (ADRs), ADR-related treatment discontinuations, time to ADR occurrence, and clinically meaningful improvement in pain-related disability (≥50% reduction in modified Pain Disability Index). Analyses were performed within and between age strata. Results: Overall, ADRs were reported by 9.0% of pridinol-treated patients and 20.8% of NSAID-treated patients (p < 0.001). In the pridinol cohort, ADR rates were virtually identical in patients <65 and ≥65 years (8.9% vs. 9.2%; p = 0.940). In contrast, NSAID-treated patients showed a pronounced age-related increase in ADR incidence (17.3% vs. 32.1%; p < 0.001). ADR-related treatment discontinuation rates under NSAIDs increased markedly with age (5.9% vs. 21.1%; p < 0.001), whereas rates under pridinol remained low and age independent (3.1% vs. 4.6%; p = 0.447). Gastrointestinal and cardiovascular ADRs were the main contributors to the age-related risk increase under NSAIDs, while corresponding events under pridinol were rare across age groups. Clinically meaningful improvement in pain-related disability was achieved with pridinol/NSAIDs in 91.9/48.0% (<65 years) and 88.1/47.7% (≥65 years; p < 0.001 for both). Conclusions: Age is a major modifier of NSAID-related risk but not of pridinol tolerability in acute (low) back pain. While NSAID-associated ADRs and treatment discontinuations increase substantially in patients aged 65 years or older, pridinol demonstrates a stable, age-independent safety profile combined with significantly better functional outcomes. These findings suggest that, particularly in older patients, mechanism-oriented alternatives such as pridinol may offer a more favorable benefit–risk profile than NSAIDs. Full article

Graphene oxide (GO)–lipid hybrid nanostructures represent a promising class of multifunctional platforms for drug delivery and fluorescence-guided cellular imaging. In this study, we developed a graphene oxide-supported lipid bilayer system composed of rhodamine-labeled phosphatidylcholine (POPC-Rhod) for the delivery of the repurposed antispasmodic drug alverine citrate (ALV) to neuroblastoma cells. The hybrid nanostructures were assembled using two drug-loading strategies and characterized by UV–Vis spectroscopy, fluorescence analysis, dynamic light scattering, and atomic force microscopy to evaluate molecular interactions, vesicle size distribution, and nanomechanical properties. In vitro studies were performed using human neuroblastoma SH-SY5Y cells and their retinoic acid-differentiated neuronal-like counterparts. Confocal microscopy confirmed efficient cellular uptake of the fluorescent lipid–graphene hybrids, while viability and mitochondrial reactive oxygen species assays revealed differentiation-dependent cellular responses. ALV-loaded hybrids induced cytotoxic effects in proliferating neuroblastoma cells, whereas differentiated neuron-like cells exhibited greater tolerance and, at moderate concentrations, preserved viability despite increased oxidative stress. These findings demonstrate that graphene oxide–lipid hybrids can act as fluorescence-traceable drug delivery platforms and highlight the potential of alverine as a candidate for repurposing in neural cancer models. The system presented here provides a proof-of-concept framework for the development of multifunctional nanocarriers integrating therapeutic delivery with imaging capabilities. Full article

Background: Nocturnal leg cramps (NLCs) are common, especially in older adults, and may cause substantial distress, sleep disturbance, and functional impairment. Despite widespread clinical use of quinine sulfate (QUI), safety concerns limit its use. Pridinol mesylate (PRI), a centrally acting antispasmodic, may offer a promising alternative in clinical practice. Objective: To evaluate the clinical effectiveness and tolerability of PRI versus QUI in patients with NLCs. Methods: We conducted a retrospective, non-interventional, propensity score-matched analysis of anonymized routine data from 1722 adult patients (861 per group) with NLCs from the German Pain e-Registry (GPeR). Patients initiating either PRI or QUI between 2018 and 2023 were included. The primary outcome was a predefined composite responder rate (≥50% reduction in NLC frequency, duration, and affected nights, with no treatment discontinuation due to adverse drug reactions [ADRs] or inefficacy). Secondary outcomes included pain intensity, quality-of-life, disability, and ADR frequency. Results: PRI treatment resulted in a significantly higher responder rate (56.9%) compared to QUI (48.4%, p < 0.001; NNT = 12) due to greater short-term reductions in NLC episodes, duration, and pain intensity. The overall ADR rates were numerically higher with PRI (8.6%) than with QUI (6.7%), but discontinuation rates due to ADRs or inefficacy were comparable between groups and occurred in 3.1/2.6% with PRI/QUI (p = 0.865). Conclusions: In this large, real-world, propensity score-matched analysis, pridinol treatment was associated with a modest short-term advantage over quinine in several efficacy outcomes, while overall tolerability appeared broadly comparable. Given the retrospective, non-interventional design and the limited 4-week observation period, these findings should be interpreted as hypothesis-generating rather than confirmatory. Full article

Background and Objectives: Cancer pain continues to be a major clinical problem nowadays. This study aims to evaluate the World Health Organization (WHO) analgesic ladder effectiveness in patients with colorectal cancer and develop machine learning models to predict treatment response for precision pain management. Materials and Methods: In a retrospective observational study, a total of 107 oncological patients were analyzed, with a detailed subgroup analysis of 42 patients with colorectal cancer, hospitalized between July and September in 2022. The pain assessment used numerical rating scales at baseline and 2–3 weeks follow-up. Clinical variables included demographics, disease staging, metastatic patterns, analgesic progression, and medication usage. Machine learning algorithms (e.g., Random Forest, CatBoost, XGBoost, and Neural Network) were used to predict pain reduction outcomes. The UMAP dimensionality reduction and clustering identified the patient phenotypes. Results: Statistical analyses included descriptive methods, Chi-square and Mann–Whitney tests, and the models’ performance was evaluated by AUC. Among patients with colorectal cancer, 73.8% achieved clinically pain improvement, with a mean reduction of 2.62 points and median improvement of 3.00 points. The metastatic site significantly affected outcomes: visceral metastases patients showed median improvement of 3.00 points with high variability, patients with bone metastases demonstrated heterogeneous responses (range: −2.00 to +8.00 points), while non-metastatic patients exhibited consistent improvement. Random Forest achieved optimal predictive performance (AUC: 0.9167), identifying the baseline pain score, bone metastases, Fentanyl usage, anticonvulsants, and antispasmodics as key predictive features. The clustering analysis revealed two distinct phenotypes, requiring different analgesic intensities. Conclusions: This study validates the WHO analgesic ladder effectiveness while demonstrating superior outcomes in patients with colorectal cancer. The machine learning models successfully predict the treatment response with excellent discriminative ability, supporting precision medicine implementation in cancer pain management. Full article

Irritable Bowel Syndrome (IBS) is a complex and multifactorial gastrointestinal disorder characterized by recurrent abdominal pain and altered bowel habits, impacting quality of life. Therapy is mainly based on relieving symptoms with specific drugs, whereas herbal and complementary remedies have gained attention in recent years. This review examines the current knowledge on herbal remedies in IBS management. Several herbal treatments, particularly peppermint oil and Iberogast, have demonstrated efficacy in randomized controlled trials. Preclinical studies have revealed promising anti-inflammatory and antispasmodic effects for herbs, e.g., curcumin, fennel oil, and cannabis derivatives. However, many studies suffer from some limitations, e.g., small sample sizes, short study durations, or methodological weaknesses. There is a lack of large-scale, long-term randomized controlled trials for most herbal remedies, and heterogeneity in study designs makes direct comparisons challenging. Moreover, limited evidence exists regarding herb–drug interactions and long-term safety profiles. Despite these limitations, certain herbal remedies may offer a valuable complementary approach for some IBS patients when used under medical supervision. Future research should focus on larger, well-designed clinical trials to establish efficacy, optimal dosing, and long-term safety, as well as elucidate specific mechanisms of action and identify patient subgroups that may benefit most from specific herbal treatments. Full article

Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL⁻¹). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article

Foeniculum vulgare Mill. (Apiaceae) is an aromatic medicinal plant known for its anti-inflammatory, antispasmodic, antiseptic, carminative, diuretic, and analgesic properties. This study aimed to investigate the effects of F. vulgare essential oil (FVEO; 25, 150, and 300 μL/L) on the cognitive performance and brain oxidative stress in a scopolamine (SCOP; 100 μM)-induced zebrafish model of cognitive impairment. Additionally, the pharmacokinetic properties and bioactivity profiles of the main FVEO constituents were predicted to be used in silico tools, including SwissADME, pkCSM, PASS online, and ADMETlab 2.0. Behavioral assays, novel tank diving test (NTT), Y-maze, and novel object recognition (NOR) test, were used to evaluate anxiety-like behavior, spatial memory, and recognition memory, respectively. Biochemical assessments of acetylcholinesterase (AChE) activity and oxidative stress biomarkers were also conducted. The results demonstrated that FVEO significantly improved cognitive performance in SCOP-treated zebrafish, normalized AChE activity, and reduced oxidative stress in the brain. These findings suggest the therapeutic potential of FVEO in ameliorating memory impairment and oxidative damage associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Full article

Background: Gastrointestinal endoscopy is crucial for diagnosing colorectal cancer and inflammatory bowel diseases, but its effectiveness can be impacted by peristalsis, poor bowel preparation, and inadequate withdrawal time. Conventional antispasmodics, though effective, may not be suitable for elderly patients or those with comorbidities. L-menthol, derived from peppermint oil, has emerged as a safer alternative. Through calcium channel blockade, L-menthol promotes GI smooth muscle relaxation. This study evaluated L-menthol’s efficacy and safety as a potential alternative to antispasmodic agents in endoscopy. Methods: Following PRISMA2020 guidelines and the Cochrane Handbook, we conducted a systematic review and meta-analysis of randomized controlled trials involving adults undergoing endoscopy, comparing L-menthol to placebo. The primary outcome was the adenoma detection rate, with secondary outcomes, including severity of peristalsis, safety, withdrawal time, and ease of examination. We searched five databases on 31 May 2023, with updates on 20 October 2024. Results: Fourteen studies were included. L-menthol reduced peristalsis during colonoscopy and upper endoscopy, achieving a suppression rate of 55.9% (560/1002 patients; odds ratio (OR) = 3.88, 95% confidence interval (95% CI): 2.13–7.07), which improved mucosal visualization. It improved ease of examination (OR = 2.53, 95% CI: 1.35–4.73), allowing endoscopists to perform procedures with less technical difficulty. However, L-menthol had no significant impact on the adenoma detection rate (OR = 1.06, 95% CI: 0.69–1.64), indicating no added benefit for lesion detection, and did not prolong withdrawal time (MD = 3.24 s, 95% CI: −101.05–107.53). Adverse event rates remained low and comparable to placebo (OR = 0.97, 95% CI: 0.74–1.27). Conclusions: L-menthol reduces peristalsis and enhances ease of examination without adverse events. Although its effect on the adenoma detection rate remains inconclusive, its antispasmodic properties make it a promising alternative for patients who cannot tolerate conventional agents. Full article

Achillea nobilis and its subspecies (A. nobilis subsp. neilreichii and A. nobilis subsp. sipylea) have been traditionally used in various ethnomedical systems across Eurasia. However, comprehensive studies on their phytochemical composition and pharmacological properties are still insufficient. This review aims to provide a critical synthesis of current knowledge regarding the botanical characteristics, geographic distribution, traditional applications, chemical constituents, and pharmacological effects of A. nobilis A structured search was conducted using eight scientific platforms, including Scopus, PubMed, Web of Science, Google Scholar, Science.gov, ScienceDirect, JSTOR, and BASE. Keywords related to phytochemistry, pharmacology, and ethnomedicine were applied, and a total of 28,000 records were initially retrieved. After a multi-stage screening process based on inclusion and exclusion criteria, 167 peer-reviewed publications from 1952 to 2023 were selected for detailed evaluation. Findings reveal a diverse range of bioactive compounds, such as flavonoids, monoterpenes, sesquiterpenes, and sesquiterpene lactones, which demonstrate antioxidant, antimicrobial, anti-inflammatory, antinociceptive, antispasmodic, and anticonvulsant activities. Most studies have focused on aerial parts and water-based extracts, while the root chemistry and organ-specific metabolite profiles remain largely unexplored. This review highlights the therapeutic potential of A. nobilis and underscores the need for future studies using multi-omics and advanced analytical techniques to support its development in pharmaceutical and nutraceutical applications. Full article

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. Full article

Background: Moringa oleifera is one of the most famous plants used for medicinal purposes. Its leaf extracts have antimicrobial activity and antioxidant activities, and reduce swelling in ulcers. Objectives: The present article aimed to determine the metabolic profile of Moringa oleifera leaf extracts from two samples originating from India and to evaluate in vitro and ex vivo their biological activities. Methods: The antioxidant properties of Moringa oleifera leaf extracts (methanol, 50% ethanol, and 70% ethanol) were studied in vitro for antimicrobial, anti-inflammatory, and antioxidant activities. The ex vivo contractile effects of the extracts were determined by assaying circularly isolated smooth muscle (SM) strips from a rat’s stomach. Results: The obtained results indicated that one of the samples had amino acid and organic acid content approximately twice that of the second sample. In all the tests, the 50% ethanol extract of both samples showed better antioxidant activity (209 mM TE 100 g⁻¹ for the DPPH method). The 70% ethanolic extract of Sample 1 exhibited the strongest antimicrobial activity, inhibiting Gram-positive Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus. The 50% ethanolic extract of both samples exhibited the highest anti-inflammatory activity, demonstrating a twice better effect than the reference drug diclofenac. Finally, the pre-incubation of SM preparations with both samples significantly enhanced the ACh-induced contractile response, increasing it by 134% and 111%, respectively. Conclusions: The findings suggested potential applications of Moringa oleifera as a suitable candidate for antimicrobial, antioxidant, anti-inflammatory, and antispasmodic supplementation for alternative pharmaceutical and nutraceutical products. Full article

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. Full article

Irritable bowel syndrome (IBS) is a common disorder of gut–brain interaction, with a multifactorial pathophysiology involving gut–brain axis dysregulation, visceral hypersensitivity, microbiota imbalance, and immune dysfunction. Traditional IBS management emphasizes dietary modifications and pharmacologic therapies. However, increasing attention has been directed toward functional foods, nutraceuticals, and herbal remedies due to their potential to target IBS pathophysiological mechanisms with favorable safety profiles. This clinical review explores the role of these adjunctive therapies, evaluating evidence from preclinical and clinical studies. Functional foods such as kiwifruit, prunes, and rye bread demonstrate benefits in bowel habit regulation through fiber content and microbiota modulation. Nutraceuticals like peppermint oil, palmitoylethanolamide, and herbal mixtures exhibit anti-inflammatory, antispasmodic, and analgesic effects. Prebiotics provide substrate-driven microbiota changes, although dosage is key, as given their fermentative properties, when used at high dosages, they can exacerbate symptoms in some individuals. Probiotics and postbiotics offer microbiota-based interventions with promising symptom relief in IBS subtypes, although factors for personalized treatment still need to be further elucidated. These strategies highlight a paradigm shift in IBS management, integrating diet-based therapies with evolving nutraceutical options to improve patient outcomes. Despite promising findings, challenges in standardizing definitions, mechanisms, and safety profiles still remain. Rigorous, large-scale trials to validate the therapeutic potential of these interventions are needed, to enhance the benefits of these compounds with an individualized treatment approach. Full article

Red currant (Ribes rubrum L.) berries are rich in bioactive compounds and exhibit nutritive and protective features. This research examined the content of secondary metabolites of the red currant variety Redpoll lyophilized juice and waste extract and their antioxidative and spasmolytic effects. The flavonol and anthocyanin contents of the samples were determined using high-performance liquid chromatography. The antispasmodic effects were assessed in in vitro conditions, and the potential impact of the samples and possible action mechanisms were revealed. The results showed the prevalence of cyanidin-3-O-glucoside as the dominant anthocyanin with higher content in the juice sample. Quercetin content, as the prevalent flavonol, was higher in the waste sample. The berry juice showed a greater ability for scavenging free radicals, whereas the waste better inhibited lipid peroxidation. The juice was a superior antispasmodic agent for spontaneous, KCl-, CaCl₂-, BaCl₂-, histamine-, and acetylcholine-induced ileal contractions. This first evaluation of the red currant variety Redpoll lyophilized juice and waste extract indicated the beneficial effects of juice as an antioxidant and spasmolytic agent. Therefore, this red currant juice sample could be designated for the prevention or treatment of gastrointestinal disorders. Full article

Background: Three herbal extracts (Asparagus racemosus Willd., Tabebuia avellanedae Lorentz, and Glycyrrhiza glabra L.) were mixed with three essential oils (Foeniculum vulgare Mill., Mentha piperita L., and Pimpinella anisum L.) to formulate a product (HEMEO) whose active compounds include saponins and steroids in Asparagus racemosus, known for their anti-inflammatory properties; glycyrrhizin and flavonoids in Glycyrrhiza glabra, which exhibit gastroprotective and antispasmodic effects; menthol in Mentha piperita, contributing with antispasmodic and antimicrobial properties; and anethole and polyphenols in Pimpinella anisum, which modulate intestinal motility and offer antimicrobial activity. Objective: HEMEO was formulated for applications in intestinal motility disorders. Methods: HEMEO was evaluated for spontaneous and induced motility effects in isolated guinea pig ileum, colon, and stomach. Ex vivo experiments were conducted using LabChart software v7.0, and the product’s antibacterial action against Helicobacter pylori and its antioxidant effects were assessed through disc diffusion and FRAP assays. The presence of the volatile compounds in the formulation was confirmed by GC-MS analysis; the TPC of HEMEO, determined using the Folin–Ciocalteu method, was 9.925 ± 0.42 mg GAE/g. Conclusions: HEMEO showed a phenolic content correlated with its antioxidant potential and in addition inhibited H. pylori growth and demonstrated notable antioxidant properties, suggesting its role as a supportive agent in digestive processes and in managing motility disorders. Full article