Medicines (Basel, Switzerland)最新文献

{"title":"Beyond the Central Nervous System: Uncovering Memantine's Modulatory Role in the Peripheral Nervous System.","authors":"Kyriaki Papadopoulou, Sophia Tsokkou, Ioannis Konstantinidis, Pavlos Pavlidis, Chrysanthi Sardeli, Dimitrios Kouvelas, Soultana Meditskou-Efthymiadou, Antonia Sioga, Theodora Papamitsou","doi":"10.3390/medicines13030025","DOIUrl":"10.3390/medicines13030025","url":null,"abstract":"<p><p><b>Background:</b> Memantine, an uncompetitive and voltage-dependent N-methyl-D-aspartate (NMDA) receptor antagonist, is clinically established for moderate-to-severe Alzheimer's disease. Its pharmacodynamic profile, low-to-moderate affinity, rapid open-channel block, and strong voltage dependency allows selective inhibition of pathological NMDA overactivation while preserving physiological neurotransmission. Increasing evidence shows that these same mechanistic principles operate in the peripheral nervous system, where NMDA receptors contribute to excitotoxicity, oxidative stress, neuroinflammation, and maladaptive nociceptive signaling. <b>Purpose:</b> To synthesize emerging preclinical and clinical evidence demonstrating memantine's modulatory and neuroprotective actions in peripheral neurons and glia and to outline implications for drug repurposing across neurology, pain medicine, oncology, supportive care, and ophthalmology. <b>Methodology:</b> A narrative integration of mechanistic studies, in vivo preclinical models, and heterogeneous clinical trials evaluating memantine's effects on peripheral sensory neurons, autonomic neurons, Schwann cells, retinal ganglion cells, and neuromuscular junction physiology. Evidence was examined across conditions involving excitotoxicity, oxidative injury, mitochondrial dysfunction, apoptotic signaling, neuroinflammation, and neuropathic pain amplification. <b>Results</b>: Memantine consistently attenuates peripheral excitotoxic calcium influx, suppresses NOX-2-mediated ROS generation, stabilizes mitochondrial membrane potential, modulates Bax/Bcl-2 signaling, and reduces neuroinflammatory cytokine activity. It also inhibits dorsal horn wind-up selectively under neuropathic conditions. These convergent mechanisms yield protective effects across chemotherapy-induced peripheral neuropathy (CIPN), diabetic neuropathy, traumatic nerve injury, phantom limb pain, retinal ganglion cell excitotoxicity, and organophosphate-induced neuromuscular toxicity. Clinical evidence includes improved multimodal neuropathy outcomes in diabetic neuropathy when combined with gabapentin, reduced phantom limb pain prevalence and intensity at six months, and a five-fold reduction in post-mastectomy neuropathic pain with pre-emptive administration. <b>Conclusions:</b> Memantine should be conceptually reframed as a system-wide neuroprotective agent with substantial translational potential beyond the CNS. Priorities for future development include NR2B-selective peripheral NMDA antagonists, peripherally restricted formulations, single-cell transcriptomic mapping of peripheral NMDA receptor subtypes, and adequately powered PNS-specific randomized trials.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13510310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracetamol Responses Depend on Temperature, Life Stage, and Genetic Background in <i>Drosophila melanogaster</i> Across Generations.","authors":"Birk N R G Hundebøl, Jesper G Sørensen","doi":"10.3390/medicines13030024","DOIUrl":"10.3390/medicines13030024","url":null,"abstract":"<p><strong>Background: </strong>A key obstacle in toxicological research is investigating long-lasting or inherited effects and addressing the potential interaction between exposure and genetic background of the test subject. Such effects can be effectively investigated in short-lived and genetically managed model organisms.</p><p><strong>Methods: </strong>To illustrate the biological complexity of the outcomes of toxicological experiments, we investigated the influence of life stages, sex, and temperatures in a generational study using paracetamol exposure as an example of drug toxicology. To also include genetic background, we used five highly inbred <i>Drosophila melanogaster</i> lines from the <i>Drosophila</i> Genetic Reference Panel (DGRP). First, we assessed acute survival to paracetamol exposure at 19 °C and 25 °C, revealing clear genotype-specific dose-response curves and increased toxicity at lower temperature. We then conducted a generational experiment across three generations, in which flies were exposed during either the larval or adult life stage, and measured starvation tolerance and spontaneous activity to capture direct, intergenerational, and transgenerational effects.</p><p><strong>Results: </strong>Results show that life stage, sex, and genotype each shaped the phenotypic outcome of paracetamol exposure. Adult exposure consistently decreased activity and increased starvation resistance, whereas juvenile exposure produced more variable and sex-dependent responses. Genotype further modulated these patterns, including markedly elevated lethality in one line at high paracetamol concentrations.</p><p><strong>Conclusions: </strong>These findings demonstrate that exposure timing and biological context critically influence toxicological outcomes, underscoring the need for methodological awareness when interpreting generational studies in model organisms and beyond.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Nasser et al. Potency of Combining <i>Eucalyptus camaldulensis</i> subsp. <i>camaldulensis</i> with Low-Dose Cisplatin in A549 Human Lung Adenocarcinomas and MCF-7 Breast Adenocarcinoma. <i>Medicines</i> 2020, <i>7</i>, 40.","authors":"Mohamad Nasser, Raghida Damaj, Othmane Merah, Akram Hijazi, Christine Trabolsi, Nour Wehbe, Malak Nasser, Batoul Al-Khatib, Ziad Damaj","doi":"10.3390/medicines13030023","DOIUrl":"10.3390/medicines13030023","url":null,"abstract":"<p><p>There was an error in the original publication [...].</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.","authors":"Davide Benedetto Tiz","doi":"10.3390/medicines13030022","DOIUrl":"10.3390/medicines13030022","url":null,"abstract":"<p><p>The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW < 1300 Da) containing amide functionality between 2021 and 2025, highlighting its continued and evolving role in addressing contemporary medical challenges. An analysis of these novel therapeutics reveals the remarkable functional versatility of the amide bond. In antiviral agents like nirmatrelvir (Paxlovid^®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati^®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combination of planarity, resonance stabilization, and capacity for robust hydrogen bonding continues to make it an essential element in the medicinal chemist's toolkit, underpinning the development of next-generation therapeutics across oncology, infectious diseases, and neurology. To provide a practical framework for drug discovery, the synthetic routes for each drug are detailed, with particular emphasis placed on the key amide-forming strategies employed.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Weight Loss: Early Real-World Evidence of Semaglutide in Obesity.","authors":"Steluța Constanța Boroghină, Amalia-Ioana Arhire, Teodora Papuc, Miruna Sînziana Chiper, Diana-Andreea Meluță, Sorana Maria Pîrcălabu, Roxana Andreea Dănăilă, Mădălina Cristache, Carmen Gabriela Barbu","doi":"10.3390/medicines13030021","DOIUrl":"10.3390/medicines13030021","url":null,"abstract":"<p><p><b>Background:</b> Obesity is a chronic, relapsing disease that often proves resistant to lifestyle measures alone. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are reshaping treatment, yet prospective real-world data remain limited. <b>Objective:</b> To prospectively assess the effects of once-weekly Semaglutide on weight, body composition, and metabolic health in obesity. Methods: An exploratory observational study of 37 patients initiating Semaglutide (mean age 31 years; 11 children and adolescents; 22 females) was conducted. All met obesity criteria (baseline BMI 34.7 kg/m²). Anthropometry, bioimpedance body composition, and fasting biochemistry were obtained at baseline and 3 months. Variables were reported as mean ± SD or median (IQR) according to normal/non-normal distribution, whether a parametric test or a Wilcoxon one was used. Parametric or non-parametric paired tests (two-sided α = 0.05) were applied. We also explored tri-ponderal mass index (TMI, kg/m³) and its correlations with metabolic markers. <b>Results</b>: At 3 months, body weight decreased by a median 8.0 kg (<i>p</i> < 0.001), BMI by 1.6 kg/m² (<i>p</i> < 0.001). Body fat percentage declined: 43.4% to 42.8% (<i>p</i> = 0.009), with a small reduction in skeletal muscle mass (-0.6 kg; <i>p</i> = 0.035). Fasting glucose improved (<i>p</i> = 0.030) and HOMA-IR fell significantly. HbA1c changes were minimal, consistent with near-normal baseline values. Triglycerides decreased, while total cholesterol, LDL-C, HDL-C, liver enzymes, creatinine, uric acid, and 25-OH vitamin D remained stable. Baseline TMI (median 20.13 kg/m³; IQR 3.80) correlated strongly with HOMA-IR (r = 0.766, <i>p</i> < 0.001) and moderately-to-strongly with body fat percentage (r = 0.621, <i>p</i> < 0.001). <b>Conclusions:</b> In this real-world cohort, Semaglutide produced rapid, clinically meaningful improvements in weight, adiposity, and insulin resistance within 3 months. Findings suggest that Semaglutide may represent a promising adjunct to lifestyle therapy in obesity management.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamon-Derived Compounds Reduce PD-L1 Expression in UV-Exposed Human Skin Cell Line.","authors":"Chidambaram Ramanathan, Richard J Bloomer, Gus Romero","doi":"10.3390/medicines13020020","DOIUrl":"10.3390/medicines13020020","url":null,"abstract":"<p><p><b>Background/Objective:</b> Ultraviolet A and B (UVAB) radiation is a major environmental factor that induces DNA damage and upregulates programmed death-ligand 1 (PD-L1) expression in skin cells, thereby contributing to immune evasion and impaired tissue repair. This study evaluated the protective effects of two purified compounds, Cinnamtannin B1 (CTB-1) and Cinnamtannin D1 (CTD-1), as well as cinnamon extract, in UVAB-irradiated human keratinocyte HaCaT cells. <b>Methods:</b> HaCaT cells were exposed to low (20 kJ/m² UVA, 1.3 kJ/m² UVB), medium (30 kJ/m² UVA, 2 kJ/m² UVB), and high (40 kJ/m² UVA, 2.7 kJ/m² UVB) UVAB doses of UVAB radiation. Dose-dependent effects of CTB-1 and CTD-1 (0, 5, 10, 25, and 50 µg/ mL) and cinnamon extract (0, 5, 10, 50, and 100 µg/mL), as well as time-dependent effects (12, 24, and 72 h), were evaluated by measuring PD-L1 expression, cell viability, and DNA damage. <b>Results:</b> CTD-1 was the most effective compound, significantly reducing UVAB-induced PD-L1 expression and DNA double-strand breaks without compromising cell viability. CTB-1 also demonstrated protective effects at specific doses and time points; however, higher concentrations reduced cell viability. Cinnamon extract was protective at low concentrations but cytotoxic at higher doses. <b>Conclusions:</b> CTD-1, CTB-1, and cinnamon extract attenuated UVAB-induced cellular damage in HaCaT cells, with CTD-1 demonstrating the most favorable protective profile. These findings support the potential of cinnamon-derived compounds as therapeutic candidates for preventing UVAB-induced skin damage and immune dysregulation.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13304358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narrative Review of Novel Nicotine-Delivery Systems and Emerging Pharmaceuticals for Tobacco Cessation.","authors":"Srilekha Mutukula, Taylor Gagne-Hatfield, Zachary R Dunbar","doi":"10.3390/medicines13020019","DOIUrl":"10.3390/medicines13020019","url":null,"abstract":"<p><p><b>Background</b>: Debate continues to swirl around the effectiveness of novel nicotine-delivery products such as snus and e-cigarettes as tobacco cessation aids. The purpose of this review is to quantify the state of research on modern products, including e-products, and established or developing pharmaceuticals on assisting nicotine users in achieving cessation. <b>Methods:</b> This study relied on a comprehensive assessment of research articles, clinical trials, drug approvals, and textbook material available via PubMed, Ovid Wolters Kluwer, and Wiley. We utilized Python 3.14.2, Anaconda3, the ShinyWeb App, and Py.Litstudy to investigate the selected literature. Our key study elements are product evolution and cessation behavior associated with e-cigarettes, snus, nicotine gum, nicotine dermal patches, bupropion, varenicline, and cytisine. <b>Results:</b> This manuscript assessed 144 manuscripts published between 1952 and 2025. E-cigarettes and snus, while containing some limited cessation benefit, were not identified to be effective enough at attaining cessation (when used exclusively) to be prescribed as cessation tools. Cytisine was identified as having very similar cessation outcomes to established pharmaceuticals such as varenicline. <b>Conclusions:</b> Since their iteration, e-cigarettes and snus products were marketed as cessation aids. This review found that there is scant evidence to support that modern snus and e-cigarette products work as cessation aids when used in exclusion of other more traditional approaches to cessative aid. Additionally, more modern pharmaceuticals such as cytisine may have benefit as solo cessation tools over novel nicotine-delivery products.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) Bacteremia-Guidelines and Recent Developments.","authors":"Ashlesha Kaushik, Julia Fomicheva, Kimberly Zellmer, Corey Thieman, Sandeep Gupta","doi":"10.3390/medicines13020018","DOIUrl":"10.3390/medicines13020018","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) remains a major cause of serious infection and is associated with substantial morbidity and mortality. Clinical presentations range from localized disease to severe, life-threatening infections, including bacteremia and sepsis with metastatic complications such as infective endocarditis and osteoarticular involvement. MRSA bacteremia carries a high risk of dissemination and death, underscoring the importance of early recognition and effective management. Optimal treatment requires timely initiation of appropriate antimicrobial therapy in conjunction with source control when indicated. Despite advancements in treatment, persistent MRSA bacteremia continues to pose significant clinical challenges. Given the complexity of these infections, a clear understanding of current treatment strategies is essential for clinicians. In this narrative review, we summarize contemporary guideline-based approaches to the management of MRSA bacteremia, highlight key pharmacologic considerations of available antimicrobial agents, and discuss knowledge gaps and recent developments in both established and emerging therapies aimed at improving outcomes in these challenging infections.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy of Fixed-Dose Diclofenac and Orphenadrine for Postoperative Pain Management: A Systematic Review.","authors":"Nikolaos Christopoulos, Karolina Akinosoglou","doi":"10.3390/medicines13020017","DOIUrl":"10.3390/medicines13020017","url":null,"abstract":"<p><strong>Background/objectives: </strong>Postoperative pain remains a significant clinical challenge, often requiring multimodal strategies to mitigate opioid-related adverse events. The fixed-dose combination (FDC) of Diclofenac, a non-steroidal anti-inflammatory drug, and Orphenadrine, a muscle relaxant, targets distinct nociceptive pathways to potentially enhance analgesia and reduce opioid consumption. This systematic review aims to evaluate the analgesic efficacy and safety profile of the fixed-dose combination of Diclofenac and Orphenadrine for postoperative pain management and quantify its opioid-sparing effect compared to standard monotherapies or placebo.</p><p><strong>Methods: </strong>A systematic search of electronic databases (MEDLINE, Scopus) and clinical trial registries (including ClinicalTrials.gov and CTIS) was conducted up to 20 September 2025. Fourteen (14) randomized controlled trials (RCTs) involving 981 adult patients undergoing various surgical procedures were included. Due to high clinical and methodological heterogeneity, a Synthesis Without Meta-analysis (SWiM) approach was utilized. The certainty of evidence was assessed using the GRADE methodology.</p><p><strong>Results: </strong>The synthesis demonstrated that the FDC may improve pain relief (measured by the Visual Analog Scale and Numeric Rating Scale scores) and may reduce opioid consumption compared to active comparators and placebo. The opioid-sparing effect could be correlated with a reduced incidence of dose-dependent adverse events, particularly nausea and vomiting. However, the overall certainty of the evidence was graded as \"Very Low\" due to the high risk of bias and lack of transparency in the included studies.</p><p><strong>Conclusions: </strong>The FDC of Diclofenac and Orphenadrine is a rational addition to multimodal postoperative analgesic regimens, which may potentially reduce the perioperative opioid burden without compromising pain control. Nevertheless, because almost all included studies suffer from severe methodological flaws, these apparent efficacy findings must be interpreted with caution. Future high-quality, pre-registered, and low-bias randomized controlled trials are required to draw firm clinical conclusions.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulforaphane Synergies with Phytochemicals and Pharmaceuticals: Implications for Healthspan.","authors":"Jed W Fahey, Hua Liu","doi":"10.3390/medicines13020016","DOIUrl":"10.3390/medicines13020016","url":null,"abstract":"<p><p>Sulforaphane, a bioactive isothiocyanate found abundantly in cruciferous vegetables, has attracted significant attention for its chemopreventive and therapeutic potential, particularly in cancer. There is now an abundance of peer-reviewed research documenting true synergies between sulforaphane and (a) cancer treatment drugs, (b) pharmaceuticals in development but not yet on the market or in the regulatory pipeline, (c) other phytochemicals, and (d) proprietary mixtures such as leaf extracts and other botanicals, as well as evidence that some cell lines resistant to various cancer drugs become more susceptible when treated with sulforaphane. Most of the published studies demonstrate evidence for synergy in cancer, including cancers of the bladder, blood, brain, breast, colon, esophagus, liver, lung, ovaries, prostate, and skin, where reducing drug dosages could yield substantial patient benefits. Importantly, non-cancer indications have also been reported, such as mitigation of cardiac toxicity, inflammation, obesity, and pain (including antihyperalgesic and antinociceptive effects). Synergistic effects are most often demonstrated in cell line models, with many studies providing robust mechanistic evidence, and some employing the gold-standard Chou-Talalay method for quantifying synergy. Current evidence on the synergistic interactions of sulforaphane with both phytochemicals and pharmaceuticals highlights underlying mechanisms such as modulation of oxidative stress, inflammation, apoptosis, and epigenetic regulation, suggesting significant clinical and therapeutic implications. By providing a comprehensive overview of sulforaphane synergies in both cancer and non-cancer contexts, we aim to inform future research and support the development of integrated therapeutic strategies.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}