Inflammopharmacology最新文献

{"title":"Repurposing Saroglitazar for neurodegenerative disorders: insight into molecular signalling pathways and neuroprotective modulations.","authors":"Shiv Kumar Kushawaha, Himanshu Kumar, Chandni Chauhan, Sahil Chaudhary, Mahendra Singh Ashawat","doi":"10.1007/s10787-025-01805-y","DOIUrl":"https://doi.org/10.1007/s10787-025-01805-y","url":null,"abstract":"<p><p>Drug repurposing has emerged as a cost-efficient strategy for neurodegenerative disorders (NDDs), leveraging existing preclinical, safety, and tolerability data to identify therapeutic candidates. NDDs, including epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), and traumatic brain injury (TBI), are characterized by neuroinflammation, oxidative stress, and neuronal degeneration, with key signaling pathways such as HMGB1, TRPA1, NF-κB, MAPK, and PI3K/Akt-GSK3β playing pivotal roles in their pathogenesis. Given the established link between type 2 diabetes mellitus and neurodegeneration, Saroglitazar, a dual PPAR-α/γ agonist, holds promise in modulating insulin signaling, oxidative stress, neuroinflammation, and key pathways, including HMGB1, TRPA1, NF-κB, MAPK, and PI3K/Akt-GSK3β. This is the first comprehensive review to examine the effects of Saroglitazar in modulating multiple pathways associated with NDDs, thereby addressing existing gaps in the literature. The review explores the mechanistic interplay among these pathways and emphasizes the potential of Saroglitazar as a neuroprotective agent, highlighting the need for further studies to validate its clinical efficacy and disease-modifying capabilities in NDDs. All supporting data were obtained from peer-reviewed literature accessed via PubMed, Web of Science, and Scopus.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing wound healing: insights from phytochemicals and advanced therapies.","authors":"Adwitiya Mitra, Ayesha Shahid, Shivangi Kumari, Tuhin Mukherjee, Shiladitya Pramanick, Satyajit Mohanty, Mohammad Azam Ansari, Krishnendu Adhikary, Pranav Kumar Prabhakar, Kavindra Kumar Kesari","doi":"10.1007/s10787-025-01806-x","DOIUrl":"10.1007/s10787-025-01806-x","url":null,"abstract":"<p><p>Wound healing is a complex process with various dimensions, often presenting as a growing concern that prompts the quest for advancements. This review emphasizes the therapeutic potential of medicinal plants rich in flavonoids, terpenoids, polyphenols, alkaloids, and steroids and discusses their valuable antibacterial, antioxidant, and anti-inflammatory properties in wound management. Cross talk of the phytochemicals with the intricate phases of wound healing, encompassing hemostasis, inflammation, proliferation, and remodeling is detailed, highlighting essential cellular and molecular mechanisms crucial for effective tissue repair. Chronic wounds, a significant global health concern, underscore the importance of advancing wound care therapies. Various treatment modalities, from platelet-rich plasma (PRP) and stem cell therapy to gene therapy, offer diverse mechanisms to promote wound closure and tissue regeneration and mitigate infection risk. Challenges such as variable efficacy, cost, and limited availability necessitate ongoing research for optimal wound management strategies. Wound dressings play a pivotal role in wound care by providing protective barriers against microbial invasion, facilitating tissue regeneration, and maintaining a moist wound environment conducive to healing. The review outlines various types of dressings, including hydrocolloid, foam, alginate, hydrogel, collagen, silver, transparent film, and composite dressings, each offering specific functions and limitations. Appropriate dressing selection depends on wound type, exudate level, and desired therapeutic outcomes. This review offers valuable insights into the complex landscape of wound-healing research and treatment. Synthesizing recent advancements in natural compounds, therapeutic interventions, and wound dressing technologies provides a comprehensive overview of current understanding and future directions in wound care.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tectoridin modulates intertwined molecular pathways in metabolic syndrome: insights from network pharmacology, molecular docking, and in vivo studies.","authors":"Ashwini Kumar Mishra, Pravat Kumar Sahoo, Rajesh Singh, Smita Jain","doi":"10.1007/s10787-025-01815-w","DOIUrl":"10.1007/s10787-025-01815-w","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ethnopharmacology explores the traditional use of natural substances, particularly plants, to treat diseases across various cultures. This study investigates Tectoridin, a bioactive isoflavone derived from traditional medicinal plants, for its therapeutic potential in metabolic syndrome using both experimental and computational methods.</p><p><strong>Aims and objectives: </strong>Metabolic syndrome is a multifactorial disorder characterised by obesity, insulin resistance, hypertension, and dyslipidemia, increasing the risk of cardiovascular diseases and type 2 diabetes. Due to its complexity, multi-targeted therapeutic strategies are essential. Tectoridin, an isoflavone glycoside isolated from Pueraria thunbergiana (Leguminosae) and Iris tectorum, exhibits potential in modulating metabolic pathways.</p><p><strong>Methods: </strong>This study integrates network pharmacology, molecular docking, and in vivo validation to explore tectoridin's therapeutic efficacy against MetS.</p><p><strong>Results: </strong>A protein-protein interaction (PPI) network analysis identified 11 hub genes, with EGFR, HSP90AA1, PPARG, TNF-α, and ESR1 playing key roles in MetS regulation. Molecular docking revealed strong binding affinities between tectoridin and these targets (binding energies: EGFR - 8.7 kcal/mol, HSP90AA1 - 8.4 kcal/mol, PPARG - 8.4 kcal/mol, TNF-α - 6.1 kcal/mol, ESR1 - 1.8 kcal/mol). In vivo studies using a high-fat diet-streptozotocin (HFD-STZ)-induced MetS rat model demonstrated that tectoridin significantly reduced BMI (from 214.12 ± 1.14 mg/dL to 99.75 ± 1.69 mg/dL), adiposity index, and liver hypertrophy. Blood glucose levels improved, with tectoridin lowering the glucose area under the curve (AUC) from 319.5 ± 11.49 to 205.21 ± 10.23. Lipid profile analysis showed an increase in HDL (53.61 ± 3.01 mg/dL) and reductions in cholesterol (77.66 ± 3.37 mg/dL), triglycerides (68.6 ± 2.64 mg/dL), and LDL (33.80 ± 2.70 mg/dL). Gene expression analysis confirmed the downregulation of EGFR, HSP90AA1, and TNF-α, with the upregulation of PPARG and ESR1. Furthermore, biochemical analysis, cell viability analysis and histopathological analysis further validated its protective effects on hepatic tissues.</p><p><strong>Conclusion: </strong>These findings establish tectoridin as a promising multi-target phytopharmaceutical candidate for MetS management, warranting further clinical investigations.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidative and anti-inflammatory effects of Carvacrol against polycystic ovary syndrome associated complications using high fat diet and Letrozole challenged rat model: a multidisciplinary study cascading in vivo, in vitro, in silico and network pharmacology approaches.","authors":"Arfah Siddiqua, Abdul Malik, Urooj Iqbal, Nabeela Tabassum Sial, Malik Hassan Mehmood, Muhammad Fayyaz Ur Rehman","doi":"10.1007/s10787-025-01809-8","DOIUrl":"10.1007/s10787-025-01809-8","url":null,"abstract":"<p><p>Polycystic ovary syndrome is a complex metabolic and endocrine disorder featuring hyperglycemia, hyperandrogenism, disrupted ovulation, and inflammation. Hyperandrogenism induces inflammation through the NLRP3/NF-қB pathway, disturbing ovarian function and causing infertility. We aimed to study the impact of Carvacrol (CAR) on PCOS-associated complications using high fat-diet (HFD) and letrozole-administered rats. Using molecular docking and network pharmacology approaches, we identified NLRP3 and NF-κB as potential target genes mediating the anti-inflammatory effects of CAR. For PCOS induction, female Sprague Dawley rats were given HFD combined with oral letrozole (1 mg/kg) for 30 consecutive days. Administration of Carvacrol (5, 10, and 20 mg/kg/day, p.o) to PCOS-developed rats for 15 days, resulted in decreased body weight, ovarian cysts, the levels of serum testosterone, luteinizing hormone, glycemic, and lipid markers. Similar activity profile has also been observed with metformin (20 mg/kg/day, p.o.), a standard treatment for PCOS. CAR treatment also exerted anti-inflammatory effects, which were evident by the observed down-regulation in the mRNA expression of NLRP3, Caspase-1, IL-18, IL-1β, and NF-κB. Administration of CAR also expressed antioxidant effects observed through a significant elevation of SOD and GSH levels. CAR treatment has also shown positive promising effects in ABTS and DPPH assays. Administration of CAR has also improved ovarian morphology and functions evaluated through histopathological and ultrasonography studies. This study shows that Carvacrol offers protection against polycystic ovary syndrome-mediated complications possibly through its attenuating effects on oxidative stressors and NLRP3/NF-қB dependent pathway, thus providing a sound basis to its therapeutic potential in PCOS.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of naturally occurring 6-shogaol: an updated comprehensive review.","authors":"Kareem A Attallah, Ahmed M El-Dessouki, Mai A Abd-Elmawla, Heba R Ghaiad, Fatma Abo-Elghiet, Aya M Mustafa, Riham A El-Shiekh, Heba Elosaily","doi":"10.1007/s10787-025-01812-z","DOIUrl":"https://doi.org/10.1007/s10787-025-01812-z","url":null,"abstract":"<p><p>Shogaol, a significant bioactive constituent of ginger, is present in several forms, including 4-, 6-, 8-, 10-, and 12-shogaol, with 6-shogaol identified as the most potent among them. Notably, 6-shogaol can be metabolized into 6-paradol, a compound that lacks pungency but retains biological activity. The primary focus of this review is to trace the diverse pharmacological effects of 6-shogaol, such as its anti-inflammatory, cardioprotective, neuroprotective, antioxidant, and anticancer properties, and to document the molecular mechanisms underlying these actions. 6-Shogaol's broad spectrum of benefits makes it valuable in the health, food, and beverage industries, where its unique taste, high biocompatibility, and ability to alleviate or prevent various health issues are particularly advantageous. Its multiple mechanisms of action, including the modulation of oxidative stress and inflammation, contribute to its reputation as a promising natural compound. By highlighting the therapeutic potential of 6-shogaol, this review aims to provide a scientific foundation for its future development, clinical application, and incorporation into functional foods or pharmaceuticals, ultimately supporting its role as a versatile agent in promoting human health.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilizing effect of green tea extract and epigallocatechin-3-gallate (EGCG) on mast cell : an in vivo study.","authors":"Md Mominul Islam, Nadiah Syafiqah Nor Azman, Sreemoy Kanti Das, Mohd Gousuddin, Md Abu Hasan Rasel, Md Robiul Islam, Nadia Izbeta Bini","doi":"10.1007/s10787-025-01800-3","DOIUrl":"https://doi.org/10.1007/s10787-025-01800-3","url":null,"abstract":"<p><p>Mast cells are vital participants in the pathophysiology of allergic reactions by a process of degranulation where bioactive mediators such as histamine, leukotrienes, interleukins and prostaglandins are released to create the local inflammatory milieu. These mediators play an important role in the onset and advancements of allergic diseases, causing bronchoconstriction, as well as increased vascular permeability and local tissue inflammation. Stabilisation of mast cells is one of the essential therapeutic approaches to prevent excessive degranulation and consequent inflammatory aftermaths in allergic conditions. A major polyphenolic component of green tea, epigallocatechin gallate (EGCG), has been postulated to have mast cell-stabilising effects due to its antioxidant and anti-inflammatory effects. It has been reported that EGCG modulates immune responses through inhibition of oxidative stress and control of proinflammatory cytokines secretion. Due to its natural origin and excellent safety profile, EGCG emerges as an alternative treatment for allergic diseases in comparison to the traditional anti-allergic pharmacotherapy such as antihistamines and corticosteroids which have adverse effects long-term usage. In the present study, in vivo anti-allergic activity of EGCG was assessed using bovine serum albumin (BSA)-induced allergy model in male Brown Norway rats. Different levels of EGCG were administered to the experimental groups, while markers of allergic responses were investigated including the histamine concentration and cytokine profiles. The administration of EGCG led to a dose-dependent inhibition of proinflammatory cytokines and histamine concentrations, which implies strong suppression of degranulation of mast cells. These findings indicate that EGCG has therapeutic promise in addressing the mast cell-based allergic diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immuno-nutritional therapy in experimental autoimmune encephalomyelitis: a translational pathway to multiple sclerosis management.","authors":"Mansur Aliyu, Ali Akbar Saboor-Yaraghi, Muhammad Ibrahim Getso, Fatema Tuz Zohora","doi":"10.1007/s10787-025-01804-z","DOIUrl":"https://doi.org/10.1007/s10787-025-01804-z","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disorder characterised by myelin degeneration in the central nervous system (CNS), leading to significant neurological impairment. Affecting approximately 2.8 million people globally and has a multifactorial aetiology involving genetic predispositions and environmental factors, particularly dietary influences. This review explores the emerging field of immuno-nutritional therapy as a novel approach for managing experimental autoimmune encephalomyelitis (EAE), a widely accepted animal model of MS. We highlight the therapeutic potential of key nutritional components, such as omega-3 fatty acids, polyphenols, and vitamins A and D, which have been shown to modulate immune responses and promote neuroprotection. These nutrients exert their effects by regulating cytokine profiles, enhancing regulatory T-cell (Treg) differentiation, and maintaining blood-brain barrier (BBB) integrity. Evidence suggests that dietary interventions can significantly modulate disease severity and progression in EAE, offering valuable insights into potential therapeutic strategies for MS patients. However, translating the findings from EAE models to human MS requires careful consideration of differences in immune responses and environmental factors. Future clinical trials designed to evaluate the long-term efficacy of dietary interventions across diverse MS populations are essential. By integrating immunomodulatory treatments with tailored nutritional strategies, there is a potential for innovative therapies that can alter disease trajectories and improve patient outcomes. A collaborative approach among nutrition scientists, immunologists, and neurologists could pave the way for effective immuno-nutritional therapies in MS management, enhancing the quality of life of those affected by this debilitating condition.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold responses and hormonal echoes: a comprehensive view of Raynaud's vascular dysfunction.","authors":"Manal Fardoun, Odette El Ghawi, Christie Dib, Leen Jaradi, Marie Therese Chaddad, Hassan Dehaini, Ali H Eid","doi":"10.1007/s10787-025-01792-0","DOIUrl":"https://doi.org/10.1007/s10787-025-01792-0","url":null,"abstract":"<p><p>Raynaud's phenomenon is a peripheral vascular disorder characterized by exaggerated vasoconstrictive response to certain stimuli, most typically cold exposure and emotional stress. Interestingly, Raynaud's phenomenon incidence is significantly higher in premenopausal females compared to age-matched males, highlighting a role of the female hormone, estrogen, in Raynaud's phenomenon pathogenesis. Indeed, estrogen plays a fundamental role in potentiating the expression and function of α_2C adrenoceptor (α_2C-AR), the sole mediator of local cooling-induced vasoconstriction. Due to the mosaic nature of Raynaud's phenomenon involving vascular, hormonal, and neuronal factors, as well as due to the lack of an appropriate animal model, the pathogenesis of Raynaud's phenomenon is not fully elucidated. Consequently, despite various therapeutic approaches aimed at mitigating symptoms of Raynaud's phenomenon, a definitive treatment for Raynaud's phenomenon is quite challenging and remains an unmet need. Therefore, a better understanding of the underlying pathophysiologic mechanisms of Raynaud's phenomenon is crucial to better delineate pharmacotherapeutic targets to help fight this elusive disease. In this paper, we dissect the molecular and cellular mechanisms underlying Raynaud's phenomenon and its risk factors, and we shed more light on the role of estrogen. We also explore traditional and current therapeutic approaches, including pharmacologic and non-pharmacologic treatments. In addition, we discuss how the advancement in molecular research offered promising avenues of Raynaud's phenomenon treatment, namely drug repurposing and molecular targeting. Nonetheless, enhanced awareness, precaution, and good patient compliance are critically important in preventing the progression of Raynaud's phenomenon and reducing its severity.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG₂ through nuclear factor-κB pathway.","authors":"Amita Verma, Bahar Ahmed, Firoz Anwar, Mahfoozur Rahman, Dinesh Kumar Patel, Gaurav Kaithwas, Ravi Rani, Prakash C Bhatt, Vikas Kumar","doi":"10.1007/s10787-025-01818-7","DOIUrl":"https://doi.org/10.1007/s10787-025-01818-7","url":null,"abstract":"","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thioridazine-derived molecule exhibits potential anti-inflammatory activity through IKK inhibition.","authors":"Shivmuni Sarup, Rajat Atre, Alexander G Obukhov, Shams Tabrez, Priyanka Yadav, Aravind Singh Kshatri, M Hassan Sk, Abdulaziz Alamri, Mohd Shahnawaz Khan, Mirza S Baig","doi":"10.1007/s10787-025-01786-y","DOIUrl":"https://doi.org/10.1007/s10787-025-01786-y","url":null,"abstract":"<p><p>Chronic inflammatory diseases are leading causes of morbidity and mortality, necessitating the development of targeted therapeutics with improved safety. Many drugs have been withdrawn from the market because of their off-target effects, particularly hERG inhibition, which leads to severe cardiotoxicity. The NF-κB pathway plays a critical role in inflammation and immune response, making IKKβ an attractive therapeutic target. Thioridazine, a known inhibitor of IKKβ, has demonstrated potential anti-inflammatory effects. However, its clinical utility is severely limited by the strong inhibition of the hERG potassium channel, which increases the risk of cardiac arrhythmias. Therefore, it is necessary to develop safer IKKβ inhibitors using rational drug design approaches. By leveraging a similar compound library and in silico techniques, we aimed to retain the original therapeutic potential of thioridazine, while minimising its drawbacks. A library of thioridazine derivatives was computationally designed and screened by molecular docking and simulations. The selected compounds were subjected to patch-clamp analysis, confocal microscopy, western blotting, and qRT-PCR to evaluate their anti-inflammatory potential and hERG affinity, respectively. TDZ-D2{10-(2-oxo-2-pyrrolidin-1-ylethyl)acridin-9-one}, a thioridazine derivative, displayed significantly lower hERG binding while maintaining strong IKKβ inhibition, preserving IκBα stability, reducing NF-κB p65 translocation, and suppressing pro-inflammatory cytokine expression. This study highlights the potential of ligand-based lead optimisation techniques for mitigating off-target effects, thereby offering a safer anti-inflammatory therapeutic candidate. By overcoming the cardiotoxicity associated with thioridazine, TDZ-D2 presents a promising avenue for drug development for inflammatory diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}