Inflammopharmacology最新文献

{"title":"Therapeutic potential of purpurin, a natural anthraquinone dye, in neuroprotection and neurological disorders.","authors":"Aya M Mustafa, Ghadir A Sayed, Shymaa Hatem, Roxane Abdel-Gawad Moussa, Dina M Hal, Mahmoud A Mansour, Mohamed S Abd El Hafeez","doi":"10.1007/s10787-025-01977-7","DOIUrl":"https://doi.org/10.1007/s10787-025-01977-7","url":null,"abstract":"<p><p>Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is a naturally occurring anthraquinone pigment derived primarily from Rubia species. Beyond its traditional use as a natural dye, purpurin has recently gained attention for its multifaceted pharmacological activities, particularly in neuroprotection. This review outlines the biosynthetic pathways leading to anthraquinone formation via the shikimate, mevalonate, and methylerythritol phosphate routes, culminating in the generation of purpurin. Structure-activity relationship analyses highlight the critical role of hydroxyl substitutions in modulating antioxidant, anticancer, antibacterial, and neuroprotective properties through radical stabilization, DNA intercalation, and metal chelation. Evidence from preclinical studies indicates that purpurin exerts beneficial effects in Alzheimer's disease, depression, ischemic stroke, and age-related cognitive decline, primarily through anti-tau aggregation, cholinesterase inhibition, serotonergic modulation, antioxidant activity, and anti-inflammatory mechanisms. While purpurin exhibits low acute toxicity and promising pharmacodynamics, its therapeutic translation remains limited by poor solubility, rapid metabolism, and low brain bioavailability. Nanotechnology-based formulations and molecular modifications are being explored to overcome these challenges. Collectively, purpurin represents a versatile bioactive scaffold with considerable potential for the development of multifunctional neuroprotective agents.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225342","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":"Exploring herbal synergies in the management of rheumatoid arthritis: a multifaceted approach to inflammation and joint health.","authors":"Shikhar Verma, Mitali Panchpuri, Vagish Dwibedi, Santosh Kumar Rath, Arti Devi","doi":"10.1007/s10787-025-01987-5","DOIUrl":"https://doi.org/10.1007/s10787-025-01987-5","url":null,"abstract":"<p><p>Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and pain, often leading to severe disability. Conventional treatments, including NSAIDs, DMARDs, and biologics, are expensive and associated with adverse effects, prompting interest in alternative therapies. Herbal synergy, which combines multiple medicinal plants, offers a promising holistic approach to RA management. This review explores the potential of herbal synergy in treating RA, focusing on the anti-inflammatory, immunomodulatory, and antioxidant properties of plants such as Curcuma longa, Boswellia serrata, Withaniasomnifera, Zingiber officinaleetc. These herbs target various RA mechanisms, including inflammatory pathways and oxidative stress, while minimizing side effects. The review highlights these herbal combinations' mechanisms, efficacy, and safety and advocates for their integration into mainstream treatment regimens under expert supervision. The development of standardized formulations, rigorous clinical trials, and robust regulatory frameworks is essential to enhance their therapeutic potential.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225264","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":"Kaempferol prevents Nrf2 from ubiquitin-mediated proteolysis to mitigate both NLRP3 inflammation and oxidative stress: implications for alleviating DSS-induced colitis in mice.","authors":"Wentian Hua, Minrui Li, Ziwei Yan, Yingchao Wang, Xiang Zhou, Zhiwen Fu, Yi Wang, Shujing Zhang, Jing Qian","doi":"10.1007/s10787-025-01966-w","DOIUrl":"https://doi.org/10.1007/s10787-025-01966-w","url":null,"abstract":"<p><strong>Background: </strong>Activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and oxidative stress are key pathological hallmarks of inflammatory bowel disease (IBD) and represent novel targets for therapeutic intervention. The therapeutic potential of the naturally occurring flavonoid kaempferol (KAE) in IBD, along with its underlying molecular mechanisms, remains incompletely understood.</p><p><strong>Methods: </strong>We established dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced systemic inflammation mouse models. KAE was administered as an intervention. In vitro, peritoneal macrophages (PMs) were stimulated to activate the NLRP3 inflammasome. We comprehensively evaluated the effects of KAE on interleukin-1β (IL-1β) release, NLRP3 inflammasome assembly, and mitochondrial reactive oxygen species (mt-ROS) production. Additionally, we assessed its impact on the Keap1-Nrf2 pathway. Molecular docking and ubiquitin-dependent degradation assays were conducted to confirm Nrf2 as a direct target of KAE.</p><p><strong>Results: </strong>KAE significantly attenuated colitis development, marked by reduced NLRP3 expression and enhanced Nrf2 activation. It inhibited both the priming and assembly phases of NLRP3 inflammasome activation. Notably, Nrf2 inhibition completely abolished KAE-mediated removal of mt-ROS and downstream suppression of NLRP3 inflammasome activation. Mechanistically, KAE prevented Nrf2 proteolysis by directly binding to Arg415 of Keap1.</p><p><strong>Conclusions: </strong>Our findings demonstrate that KAE acts as an mt-ROS scavenger to protect against inflammatory pyroptosis, offering novel mechanistic insights and a promising therapeutic strategy for colitis treatment.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225355","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":"Inflammation and immune biomarkers: new frontiers in understanding and managing diabetes complications.","authors":"Polu Picheswara Rao, Shubham Mishra, Jaya Gupta, Manish Vyas, Malakapogu Ravindra Babu","doi":"10.1007/s10787-025-01996-4","DOIUrl":"https://doi.org/10.1007/s10787-025-01996-4","url":null,"abstract":"<p><p>Chronic inflammation and immune dysregulation are central to the development and progression of diabetes complications, redefining existing paradigms of disease pathogenesis and management. Key pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), contribute to tissue injury in the vasculature, kidneys, retina, and peripheral nerves by activating systemic and local inflammatory cascades. Emerging evidence highlights the utility of haematological inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) as accessible, cost-effective predictors of risk for both microvascular and macrovascular complications in diabetes. These markers reflect the ongoing immune activation linked to insulin resistance, beta-cell dysfunction, and oxidative stress. Integrating these biomarkers with genomic and proteomic data enhances precision medicine approaches for complication risk stratification and individualized therapy. Novel anti-inflammatory and immunomodulatory treatments, alongside lifestyle interventions, show promise in mitigating chronic inflammation's effects, potentially reducing the burden of diabetic complications beyond conventional glycaemic control. This review critically appraises the molecular mechanisms of immune-mediated damage in diabetes, evaluates the prognostic and diagnostic value of emerging inflammatory biomarkers, and discusses therapeutic advances aimed at targeting inflammation. Challenges remain in optimizing biomarker validation and translating molecular insights into routine clinical practice. Ultimately, embedding inflammation-focused strategies into diabetes management promises to enhance preventive and therapeutic outcomes, alleviating the global impact of diabetes complications.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225188","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":"Silybum marianum seeds mitigate pro-inflammatory functions of human neutrophils and alleviate ulcerative colitis in rats.","authors":"Ahmed Kouki, Riadh Marrouchi, Abdelaziz Souli, Salwa Bouabdallah, Wafa Ferjani, Pham My-Chan Dang, Amadou Dicko, Jamel El-Benna, Mossadok Ben-Attia","doi":"10.1007/s10787-025-01998-2","DOIUrl":"https://doi.org/10.1007/s10787-025-01998-2","url":null,"abstract":"<p><p>Pro-inflammatory signaling targets and free radicals contribute to the occurrence of ulcerative colitis (UC). Chemical drugs can reduce the UC, whereas their side effects limit their applications. Currently, plant remedies present a promising field for pharmaceutical research. Our study aims to screen bioactive compounds in the aqueous extract from Silybum marianum seeds (AESS) and determine its effect on neutrophil pro-inflammatory functions and colitis. The phytochemical profile and antioxidant potential of AESS were investigated. Human neutrophils were used to assess AESS cytotoxicity and its effects on oxygen-free radicals using chemiluminescence. The western blot was used to evaluate the degranulation mechanism. Furthermore, azurophilic granules, xanthine-xanthine oxidase (X-XO), and horseradish peroxidase (HRP) were used to examine the AESS effects on myeloperoxidase (MPO), superoxide anion (O₂^-.) and hydrogen peroxide (H₂O₂). For the UC, rats were given oral (p.o.) doses of AESS and sulfasalazine (SSZ) for one week before colitis induction, then histological structure and inflammatory and oxidative markers were examined. Findings showed that AESS exhibited antioxidant capacities due to its flavonoids and mainly their flavonolignans, such as silychristin, silydianin, and silibinin A and silibinin B. Myeloperoxidase and HRP activities demonstrated that AESS decreased total oxygen radicals, H₂O₂ and hypochlorous acid (HOCl), and modulated neutrophil degranulation. AESS (100 and 1000 mg/kg, p.o.) prevents the rise of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and preserves the microstructure of the colon and its redox status during the UC. Flavonolignans of AESS possess anti-inflammatory and antioxidant potentials, making it a safe candidate to prevent inflammation.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225305","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":"Biochemical investigations, in silico study and targeted delivery aspects of plant phytosterols: β-sitosterol.","authors":"Tejaswini V Jagtap, Ashwini R Madgulkar, Mangesh R Bhalekar","doi":"10.1007/s10787-025-01951-3","DOIUrl":"https://doi.org/10.1007/s10787-025-01951-3","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disorder marked by persistent joint inflammation, cartilage deterioration, and systemic effects. Conventional treatment regimens, including biologics and non-steroidal anti-inflammatory drugs (NSAIDs), are often accompanied by significant drawbacks, underscoring the need for novel therapeutic strategies. Among plant-derived bioactives, phytosterols have gained attention for their immunomodulatory and anti-inflammatory properties, with beta-Sitosterol (β-SS) standing out as a potent candidate for RA management. This review provides a comprehensive overview of β-sitosterol (β-SS), highlighting its biochemical properties, therapeutic significance, and mechanisms of action in rheumatoid arthritis (RA). β-SS modulates inflammatory signaling pathways by downregulating pro-inflammatory cytokines, including tumor necrosis factors and interleukins, while simultaneously attenuating oxidative stress. Through these actions, β-SS helps preserve cartilage integrity and supports bone health. Computational studies, including molecular docking and molecular dynamics simulations, have validated its interaction with RA-associated targets, suggesting its potential role in disease modulation. Advances in nanocarrier-based drug delivery systems, including polymeric nanoparticles, liposomes, and micelles, have shown promise in enhancing β-SS stability, controlled release and targeted accumulation in inflamed synovial tissues. Additionally, the review highlights regulatory considerations, technological innovations, and future research avenues to optimize β-SS-based RA interventions. With the integration of computational modeling and modern formulation strategies, β-SS presents a compelling natural alternative for improving RA therapeutics.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228371","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":"Pretreatment with probiotics (Bacillus safensis NMCC-189 and Bacillus clausii) prevents epileptogenesis in mice via modulation of BBB integrity, oxidative stress, and neurotransmitter balance.","authors":"Maryam Khan Sherwani, Jehan Zeb Khan, Shakira Ghazanfar, Fahim Hilal, Rimsha Noor, Muhammad Khalid Tipu","doi":"10.1007/s10787-025-01990-w","DOIUrl":"https://doi.org/10.1007/s10787-025-01990-w","url":null,"abstract":"<p><p>Epilepsy remains a difficult neurological condition to treat using conventional therapies. Emerging evidence links gut microbiota to the onset and progression of neurological disorders, including epilepsy. In this study, pretreatment with Bacillus safensis NMCC-189 and Bacillus clausii (probiotics) on epileptogenesis was evaluated. The probiotics were administered orally (10⁸ CFU/ml/day) for 14 days, followed by PTZ administration (60 mg/kg i.p) on day 14. The colon length, biochemical/microbiological analysis of fecal matter with oxidative stress markers, confirmed the colonization of the colon with the bacterium in the mice and improved colon health. The mice supplemented with the probiotics bacteria showed significant anticonvulsant effects via delaying onset, reducing severity and duration of the seizures with no mortality in comparison to the non-supplemented PTZ-kindled mice. Protective action in the supplemented mice can be explained by reduced oxidative stress in the brain tissue. Moreover, RT-PCR results showed that prior administration of Bacillus safensis NMCC-189 and Bacillus clausii successfully restored the expression of tight junction (ZO-1, Occludin, Claudin), and normalized glutamatergic (NR1, NR2A, NR2B, mGluR1, GluA1, GluA2) and GABAergic (GABRA1, GABRB1) gene expression altered by PTZ administration, indicating strong neuroprotective and barrier-preserving effects. These findings highlight the potential of probiotics to mitigate excitotoxicity, restore neurotransmitter balance, and protect epithelial and blood-brain barriers in epilepsy. This study highlights Bacillus safensis NMCC-189 and Bacillus clausii as promising probiotics that modulate gut microbiota and exhibit neuroprotective effects, targeting key mechanisms of epileptogenesis. Furthermore, being part of microbial flora, these probiotics lack any side effects, unlike traditional anti-epileptic drugs.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212580","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":"Quinic acid alleviates inflammatory responses and oxidative stress in Freund's complete adjuvant-induced arthritic rat model and associated risk factors of atherosclerosis.","authors":"Iqra, Ali Sharif, Bushra Akhtar, Chuxiao Shao, Shuanghu Wang, Ayesha Younas","doi":"10.1007/s10787-025-01930-8","DOIUrl":"https://doi.org/10.1007/s10787-025-01930-8","url":null,"abstract":"<p><strong>Background: </strong>Arthritis is an inflammatory disease which causes inflammation, damages joint, and increases the risk of cardiovascular disorders like atherosclerosis. Quinic acid, a naturally occurring compound, exhibits anti-inflammatory and antioxidant potential.</p><p><strong>Method: </strong>The current study was aimed to estimate the pharmacological effects of quinic acid in Freund complete adjuvant-induced arthritis and its possible impact on associated predisposing biomarkers of atherosclerosis development. Quinic acid at various doses (25, 50, and 100 mg/kg) and methotrexate as reference drug were administered, with one group receiving combination treatment. Body weight changes, paw size, arthritic and joint stiffness score, hematological parameters, lipid profile, asymmetric dimethylarginine, homocysteine, oxidative stress, inflammatory biomarkers, and histopathological evaluation of ankle joint and heart tissues were performed to ascertain the severity of arthritis and predisposing biomarkers of atherosclerosis.</p><p><strong>Results: </strong>The findings indicated that combination treatment significantly improved (p < 0.001) body weight, hematological parameters, high density lipoprotein levels, antioxidant enzyme concentrations, and expressions of dimethyl arginine dimethyl amino hydrolase and cortistatin. Simultaneously, it substantially reduces (p < 0.001) paw size, joint stiffness, arthritic score, platelets and leucocyte count, lipid markers, asymmetric dimethylarginine, homocysteine, malondialdehyde, and nitrite levels, whereas downregulation of mRNA expression of inflammatory markers (interleukin-6, interleukin-1β, tumor necrosis factor-α) was observed. It also significantly (p < 0.001) improves the histopathological parameters of ankle joint and heart tissue.</p><p><strong>Conclusion: </strong>It was concluded that quinic acid possessed hypolipidemic, anti-inflammatory, and antioxidant properties and may be an effective therapeutic substance for the management of polyarthritis and predisposing markers of atherosclerosis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225332","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":"Genetic changes in regulatory immune cells induced by pramipexole and rotigotine: implications for the treatment of Parkinson's disease.","authors":"Diana Denisse Álvarez-Luquín, Adrián Guevara-Salinas, Edgar Sevilla-Reyes, Jorge Rosas-García, Miriam Bravo-Martinez, Gloria Erandi Pérez-Figueroa, Vera Teresa Vega-Angeles, Dafne Díaz-Rivera, Carlos Castellanos-Barba, Laura Adalid-Peralta","doi":"10.1007/s10787-025-01949-x","DOIUrl":"https://doi.org/10.1007/s10787-025-01949-x","url":null,"abstract":"<p><p>Parkinson's disease is a chronic degenerative disorder characterized by the death of dopaminergic neurons, associated with persistent inflammation in the central nervous system. Immunoregulatory cells are known to play a critical role in controlling inflammation and providing neuroprotection. While dopamine agonists, such as pramipexole and rotigotine, have proven effects on immune cells, their activity on other types of immunoregulatory cells remains unclear. This study aims to elucidate the genetic changes induced by these dopaminergic agonists in immunoregulatory cells (Tregs, CD8regs, Bregs, and the monocyte subpopulations CM, IM, and nCM) and their potential impact on regulation and neuroprotection. All immunoregulatory cell populations studied showed distinct transcriptional profiles regardless of the agonist used for stimulation. Monocytes showed more terms related to neuroprotection on gene ontology analysis. Our results suggest that different agonists induce distinct patterns of gene expression in immunoregulatory cells, affecting different signaling pathways associated with cellular components, biological processes, and molecular functions, mostly associated with suppressor function and with possible effects on neurons. These findings may help us understand and potentially improve the immune effects of current treatments.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212571","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":"Asperuloside: an emerging therapeutic candidate for Parkinson's disease through molecular mechanistic insights.","authors":"Shiv Kumar Kushawaha, Kanika Vashisht, Himanshu Kumar, Mahendra Singh Ashawat, Ashish Baldi","doi":"10.1007/s10787-025-01981-x","DOIUrl":"https://doi.org/10.1007/s10787-025-01981-x","url":null,"abstract":"<p><p>Parkinson's disease is a progressively debilitating neurodegenerative disorder marked by the loss of dopaminergic neurons, with chronic neuroinflammation and oxidative stress playing pivotal roles in its pathogenesis. While current therapeutic regimens provide only symptomatic relief without halting disease progression, attention is shifting toward multi-targeted, disease-modifying strategies. Asperuloside (ASP), a naturally occurring iridoid glycoside derived from medicinal plants, has emerged as a promising neuroprotective candidate with multi-modal therapeutic potential. It exhibits potent anti-inflammatory, antioxidant, and autophagy-enhancing properties by modulating key signaling pathways such as Notch, PI3K/Akt/mTOR, and NF-κB. ASP exerts neuroprotective effects by attenuating glial cell activation, suppressing pro-inflammatory cytokines, restoring mitochondrial function, and promoting neuronal survival. Notably, it facilitates the autophagic clearance of toxic protein aggregates, restores redox balance, and enhances synaptic plasticity and neurogenic signaling. Its regulatory impact on Notch signaling is particularly significant in reprogramming glial phenotypes and fostering neurogenesis. Moreover, ASP's oral bioavailability and potential for brain-targeted delivery position it as a strong translational candidate. Its ability to influence epigenetic regulation, promote selective autophagy (e.g., mitophagy), and synergize with existing pharmacotherapies warrants further investigation. Collectively, ASP represents a next-generation, multi-target neurotherapeutic capable of modulating the intricate network of degenerative pathways in Parkinson's disease.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225226","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}