Archives of Pharmacal Research最新文献

{"title":"Evaluating the clinical effects of GLP-1 receptor agonists for Alzheimer's and Parkinson's diseases using minimal clinically important difference: systematic review and meta-analysis.","authors":"Yomna Elghanam, Eunyoung Kim","doi":"10.1007/s12272-026-01615-y","DOIUrl":"https://doi.org/10.1007/s12272-026-01615-y","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are promising candidates for Alzheimer's disease (AD) and Parkinson's disease (PD). However, their effects in non-diabetic populations, independent of metabolic confounding, remain unclear. We evaluated the effects of GLP-1RAs on cognition, clinical outcomes, biomarkers, and safety in non-diabetic individuals with PD, AD, and mild cognitive impairment. We assessed the clinical meaningfulness of these effects using minimal clinically important difference thresholds. Relevant studies were retrieved from PubMed, Embase, and Web of Science from inception to November 2025. A random-effects meta-analysis was applied to calculate standardized mean differences (SMDs), mean differences (MDs), and risk ratios with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD420261277032). Fourteen randomized controlled trials enrolling 1260 participants were included. GLP-1RAs showed a small statistically significant improvement in global cognition (SMD 0.14, 95% CI 0.01 to 0.27; I² = 7%), supported by high-certainty evidence. Despite statistical significance, findings suggest only a trivial probability (1%) of a clinically important benefit. Conversely, GLP-1RAs were associated with poorer verbal fluency (SMD - 0.43, 95% CI - 0.79 to - 0.08; I² = 0%), supported by high-certainty evidence. For clinical severity, function, depression, and PD-related outcomes, pooled estimates generally favored GLP-1RAs, but none reached statistical significance. A significant between-disease subgroup difference was observed for function. In the PD subgroup, GLP-1RAs significantly improved depression symptoms relative to control (MD - 2.09, 95% CI - 3.99 to - 0.20; I² = 0%). Nevertheless, this magnitude of improvement remained below the threshold for clinically important benefit. Biomarker findings were inconsistent across trials. GLP-1RAs significantly reduced weight and were associated with poorer tolerability and increased gastrointestinal adverse events. Current evidence provides no convincing support for a clinically meaningful or disease-modifying effect of GLP-1RAs, and adverse effects may limit their clinical utility. Large-scale trials are needed to definitively weigh potential benefits against associated risks.</p>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural compounds targeting inflammatory signaling and cell adhesion molecules in ischemic acute kidney injury.","authors":"Sally A Fahim, Ahmed M El-Dessouki, Nada Osama, Sherif S Abdel Mageed, Mahrous H Mahrous, Reham A Mohammed, Ahmed S Kamel, Kareem Abdou, Joon Hyung Yeo, Riham A El-Shiekh, Nehal I Rizk","doi":"10.1007/s12272-026-01601-4","DOIUrl":"https://doi.org/10.1007/s12272-026-01601-4","url":null,"abstract":"<p><p>Ischemic acute kidney injury (AKI) remains a major clinical challenge, characterized by high morbidity, mortality, and a substantial risk of progression to chronic kidney disease. Accumulating evidence indicates that ischemic AKI is not merely a transient hemodynamic disorder but a complex, biologically orchestrated process driven by microvascular dysfunction, innate immune activation, inflammatory signaling, and maladaptive tissue repair. Despite advances in supportive care, effective disease-modifying therapies are still lacking. Recent studies have highlighted that key signaling pathways, including Toll-like receptor/nuclear factor-κB (TLR/NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), purinergic P2X7 receptor-inflammasome signaling, heat-shock protein-mediated stress responses, and phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) cascades, govern the initiation, amplification, and resolution of ischemic renal injury. These pathways converge on downstream cellular effectors such as cell adhesion molecules (CAMs), which orchestrate leukocyte recruitment, endothelial-epithelial interactions, and spatial propagation of inflammation within the renal microvasculature. Natural compounds have emerged as promising therapeutic candidates for ischemic AKI due to their pleiotropic pharmacological properties and ability to modulate multiple pathogenic signaling networks simultaneously. A growing body of experimental evidence demonstrates that polyphenols, glycosides, saponins, and related phytochemicals attenuate ischemic renal injury by suppressing inflammatory signaling, reducing CAM expression, preserving microcirculatory integrity, and promoting adaptive repair. Furthermore, advances in nanocarrier-based delivery systems have substantially enhanced the translational potential of these compounds by improving bioavailability, renal targeting, and pathway-specific modulation. In this review, we provide a comprehensive, signaling-centered analysis of ischemic AKI pathogenesis and systematically map natural compounds to their molecular targets and downstream inflammatory effectors. By integrating mechanistic insights with emerging nanotherapeutic strategies, this work offers a structured framework for the rational development of multi-target, mechanism-based interventions for ischemic AKI. It highlights key challenges and future directions for clinical translation.</p>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction in endothelial senescence: implications for vascular remodeling and therapeutic strategies","authors":"Wen Li,&nbsp;Jinteng Liu,&nbsp;Xinyin Fu,&nbsp;Yu Liu,&nbsp;Yiqian Xu,&nbsp;Xingyue Fang,&nbsp;Qingyun Guo,&nbsp;Qibing Liu","doi":"10.1007/s12272-026-01614-z","DOIUrl":"10.1007/s12272-026-01614-z","url":null,"abstract":"<div><p>Vascular remodeling (VR) is a structural and functional adaptation of the vessel wall to hemodynamic, metabolic, and inflammatory stress. When persistent and dysregulated, it contributes to the progression of atherosclerosis, hypertension, pulmonary arterial hypertension, and brain microvascular disease. Endothelial senescence is increasingly recognized as a key component of this maladaptive transition, characterized by impaired endothelial homeostasis, reduced nitric oxide bioavailability, and a senescence-associated secretory phenotype (SASP) that can reshape vascular cell–cell communication and extracellular matrix remodeling. Recent evidence further suggests that mitochondrial dysfunction is closely linked to endothelial senescence through multiple mechanisms, including mtROS accumulation, mitochondrial DNA (mtDNA) damage and leakage, disturbed mitochondrial dynamics, and impaired mitophagy flux. In this review, we integrate these findings into a vascular-bed- and disease-stage-stratified conceptual framework, termed the mitochondrial dysfunction–endothelial senescence–vascular remodeling (MD–ES–VR) axis. Within this framework, mechanisms and interventions are interpreted according to evidence strength, causal level, vascular context, and remodeling stage. Current evidence most consistently supports roles for mitochondrial dysfunction in amplifying endothelial injury, inflammatory senescence-like signaling, and remodeling progression, whereas definitive proof for reversal of established structural lesions remains limited. We therefore propose that future studies should combine endothelial-specific and time-resolved designs with quantitative mitochondrial and senescence readouts and robust structural endpoints to better define causality, therapeutic windows, and translational potential.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"446 - 474"},"PeriodicalIF":7.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin sensitizes hepatocytes to endotoxin toxicity via interleukin-1β signaling and drives adaptive immune activation in the liver","authors":"Ananda Baral,&nbsp;Pil-Hoon Park","doi":"10.1007/s12272-026-01611-2","DOIUrl":"10.1007/s12272-026-01611-2","url":null,"abstract":"<div><p>Leptin, an adipose tissue-derived hormone, regulates multiple aspects of hepatic physiology beyond its well-established metabolic functions. Accumulating evidence indicates that leptin influences hepatocyte viability, yet its role in endotoxin-induced liver injury remains incompletely understood. In this study, we investigated the sensitizing effect of leptin on lipopolysaccharide (LPS)-induced hepatocyte toxicity. We found that leptin at a physiologically relevant concentration (20 ng/ml) markedly sensitized hepatocytes to LPS-stimulated apoptosis, whereas leptin or LPS alone exerted no significant effect. This sensitizing effect was not observed in hepatocytes derived from hepatocyte-specific interleukin-1 receptor type 1 (IL1R1)-deficient mice, indicating a critical role for IL-1R1 signaling in these effects. Essentially similar results were obtained for apoptotic cell death, as demonstrated by Annexin-V/7-AAD staining and altered expression of key biochemical markers of apoptosis. Moreover, leptin/LPS-induced apoptosis was significantly attenuated by neutralization of IL-1β, but not by an IL-1α antibody. The in vitro observations were further validated in vivo, where combined administration of leptin and LPS induced pronounced liver injury, as evidenced by elevated serum AST/ALT levels and enhanced apoptotic signaling, all of which were substantially prevented in hepatocyte-specific IL1R1 knockout mice. Additionally, co-treatment with leptin and LPS elicited robust inflammatory cytokine production under both in vitro and in vivo conditions; this effect was absent in IL1R1-deficient models. Notably, combined leptin and LPS stimulation promoted Th17 differentiation from naïve T cells, leading to B cell activation and enhanced antibody production in an IL1R1-dependent manner. Collectively, these results suggest that leptin sensitizes hepatocytes to endotoxin-induced apoptosis via IL-1β signaling-dependent mechanism, thereby amplifying hepatic inflammation and adaptive immune activation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"534 - 553"},"PeriodicalIF":7.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosides in Meliaceae and Rutaceae sources: phytochemistry and pharmacological activities","authors":"Risma Rahmawati,&nbsp;Al Arofatus Naini,&nbsp;Sofa Fajriah,&nbsp;Sri Rahayu,&nbsp; Nurlelasari,&nbsp;Unang Supratman","doi":"10.1007/s12272-026-01613-0","DOIUrl":"10.1007/s12272-026-01613-0","url":null,"abstract":"<div><p>Glycosides are widely distributed plant secondary metabolites and constitute an important source of chemical diversity in Meliaceae and Rutaceae families. Therefore, this review aimed to compile glycosides reported from Meliaceae and Rutaceae families over four decades of investigation (1983–2024), covering flavonoid, aromatic, terpenoid, and other structurally distinct groups. Across these classes, reported biological activities included antioxidant, anti-inflammatory, antimicrobial, and cytotoxic effects, and other activities. The result showed that after comparing available data, biological activity was largely associated with aglycone framework, while glycosylation mainly contributed to structural diversification and influenced physicochemical properties such as solubility and stability. By collecting phytochemical classifications and reported bioactivity data, this review focused on clarifying general trends in glycoside distribution in Meliaceae and Rutaceae, thereby bridging the knowledge gaps in structure–activity relationships and pharmacological evaluation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"417 - 445"},"PeriodicalIF":7.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling regorafenib resistance: metabolic reprogramming, tumor plasticity, and novel approaches to overcome therapy failure","authors":"Xiaokun Liu,&nbsp;Xiao Gao,&nbsp;Yuling Yang,&nbsp;Di Yang,&nbsp;Yani Sun,&nbsp;Yuxuan Yang,&nbsp;Tao Zhao,&nbsp;Ning Li","doi":"10.1007/s12272-026-01612-1","DOIUrl":"10.1007/s12272-026-01612-1","url":null,"abstract":"<div><p>Regorafenib, a multi-kinase inhibitor, has demonstrated clinical efficacy in various malignancies, including hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastrointestinal stromal tumors (GISTs). However, the emergence of resistance significantly limits its long-term therapeutic benefits. Rather than representing isolated molecular events, regorafenib resistance can be conceptualized as a dynamic process of “adaptive network collapse and rewiring”. Owing to its broad inhibition of angiogenic, stromal, and tumor-intrinsic kinases, regorafenib induces an initial collapse of signaling networks, which subsequently drives compensatory rewiring through receptor tyrosine kinase (RTK) bypass activation, cytokine-mediated feedback, and transcriptional reprogramming. Within this framework, resistance mechanisms can be hierarchically organized into drug-proximal adaptive signaling (VEGFR-associated pathways and RTK bypass), network-level regulatory processes (epigenetic modulation, drug transporters, and cancer stemness), and downstream phenotypic adaptations, including metabolic reprogramming, epithelial–mesenchymal transition (EMT), autophagy, and tumor microenvironment remodeling. These processes function in a coordinated manner to restore network robustness under sustained pharmacological pressure. Importantly, this integrative perspective provides a rationale for therapeutic intervention. While downstream adaptations may contribute to resistance maintenance, targeting key nodes of network rewiring—such as EGFR, STAT3, and microenvironmental signaling pathways—may offer more effective and durable strategies. Accordingly, combination approaches integrating regorafenib with targeted agents, immune checkpoint inhibitors (ICIs), metabolic modulators, or emerging therapeutic platforms are discussed. Overall, this review provides a systems-level understanding of regorafenib resistance and highlights the importance of mechanism-guided combination therapies and biomarker-driven strategies to improve clinical outcomes.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"475 - 499"},"PeriodicalIF":7.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent paclitaxel formulation strategies: expanding the therapeutic index by addressing biopharmaceutical and toxicity limitations","authors":"Jihoon Lee,&nbsp;Min-Koo Choi,&nbsp;Im-Sook Song","doi":"10.1007/s12272-026-01609-w","DOIUrl":"10.1007/s12272-026-01609-w","url":null,"abstract":"<div><p>Paclitaxel (PTX) is a standard-of-care antineoplastic agent that stabilizes microtubules. However, its clinical utility is limited by dose limiting toxicities (e.g., myelosuppression and neuropathy), influencing decades of formulation development. Therefore, this review aims to analyze formulation strategies developed to address the three primary limitations. First, solvent-free formulations (e.g., albumin-bound PTX) mitigated the solvent-related toxicity and nonlinear pharmacokinetics of Cremophor EL-based PTX, improving the safety profile by eliminating hypersensitivity reactions. Second, intravenous formulations using liposomes or polymeric micelles for mitigating dose limiting toxicities via prolonged circulation and enhanced tumor retention demonstrated inconsistent clinical translation. Recently, active targeting platforms aimed to keep PTX largely inactive systemically while promoting mechanism-triggered delivery or tumoral uptake are under preclinical evaluation to expand the therapeutic index. Third, poor oral bioavailability, attributed to P-glycoprotein (P-gp)-mediated efflux and first-pass metabolism, was addressed via two strategies: gut-specific P-gp inhibition and lipid-based bypass formulations; however, interpatient absorption variability remains limited. In this review, decades of formulation research, tracing the evolution of PTX from a challenging molecule to a versatile therapeutic platform, were synthesized, highlighting the effect of addressing key biopharmaceutical and toxicity limitations in expanding its therapeutic index. Additionally, we examined the factors contributing to the frequent failure of passive targeting strategies to separate tumor exposure from systemic toxicity in human solid tumors. In conclusion, understanding PTX formulation strategies may facilitate future therapies to adopt flexible administration routes, incorporate biomarker-guided decision-making, and achieve controlled systemic exposure to reduce intrinsic dose-limiting toxicities.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"500 - 533"},"PeriodicalIF":7.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-026-01609-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entrectinib attenuates LPS-induced neuroinflammation by inhibiting JNK, p38, and AKT pathways and ameliorates cognitive impairment","authors":"Hanwoong Woo,&nbsp;Sung Wook Kim,&nbsp;Sohee Kim,&nbsp;Sehyun Chae,&nbsp;Jieun Kim","doi":"10.1007/s12272-026-01608-x","DOIUrl":"10.1007/s12272-026-01608-x","url":null,"abstract":"<div><p>Entrectinib, a Food and Drug Administration-approved medication for cancers such as non-small cell lung cancer, inhibits tropomyosin receptor kinases and penetrates the blood–brain barrier. Despite its approval, the effects of Entrectinib on neuroinflammatory responses and cognitive function within the central nervous system remain unclear. This study demonstrates that Entrectinib modulates lipopolysaccharide (LPS)-induced pro- and anti-inflammatory factors by suppressing JNK, p38, and AKT signaling, as well as NF-κB and STAT3 activity, in primary microglia. Entrectinib reduced CD16/32 levels, increased CD206 expression, enhanced phagocytic activity, and upregulated receptors and cytoskeletal genes in vitro. Additionally, Entrectinib decreased proinflammatory cytokines and inhibited JNK/p38/AKT and NF-κB/STAT3 signaling in the hippocampus of LPS-treated mice. Notably, Entrectinib ameliorated LPS-induced memory impairments in vivo. Collectively, these findings indicate that Entrectinib attenuates neuroinflammation and improves memory performance, supporting its potential therapeutic relevance for neuroinflammation-associated cognitive disorders.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 3","pages":"393 - 415"},"PeriodicalIF":7.5,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-026-01608-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide mitigates atherosclerosis progression and modulates oxLDL-mediated proatherogenic effects in macrophages: evidence for M1/M2 homeostasis restoration","authors":"Mengjie Kang,&nbsp;HaoLin Ren,&nbsp;Yanru Zhen,&nbsp;Limin Liu,&nbsp;Qian Xu,&nbsp;Yue Ma,&nbsp;Lu Zhang,&nbsp;Hui Jia,&nbsp;Qing Chen,&nbsp;Yuhan Jiang,&nbsp;Junjia Gao,&nbsp;Yueyang Liu,&nbsp;Ming-Sheng Zhou","doi":"10.1007/s12272-026-01610-3","DOIUrl":"10.1007/s12272-026-01610-3","url":null,"abstract":"<div><p>Tirzepatide (TZP), a novel dual agonist of glucagon-like peptide (GLP)-1/glucose-dependent insulinotropic polypeptide (GIP) receptors (GLP-1R/GIPR), has been shown to reduce cardiovascular (CV) risk in patients with diabetes or obesity. This study investigated anti-atherosclerotic effects of TZP and the underlying mechanisms using apo E^−/− mice and cultured macrophages. In the present study, apo E^−/− mice were fed a high fat/high cholesterol (HF) diet with or without TZP treatment for 12 weeks. Atherosclerotic lesions, metabolic parameters, and M1/M2 macrophage homeostasis were assessed. In vitro, RAW264.7 and THP-1 macrophages were treated with oxLDL and TZP to evaluate foam cell formation, inflammation, and signaling pathways. The results showed that TZP significantly lowered body weight, plasma lipids, and atherosclerotic burden in vivo, and favorably modulated the expression of M1/M2 macrophage markers. ANCOVA suggested that the anti-atherosclerotic effect may be partially independent of metabolic improvements, although further studies are needed for confirmation. While these data support macrophage modulation as a key mechanism, other vascular cell types and plaque components likely contribute to the observed plaque-stabilizing effects. In vitro, TZP inhibited oxidized Low-density Lipoprotein (oxLDL)-induced cholesterol accumulation and foam cell formation, cluster of differentiation (CD) 36 expression and M1 inflammatory markers while promoting M2 markers. These effects were blocked by combined GLP-1R/GIPR antagonism and further confirmed in human THP-1 macrophages. Mechanistically, the anti-inflammatory effects and modulation of M1/M2 macrophage homeostasis by TZP were mediated via activating kruppel-like factor 4/the peroxisome proliferator-activated receptor γ pathway. Collectively, these findings indicate that TZP confers CV protection and anti-atherosclerotic benefits through both lipid-lowering dependent and independent mechanisms, highlighting its therapeutic potential for diabetic and obese patients who are at high risk of atherosclerotic CV diseases.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 4","pages":"554 - 574"},"PeriodicalIF":7.5,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bavachin suppresses NF-κB signaling and angiogenic pathways to alleviate rheumatoid arthritis","authors":"Debolina Chakraborty,&nbsp;Swati Malik,&nbsp;Ashish Sarkar,&nbsp;Sonia Mann,&nbsp;Prachi Agnihotri,&nbsp;Mohd Saquib,&nbsp;Lovely Joshi,&nbsp;Vijay Kumar,&nbsp;Sagarika Biswas","doi":"10.1007/s12272-026-01606-z","DOIUrl":"10.1007/s12272-026-01606-z","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder that primarily affects females. Estrogen deficiency plays a key role in its development, prompting interest in phytoestrogens as safer alternatives to synthetic estrogen therapies. Our previous in-silico analysis identified Bavachin (BVN) as a potent phytoestrogen capable of targeting the NF-κB complex. This study investigates the therapeutic and mechanistic effects of BVN in mitigating the pathogenesis and inflammation associated with RA. BVN treatment significantly reduced the levels of key inflammatory markers, including IL-6, IL-1β, TNF-α, and NF-κB p65, in RA fibroblast-like synoviocytes (RA-FLS). Additionally, BVN demonstrated a protective effect by significantly decreasing the expression of cell adhesion and angiogenesis factors, such as VTN, SPARC, VEGF, and Cadherin, in TNF-α-induced synovial cells and RA-FLS, as assessed using Western blotting and immunocytochemistry assays. BVN also affected the binding of VTN and SPARC protein, inhibiting angiogenic progression. The therapeutic effects of BVN were confirmed via in vivo studies using a collagen-induced arthritis (CIA) rat model. Treatment with BVN significantly reduced paw inflammation, arthritic scores, immune cell infiltration, and plasma levels of IL-6, IL-1β, and TNF-α while also decreasing the deposition of VTN and SPARC in the rat synovial tissues. Our findings thus suggest that BVN has the potential to serve as a natural therapy for managing RA pathogenesis and reducing associated inflammation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"49 3","pages":"339 - 356"},"PeriodicalIF":7.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}