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FOOD CHEMISTRY · 2026 · IF 10.4

Stereoisomer-specific allosteric activation of xanthine oxidoreductase by shikonin and alkannin: mechanistic insights and hyperuricemia risk assessment

Li Liu,Huizhi Zhan,Yonglan Chen,Jing Long,Yuxin Lan,Huan Liu,Gan Qiao,Maolin Chen,Shi Zhen,Bing He,Liangliang Zhu,Xiaoyi Qi,Muhan Lü,Sicheng Liang

Shikonin and alkannin activate XOR by binding the Trp336 allosteric pocket, independent of the Cys536-Cys993 disulfide bond. • Alkannin activates XOR more potently than shikonin due to higher binding affinity driving the XDH-to-XO transition. • Shikonin and alkannin can significantly antagonize the urate-lowering effect of allopurinol by activating XOR. Xanthine oxidoreductase (XOR), the rate-limiting enzyme in uric acid metabolism, reversibly interconverts between dehydrogenase (XDH) and oxidase (XO) forms. Our previous study revealed allosteric activation of XOR by 1,4-naphthoquinones, highlighting their potential risk in food industry. Herein, we employed the isomeric 1,4-naphthoquinone probes shikonin (SHI) and alkannin (ALK) to elucidate the underlying mechanism. Site-directed mutagenesis demonstrated that SHI and ALK activate XOR by binding a Trp336-centered allosteric pocket, independent of classic Cys536-Cys993 bond. This binding destabilizes the relay cluster, promoting the XDH-to-XO transition. ALK showed stronger species-biased activation of XOR (human > rat > mouse ≈ microorganism). Both ligands enhanced catalytic efficiency and antagonized allopurinol's urate-lowering action. Molecular dynamics and MM/GBSA analyses indicated that ALK formed more stable hydrogen bonds and bound more strongly. These mechanistic insights were corroborated in vivo in rats, revealing a novel allosteric activation pathway with implications for XOR-targeted therapies and food safety risk assessment. Download: Download high-res image (134KB) Download: Download full-size image

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APPLIED SURFACE SCIENCE · 2026 · IF 6.6

Electric-triggered coordination disassembly for red-shifted phosphorescence and electrochromic light-emitting diodes

Jia Yi Chen,Li Ya Liang,Shuai Chang,Ya Ting Gao,Jian Lv,Bin Bin Chen,Da Wei Li

Aluminum/hypoxanthine phosphorescent materials (Al/HX-PMs) exhibit enhanced RTP via coordination rigidity. • The RTP lifetime and intensity of Al/HX-PMs are 2.89 and 5.18 times those of HX, respectively. • Pronounced electrophosphorochromism is observed under applied current via cleavage of Al 3+ –HX coordination bonds. Metal-organic electrophosphorochromic materials are crucial for advancing the next generation of optoelectronic technology, but developing new strategies to achieve low-cost and high-efficiency electrophosphorochromism still faces challenges. Herein, we report a metal–organic phosphorescent material (Al/HX-PMs) synthesized from low-cost hypoxanthine (HX) and aluminum sulfate (Al 2 (SO 4 ) 3 ). Owing to the coordination rigidity, Al/HX-PMs exhibit significantly enhanced room-temperature phosphorescence (RTP) performance, with the lifetime prolonged by 2.89 times (from 148.77 ms to 429.75 ms) and the RTP intensity enhanced by up to 5.18 times compared to pure HX. Remarkably, Al/HX-PMs display pronounced electrophosphorochromism, as the emission progressively red-shifts from 503 nm to 592 nm with increasing current. This spectral evolution is attributed to the electrically triggered cleavage of coordination bonds, which induces dissociation into molecular constituents and enables direct structural control over luminescence. This work not only offers a new design strategy for low-cost electrically responsive phosphorescent materials, but also presents a feasible route toward fabricating correlated color temperature tunable light-emitting diodes. A metal–organic phosphorescent material (Al/HX-PMs) is synthesized from low-cost hypoxanthine and aluminum sulfate, exhibiting enhanced room-temperature phosphorescence (2.89-fold prolonged lifetime and 5.18-fold increased intensity) and pronounced electrophosphorochromism (red-shift from 503 nm to 592 nm with increasing current), which is attributed to the electrically triggered cleavage of coordination bonds. Download: Download high-res image (176KB) Download: Download full-size image

CAS / MDL: 68-94-0
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Pharmaceuticals · 2026 ·Vol. 19 ·期 8 ·1261 · IF 5.7

Cinnamaldehyde Attenuates Hyperuricemia-Associated Renal Injury by Modulating Urate Transporters and AIF1- and CMPK2/NLRP3-Related Inflammatory Signaling

Yongxin Sun,Hao Tan,Jingyu Zhang,Zengyu Zhang,Shuang Huai,Manli Wang

Background:Hyperuricemia is a well-established risk factor for both chronic kidney disease and gout. Currently available urate-lowering drugs, however, are frequently compromised by hepatorenal toxicity and gastrointestinal adverse effects. Cinnamaldehyde, the principal bioactive constituent of the traditional Chinese medicine cinnamon, has documented renoprotective properties, yet its integrated effects on hyperuricemia-associated renal injury remain incompletely defined.Objectives:This study investigated the therapeutic effects of cinnamaldehyde on hyperuricemia and explored the molecular mechanisms involved.Materials and Methods:An in vivo hyperuricemia model was established in KM mice by co-administration of potassium oxonate and hypoxanthine for 14 consecutive days, and an in vitro injury model was generated by exposing HK-2 human renal tubular epithelial cells to uric acid. For the in vivo study, mice were divided into five groups (control, model, febuxostat, low-dose CA, and high-dose CA;n= 9 per group) and were treated by oral gavage. Serum biochemical indices, renal and intestinal histopathology, inflammatory cytokines, renal urate transporter proteins (OAT1, OCT2, ABCG2, and SLC2A9), and components related to AIF1 and CMPK2/NLRP3 inflammasome signaling (ASC, caspase-1, IL-18, and IL-1β) were examined. Western blotting, qPCR, immunofluorescence, apoptosis analysis, mitochondrial membrane potential assessment, transmission electron microscopy, siRNA-mediated knockdown, and 16S rRNA gene sequencing were used to characterize the relevant mechanisms.Results:CA reduced serum uric acid (p≤ 0.001 vs. model), creatinine (p≤ 0.01 vs. model), and blood urea nitrogen (p≤ 0.01 vs. model), alleviated renal and intestinal histopathological injury, and decreased circulating and renal inflammatory cytokines. Cinnamaldehyde increased ABCG2, OAT1, and OCT2 protein expression and reduced SLC2A9 expression (allp≤ 0.05 vs. model). In vivo and in vitro, cinnamaldehyde suppressed AIF1- and CMPK2/NLRP3-related inflammatory proteins, reduced uric acid-induced apoptosis, and preserved mitochondrial membrane potential and ultrastructure. Fecal 16S rRNA sequencing suggested changes in selected microbial taxa, although alpha-diversity and BrayCurtis-based PERMANOVA/ANOSIM analyses did not demonstrate significant global community separation.Conclusions:These findings suggest that CA alleviates hyperuricemia-associated renal injury by regulating renal urate transporters, attenuating AIF1- and CMPK2/NLRP3-related inflammatory signaling, accompanied by compositional shifts in selected gut microbial taxa that warrant further mechanistic investigation. The study provides experimental support for further evaluation of cinnamaldehyde as a multi-target candidate for hyperuricemia-related renal injury.

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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

A colorimetric and photothermal dual-mode nanozyme platform: Multimodal deep learning guided real-time freshness sensing and predicting of aquatic products under challenging lighting conditions

Jingqi Shen,Weijia Zhang,Miaolin Duan,Di Zhang,Pengyao Xie,Zunying Liu,Lirong Xiang,Fei Jia

A colorimetric and photothermal dual-mode method was conducted for hypoxanthine detection. • The 2D Fe/Ni-MOF-based sensing platform demonstrated excellent sensitivity, accuracy and biocompatibility. • The dual-mode method was developed for the early evaluation of freshness in aquatic products. • A LAMF-Net model was trained with accuracy >97% for freshness prediction under challenging lighting conditions. • Rapid freshness assessment was enabled via self-developed intelligent online detection platform. Timely and accurate freshness assessment of aquatic products with complex matrices remains significant challenge. Hypoxanthine (Hx)-based monitoring methods using colorimetric sensing with smartphone are widely used but affected by variable lighting conditions throughout the food supply chain, causing detection results remain inaccurate. Here, a colorimetric/photothermal dual-mode Hx detection and freshness prediction platform was constructed by cascading a thermostable 2D Fe/Ni-MOF nanosheet with xanthine oxidase, enabling stable and sensitive on-site detection of Hx. A linear response to Hx was exhibited in the range of 0.2–100 μM, with detection limits of 0.12 μM (colorimetric mode) and 4.21 μM (photothermal mode), respectively. To address ambient lighting effects, seven lighting conditions (~50, ~100, ~500, ~1000, ~5000, ~10,000, and ~50,000 lx) were simulated to construct a dataset integrating lighting, colorimetric, and photothermal information for the model training and testing. A light-adaptive multimodal fusion network based on YOLOv11 and Multi-Layer Perceptron (MLP) achieved a prediction accuracy of 98% in freshness classification, remarkably higher than that of the single colorimetric (89%) and photothermal (93%) modes, when trained on 4536 labeled images and 108 photothermal data points, demonstrating strong robustness under complex and varying lighting conditions. Coupled with the self-developed “Food Track” application, this work not only provides a practical and reliable approach for the early freshness prediction in aquatic products, but also highlights the potential of multimodal fusion algorithms to handle lighting variations in food supply chains. Download: Download high-res image (120KB) Download: Download full-size image

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FOOD CHEMISTRY · 2026 · IF 10.4

Soft matter-engineered pH-responsive hydrogels for encapsulation, protection, and controlled intestinal release of probiotics (Lacticaseibacillus paracasei YWC-01)

Xiaoyu Cao,Sisheng Li,Qianqian Xu,Zilun Lei,Bo Jiao,David Julian McClements,Hai Yan

pH-responsive hydrogel microcapsules were fabricated from pea protein isolate (PPI) and low-methoxyl pectin (LMP) for the targeted intestinal delivery of Lacticaseibacillus paracasei YWC-01, a probiotic capable of biodegrading uric acid precursors in vitro . Microgels with interpenetrating networks were fabricated via emulsion-templating: probiotics, PPI, LMP, CaCl₂, and glucono-δ-lactone were emulsified in oil and crosslinked by Ca 2+ . Optimized formulation (5% w / v PPI) achieved 94.80% encapsulation efficiency. Microgel size (43–63 μm) was controlled by adjusting Span 80 surfactant concentration. FTIR confirmed probiotic encapsulation via noncovalent interactions, while TEM revealed bacterial clustering within hydrogel voids. In vitro digestion demonstrated exceptional protection: encapsulated probiotics maintained >9 log 10 CFU/g viability (<0.4 log reduction), versus 3.2 log reduction in free cells. Metabolomics indicated encapsulation preserved bioactivity and significantly upregulated functional metabolites potentially enhancing gut microbiota modulation and anti-inflammatory effects. This work establishes an effective oral delivery platform that significantly enhances probiotic gastrointestinal survival and enables targeted release.

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Crystals · 2026 ·Vol. 16 ·期 2 ·126 · IF 2.9

Bio-Purines as Co-Formers in Resveratrol Amorphous Systems

Yuhang Liu,Ziqing Wu,Fenghua Chen,Yongming Liu,Rongrong Xue

In the organic biomineralization of guanine (GUA), amorphous GUA is utilized to enhance its solubility, facilitating its transport for the formation of biominerals, and GUA nanocrystals are employed to protect tissues from ultraviolet damage. These principles of GUA biomineralization inspire us to improve the solubility and photostability of trans-resveratrol (RES) using bio-purines, which limits its bioavailability. Bio-purines, such as GUA, hypoxanthine (HYP), and adenine (ADE), were used as co-formers in the amorphous systems of RES. Amorphous RES-2Purines with a 1:2 molar ratio were prepared via the neat ball-milling method and confirmed by powder X-ray diffraction, Raman spectroscopy, and diffuse reflectance spectroscopy. The stability, dissolution profiles, and photostability of RES-2Purines were comprehensively compared. RES-2Purines show high amorphous-to-crystalline transformation temperatures (>100 °C), confirmed by the differential scanning calorimetry-thermogravimetric analysis. Both RES-2HYP and RES-2ADE show an enhanced RES solubility (about 1.6-fold that of raw RES) in water and the simulated gastric fluid (pH 1.2). RES-2Purines can recrystallize quickly after being dispersed in water, which limits the solubility enhancements of RES-2Purines. RES-2Purines have better photostability than raw RES. Bio-purines are promising co-formers for amorphous systems to enhance the solubility and photostability of poorly water-soluble compounds.

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JOURNAL OF FOOD SCIENCE · 2026 ·Vol. 91 ·期 2 ·e70897 · IF 4.1

A Novel Strategy in Managing Spent Probiotic Culture Media: Metabolome Identified Functional Candidates Against Hyperuricemia

Hongyu Zhang,Da Wang,Xiangheng Cao,Baiyu Zheng,Ruiyang Qiu,Wenhui Xu,Koukou Duan,Shuping Wei,Mengge Zhao,Shichao Han

With the rapid expansion of the probiotics industry, the management of spent culture media has emerged as a pressing concern. However, it also represents a potential resource for functional food development. In this study, we investigated and screened anti-hyperuricemia (HUA) metabolites of Lactobacillus paracasei (LP) from spent media (META). Administration of META significantly reduced serum uric acid (UA) (SUA) levels ( p < 0.05), improved kidney function, and alleviated inflammatory infiltration. Furthermore, META modulated UA metabolism by regulating key enzymes (xanthine oxidase [XOD] and adenosine deaminase [ADA]) and urate transporters (organic anion transporter 3 [OAT3], glucose transporter 9 [GLUT9], and urate transporter 1 [URAT1]), while mitigating HUA-induced inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway. To identify bioactive compounds, untargeted metabolomics based on UHPLC-QTOF-MS/MS detected 361 upregulated metabolites. Network pharmacology and molecular docking (MD) analyses further highlighted potential candidates, including 2-isopropylmaleate and ricinoleic acid methyl ester. Collectively, these findings suggest that probiotic culture media waste may serve as a promising natural source for the development of anti-HUA functional foods. Further studies are warranted to assess the bioavailability and efficacy of these metabolites both in vitro and in vivo.

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Food & Function · 2026 · IF 6.3

Bioconversion properties of the urate-lowering probiotic fermented Aronia melanocarpa (black chokeberry) and its antihyperuricemic capacity via regulating metabolic/immune pathways and gut microbiota

Hongyu Zhang,Chaoran Li,Tianjiao Li,Fuyu Li,Xiangheng Cao,Yang Yang,Da Wang,Mingyou Yuan,Qiuyi Li,Xuebo Liu,Mengge Zhao

Hyperuricemia (HUA) is a worldwide metabolic disorder. We developed a functional fermented beverage by fermenting Aronia melanocarpa (AR) with the urate-lowering probiotic Lactobacillus paracasei N1115 (LP). Firstly, untargeted metabolomics revealed that LP balanced its aroma and imparted a lactic flavor to AR and increased the concentrations of certain compounds with anti-HUA properties (e.g., caffeic acid and shikimic acid). In HUA mice, AR, fermented AR (FAR) and sterilized FAR (FARS) reduced serum uric acid, improved renal function, and suppressed inflammation via the TLR4/MyD88/NF-κB pathway. They also down-regulated the levels of XOD, ADA and URAT1. The fermented beverage showed superior efficacy, enhancing XOD inhibition by about 30% and additionally inhibiting GLUT9. FAR and FARS increased fecal butyrate, likely by enriching Faecalibaculum and Anaerostipes. Because the anti-HUA patterns of FAR and FARS were similar, and no colonization of Lactobacillus was observed, the postbiotics may serve as the primary factors contributing to the enhanced anti-HUA activity of the fermented beverage.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Mechanism of Portulaca oleracea acidic polysaccharide in ameliorating renal injury in hyperuricemia mice by regulating the CMPK2/NLRP3 pathway

Chunyu Wang,Yixin Zheng,Qingwen Cui,Yuxin Jiang,Jinhe Wang,Tianyu Zhang,Yuxin Song,Xiao Guo,Manli Wang,Liping An

Portulaca oleracea acidic polysaccharide (POPW-A) demonstrates significant efficacy in anti-inflammatory and immune-enhancing properties. Intervention with POPW-A reduced blood uric acid levels and significantly up-regulated uric acid transporter expression in hyperuricemic (HUA) model mice. Additionally, it suppressed the activation of the NLRP3 inflammasome by down-regulating AIF-1 and CMPK2 protein expression, thereby alleviating renal inflammation. The polysaccharide components of POPW-A were screened after purifying. Among them, the POPW-Ab component effectively enhanced the expression of uric acid transport proteins and suppressed the activation of the NLRP3 inflammasome. Structural analysis confirmed that POPW-Ab is a pectin polysaccharide composed primarily of a homogalacturonan (HG) domain with a backbone of →4)-α-D-GalpA-(1→, along with a minor rhamnogalacturonan-I (RG-I) domain containing side chains of →5)-α-L-Araf-(1→. After silencing the CMPK2 gene in model cells, the protective effects of POPW-Ab were counteracted. Conversely, overexpression of the CMPK2 gene restored the intervention efficacy of POPW-Ab. Therefore, POPW-Ab is likely the fundamental material basis for the bioactivity of Portulaca oleracea polysaccharides. The underlying mechanism involves targeted down-regulation of CMPK2 gene expression, thereby inhibiting NLRP3 inflammasome activation and subsequent release of pro-inflammatory cytokines. These findings suggest that POPW-Ab holds promise as a potential therapeutic agent for HUA and its associated renal complications.

CAS / MDL: 2207-75-2 68-94-0
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Nature Communications · 2026 · IF 18.1

Engineering technology of implantable galvanic cells for silencing the bone-neural axis in gouty arthritis therapy

Cao Jie,Yang Nailin,Gong Fei,Wang Xi,Qiao Xinyi,Pan Xiaoxiao,Du Qialu,Cai Yichi,Wu Jie,Huang Yechen,Wang Yichen,Han Zhihui,Cheng Liang

Gouty arthritis faces multiple challenges, such as recalcitrance to cure and recurrent flares, owing to its intricate pathophysiological microenvironment. Recent studies have focused on urate reduction, pain relief, or anti-inflammation effects alone, which often fail to provide satisfactory results. To address these challenges, an implantable manganese platinum microscale galvanic cell (Mn@Pt micro-GC) is developed. This system utilizes the urate oxidase-like activity of platinum to degrade deposited monosodium urate crystals, while the Mn 2+ and hydrogen gas work synergistically to effectively reversing the pro-inflammatory environment. In addition to decreasing the production of pain signals associated with gout, Mn@Pt micro-GC effectively inhibits pain signal transmission along the CXCL5-neuronal CXCR2-TRPA1 axis through continuous electrical stimulation. This multimodal treatment approach emphasizes the strong relationship between bone and nerve in gout, taking into account the importance of reducing uric acid, anti-inflammation, and pain relief in gout therapy, which has led to improved treatment results.

CAS / MDL: 2207-75-2 68-94-0
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2026 · IF 5.2

A self-nanoemulsifying drug delivery system loaded with esculin-phospholipid complex to improve oral absorption and anti-hyperuricemic efficacy of esculin

Yue Zheng,Huan Xu,Dongjing Liu,Liping Feng,Biyang Yao,Ziyu Liao,Yunxuan Zhou,Jingrui Wang,Yanyue Qin,Yingchun Zeng

An esculin-phospholipid complex-based self-nanoemulsifying drug delivery system (EPC-SNEDDS) was successfully developed and optimized. • As The first reported oral nanoformulation for ESC, EPC-SNEDDS significantly improved its oral bioavailability. • The mechanisms by which EPC-SNEDDS improved the oral absorption of ESC were elucidated, including improved stability, enhanced intestinal permeability, and promoted lymphatic absorption. • Oral administration of EPC-SNEDDS normalized serum uric acid (UA) levels in hyperuricemic mice and concurrently exhibited favorable renal protective effects. • Orally administered EPC-SNEDDS not only significantly inhibited UA production, but also potently promoted its excretion. Hyperuricemia (HUA) is the second most prevalent metabolic disease with unmet clinical needs persisting in its pharmacotherapy. Esculin (ESC) is an active coumarin with anti-hyperuricemic effects. However, its poor solubility, low membrane permeability, and significant first-pass effect limit its oral absorption and application. Self-nanoemulsifying drug delivery system (SNEDDS) has attracted extensive attention as a versatile platform to improve the oral bioavailability of poorly soluble and low-permeability drugs. Herein, an ESC-phospholipid complex (EPC) was prepared to enhance the lipophilicity of ESC and consequently its compatibility with SNEDDS. Subsequently, an EPC-loaded SNEDDS (EPC-SNEDDS) was developed for the oral delivery of ESC. Its composition was screened via pseudo-ternary phase diagrams and further optimized via a Box-Behnken design. The optimal formulation consisted of Lauroglycol 90, Tween 80, and Transcutol P (21.6:41.4:37.2, w/w/w ). After aqueous dispersion, EPC-SNEDDS rapidly formed nanoemulsions with a small droplet size (27.78 ± 0.71 nm), narrow particle size distribution (PDI = 0.149 ± 0.007), and high stability. Moreover, the formulation increased the oral bioavailability of ESC by 2.88-fold, which could be ascribed to improved stability, membrane permeability and lymphatic transport. In hyperuricemic mice, oral EPC-SNEDDS effectively suppressed serum and hepatic xanthine oxidase activity and promoted uric acid excretion, exhibiting superior urate-lowering efficacy compared with free ESC and EPC. Collectively, the integration of phospholipid complexes with SNEDDS provides a feasible strategy for efficient oral administration of ESC, and EPC-SNEDDS represents a promising therapeutic approach for HUA treatment. Download: Download high-res image (244KB) Download: Download full-size image

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JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY · 2026 ·Vol. 40 ·期 8 ·e71058 · IF 3.6

Isobavachin Attenuates Renal and Cardiac Injury in Chronic Hyperuricemia via Modulation of NF‐κB and NLRP3 Signaling Pathways

Yongmei Li,Yuexin Xu,Wenjie Ye,Zeqi Yu,Zhenkun Wu,Xinyi Liu,Xuhong Huang,Jianxin Pang,Zean Zhao,Ting Wu

Hyperuricaemia (HUA) is a recognized risk factor for cardiovascular and renal diseases. Isobavachin, a dihydroflavone derivative, demonstrates significant efficacy in reducing uric acid levels. This study investigated the nephroprotective and cardioprotective effects and molecular mechanisms of isobavachin. Through integrative network pharmacology, pathway enrichment analysis, and molecular docking, NF‐κB was identified as a potential target of isobavachin in the context of hyperuricemia‐related cardiac and renal injury. Isobavachin treatment inhibited the activation of the NF‐κB pathway, leading to cytoprotection in uric acid (UA)‐stimulated mRTEC and H9C2 cells. In chronic HUA mice, isobavachin treatment significantly improved renal pathology and reduced renal collagen deposition by inhibiting epithelial‐to‐mesenchymal transition. Isobavachin administration demonstrated therapeutic efficacy in attenuating myocardial injury, hypertrophy, and fibrotic remodeling. Notably, the anti‐inflammatory effects of isobavachin were particularly evident in both renal and cardiac tissues, primarily mediated through its dual regulatory capacity in suppressing NF‐κB pathway activation and NLRP3 inflammasome formation. In conclusion, isobavachin ameliorated cardiac and renal damage caused by chronic HUA, suggesting a new strategy to prevent HUA. Isobavachin alleviates HUA‐induced oxidative stress, inflammation, and fibrosis in the kidney and heart, potentially through its dual role in promoting UA excretion and inhibiting NF‐κB signaling and NLRP3 inflammasome activation.

CAS / MDL: 2207-75-2 68-94-0
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