INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
·
IF 8.7
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.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
·
IF 2.2
Ya Li,Xinxin Li,Huaxian Li,Weiwei Yan,Qing Dai,Peijun Han,Wenlan Wang
This study aimed to investigate the ameliorative effect of hyperbaric oxygen (HBO) on a rat model of hyperuricemia induced by combined drugs and its underlying mechanism. A rat model of drug-induced hyperuricemia (HUA)was established by using a combination of yeast, potassium oxonate (PO) and hypoxanthine (Hx). During the modeling process, hyperbaric oxygen therapy was also administered. Serum uric acid (UA), creatinine (Cr)and blood urea nitrogen (BUN)levels were measured, and HE staining was used to evaluate the histopathological damage of small intestine and kidney tissues. Serum non-targeted metabolomics analysis was conducted, and 16 S rRNA gene sequencing was used to analyze the changes in intestinal flora structure, to evaluate the therapeutic effect of hyperbaric oxygen therapy. The results showed that HBO therapy could significantly reduce the UA, Cr and BUN levels and alleviate the histopathological damage of small intestine and kidney tissues in model rats. At the same time, HBO therapy could regulate the imbalance of intestinal flora, reduce potential pathogenic bacteria, and reduce the endogenous production of UA by decreasing the relative abundance of Bacteroides and Alistipes . Further serum metabolomics analysis indicated that HBO therapy could improve the differential metabolites in HUA rats, and the pathways of these differential metabolites were mainly related to glutathione metabolism, as well as d -glutamine and d -glutamate metabolism. HBO therapy could regulate key pathways such as purine metabolism and amino acid metabolism, and promote the generation of UA excretion-related metabolites. This study confirmed that HBO could improve combined drug-induced HUA by remodeling the intestinal flora structure and regulating the host metabolic pathways, providing new experimental evidence and potential targets for non-pharmacological treatment of HUA.
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高影响因子
PHYTOMEDICINE
·
2026
·
IF 8.3
Guosen Ou,Jialin Wu,Shiqi Wang,Wensong Bi,Rui Peng,Pei Liu,Yawen Jiang,Yaokang Chen,Huachong Xu,Li Deng,Huan Zhao,Xiaoyin Chen,Lu Xu
Background : Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid. Methods : A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium . Results : In the HUA model, elevated sUA levels ( P <0.01), activation of the renal NLRP3 inflammasome ( P <0.05), renal edema, and impaired renal function were accompanied by gut microbiota dysbiosis. PTGA extract markedly reduced sUA levels by approximately 70% compared to the model group ( P < 0.01), regulated uric acid transporter expression in both the intestine and kidney ( P <0.05), and reshaped gut microbiota composition. Moreover, PTGA enhanced intestinal uric acid catabolism of uric acid in the intestine. FMT and Lachnospiraceae bacterium supplementation experiments further confirmed the regulation of the gut microbiota is a key mediator of PTGA’s therapeutic efficacy. Conclusion : This study demonstrates that PTGA exerts hypouricemic and renoprotective effects through modulation of the gut-kidney axis by enriching Lachnospiraceae , promoting intestinal uric acid catabolism, and suppressing renal NLRP3 inflammasome activation. These findings provide novel mechanistic insights into the gut microbiota-dependent therapeutic action of herbal medicine, distinguishing this work from previous studies focused solely on direct organ-level effects.
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Antioxidants
·
2026
·Vol. 15
·期 8
·1015
·
IF 8.2
Xinyu Heng,Shaohong Huang,Qingyao Luo,Ke Zhang,Pei Liu,Yanan Zhu,Ruoxuan Deng,Ning Sun,Chen Qian,Chao Ye,Hai Yang
Hyperuricemia (HUA) is a chronic metabolic disorder resulting from abnormal uric acid (UA) metabolism. Common clinical drugs for HUA have serious and inevitable adverse effects. Blue honeysuckle (Lonicera caeruleaL.), a traditional edible berry with antioxidant and anti-inflammatory properties, shows great potential for alleviating HUA. This study prepared blue honeysuckle extract (BHE) and identified its main components as chlorogenic acid, quercetin, kaempferol, anthocyanin, etc., using LC-MS analysis. After in vitro digestion, BHE at concentrations ≥ 10 mg/mL retained over 70% of active components and biological activities. In HUA mice, BHE reduced serum UA levels, alleviated oxidative stress and inflammation, decreased UA production by inhibiting xanthine oxidase activity, and promoted renal and intestinal UA excretion through dual regulation of urate transporters. Additionally, BHE repaired the intestinal barrier, remodeled the gut microbiota structure, and improved UA metabolism disorders. This study supports BHE as a potential functional food ingredient for alleviating HUA.
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Pharmaceuticals
·
2026
·Vol. 19
·期 8
·1261
·
IF 5.7
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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Food & Function
·
2026
·
IF 6.3
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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Pharmaceuticals
·
2026
·Vol. 19
·期 3
·490
·
IF 5.7
Hailong Zhang,Jiaxin Huang,Wenji Yang,Wenhu Zhou,Jinsong Ding,Qianbin Li,Gaoyun Hu
Background : Hyperuricemia (HUA) is a metabolic disorder that severely threatens human health. Chronic uric acid (UA) overload promotes the progression of tubulointerstitial fibrosis (TIF), leading to impaired UA excretion. Our previous studies identified HIPK2 inhibitor XRF-1021, which exhibits robust anti-TIF activity and lowers UA levels in vivo. This study aimed to elucidate its UA-lowering mechanism and therapeutic potential for HUA. Methods : Uricase and xanthine oxidase (XOD) assays were performed to assess effects on UA degradation/production. HEK293T cells transiently expressing UA transporters and gene-knockdown rats were used to evaluate transporter inhibition, while HK-2 cells were analyzed by Western blot. Pharmacokinetics were characterized in rats. Efficacy was tested in potassium oxonate-induced acute HUA rats, diet/adenine-induced chronic HUA quails, and adenine-induced mice with HUA secondary to TIF. Maximum tolerated dose and long-term toxicity were assessed in rats. Results : XRF-1021 neither activated uricase nor inhibited XOD, indicating no direct effect on UA catabolism or synthesis. Instead, XRF-1021 inhibited URAT1 and GLUT9, reducing renal UA reabsorption, while sparing OAT3, OAT4, and ABCG2 activity and upregulating OAT3 and NPT4, suggesting minimal risk of disrupting drug or uremic toxin handling. XRF-1021 showed dose-dependent systemic exposure in rats, lowered serum UA, and provided renal protection in vivo. LD 50 values were 2345.4 mg/kg (male) and 1078.9 mg/kg (female), with no obvious toxicity after long-term dosing. Conclusions : XRF-1021 lowers UA by inhibiting URAT1 and GLUT9 to enhance renal UA excretion and provides kidney protection, supporting XRF-1021 as a promising candidate for HUA therapy.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Jiao Kong,Yujia Chen,Shuanghui Lu,Lvexiang Yuan,Tao He,Minlei Dong,Yingqiong Zhang,Xiaoyi Pan,Hui Zhou,Huidi Jiang
Ethnopharmacological relevance The pollen of Brassica campestris L. (BCP, syn. Brassica rapa L. subsp. oleifera (DC.) Metzg.), included in the Chinese Pharmacopoeia as a licensed patent medicine (Pule'an tablets), is used clinically for kidney-qi deficiency-related lower urinary tract symptoms in chronic prostatitis and benign prostatic hyperplasia. Prostatic obstruction is a common cause of obstructive uropathy that may progress to renal fibrosis. However, the renoprotective effects and the underlying mechanism remain to be fully elucidated. Aim of the study To study the renoprotective effects, the active fraction, the effective components of BCP and the underlying mechanisms. Materials and methods Mouse models of hyperuricemic nephropathy (HN) and unilateral ureteral obstruction (UUO) were established to evaluate the renoprotective effects of BCP. Transcriptomics and liquid chromatography-mass spectrometry were applied to explore potential mechanisms and intrarenal constituents. Erastin- and uric acid (UA)-induced HK-2 cells were employed to validate the cytoprotective effects of the potential active compounds, whose binding capability with direct target was confirmed by CETSA/SPR. Results BCP dose-dependently reduced UA levels and reversed the protein expression of UA-producing enzymes and renal transporters (for reabsorption and excretion) in HN mice. Additionally, BCP improved renal injury and fibrosis in HN mice and UUO mice by reducing UA and direct renoprotection, in which the flavonoids of BCP played a crucial role. Meanwhile, BCP alleviated renal fibrosis by inhibiting the β-catenin/TCF4-ferroptosis axis, which was achieved mainly by its bioactive components, kaempferol and kaempferol-3-glucuronide (K-3-G), in HK-2 cells. Furthermore, kaempferol and K-3-G were demonstrated to directly bind with β-catenin, block the transcriptional activation of β-catenin, and subsequently suppress ferroptosis. Conclusions BCP and its major bioactive compounds, kaempferol and K-3-G, exert nephroprotective effects by inhibiting the β-catenin/TCF4-ferroptosis axis.
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JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2026
·Vol. 40
·期 8
·e71058
·
IF 3.6
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.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Cong Liu,Huan Zhang,Huihui Zhang,Yi Zhao,Chen Wu,Qinxiong Lin,Yubin Luo,Liangkai Wei,Jianqiu Chen,Xinyu Rao,Siyi Xiong,Hanmeng Shen,Shuyan Hong,Zhaohua Shi,Shijin Yin,Zhou Lan,Lvyi Chen
Chebulic acid, gallic acid, and corilagin predominated among the seven quantified analytical markers in the TRP aqueous extract. • TRP acts as a potent microbiota modulator to ameliorate renal injury. • The lysophospholipid-TLR4 axis serves as one of the pathological drivers of HUA-associated chronic renal injury. • LPC 16:0 and LPC 18:1 trigger renal inflammation by activating the TLR4 pathway. Background Hyperuricemia (HUA) is a metabolic disorder with an escalating global prevalence, and its progression to HUA-associated nephropathy represents an important contributor to chronic kidney injury. Emerging evidence highlights a bidirectional relationship between uric acid and lipid metabolism, with dyslipidemia contributing to the pathological progression of HUA-related complications. Triphala (TRP), a classic Tibetan herbal formula with broad metabolic regulatory properties, was selected as a potential intervention for the complex metabolic disturbances associated with HUA. However, its therapeutic efficacy and the precise molecular mechanisms underlying its effects in HUA remain to be fully elucidated. Purpose This study aimed to investigate the protective effects of TRP on hyperuricemia-associated nephropathy and to elucidate the underlying mechanisms. Methods High-performance liquid chromatography (HPLC) was first employed to identify and quantify seven representative constituents in the TRP aqueous extract. To evaluate the efficacy of TRP, an HUA mouse model was established through the combined administration of intraperitoneal potassium oxonate injections and a yeast-containing diet. A multi-omics strategy integrating 16S rRNA sequencing, metabolomics and lipidomics elucidated TRP's impact on the gut microbiota and host metabolism. Critically, fecal microbiota transplantation (FMT), TLR4 blockade experiments, and in vitro assays were employed to evaluate the contribution of TRP-modulated microbiota and the LPC-TLR4 pathway to the protective effects of TRP. Results HPLC identified chebulic acid, gallic acid, and corilagin as the major representative constituents of TRP aqueous extract. TRP dose-dependently reduced serum uric acid, improved renal function by lowering serum creatinine (Cr) and blood urea nitrogen (BUN) levels, increased the fractional excretion of uric acid (FEUA), and alleviated tubular injury and fibrosis. These improvements were accompanied by normalized urate transporters (downregulated URAT1/GLUT9; restored OAT1/OAT3) and suppressed renal inflammatory cytokines. Multi-omics analysis revealed that TRP reversed HUA-induced dysbiosis by suppressing opportunistic pathogens (e.g., Parasutterella, Allobaculum ) and enriching beneficial genera (e.g., Bifidobacterium, Akkermansia ), specifically reducing pro-inflammatory LPC (e.g., LPC16:0, LPC18:1). TRP and FMT effectively inhibited the TLR4/MyD88/NF-κB signaling axis and reduced LPC accumulation within the kidney. In vitro experiments validated that these specific LPC directly trigger TLR4 expression and TNF-α release, confirming the potential role of the microbiota-driven lysophospholipid-TLR4 pathway in HUA-associated chronic renal inflammation. Conclusion TRP ameliorates HUA and renal inflammation by remodeling the gut microbiota to suppress the aberrant accumulation of pro-inflammatory lysophospholipids, thereby deactivating the TLR4-mediated inflammatory cascade. These findings establish the gut microbiota-glycerophospholipid metabolism-renal inflammation axis as a potential therapeutic target and validate TRP as a relevant strategy for targeting the gut microbiome to treat systemic metabolic disease. Download: Download high-res image (331KB) Download: Download full-size image
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Journal of Future Foods
·
2026
·
IF 10.6
Zhi Wei,Pengfei Meng,Yanxin Wang,Xiaolong Chen,Wenjun Li,Jiajie Xu,Kai Liao,Xing Zhang,Chenyang Lu
With rising global hyperuricemia due to lifestyle changes, conventional assays and mouse models faced limitations in technical complexity and cost. In this study, we established a zebrafish model of hyperuricemia through a combined genetic and dietary induction approach. Wild-type zebrafish were treated with the uricase inhibitor potassium oxonate (PO) and the uric acid precursor xanthine, resulting in uric acid levels increasing to approximately 2-fold that of wild-type. To reduce reliance on PO and create a more stable model, we knocked out the uox gene encoding uricase using CRISPR/Cas9. The resulting mutant uox -/- increased the uric acid level to 2.83-fold compared to wild-type zebrafish. Treatment with xanthine further increased the uric acid to 3.79-fold compared to wild-type zebrafish, thereby generating a zebrafish hyperuricemia model with highly elevated uric acid. Subsequently, high-throughput screening of tuna protein hydrolysate identified a dominant peptide, Lys-Asn-Arg-Ala-Lys (KNRAK), predicted to target xanthine oxidase via molecular docking. KNRAK effectively reduced uric acid levels by 74.4% and 29.8% in hyperuricemia models derived from wild-type and uox -/- zebrafish, respectively. Transcriptomic analysis revealed that KNRAK reduced uric acid accumulation in the wild-type derived model by modulating purine metabolism, oxidative stress responses, and urate transport–related pathways, whereas in the uox -/- derived model, KNRAK attenuated NF-κB/MAPK-mediated inflammatory signaling. In summary, this study developed a zebrafish hyperuricemia model with high uric acid levels through combined genetic and dietary induction, and identifies KNRAK as a promising therapeutic peptide with dual mechanisms of action.
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FOOD CHEMISTRY
·
2026
·
IF 10.4
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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