PharmaNutrition最新文献_第3页

Mechanistic advances in hyperuricemia and anti-hyperuricemia therapies 高尿酸血症和抗高尿酸血症治疗的机制进展

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-10-27 DOI: 10.1016/j.phanu.2025.100456

Mingyue Ao , Xi Zhang , Ru Chen , Chun Xiao , Yinhua Liu , Min Gao , Ya Zhang

Hyperuricemia (HUA) is a systemic metabolic disorder characterized by disturbances in uric acid metabolism and elevated serum uric acid levels, and it is a major risk factor for gout. It has risen to become the second largest metabolic disease threatening human health, and is known as one of the "four highs" along with hypertension, hyperlipidemia, and hyperglycemia. At present, clinical treatment for HUA can be divided into three categories: inhibiting uric acid production, promoting uric acid excretion, and decomposing uric acid. Although the mechanism is clear and the effect is significant, there are varying degrees of safety risks involved. Therefore, a growing number of studies are dedicated to finding new pathogenic mechanisms or potential therapeutic targets for HUA. It is of great significance to comprehensively understand HUA and develop feasible and effective treatment methods. In this review, we systematically elucidate the pathogenesis, related drug treatment progress, and strategies for regulating HUA by gut microbiota. At the same time, the effects of different dietary structures on gut microbiota and the impact of gut microbiota on purine and uric acid metabolism were explored. In addition, the intervention effects of probiotics and prebiotics on HUA were systematically evaluated, in order to provide theoretical basis for the research and development of uric acid lowering drugs.

高尿酸血症（HUA）是一种以尿酸代谢紊乱和血清尿酸水平升高为特征的全身性代谢紊乱，是痛风的主要危险因素。它已成为威胁人类健康的第二大代谢性疾病，与高血压、高脂血症、高血糖症并称为“四高”。目前临床上对HUA的治疗可分为抑制尿酸生成、促进尿酸排泄、分解尿酸三类。虽然作用机制明确，效果显著，但存在不同程度的安全风险。因此，越来越多的研究致力于寻找HUA的新的致病机制或潜在的治疗靶点。全面认识HUA，制定可行有效的治疗方法具有重要意义。在本文中，我们系统地阐述了HUA的发病机制、相关药物治疗进展以及肠道微生物群调节HUA的策略。同时，探讨了不同饲粮结构对肠道菌群的影响，以及肠道菌群对嘌呤和尿酸代谢的影响。此外，系统评价益生菌和益生元对HUA的干预效果，为降尿酸药物的研发提供理论依据。

{"title":"Mechanistic advances in hyperuricemia and anti-hyperuricemia therapies","authors":"Mingyue Ao , Xi Zhang , Ru Chen , Chun Xiao , Yinhua Liu , Min Gao , Ya Zhang","doi":"10.1016/j.phanu.2025.100456","DOIUrl":"10.1016/j.phanu.2025.100456","url":null,"abstract":"<div><div>Hyperuricemia (HUA) is a systemic metabolic disorder characterized by disturbances in uric acid metabolism and elevated serum uric acid levels, and it is a major risk factor for gout. It has risen to become the second largest metabolic disease threatening human health, and is known as one of the \"four highs\" along with hypertension, hyperlipidemia, and hyperglycemia. At present, clinical treatment for HUA can be divided into three categories: inhibiting uric acid production, promoting uric acid excretion, and decomposing uric acid. Although the mechanism is clear and the effect is significant, there are varying degrees of safety risks involved. Therefore, a growing number of studies are dedicated to finding new pathogenic mechanisms or potential therapeutic targets for HUA. It is of great significance to comprehensively understand HUA and develop feasible and effective treatment methods. In this review, we systematically elucidate the pathogenesis, related drug treatment progress, and strategies for regulating HUA by gut microbiota. At the same time, the effects of different dietary structures on gut microbiota and the impact of gut microbiota on purine and uric acid metabolism were explored. In addition, the intervention effects of probiotics and prebiotics on HUA were systematically evaluated, in order to provide theoretical basis for the research and development of uric acid lowering drugs.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100456"},"PeriodicalIF":2.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vitamin D does not mitigate monocyte adhesion to vascular endothelial cells in an in vitro pro-inflammatory model 在体外促炎模型中，维生素D不能减轻单核细胞对血管内皮细胞的粘附

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-09-19 DOI: 10.1016/j.phanu.2025.100454

Mirko Marino , Samuele Venturi , Peter Møller , Marco Rendine , Daniela Martini , Patrizia Riso , Cristian Del Bo'

Vitamin D deficiency has been associated with cardiovascular risk factors, including endothelial dysfunction, a critical step in the pathogenesis of atherosclerosis. This study aimed to evaluate the effects of 1α,25-dihydroxycholecalciferol (VD3) on monocyte (THP-1) adhesion to human umbilical vein endothelial cells (HUVECs) under a pro-inflammatory condition. Endothelial cell activation was induced with tumor necrosis factor-alpha (TNF-α, 100 ng/mL), and cells were treated with VD3 at concentrations ranging from 0.1 to 100 nM. Monocyte adhesion was quantified spectrophotometrically, while levels of vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and cluster of differentiation 15 (CD15) were assessed using ELISA. TNF-α significantly increased THP-1 cell adhesion to HUVECs compared to the control group (p < 0.05). Co-treatment with VD3 at all concentrations tested did not reduce monocyte adhesion, showing levels similar to the TNF-α only group, and significantly higher than the negative control (p < 0.05). Furthermore, TNF-α significantly upregulated VCAM-1 expression (p < 0.05), which was unaffected by VD3. E-selectin and CD15 levels remained unchanged under all experimental conditions. These results do not support a modulatory role for VD3 in the early stages of atherogenesis, specifically in reducing endothelial cell activation and monocyte adhesion. While vitamin D has shown beneficial effects in other aspects of cardiovascular health, its impact on vascular inflammation and adhesion processes remains uncertain and needs further investigation.

维生素D缺乏与心血管危险因素有关，包括内皮功能障碍，这是动脉粥样硬化发病机制的关键步骤。本研究旨在评价促炎条件下1α，25-二羟基胆骨化醇（VD3）对单核细胞（THP-1）粘附人脐静脉内皮细胞（HUVECs）的影响。用肿瘤坏死因子-α （TNF-α, 100 ng/mL）诱导内皮细胞活化，并用浓度为0.1至100 nM的VD3处理细胞。采用分光光度法定量单核细胞粘附，ELISA法检测血管细胞粘附分子1 （VCAM-1）、e -选择素（E-selectin）和CD15 （cluster of differentiation 15）水平。与对照组相比，TNF-α显著增加THP-1细胞对huvec的粘附（p <； 0.05）。与所有测试浓度的VD3共同处理均未降低单核细胞粘附，其水平与仅TNF-α组相似，并显著高于阴性对照组（p <； 0.05）。此外，TNF-α显著上调VCAM-1的表达（p <； 0.05），而VD3不受影响。E-selectin和CD15水平在所有实验条件下均保持不变。这些结果不支持VD3在动脉粥样硬化早期阶段的调节作用，特别是在降低内皮细胞活化和单核细胞粘附方面。虽然维生素D在心血管健康的其他方面显示出有益的作用，但其对血管炎症和粘连过程的影响仍不确定，需要进一步研究。

{"title":"Vitamin D does not mitigate monocyte adhesion to vascular endothelial cells in an in vitro pro-inflammatory model","authors":"Mirko Marino , Samuele Venturi , Peter Møller , Marco Rendine , Daniela Martini , Patrizia Riso , Cristian Del Bo'","doi":"10.1016/j.phanu.2025.100454","DOIUrl":"10.1016/j.phanu.2025.100454","url":null,"abstract":"<div><div>Vitamin D deficiency has been associated with cardiovascular risk factors, including endothelial dysfunction, a critical step in the pathogenesis of atherosclerosis. This study aimed to evaluate the effects of 1α,25-dihydroxycholecalciferol (VD3) on monocyte (THP-1) adhesion to human umbilical vein endothelial cells (HUVECs) under a pro-inflammatory condition. Endothelial cell activation was induced with tumor necrosis factor-alpha (TNF-α, 100 ng/mL), and cells were treated with VD3 at concentrations ranging from 0.1 to 100 nM. Monocyte adhesion was quantified spectrophotometrically, while levels of vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and cluster of differentiation 15 (CD15) were assessed using ELISA. TNF-α significantly increased THP-1 cell adhesion to HUVECs compared to the control group (p < 0.05). Co-treatment with VD3 at all concentrations tested did not reduce monocyte adhesion, showing levels similar to the TNF-α only group, and significantly higher than the negative control (p < 0.05). Furthermore, TNF-α significantly upregulated VCAM-1 expression (p < 0.05), which was unaffected by VD3. E-selectin and CD15 levels remained unchanged under all experimental conditions. These results do not support a modulatory role for VD3 in the early stages of atherogenesis, specifically in reducing endothelial cell activation and monocyte adhesion. While vitamin D has shown beneficial effects in other aspects of cardiovascular health, its impact on vascular inflammation and adhesion processes remains uncertain and needs further investigation.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100454"},"PeriodicalIF":2.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional food prevents diabetic nephropathy in a rat model through inhibition of aldose reductase and accumulation of advanced glycation end-products 功能性食物通过抑制醛糖还原酶和晚期糖基化终产物的积累来预防大鼠模型中的糖尿病肾病

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-29 DOI: 10.1016/j.phanu.2025.100446

Krishna Kalyan Kalahasti, Marka Nagaraju, Sneha Jakhotia, S.Sreenivasa Reddy, G.Bhanuprakash Reddy

Diabetic nephropathy (DN) is a chronic microvascular complication of diabetes mellitus, characterized by glomerulomegaly, podocytopathy, and proteinuria. Among the many molecular mechanisms, accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation and sorbitol accumulation due to increased aldose reductase (AR) activity are implicated in DN. We previously identified some functional foods and their bioactive molecules for inhibitory potential against AGE formation and, AR activity. Based on those studies, in this study, we formulated a functional food (FF) mix- composed of amla, turmeric, cinnamon, ginger, and black pepper in a specific proportion and tested its efficacy against DN in a rat model. Two-month-old Sprague Dawley rats were grouped into control (C), streptozotocin-induced diabetes (D), and diabetes treated with FF at two doses (FF1–0.85 g and FF2–4.25 g/ 100 g diet). The animals were maintained for 20 weeks on respective diets after the induction of diabetes. Elevated serum albumin, creatinine, and urea were observed in the untreated diabetic group compared to the control. These changes were significantly ameliorated by FF supplementation. FF2 showed better efficacy than FF1 in preventing proteinuria, as reflected in the albumin and creatinine ratio. Further, FF prevented diabetes induced AGE accumulation, inflammation, and activation of the polyol pathway in the kidney. The FF decreased the expression of TGF-β in the diabetic kidney and prevented fibrotic changes. Most importantly, FF prevented the depletion of podocyte slit diaphragm proteins and histological changes. These results provide a mechanistic basis of FF and its potential against progression of DN in a rat model.

糖尿病肾病（DN）是糖尿病的一种慢性微血管并发症，以肾小球肿大、足细胞病和蛋白尿为特征。在许多分子机制中，非酶糖基化引起的晚期糖基化终产物（AGEs）的积累和醛糖还原酶（AR）活性增加引起的山梨醇积累与DN有关。我们之前已经确定了一些功能食品及其生物活性分子对AGE形成和AR活性的抑制潜力。在此基础上，本研究配制了一种由amla、姜黄、肉桂、生姜和黑胡椒按一定比例组成的功能食品（FF）混合物，并在大鼠模型上测试了其抗DN的功效。2月龄Sprague Dawley大鼠分为对照组(C)、链脲佐菌素诱导糖尿病组(D)和两种剂量FF （FF1-0.85 g和FF2-4.25 g/ 100 g日粮）治疗糖尿病组。诱导糖尿病后，各组分别饲喂不同的饲料，饲养20周。与对照组相比，未经治疗的糖尿病组血清白蛋白、肌酐和尿素升高。这些变化在补充FF后得到显著改善。FF2在预防蛋白尿方面的效果优于FF1，这可以从白蛋白和肌酐比值中体现出来。此外，FF还能预防糖尿病诱导的AGE积累、炎症和肾脏多元醇途径的激活。FF可降低糖尿病肾组织TGF-β的表达，防止纤维化改变。最重要的是，FF阻止足细胞狭缝膜蛋白的消耗和组织学改变。这些结果提供了FF的机制基础及其在大鼠模型中抗DN进展的潜力。

{"title":"Functional food prevents diabetic nephropathy in a rat model through inhibition of aldose reductase and accumulation of advanced glycation end-products","authors":"Krishna Kalyan Kalahasti, Marka Nagaraju, Sneha Jakhotia, S.Sreenivasa Reddy, G.Bhanuprakash Reddy","doi":"10.1016/j.phanu.2025.100446","DOIUrl":"10.1016/j.phanu.2025.100446","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is a chronic microvascular complication of diabetes mellitus, characterized by glomerulomegaly, podocytopathy, and proteinuria. Among the many molecular mechanisms, accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation and sorbitol accumulation due to increased aldose reductase (AR) activity are implicated in DN. We previously identified some functional foods and their bioactive molecules for inhibitory potential against AGE formation and, AR activity. Based on those studies, in this study, we formulated a functional food (FF) mix- composed of amla, turmeric, cinnamon, ginger, and black pepper in a specific proportion and tested its efficacy against DN in a rat model. Two-month-old Sprague Dawley rats were grouped into control (C), streptozotocin-induced diabetes (D), and diabetes treated with FF at two doses (FF1–0.85 g and FF2–4.25 g/ 100 g diet). The animals were maintained for 20 weeks on respective diets after the induction of diabetes. Elevated serum albumin, creatinine, and urea were observed in the untreated diabetic group compared to the control. These changes were significantly ameliorated by FF supplementation. FF2 showed better efficacy than FF1 in preventing proteinuria, as reflected in the albumin and creatinine ratio. Further, FF prevented diabetes induced AGE accumulation, inflammation, and activation of the polyol pathway in the kidney. The FF decreased the expression of TGF-β in the diabetic kidney and prevented fibrotic changes. Most importantly, FF prevented the depletion of podocyte slit diaphragm proteins and histological changes. These results provide a mechanistic basis of FF and its potential against progression of DN in a rat model.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"33 ","pages":"Article 100446"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced therapeutic efficacy of nanocurcumin over free curcumin in the management of diabetes mellitus 纳米姜黄素治疗糖尿病的疗效优于游离姜黄素

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-29 DOI: 10.1016/j.phanu.2025.100445

Pratibha Chauhan , GBKS Prasad

Objectives

Numerous scientific studies have revealed that curcumin is a pleiotropic molecule and influences multiple signaling pathways but is rapidly eliminated from the body due to its poor bioavailability. In the present study, nanocurcumin was synthesized and evaluated the therapeutic efficacy of nanocurcuminin comparison to those of free curcumin in human subjects with type II diabetes mellitus.

Design

Curcumin nanoparticles (NPs) have been synthesized then analyzed employing particle size analyzer and X-ray diffraction, while therapeutic efficacy of nanocurcumin has been assessed by evaluating blood glucose level (BGL), lipid profiles, as well as oxidative stress markers. This randomized trial included subjects (n = 60) with criteria of type II diabetes mellitus(T2DM). Subjects had been allocated randomly for receiving either curcumin or nanocurcumin capsules (1000 mg/day and 600 mg/day, accordingly) for 12 weeks. Nanocurcumin capsules' therapeutic function has been investigated by monitoring blood glucose, lipid profile, oxidative stress biomarkers, and glycosylated hemoglobin, along with DNA damage, prior to and after therapy.

Results

Particle size analysis indicated an average particle size of 78 nm of nanocurcumin. 'Nanocurcumin capsules' daily administration for 12 weeks drastically reduced BGLs. Compared to free curcumin, nanocurcumin exhibited a markedly enhanced antihyperglycemic effect. It could additionally preserve lipid homeostasis. Subject demonstrated improvements in enzymatic as well as non-enzymatic biochemical indicators of oxidative stress. When compared directly with free curcumin, nanocurcumin proved to be a more effective antioxidant, indicating enhanced bioavailability and efficacy in mitigating oxidative damage.

Conclusion

Current research results demonstrated ‘Nanocurcumin capsules’ anti-hyperglycemic, anti-hyperlipidemic and anti-oxidative potential in subjects with diabetes mellitus (DM). Nanocurcumin therapeutic potential had been prominent than curcumin.

目的大量科学研究表明，姜黄素是一种多效性分子，可影响多种信号通路，但由于其生物利用度差，可迅速从体内清除。本研究合成了纳米姜黄素，并比较了纳米姜黄素与游离姜黄素对2型糖尿病患者的治疗效果。合成了设计型姜黄素纳米颗粒（NPs），采用粒径分析仪和x射线衍射仪对其进行了分析，并通过血糖、血脂和氧化应激指标评价了纳米姜黄素的治疗效果。该随机试验纳入了符合2型糖尿病（T2DM）标准的受试者（n = 60）。受试者被随机分配接受姜黄素或纳米姜黄素胶囊（分别为1000 mg/天和600 mg/天），为期12周。通过监测治疗前后的血糖、血脂、氧化应激生物标志物、糖化血红蛋白以及DNA损伤，研究了纳米姜黄素胶囊的治疗功能。结果粒径分析表明，纳米姜黄素的平均粒径为78 nm。每天服用“纳米姜黄素胶囊”12周，可显著降低bgl。与游离姜黄素相比，纳米姜黄素表现出明显增强的降糖作用。此外，它还能保持脂质稳态。受试者表现出氧化应激的酶和非酶生化指标的改善。与游离姜黄素相比，纳米姜黄素是一种更有效的抗氧化剂，具有更高的生物利用度和减轻氧化损伤的功效。结论纳米姜黄素胶囊对糖尿病患者具有抗高血糖、抗高脂血症和抗氧化作用。纳米姜黄素的治疗潜力比姜黄素更突出。

{"title":"Enhanced therapeutic efficacy of nanocurcumin over free curcumin in the management of diabetes mellitus","authors":"Pratibha Chauhan , GBKS Prasad","doi":"10.1016/j.phanu.2025.100445","DOIUrl":"10.1016/j.phanu.2025.100445","url":null,"abstract":"<div><h3>Objectives</h3><div>Numerous scientific studies have revealed that curcumin is a pleiotropic molecule and influences multiple signaling pathways but is rapidly eliminated from the body due to its poor bioavailability. In the present study, nanocurcumin was synthesized and evaluated the therapeutic efficacy of nanocurcuminin comparison to those of free curcumin in human subjects with type II diabetes mellitus.</div></div><div><h3>Design</h3><div>Curcumin nanoparticles (NPs) have been synthesized then analyzed employing particle size analyzer and X-ray diffraction, while therapeutic efficacy of nanocurcumin has been assessed by evaluating blood glucose level (BGL), lipid profiles, as well as oxidative stress markers. This randomized trial included subjects (n = 60) with criteria of type II diabetes mellitus(T2DM). Subjects had been allocated randomly for receiving either curcumin or nanocurcumin capsules (1000 mg/day and 600 mg/day, accordingly) for 12 weeks. Nanocurcumin capsules' therapeutic function has been investigated by monitoring blood glucose, lipid profile, oxidative stress biomarkers, and glycosylated hemoglobin, along with DNA damage, prior to and after therapy.</div></div><div><h3>Results</h3><div>Particle size analysis indicated an average particle size of 78 nm of nanocurcumin. 'Nanocurcumin capsules' daily administration for 12 weeks drastically reduced BGLs. Compared to free curcumin, nanocurcumin exhibited a markedly enhanced antihyperglycemic effect. It could additionally preserve lipid homeostasis. Subject demonstrated improvements in enzymatic as well as non-enzymatic biochemical indicators of oxidative stress. When compared directly with free curcumin, nanocurcumin proved to be a more effective antioxidant, indicating enhanced bioavailability and efficacy in mitigating oxidative damage.</div></div><div><h3>Conclusion</h3><div>Current research results demonstrated ‘Nanocurcumin capsules’ anti-hyperglycemic, anti-hyperlipidemic and anti-oxidative potential in subjects with diabetes mellitus (DM). Nanocurcumin therapeutic potential had been prominent than curcumin.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"33 ","pages":"Article 100445"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The regulation of gut microbiota and urate lowering: A study on the mechanisms of action of probiotics and plant components 肠道菌群调节和尿酸降低：益生菌和植物成分作用机制的研究

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-25 DOI: 10.1016/j.phanu.2025.100450

Zhihua Xing , Yue Xu , Wen Jiang , Mingyu Gao , Guanghuan Shen , Yingjie Liu , Na Ling , Linlin Cui

The gut microbiota system serves as a "barometer" of human health, with significant differences observed in the intestinal microbiome between individuals with hyperuricemia (HUA) and gout compared to those in the general population. This article comprehensively reviews the correlation between gut microbiota and HUA and uric acid-lowering substances that regulate the gut microbiota. It elucidates the mechanisms underlying the occurrence and progression of HUA associated with the gut microbiota. It summarizes the effects and mechanisms through which probiotics, plant polysaccharides, and plant small molecular compounds reduce serum uric acid by modulating the gut microbiota. It is hoped that this review will provide a theoretical basis for the development of strategies for uric acid-lowering drugs targeting the gut microbiota, serving as a reference for subsequent in-depth research.

肠道菌群系统是人类健康的“晴雨表”，与普通人群相比，高尿酸血症（HUA）和痛风患者的肠道菌群存在显著差异。本文全面综述了肠道菌群与HUA和调节肠道菌群的降尿酸物质之间的关系。它阐明了与肠道微生物群相关的HUA发生和进展的机制。综述了益生菌、植物多糖和植物小分子化合物通过调节肠道菌群来降低血清尿酸的作用及其机制。希望本综述能为针对肠道菌群的降尿酸药物策略的制定提供理论依据，为后续的深入研究提供参考。

引用次数: 0

Flavonoids and macrophage polarization: Key players in the immunomodulation of cardiometabolic syndrome and related therapies 黄酮类化合物和巨噬细胞极化：心脏代谢综合征免疫调节和相关治疗的关键参与者

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-25 DOI: 10.1016/j.phanu.2025.100449

Parisa Ahmadi , Soroush Taherkhani , Maryam Honardoost , Atousa Janzadeh

Cardiometabolic syndrome (CMS) is a major public health challenge characterized by obesity, insulin resistance, hypertension, and chronic inflammation, which increase the risk of type 2 diabetes (T2D) and cardiovascular disease. In this context, inflammatory M1 macrophages are pivotal, as they produce proinflammatory cytokines and contribute to oxidative stress, insulin resistance, and lipid accumulation in adipose tissue. Polyphenols with anti-inflammatory, antioxidant, and antiobesity properties alleviate CMS by promoting M2 macrophage differentiation and reprogramming M1 macrophages toward the M2 phenotype. Flavonoids inhibit inflammatory pathways such as NF-kB and activator protein-1 (AP-1); reduce the expression of proinflammatory markers such as TLR4, NOD-like receptor family pyrin domain-containing 3 (NLRP-3), and inducible nitric oxide synthase (iNOS); and enhance anti-inflammatory responses, including IL-10, Nrf-1, and peroxisome proliferator-activated receptor (PPAR) expression. They prevent foam cell formation by decreasing LPX-1, CD36, scavenger receptor-A, B1, and LOX-1 expression while increasing ABCA1 and ABCG1 levels. Flavonoids are antiobesity agents that decrease the infiltration of macrophages in adipose tissue and suppress the M1 phenotype in adipose tissue macrophages, lowering inflammation and leading to the suppression of lipogenesis and stimulation of lipolysis in adipocytes. This review highlights the importance of macrophage activation in metabolic imbalance and the potential of flavonoids in treating CMS through the induction of M2 macrophages.

心血管代谢综合征（CMS）是一个主要的公共卫生挑战，其特征是肥胖、胰岛素抵抗、高血压和慢性炎症，增加了2型糖尿病（T2D）和心血管疾病的风险。在这种情况下，炎性M1巨噬细胞是关键，因为它们产生促炎细胞因子，并有助于氧化应激、胰岛素抵抗和脂肪组织中的脂质积累。具有抗炎、抗氧化和抗肥胖特性的多酚通过促进M2巨噬细胞分化和将M1巨噬细胞重编程为M2表型来缓解CMS。黄酮类化合物抑制NF-kB和激活蛋白-1 （AP-1）等炎症通路；降低促炎标志物TLR4、nod样受体家族pyrin - domain-containing 3 （NLRP-3）、诱导型一氧化氮合酶（iNOS）的表达；并增强抗炎反应，包括IL-10、Nrf-1和过氧化物酶体增殖物激活受体（PPAR）的表达。它们通过降低LPX-1、CD36、清扫剂受体a、B1和LOX-1的表达，同时增加ABCA1和ABCG1的水平，从而阻止泡沫细胞的形成。类黄酮是一种抗肥胖药物，可减少脂肪组织中巨噬细胞的浸润，抑制脂肪组织巨噬细胞的M1表型，降低炎症，抑制脂肪细胞的脂肪生成和刺激脂肪分解。本文综述了巨噬细胞激活在代谢失衡中的重要性，以及黄酮类化合物通过诱导M2巨噬细胞治疗CMS的潜力。

{"title":"Flavonoids and macrophage polarization: Key players in the immunomodulation of cardiometabolic syndrome and related therapies","authors":"Parisa Ahmadi , Soroush Taherkhani , Maryam Honardoost , Atousa Janzadeh","doi":"10.1016/j.phanu.2025.100449","DOIUrl":"10.1016/j.phanu.2025.100449","url":null,"abstract":"<div><div>Cardiometabolic syndrome (CMS) is a major public health challenge characterized by obesity, insulin resistance, hypertension, and chronic inflammation, which increase the risk of type 2 diabetes (T2D) and cardiovascular disease. In this context, inflammatory M1 macrophages are pivotal, as they produce proinflammatory cytokines and contribute to oxidative stress, insulin resistance, and lipid accumulation in adipose tissue. Polyphenols with anti-inflammatory, antioxidant, and antiobesity properties alleviate CMS by promoting M2 macrophage differentiation and reprogramming M1 macrophages toward the M2 phenotype. Flavonoids inhibit inflammatory pathways such as NF-kB and activator protein-1 (AP-1); reduce the expression of proinflammatory markers such as TLR4, NOD-like receptor family pyrin domain-containing 3 (NLRP-3), and inducible nitric oxide synthase (iNOS); and enhance anti-inflammatory responses, including IL-10, Nrf-1, and peroxisome proliferator-activated receptor (PPAR) expression. They prevent foam cell formation by decreasing LPX-1, CD36, scavenger receptor-A, B1, and LOX-1 expression while increasing ABCA1 and ABCG1 levels. Flavonoids are antiobesity agents that decrease the infiltration of macrophages in adipose tissue and suppress the M1 phenotype in adipose tissue macrophages, lowering inflammation and leading to the suppression of lipogenesis and stimulation of lipolysis in adipocytes. This review highlights the importance of macrophage activation in metabolic imbalance and the potential of flavonoids in treating CMS through the induction of M2 macrophages.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"33 ","pages":"Article 100449"},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hesperetin as a potential therapeutic agent for colorectal cancer: Targeting PI3K/AKT and EMT in cell lines through network pharmacology-guided strategies 橙皮苷作为结直肠癌的潜在治疗剂：通过网络药理学引导策略靶向细胞系中的PI3K/AKT和EMT

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-24 DOI: 10.1016/j.phanu.2025.100447

Junyi Xue , Jianmin Liao , Haixing Ju , Yuanyuan Lu

Hesperetin is a naturally occurring flavonoid compound abundantly present in citrus fruit peels and Traditional Chinese Medicinal (TCM). It exhibits diverse pharmacological properties and represents a promising multi-target candidate for anticancer therapy. This study systematically investigated the molecular mechanisms underlying the anti-colorectal cancer (CRC) effects of hesperetin by integrating network pharmacology, molecular docking, and experimental validation. Network pharmacology analysis identified 42 core targets of hesperetin in CRC, with molecular docking confirming strong binding affinities (binding energy < −7 kcal/mol) between hesperetin and key proteins, including Epidermal Growth Factor Receptor (EGFR), Threonine Kinase 1 (AKT1), Proto-oncogene Tyrosine-protein Kinase Src (SRC), Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), and Matrix Metalloproteinase-9 (MMP9). In vitro experiments demonstrated that hesperetin dose-dependently inhibited the proliferation, migration, and invasion of HCT116 and Lovo cells. Mechanistically, hesperetin reversed epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating N-cadherin, Vimentin, and Snail at both protein and mRNA levels. Western blot analysis revealed that hesperetin suppressed PI3K/AKT pathway activation by reducing phosphorylation of PI3K (Tyr458) and AKT (Ser473). Clinical data further validated the therapeutic relevance of these targets, showing that high expression of EGFR, AKT1, PIK3CA, and MMP9 correlated with poor prognosis in CRC patients. Collectively, these findings establish hesperetin as a promising multi-target nutritional supplement agent against CRC, demonstrating dual modulation of both PI3K/AKT signaling and EMT progression.

橙皮素是一种天然存在的类黄酮化合物，大量存在于柑橘类水果果皮和传统中药中。它具有多种药理特性，是一种很有前途的抗癌多靶点候选药物。本研究通过网络药理学、分子对接和实验验证相结合，系统探讨橙皮苷抗结直肠癌（CRC）作用的分子机制。网络药理学分析鉴定出42个橙皮素在结直肠癌中的核心靶点，分子对接证实了较强的结合亲和力(结合能<；−7 kcal/mol)，包括表皮生长因子受体（EGFR）、苏氨酸激酶1 （AKT1）、原癌基因酪氨酸蛋白激酶Src （Src）、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α (PIK3CA)和基质金属蛋白酶-9 （MMP9）。体外实验表明橙皮苷能剂量依赖性地抑制HCT116和Lovo细胞的增殖、迁移和侵袭。在机制上，橙皮素通过上调E-cadherin和下调N-cadherin、Vimentin和Snail蛋白和mRNA水平逆转上皮-间质转化（EMT）。Western blot分析显示，橙皮素通过降低PI3K （Tyr458）和AKT （Ser473）的磷酸化来抑制PI3K/AKT通路的激活。临床数据进一步验证了这些靶点的治疗相关性，表明EGFR、AKT1、PIK3CA和MMP9的高表达与CRC患者的不良预后相关。综上所述，这些研究结果表明橙皮苷是一种很有前景的多靶点营养补充剂，可用于治疗结直肠癌，并显示PI3K/AKT信号通路和EMT进展的双重调节。

{"title":"Hesperetin as a potential therapeutic agent for colorectal cancer: Targeting PI3K/AKT and EMT in cell lines through network pharmacology-guided strategies","authors":"Junyi Xue , Jianmin Liao , Haixing Ju , Yuanyuan Lu","doi":"10.1016/j.phanu.2025.100447","DOIUrl":"10.1016/j.phanu.2025.100447","url":null,"abstract":"<div><div>Hesperetin is a naturally occurring flavonoid compound abundantly present in citrus fruit peels and Traditional Chinese Medicinal (TCM). It exhibits diverse pharmacological properties and represents a promising multi-target candidate for anticancer therapy. This study systematically investigated the molecular mechanisms underlying the anti-colorectal cancer (CRC) effects of hesperetin by integrating network pharmacology, molecular docking, and experimental validation. Network pharmacology analysis identified 42 core targets of hesperetin in CRC, with molecular docking confirming strong binding affinities (binding energy < −7 kcal/mol) between hesperetin and key proteins, including Epidermal Growth Factor Receptor (EGFR), Threonine Kinase 1 (AKT1), Proto-oncogene Tyrosine-protein Kinase Src (SRC), Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), and Matrix Metalloproteinase-9 (MMP9). In vitro experiments demonstrated that hesperetin dose-dependently inhibited the proliferation, migration, and invasion of HCT116 and Lovo cells. Mechanistically, hesperetin reversed epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating N-cadherin, Vimentin, and Snail at both protein and mRNA levels. Western blot analysis revealed that hesperetin suppressed PI3K/AKT pathway activation by reducing phosphorylation of PI3K (Tyr458) and AKT (Ser473). Clinical data further validated the therapeutic relevance of these targets, showing that high expression of EGFR, AKT1, PIK3CA, and MMP9 correlated with poor prognosis in CRC patients. Collectively, these findings establish hesperetin as a promising multi-target nutritional supplement agent against CRC, demonstrating dual modulation of both PI3K/AKT signaling and EMT progression.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"33 ","pages":"Article 100447"},"PeriodicalIF":2.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotective potential of saffron metabolites in Parkinson's disease 藏红花代谢物对帕金森病的神经保护作用

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-07-24 DOI: 10.1016/j.phanu.2025.100448

Mohamed Ben El Caid , Mohamed Ait Haddou , Ouahid El Asri , Laila Aboudlou , Lalla Hadda Atyane , Vikas Ramteke , Rachid Ait Hammou

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Although current pharmaceutical treatments mitigate symptoms, these frequently induce adverse effects and may not prevent disease progression, highlighting the need for safer neuroprotective alternatives. Natural products like saffron (Crocus sativus L.) have emerged as promising candidates due to their pharmacological and nutritional properties. While prior studies have investigated saffron and its extracts in the context of PD, no review has comprehensively analyzed the specific roles of its major secondary metabolites. Saffron’s bioactive compounds, particularly crocetin, crocins, and safranal, have demonstrated significant therapeutic potential across in vitro, in vivo, and clinical studies. Crocetin has been shown to inhibit α-synuclein aggregation and preserve mitochondrial integrity. Crocins exhibit neuroprotective effects, including inhibition of amyloid fibril formation, protection of dopaminergic neurons, and enhancement of synaptic plasticity through pathways such as PI3K/Akt/mTOR. Notably, picrocrocin remains unstudied mainly, representing a significant research gap. Safranal has shown efficacy in preclinical PD models, with promising effects on dopaminergic neuron preservation, motor function improvement, and apoptosis regulation. However, clinical trials are warranted to validate its therapeutic potential further. This review highlights existing findings, critically examines the literature, and identifies underexplored mechanisms, including neurotrophic and mitochondrial pathways, as promising targets for future research, ultimately paving the way for innovative therapeutic strategies in PD management.

帕金森病（PD）是一种以多巴胺能神经元逐渐丧失为特征的衰弱性神经退行性疾病。虽然目前的药物治疗减轻了症状，但这些治疗经常引起不良反应，可能无法预防疾病进展，因此需要更安全的神经保护替代品。藏红花（Crocus sativus L.）等天然产品由于其药理和营养特性而成为有希望的候选者。虽然已有研究对藏红花及其提取物在帕金森病中的作用进行了研究，但尚未有文献对其主要次生代谢产物的具体作用进行全面分析。藏红花的生物活性化合物，特别是藏红花素、藏红花素和藏红花醛，已经在体外、体内和临床研究中显示出显著的治疗潜力。Crocetin抑制α-synuclein聚集并保持线粒体完整性。藏蜂素具有神经保护作用，包括抑制淀粉样蛋白纤维的形成，保护多巴胺能神经元，并通过PI3K/Akt/mTOR等通路增强突触可塑性。值得注意的是，微芥子素的研究仍处于空白状态，研究空白很大。Safranal在临床前PD模型中显示出疗效，在多巴胺能神经元保存、运动功能改善和细胞凋亡调节方面具有良好的作用。然而，临床试验需要进一步验证其治疗潜力。这篇综述强调了现有的发现，批判性地检查了文献，并确定了未被探索的机制，包括神经营养和线粒体途径，作为未来研究的有希望的目标，最终为PD治疗的创新治疗策略铺平了道路。

{"title":"Neuroprotective potential of saffron metabolites in Parkinson's disease","authors":"Mohamed Ben El Caid , Mohamed Ait Haddou , Ouahid El Asri , Laila Aboudlou , Lalla Hadda Atyane , Vikas Ramteke , Rachid Ait Hammou","doi":"10.1016/j.phanu.2025.100448","DOIUrl":"10.1016/j.phanu.2025.100448","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Although current pharmaceutical treatments mitigate symptoms, these frequently induce adverse effects and may not prevent disease progression, highlighting the need for safer neuroprotective alternatives. Natural products like saffron (<em>Crocus sativus</em> L.) have emerged as promising candidates due to their pharmacological and nutritional properties. While prior studies have investigated saffron and its extracts in the context of PD, no review has comprehensively analyzed the specific roles of its major secondary metabolites. Saffron’s bioactive compounds, particularly crocetin, crocins, and safranal, have demonstrated significant therapeutic potential across <em>in vitro</em>, <em>in vivo</em>, and clinical studies. Crocetin has been shown to inhibit α-synuclein aggregation and preserve mitochondrial integrity. Crocins exhibit neuroprotective effects, including inhibition of amyloid fibril formation, protection of dopaminergic neurons, and enhancement of synaptic plasticity through pathways such as PI3K/Akt/mTOR. Notably, picrocrocin remains unstudied mainly, representing a significant research gap. Safranal has shown efficacy in preclinical PD models, with promising effects on dopaminergic neuron preservation, motor function improvement, and apoptosis regulation. However, clinical trials are warranted to validate its therapeutic potential further. This review highlights existing findings, critically examines the literature, and identifies underexplored mechanisms, including neurotrophic and mitochondrial pathways, as promising targets for future research, ultimately paving the way for innovative therapeutic strategies in PD management.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"33 ","pages":"Article 100448"},"PeriodicalIF":2.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

L-Arginine mitigates high glucose-induced podocyte injury via NRF2 pathway activation l -精氨酸通过激活NRF2通路减轻高糖诱导的足细胞损伤

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-03-01 DOI: 10.1016/j.phanu.2025.100439

Xiandeng Li , Huiting Chen , Hang Han, Guojiang Zhang, Xiao Zhang, Qinjian Zhao

L-Arginine, a semi-essential amino acid involved in the ornithine cycle, exhibits therapeutic potential in diabetes through benefits demonstrated in both animal models and human studies. However, the precise mechanisms underlying its effects remain incompletely understood. Podocytes play a crucial role in the pathogenesis of diabetic nephropathy (DN), with podocyte injury contributing significantly to disease progression. In this study, we demonstrated that L-arginine treatment improved podocyte viability, decreased oxidative stress and inflammation markers, and upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression and its nuclear translocation, along with its downstream antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), in a dose-dependent manner. Importantly, these protective effects were reversed by the NRF2 inhibitor ML385 and Nrf2 RNA interference (RNAi), suggesting that L-arginine’s protective mechanism is likely mediated through the NRF2 pathway. These findings emphasize the potential of L-arginine as a therapeutic agent for DN by protecting podocytes from high glucose-induced oxidative stress and injury.

l -精氨酸是一种参与鸟氨酸循环的半必需氨基酸，在动物模型和人体研究中都显示出治疗糖尿病的潜力。然而，其作用背后的确切机制仍不完全清楚。足细胞在糖尿病肾病（DN）的发病机制中起着至关重要的作用，足细胞损伤对疾病进展起着重要作用。在这项研究中，我们证明了l -精氨酸处理提高足细胞活力，降低氧化应激和炎症标志物，上调核因子红细胞2相关因子2 （NRF2）表达及其核易位，以及其下游抗氧化酶，血红素加氧酶-1 （HO-1）和NAD(P)H醌脱氢酶1 (NQO1)，并呈剂量依赖性。重要的是，这些保护作用被NRF2抑制剂ML385和NRF2 RNA干扰（RNAi）逆转，这表明l -精氨酸的保护机制可能是通过NRF2途径介导的。这些发现强调了l -精氨酸通过保护足细胞免受高糖诱导的氧化应激和损伤而作为DN治疗剂的潜力。

{"title":"L-Arginine mitigates high glucose-induced podocyte injury via NRF2 pathway activation","authors":"Xiandeng Li , Huiting Chen , Hang Han, Guojiang Zhang, Xiao Zhang, Qinjian Zhao","doi":"10.1016/j.phanu.2025.100439","DOIUrl":"10.1016/j.phanu.2025.100439","url":null,"abstract":"<div><div>L-Arginine, a semi-essential amino acid involved in the ornithine cycle, exhibits therapeutic potential in diabetes through benefits demonstrated in both animal models and human studies. However, the precise mechanisms underlying its effects remain incompletely understood. Podocytes play a crucial role in the pathogenesis of diabetic nephropathy (DN), with podocyte injury contributing significantly to disease progression. In this study, we demonstrated that L-arginine treatment improved podocyte viability, decreased oxidative stress and inflammation markers, and upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression and its nuclear translocation, along with its downstream antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), in a dose-dependent manner. Importantly, these protective effects were reversed by the NRF2 inhibitor ML385 and <em>Nrf2</em> RNA interference (RNAi), suggesting that L-arginine’s protective mechanism is likely mediated through the NRF2 pathway. These findings emphasize the potential of L-arginine as a therapeutic agent for DN by protecting podocytes from high glucose-induced oxidative stress and injury.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"31 ","pages":"Article 100439"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opportunities and challenges associated with rheumatoid arthritis: The role of natural polyphenol products 与类风湿性关节炎相关的机遇和挑战：天然多酚产品的作用

IF 2.4 Q3 NUTRITION & DIETETICS

PharmaNutrition

Pub Date : 2025-02-24 DOI: 10.1016/j.phanu.2025.100438

Kai Chen , Hua Zhang , Qinwei Fu , Chunli Wu , Jianlin Wu

RA is a chronic inflammatory disease commonly found in industrialized nations, characterized by ongoing joint destruction. Its pathogenesis involves a complex interaction between the innate and adaptive immune systems, resulting in the excessive production of inflammatory mediators. These mediators contribute to various chronic diseases, including RA, which necessitates drug interventions to regulate their release. Herbal plants have historically been a rich source of bioactive compounds with therapeutic potential, many of which are now widely used as medications. Treatments for RA focus on inhibiting oxidative stress, downregulating pro-inflammatory cytokines such as IL-1, IL-6, TNF-α, and NF-κB, suppressing matrix metalloproteinases that damage cartilage, enhancing antioxidant activity, and modulating macrophage phenotypes. Flavonoids, a subclass of polyphenols, stand out for their antioxidant and anti-inflammatory properties. They help alleviate RA by inhibiting the production of inflammatory cytokines, reducing oxidative stress, suppressing the proliferation of lymphocytes and synovial cells, inducing apoptosis, and regulating energy metabolism. This review emphasizes the potential of natural polyphenols, primarily flavonoids, as promising candidates for RA treatment, providing insights into their mechanisms and the prospects for future drug development.

类风湿性关节炎是一种常见于工业化国家的慢性炎症性疾病，其特征是持续的关节破坏。其发病机制涉及先天免疫系统和适应性免疫系统之间复杂的相互作用，导致炎症介质的过量产生。这些介质有助于各种慢性疾病，包括类风湿性关节炎，这需要药物干预来调节其释放。草本植物历来是具有治疗潜力的生物活性化合物的丰富来源，其中许多现在被广泛用作药物。RA的治疗重点是抑制氧化应激，下调IL-1、IL-6、TNF-α和NF-κB等促炎细胞因子，抑制损伤软骨的基质金属蛋白酶，增强抗氧化活性，调节巨噬细胞表型。黄酮类化合物是多酚的一个亚类，具有抗氧化和抗炎的特性。它们通过抑制炎症细胞因子的产生、减少氧化应激、抑制淋巴细胞和滑膜细胞的增殖、诱导细胞凋亡和调节能量代谢来帮助缓解RA。这篇综述强调了天然多酚，主要是黄酮类化合物，作为RA治疗的有希望的候选者的潜力，提供了对其机制的见解和未来药物开发的前景。

{"title":"Opportunities and challenges associated with rheumatoid arthritis: The role of natural polyphenol products","authors":"Kai Chen , Hua Zhang , Qinwei Fu , Chunli Wu , Jianlin Wu","doi":"10.1016/j.phanu.2025.100438","DOIUrl":"10.1016/j.phanu.2025.100438","url":null,"abstract":"<div><div>RA is a chronic inflammatory disease commonly found in industrialized nations, characterized by ongoing joint destruction. Its pathogenesis involves a complex interaction between the innate and adaptive immune systems, resulting in the excessive production of inflammatory mediators. These mediators contribute to various chronic diseases, including RA, which necessitates drug interventions to regulate their release. Herbal plants have historically been a rich source of bioactive compounds with therapeutic potential, many of which are now widely used as medications. Treatments for RA focus on inhibiting oxidative stress, downregulating pro-inflammatory cytokines such as IL-1, IL-6, TNF-α, and NF-κB, suppressing matrix metalloproteinases that damage cartilage, enhancing antioxidant activity, and modulating macrophage phenotypes. Flavonoids, a subclass of polyphenols, stand out for their antioxidant and anti-inflammatory properties. They help alleviate RA by inhibiting the production of inflammatory cytokines, reducing oxidative stress, suppressing the proliferation of lymphocytes and synovial cells, inducing apoptosis, and regulating energy metabolism. This review emphasizes the potential of natural polyphenols, primarily flavonoids, as promising candidates for RA treatment, providing insights into their mechanisms and the prospects for future drug development.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"32 ","pages":"Article 100438"},"PeriodicalIF":2.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0