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Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization. Anthocran®Phytosome®:预防尿路感染和尿路导尿后的症状。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 DOI: 10.1080/19390211.2021.1972074
Roberto Cotellese, Andrea Ledda, Gianni Belcaro, Maria R Cesarone, Claudia Scipione, Valeria Scipione, Mark Dugall, Beatrice Feragalli, Antonella Riva, Pietro Allegrini, Giovanna Petrangolini, Stefano Togni

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

在这项初步的试点注册研究中,我们研究了通过卵磷脂为基础的系统口服补充标准蔓越莓提取物(Anthocran®Phytosome®,Indena)对预防复发性尿路感染(r - uti)的影响。我们纳入了64名其他方面健康的受试者,他们接受了外科手术,并因高风险uti或既往r - uti病史而需要术后导尿。患者以120 mg/天(n = 12)或240 mg/天(n = 12)的剂量补充标准蔓越莓提取物,或被分配到由标准管理(SM;N = 18)或呋喃妥因(N = 22)治疗4周。4周后,与SM组或呋喃妥因组相比,接受标准化蔓越莓补充剂的患者在视觉模拟量表上的UTI症状有更有效的减轻。与对照组相比,服用补品的患者血尿和尿液细菌污染发生率降低(p < 0.05)
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引用次数: 3
Qualifications and Competence to Prescribe Dietary Supplements: Perception of Fitness Instructors. 处方膳食补充剂的资格和能力:健身教练的看法。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 DOI: 10.1080/19390211.2021.1963025
Dina A M Miragaia, Monique N P Trindade, Carla A B Pereira

This research aims to understand fitness instructors and personal trainers' perception of their qualifications and competence to prescribe dietary supplements. To this end, a questionnaire was applied to 154 fitness instructors and personal trainers with professional functions in health clubs/gyms. The results obtained show that the sale of these products in gyms is seen as stimulating their consumption and that most fitness professionals consider professionals in this area do not have competence to prescribe this type of service. The lack of confidence about knowledge of dietary supplements; degree courses with a weak curriculum in this domain; and the shortage of curricular units related to dietary supplements are possible reasons for these professionals not feeling sure about giving advice on this matter. Regarding ways of updating knowledge, although these professionals consider academic journals, conferences, congresses and nutrition courses as the most reliable sources of information, they resort more frequently to the Internet, despite considering this source as the least reliable. These results can have direct implications for various stakeholders, particularly for consumers to be more informed about the risks involved in consuming dietary supplements without due orientation; for fitness professionals who have little knowledge about this type of substance; for gym managers who need to understand the implications of selling this type of product in their establishments; for teaching institutions, who should reflect on, and organize their academic curricula in order to provide sufficient grounding for fitness professionals to feel safe and confident about their knowledge in this area; and for the producers of these products, in order to improve information about, and the safety of the substances they put on the market.

本研究旨在了解健身教练和私人教练对他们开具膳食补充剂的资格和能力的看法。为此目的,对154名在健身俱乐部/健身房具有专业职能的健身教练和私人教练进行了问卷调查。结果表明,在健身房销售这些产品被认为是刺激了他们的消费,大多数健身专业人士认为这一领域的专业人士没有能力规定这类服务。对膳食补充剂知识缺乏信心;该领域课程薄弱的学位课程;与膳食补充剂相关的课程单元的短缺可能是这些专业人士对在这个问题上给出建议感到不确定的原因。关于更新知识的方式,尽管这些专业人士认为学术期刊、会议、大会和营养课程是最可靠的信息来源,但他们更频繁地求助于互联网,尽管他们认为这是最不可靠的来源。这些结果可以对各种利益相关者产生直接影响,特别是对消费者来说,在没有适当指导的情况下,他们更了解摄入膳食补充剂的风险;对于对这类物质知之甚少的健身专业人士;对于需要了解在其场所销售此类产品的含义的健身房经理;对于教学机构来说,他们应该反思并组织他们的学术课程,为健身专业人士提供足够的基础,让他们对自己在这方面的知识感到安全和自信;对于这些产品的生产商来说,为了提高他们投放市场的物质的信息和安全性。
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引用次数: 5
Effect of Tribulus terrestris L. supplementation on Exercise-Induced Oxidative Stress and Delayed Onset Muscle Soreness Markers: A Pilot Study. 补充Tributus terrestris L.对运动诱导的氧化应激和延迟性肌肉酸痛标志物的影响:一项初步研究。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-09-08 DOI: 10.1080/19390211.2022.2120147
Leila Ataei, Christoforos D Giannaki, Christos Petrou, George Aphamis

Tribulus terrestris L. contains compounds with antioxidant and anti-inflammatory properties, but its effects on exercise-induced oxidative stress and inflammatory responses are unclear. The aim of this study was to examine whether Tribulus terrestris L. supplementation can attenuate oxidative stress and inflammatory responses to acute aerobic exercise and improve DOMS. In a randomized, double-blind, crossover design study, thirteen healthy men received either a daily supplement of Tribulus terrestris L. or a placebo for 4 weeks (2-week wash-out period between trials). Before and after the supplementation periods, participants performed an exercise test to exhaustion (75% VO2max). DOMS, thigh girth, and knee joint range of motion (KJRM) were assessed before and after the exercise (2, 24, and 48 h). Blood samples were analyzed for reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG ratio, protein carbonyls, total antioxidant capacity, creatine kinase activity, white blood cell count, and TBARS. Acute exercise to exhaustion induced inflammatory responses and changed the blood redox status in both Tribulus and Placebo groups (p < 0.050). Tribulus terrestris L. improved GSH fall (p = 0.005), GSSG rise (p = 0.001) and maintained a higher level of GSH/GSSG ratio at the 2 h point (p = 0.034). TBARS were lowered, protein carbonyls, creatine kinase activity, and white blood cell count elevation diminished significantly (p < 0.050). Tribulus terrestris L. administration did not affect DOMS, thigh girth, or KJRM (p > 0.050). 4-weeks of Tribulus terrestris L. supplementation effectively attenuates oxidative stress responses but cannot improve DOMS.

terrestris L.含有具有抗氧化和抗炎特性的化合物,但其对运动诱导的氧化应激和炎症反应的影响尚不清楚。本研究的目的是检验补充Tributus terrestris L.是否可以减轻对急性有氧运动的氧化应激和炎症反应,并改善DOMS。在一项随机、双盲、交叉设计的研究中,13名健康男性接受了每日补充的terrestris L.或安慰剂4 周(试验之间的2周冲洗期)。在补充期前后,参与者进行了一次运动测试,直到筋疲力尽(75%VO2max)。在运动前后评估DOMS、大腿围和膝关节活动范围(KJRM)(2、24和48 h) 。分析血液样本中的还原型(GSH)和氧化型(GSSG)谷胱甘肽、GSH/GSSG比率、蛋白质羰基、总抗氧化能力、肌酸激酶活性、白细胞计数和TBARS。急性运动衰竭引起炎症反应,并改变了Tribulus和安慰剂组的血液氧化还原状态(p terrestris L.提高GSH含量(p = 0.005),GSSG上升(p = 0.001),并在2 h点(p = 0.034)。TBARS降低,蛋白羰基、肌酸激酶活性和白细胞计数升高显著降低(p Tributus terrestris L.给药不影响DOMS、大腿围或KJRM(p > 0.050)。4周的Tributus terrestris L.补充有效地减弱了氧化应激反应,但不能改善DOMS。
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引用次数: 1
Dietary Supplement Intake is Associated with Healthier Lifestyle Behaviors in College Students Attending a Regional University in the Southeast: A Cross-Sectional Study. 东南某地区大学大学生膳食补充剂摄入与更健康的生活方式行为相关:一项横断面研究。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-10-18 DOI: 10.1080/19390211.2022.2134532
Andrea Y Arikawa, Jill Snyder, Jenifer M Ross, Michel Harris, Doreen Perez, Michele Bednarzyk

The relationship between intake of dietary supplements and biomarkers such as insulin and insulin-like growth factor has not been well explored. The primary aim of this cross-sectional study was to investigate the associations between supplement intake and biological and lifestyle factors. We hypothesized that dietary supplement intake was associated with healthier lifestyle behaviors. College students attending a Southeast university were recruited between January 2018 and April 2019. Blood samples were collected to measure insulin, insulin-like growth factor 1 (IGF-1) and alanine aminotransferase (ALT). Statistical tests employed were linear regression and analysis of variance. Ninety-eight participants completed the study and 91% reported taking at least one supplement, while 5.1% reported taking 9+ supplements once per week. There were no differences in levels of insulin, IGF-1 and ALT by levels of dietary supplement intake. Although there were no differences in HEI-2015 score among the groups, those who consumed five or more supplements met a higher percentage of the recommended intake for fruits, performed aerobic exercise for longer duration, and had lower body fat percentage compared to participants who consumed two or less supplements at least once per week. These findings are consistent with previous studies and suggest that dietary supplement intake is highly prevalent in college students, and it may be related to healthy lifestyle behaviors. Future studies should employ mixed methodology to examine reasons by which college students consume dietary supplements and to assess perceived and direct health benefits associated with consumption.

膳食补充剂的摄入与胰岛素和胰岛素样生长因子等生物标志物之间的关系尚未得到很好的探讨。这项横断面研究的主要目的是调查补充剂摄入与生物学和生活方式因素之间的关系。我们假设膳食补充剂的摄入与更健康的生活方式行为有关。就读于东南大学的大学生在2018年1月至2019年4月期间被招募。采集血样以测量胰岛素、胰岛素样生长因子1(IGF-1)和丙氨酸氨基转移酶(ALT)。采用的统计检验是线性回归和方差分析。98名参与者完成了这项研究,91%的参与者报告至少服用了一种补充剂,5.1%的参与者报告每周服用一次以上的补充剂。不同膳食补充剂摄入水平的胰岛素、IGF-1和ALT水平没有差异。尽管各组之间的HEI-2015评分没有差异,但与每周至少摄入一次两种或更少补充剂的参与者相比,摄入五种或五种以上补充剂的参与者达到了更高比例的水果推荐摄入量,进行了更长时间的有氧运动,体脂百分比更低。这些发现与之前的研究一致,并表明膳食补充剂的摄入在大学生中非常普遍,它可能与健康的生活方式行为有关。未来的研究应该采用混合方法来研究大学生食用膳食补充剂的原因,并评估与食用相关的感知和直接健康益处。
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引用次数: 1
Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents. 五种常见甘草及其植物化学成分的草药-药物相互作用潜力评估
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-03-18 DOI: 10.1080/19390211.2022.2050875
Mona H Haron, Bharathi Avula, Zulfiqar Ali, Amar G Chittiboyina, Ikhlas A Khan, Jing Li, Vivian Wang, Charles Wu, Shabana I Khan

The dried roots and rhizomes of Glycyrrhiza species (G. glabra, G. uralensis and G. inflata), commonly known as licorice, have long been used in traditional medicine. In addition, two other species, G. echinata and G. lepidota are also considered "licorice" in select markets. Currently, licorice is an integral part of several botanical drugs and dietary supplements. To probe the botanicals' safety, herb-drug interaction potential of the hydroethanolic extracts of five Glycyrrhiza species and their key constituents was investigated by determining their effects on pregnane X receptor, aryl hydrocarbon receptor, two major cytochrome P450 isoforms (CYP3A4 and CYP1A2), and the metabolic clearance of antiviral drugs. All extracts enhanced transcriptional activity of PXR and AhR (>2-fold) and increased the enzyme activity of CYP3A4 and CYP1A2. The highest increase in CYP3A4 was seen with G. echinata (4-fold), and the highest increase in CYP1A2 was seen with G. uralensis (18-fold) and G. inflata (16-fold). Among the constituents, glabridin, licoisoflavone A, glyasperin C, and glycycoumarin activated PXR and AhR, glabridin being the most effective (6- and 27-fold increase, respectively). Licoisoflavone A, glyasperin C, and glycycoumarin increased CYP3A4 activity while glabridin, glyasperin C, glycycoumarin, and formononetin increased CYP1A2 activity (>2-fold). The metabolism of antiretroviral drugs (rilpivirine and dolutegravir) was increased by G. uralensis (2.0 and 2.5-fold) and its marker compound glycycoumarin (2.3 and 1.6-fold). The metabolism of dolutegravir was also increased by G. glabra (2.8-fold) but not by its marker compound, glabridin. These results suggest that licorice and its phytochemicals could affect the metabolism and clearance of certain drugs that are substrates of CYP3A4 and CYP1A2.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2050875 .

甘草品种(Glycyrrhiza species)(G. glabra、G. uralensis 和 G. inflata)的干燥根茎和根状茎俗称甘草,长期以来一直被用于传统医药中。此外,另外两个品种,即 G. echinata 和 G. lepidota,在某些市场上也被视为 "甘草"。目前,甘草是多种植物药和膳食补充剂的组成部分。为了探究植物药的安全性,我们研究了五种甘草及其主要成分的水乙醇提取物的草药-药物相互作用潜力,确定了它们对孕烷 X 受体、芳香烃受体、两种主要细胞色素 P450 同工酶(CYP3A4 和 CYP1A2)以及抗病毒药物代谢清除率的影响。所有提取物都增强了 PXR 和 AhR 的转录活性(大于 2 倍),并提高了 CYP3A4 和 CYP1A2 的酶活性。G. uralensis(18 倍)和 G. inflata(16 倍)对 CYP3A4 的增幅最大。在这些成分中,苁蓉黄素、甘草异黄酮 A、甘草黄素 C 和甘草香豆素能激活 PXR 和 AhR,其中苁蓉黄素的效果最好(分别增加了 6 倍和 27 倍)。甘草异黄酮 A、甘草甜素 C 和甘草香豆素提高了 CYP3A4 活性,而苁蓉黄素、甘草甜素 C、甘草香豆素和福莫尼定提高了 CYP1A2 活性(>2 倍)。G. uralensis(2.0 倍和 2.5 倍)及其标记化合物甘氨酰香豆素(2.3 倍和 1.6 倍)增加了抗逆转录病毒药物(利匹韦林和多罗特拉韦)的代谢。甘草对多罗替拉韦的代谢也有促进作用(2.8 倍),但其标记化合物甘草次苷却没有促进作用。这些结果表明,甘草及其植物化学物质可能会影响作为 CYP3A4 和 CYP1A2 底物的某些药物的代谢和清除。本文的补充数据可在 https://doi.org/10.1080/19390211.2022.2050875 上在线获取。
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引用次数: 0
A Single Dosage of l-Arginine Oral Supplementation Induced Post-Aerobic Exercise Hypotension in Hypertensive Patients. 单剂量左旋精氨酸口服补充剂诱导高血压患者有氧运动后低血压。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-07-29 DOI: 10.1080/19390211.2022.2106006
Juliano Casonatto, João Vagner Cavalari

Lowering of peripheral vascular resistance is one of the primary processes involved in blood pressure decrease. Nitric oxide plays a significant role in this process and the availability of l-arginine is a crucial element in nitric oxide biosynthesis. Oral l-arginine supplementation may therefore be a potentiating element in post-exercise hypotension, mediated by its vasodilator action. Thus, the purpose of this study was to investigate if a single dose of l-arginine oral supplementation might impact the post-aerobic exercise blood pressure responses in treated hypertensive individuals. A double-blind, randomized, placebo-controlled crossover trial was conducted. The sample included male (4) and female (6) subjects [62 ± 10 years]. The participants were randomized to ingest one sachet containing 8 grams of l-arginine or placebo (corn starch) dissolved in water (100 ml). The substances were self-administered 120 min before the experimental or control session. The exercise was conducted on a treadmill and consisted of: a 5 min warm-up (50-65% HRreserve); 40 min of running/walking at 60-70% HRreserve; and a 5 min progressive cooldown. After the exercise sessions, blood pressure was measured every 10 min for 60 min. The l-arginine supplementation arm led to significant post-exercise systolic hypotension (mean post-exercise) in relation to rest period (117 ± 12 vs 125 ± 15 mmHg - p = 0.004 [l-arginine] and 121 ± 11 vs 125 ± 15 - p = 0.341 [placebo]). In addition, a systolic net effect of -6.9 ± 3.6 mmHg [p = 0.046] was identified for the mean post-exercise values. Therefore, this study showed that a single dosage of l-arginine oral supplementation induced post-aerobic exercise hypotension in hypertensive patients.

外周血管阻力的降低是血压下降的主要过程之一。一氧化氮在这一过程中发挥着重要作用,l-精氨酸的可用性是一氧化氮生物合成的关键元素。因此,口服补充l-精氨酸可能是运动后低血压的增强因素,由其血管舒张作用介导。因此,本研究的目的是调查单剂量口服补充l-精氨酸是否会影响接受治疗的高血压患者有氧运动后的血压反应。进行了一项双盲、随机、安慰剂对照的交叉试验。样本包括男性(4)和女性(6)受试者[62 ± 10 年]。参与者被随机摄入一袋含有8克溶解在水中的l-精氨酸或安慰剂(玉米淀粉)(100 ml)。这些物质是自行服用的120 min。这项运动是在跑步机上进行的,包括: 最小预热(50-65%的HRreserve);40 以60-70%的心率储备进行跑步/步行的分钟数;和一个5 最小渐进冷却时间。运动后,每10次测量一次血压 60分钟 min.补充l-精氨酸组导致运动后与休息期相关的显著收缩性低血压(运动后平均值)(117 ± 12对125 ± 15 毫米汞柱-p = 0.004[l-精氨酸]和121 ± 11对125 ± 15-p = 0.341[安慰剂])。此外,收缩净效应为-6.9 ± 3.6 毫米汞柱[p = 0.046]确定运动后的平均值。因此,本研究表明,单剂量口服补充l-精氨酸可诱导高血压患者有氧运动后低血压。
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引用次数: 0
Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2. 抗SARS-CoV-2病毒RNA依赖性RNA聚合酶复合物(nsp7/nsp8/nsp12)的植物源性天然非核苷类似物抑制剂(NNAIs)
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 DOI: 10.1080/19390211.2021.2006387
Sreus A G Naidu, Ghulam Mustafa, Roger A Clemens, A Satyanarayan Naidu

The emergence of fast-spreading SARS-CoV-2 mutants has sparked a new phase of COVID-19 pandemic. There is a dire necessity for antivirals targeting highly conserved genomic domains on SARS-CoV-2 that are less prone to mutation. The nsp12, also known as the RNA-dependent RNA-polymerase (RdRp), the core component of 'SARS-CoV-2 replication-transcription complex', is a potential well-conserved druggable antiviral target. Several FDA-approved RdRp 'nucleotide analog inhibitors (NAIs)' such as remdesivir, have been repurposed to treat COVID-19 infections. The NAIs target RdRp protein translation and competitively block the nucleotide insertion into the RNA chain, resulting in the inhibition of viral replication. However, the replication proofreading function of nsp14-ExoN could provide resistance to SARS-CoV-2 against many NAIs. Conversely, the 'non-nucleoside analog inhibitors (NNAIs)' bind to allosteric sites on viral polymerase surface, change the redox state; thereby, exert antiviral activity by altering interactions between the enzyme substrate and active core catalytic site of the RdRp. NNAIs neither require metabolic activation (unlike NAIs) nor compete with intracellular pool of nucleotide triphosphates (NTPs) for anti-RdRp activity. The NNAIs from phytonutrient origin are potential antiviral candidates compared to their synthetic counterparts. Several in-silico studies reported the antiviral spectrum of natural phytonutrient-NNAIs such as Suramin, Silibinin (flavonolignan), Theaflavin (tea polyphenol), Baicalein (5,6,7-trihydroxyflavone), Corilagin (gallotannin), Hesperidin (citrus bioflavonoid), Lycorine (pyrrolidine alkaloid), with superior redox characteristics (free binding energy, hydrogen-bonds, etc.) than antiviral drugs (i.e. remdesivir, favipiravir). These phytonutrient-NNAIs also exert anti-inflammatory, antioxidant, immunomodulatory and cardioprotective functions, with multifunctional therapeutic benefits in the clinical management of COVID-19.

快速传播的SARS-CoV-2突变体的出现引发了COVID-19大流行的新阶段。目前迫切需要针对SARS-CoV-2上不易突变的高度保守的基因组结构域开发抗病毒药物。nsp12,也被称为rna依赖性rna聚合酶(RdRp),是“SARS-CoV-2复制转录复合体”的核心成分,是一个潜在的保守的可药物抗病毒靶点。fda批准的几种RdRp“核苷酸类似物抑制剂”(NAIs),如remdesivir,已被重新用于治疗COVID-19感染。nai靶向RdRp蛋白的翻译,并竞争性地阻断核苷酸插入RNA链,从而抑制病毒复制。然而,nsp14-ExoN的复制校对功能可以提供对SARS-CoV-2对许多nai的抗性。相反,“非核苷类似物抑制剂(NNAIs)”与病毒聚合酶表面的变构位点结合,改变氧化还原状态;因此,通过改变酶底物与RdRp活性核心催化位点之间的相互作用来发挥抗病毒活性。NNAIs不需要代谢激活(与NAIs不同),也不与细胞内三磷酸核苷酸(NTPs)竞争抗rdrp活性。与合成的nnai相比,来自植物营养素的nnai是潜在的抗病毒候选物。一些计算机上的研究报道了天然植物营养素- nnai的抗病毒谱,如苏拉明、水飞蓟宾(黄酮木质素)、茶黄素(茶多酚)、黄芩素(5,6,7-三羟基黄酮)、花椰菜素(没食子单宁)、橙皮苷(柑橘类生物类黄酮)、石蒜碱(吡啶生物碱),它们比抗病毒药物(如瑞德西韦、法维拉韦)具有更好的氧化还原特性(自由结合能、氢键等)。这些植物营养素- nnai还具有抗炎、抗氧化、免疫调节和心脏保护功能,在COVID-19的临床管理中具有多功能治疗益处。
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引用次数: 10
SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control. SARS-CoV-2感染失调宿主铁(Fe)-氧化还原稳态(Fe- r - h):铁氧化还原调节剂、铁下沉抑制剂、抗凝血剂和铁螯合剂在COVID-19控制中的作用
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 DOI: 10.1080/19390211.2022.2075072
Sreus A G Naidu, Roger A Clemens, A Satyanarayan Naidu

Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I - Hypoxia correlates with reduced O2 transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Phase-II - Hyperferritinemia results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients. Phase-III - Thromboembolism is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.

SARS-CoV-2感染患者铁代谢严重失衡在COVID-19的每个症状(轻、中、重度)临床阶段都很突出。第一阶段-缺氧与红细胞氧转运减少、HIF-1α过度表达、线粒体生物能量学改变和宿主代谢重编程(HMR)相关。ii期-高铁素血症是由铁超载增加引起的,这会引发暴发性促炎反应——急性细胞因子释放综合征(CRS)。细胞因子水平升高(即il - 6、TNFα和CRP)与COVID-19患者铁蛋白/TF比值的改变密切相关。iii期:血栓栓塞是红细胞功能障碍的结果,血红素释放,凝血酶原时间增加,d -二聚体升高,累积与危及生命的严重凝血功能障碍相关,如ARDS和多器官衰竭。综上所述,Fe-R-H失调与COVID-19的每个症状阶段都有关。铁-r - h调节因子,如乳铁蛋白(LF)、血氧合酶-1 (HO-1)、促红细胞生成素(EPO)和hepcidin调节剂是先天的生物补充,通过优化铁代谢来隔离铁,中和铁介导的自由基,减少氧化应激,提高宿主防御能力。由于其在“细胞因子风暴”中的关键作用,铁下垂是一个潜在的干预目标。铁死亡抑制剂如铁他汀-1、利蒲他汀-1、槲皮素和褪黑素可以通过激活Nrf2和HO-1信号通路,阻止线粒体脂质过氧化,上调抗氧化剂/GSH水平,并消除铁超载诱导的细胞凋亡。铁螯合剂如肝素、去铁胺、咖啡酸、姜黄素、α-硫辛酸和植酸可以防止铁下垂,恢复线粒体功能、铁氧化还原电位,并重新平衡铁-r - h状态。因此,铁-r - h恢复是一种宿主生物标志物驱动的潜在战斗策略,可用于有效的COVID-19临床和康复后管理。
{"title":"SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control.","authors":"Sreus A G Naidu,&nbsp;Roger A Clemens,&nbsp;A Satyanarayan Naidu","doi":"10.1080/19390211.2022.2075072","DOIUrl":"https://doi.org/10.1080/19390211.2022.2075072","url":null,"abstract":"<p><p>Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. <i>Phase-I</i> - <i>Hypoxia</i> correlates with reduced O<sub>2</sub> transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). <i>Phase-II - Hyperferritinemia</i> results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients<i>. Phase-III - Thromboembolism</i> is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195049","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: 10
Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes. 大剂量绿茶提取物的肝毒性:儿茶酚-O-甲基转移酶和尿苷5'-二磷酸葡萄糖醛酸基转移酶1A4基因型的影响。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-09-30 DOI: 10.1080/19390211.2022.2128501
Laura Acosta, Laura Byham-Gray, Mindy Kurzer, Hamed Samavat

The predominant catechin in green tea, epigallocatechin gallate (EGCG), may be hepatotoxic in high doses. Our objective was to investigate the influence of catechol-O-methyltransferase (COMT) and uridine 5'-diphospho-glucuronosyltransferase 1A4 (UGT1A4) genotypes on changes in liver injury biomarkers in response to long-term, high-dose green tea extract (GTE) supplementation among postmenopausal women. A secondary analysis was conducted using data from the Minnesota Green Tea Trial (N = 1,075), in which participants were randomized to consume high-dose GTE (843 mg/day EGCG) or placebo capsules for 12 months. Analysis of covariance adjusting for potential confounders was performed to examine changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST: ALT ratio, and alkaline phosphatase from baseline to months 3, 6, 9, and 12 across COMT and UGT1A4 genotypes. Mean age and BMI within the GTE group (n = 400) were 59.8 yrs and 25.1 kg/m2, respectively, and 98% of subjects were white. From baseline to month 3, mean AST: ALT ratio change was +1.0% in the COMT (rs4680) A/G genotype versus -4.8% in the A/A genotype (p = 0.03). From baseline to months 6 and 9, respectively, mean ALT change was +78.1% and +82.1% in the UGT1A4 (rs6755571) A/C genotype versus +28.0% and +30.1% in the C/C genotype (p < 0.001 and p = 0.004, respectively). The UGT1A4 (rs6755571) A/C genotype may be an important risk factor for clinically-relevant serum transaminase elevations with 6-9 months of high-dose GTE supplementation among postmenopausal women. Understanding the genetic underpinnings of GTE-related hepatotoxicity may allow for a genetically-informed paradigm for therapeutic use of GTE.

绿茶中主要的儿茶素,表没食子儿茶素没食子酸盐(EGCG),在高剂量下可能具有肝毒性。我们的目的是研究儿茶酚-O-甲基转移酶(COMT)和尿苷5'-二磷酸葡萄糖醛酸基转移酶1A4(UGT1A4)基因型对绝经后妇女长期高剂量补充绿茶提取物(GTE)后肝损伤生物标志物变化的影响。使用明尼苏达绿茶试验的数据进行二次分析(N = 1075),其中参与者被随机分配服用高剂量GTE(843 mg/天EGCG)或安慰剂胶囊 月。对潜在混杂因素进行协方差调整分析,以检查COMT和UGT1A4基因型从基线到第3、6、9和12个月的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、AST:ALT比率和碱性磷酸酶的变化。GTE组的平均年龄和BMI(n = 400)为59.8 25.1岁 kg/m2,98%的受试者为白人。从基线到第3个月,COMT(rs4680)A/G基因型的平均AST:ALT比率变化为+1.0%,而A/A基因型的变化为-4.8%(p = 从基线到第6个月和第9个月,UGT1A4(rs6755571)A/C基因型的平均ALT变化分别为+78.1%和+82.1%,而C/C基因型的变化分别为+28.0%和+30.1%(p p = 0.004)。UGT1A4(rs6755571)A/C基因型可能是临床相关血清转氨酶升高的重要危险因素,6-9 绝经后妇女高剂量GTE补充数月。了解GTE相关肝毒性的遗传基础可能为GTE的治疗应用提供一个基因知情的范例。
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引用次数: 0
Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. 根据 PXR 和 AhR 对 CYP3A4 和 CYP1A2 的影响,评估美国市场上常用植物药的草药-药物相互作用潜力。
IF 2.5 Q2 Agricultural and Biological Sciences Pub Date : 2023-01-01 Epub Date: 2022-08-26 DOI: 10.1080/19390211.2022.2110351
Mona H Haron, Olivia Dale, Katherine Martin, Bharathi Avula, Amar G Chittiboyina, Ikhlas A Khan, Bill J Gurley, Shabana I Khan

In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively). Of the 30 botanicals tested, 21 induced PXR and 29 induced AhR transcriptional activities. Out of the 21 botanicals that induced hPXR transcriptional activity, 14 yielded >50% induction in CYP3A4 activity at concentrations ranging from 6 to 60 µg/mL and 16 out of the 29 botanicals that activated hAhR yielded >50% induction in CYP1A2 activity at concentrations ranging from 3 to 30 µg/mL. Moreover, eight botanicals (G. gummi-gutta [garcinia], Hemp [low and high CBD content], H. perforatum [St. John's wort], M. vulgare [horehound], M. oleifera [moringa], O. vulgare [oregano], P. johimbe [yohimbe] and W. somnifera [ashwagandha]) yielded >50% induction in both CYP3A4 and CYP1A2 activity. Herbal products are mixtures of phytoconstituents, any of which could modulate drug metabolism. Our data reveals that several top-selling botanicals may pose herb-drug interaction (HDI) risks via CYP450 induction. While in vitro experiments can provide useful guidance in assessing a botanical's HDI potential, their clinical relevance needs to be investigated in vivo. Botanicals whose effects on hPXR/CYP3A4, and hAhR/CYP1A2 activity were most pronounced will be slated for further clinical investigation.

在这项研究中,对美国常用于草药膳食补充剂成分的 30 种畅销植物(草药)的水乙醇提取物进行了筛选,以确定它们是否有可能激活人类孕烷 X 受体(hPXR)和人类芳基烃受体(hAhR),并提高受 hPXR 和 hAhR 调节的药物代谢细胞色素 P450 酶(即分别为 CYP3A4 和 CYP1A2)的活性。在测试的 30 种植物药中,21 种诱导 PXR,29 种诱导 AhR 转录活性。在诱导 hPXR 转录活性的 21 种植物药中,14 种植物药在 6 至 60 微克/毫升的浓度范围内对 CYP3A4 活性的诱导率大于 50%;在激活 hAhR 的 29 种植物药中,16 种植物药在 3 至 30 微克/毫升的浓度范围内对 CYP1A2 活性的诱导率大于 50%。此外,八种植物药(G. gummi-gutta[大蒜素]、大麻[低和高 CBD 含量]、H. perforatum[圣约翰草]、M. vulgare[霍香草]、M.oleifera [moringa]、O. vulgare [oregano]、P. johimbe [yohimbe] 和 W. somnifera [ashwagandha])对 CYP3A4 和 CYP1A2 活性的诱导率均大于 50%。草药产品是植物成分的混合物,其中任何一种成分都可能调节药物代谢。我们的数据显示,几种最畅销的植物药可能会通过 CYP450 诱导产生草药-药物相互作用(HDI)风险。虽然体外实验可以为评估植物药的 HDI 潜力提供有用的指导,但其临床相关性还需要在体内进行研究。对 hPXR/CYP3A4 和 hAhR/CYP1A2 活性影响最明显的植物药将被列为进一步临床研究的对象。
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引用次数: 0
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Journal of Dietary Supplements
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