Ginsenoside Rd: A promising target for ischemia-reperfusion injury therapy (A mini review).

Ischemia-reperfusion injury (IRI) represents a prevalent pathological phenomenon. Traditional treatment approaches primarily aim at restoring blood supply to ischemic organs, disregarding the consequent damage caused by IRI. Belonging to the class of protopanaxadiol ginsenosides that are found in Panax ginseng, ginsenoside Rd (GSRd) demonstrates notable safety alongside a diverse range of biological functions. Its active components exhibit diverse pharmacological effects, encompassing anti-inflammatory, anti-tumor, neuroprotective, cardiovascular-protective, and immune-regulatory properties, making it a promising candidate for addressing multiple medical conditions. GSRd shields against I/R injury by employing crucial cellular mechanisms, including the attenuation of oxidative stress, reduction of inflammation, promotion of cell survival signaling pathways, and inhibition of apoptotic pathways. Additionally, GSRd regulates mitochondrial function, maintains calcium homeostasis, and modulates the expression of genes involved in I/R injury. This review seeks to consolidate the pharmacological mechanism of action of GSRd within the context of IRI. Our objective is to contribute to the advancement of GSRd-related pharmaceuticals and provide novel insights for clinicians involved in developing IRI treatment strategies.

Medium chain triglycerides improve the growth performance, immune and antioxidant functions, and intestinal health of weaned rabbits.

The purpose is to study the effects of different doses of medium chain triglyceride (MCT) on growth performance, immune and oxidative functions, and intestinal health of weaned rabbits. A total of 600 weaned rabbits weighing about 993.26 g and at 35 d of age were randomly divided into five groups. The control group was fed a basal diet containing 2400 mg/kg soybean oil, and the experimental group was substituted with 600, 1200, 1800, and 2400 mg/kg MCT. The whole trial period lasted for 48 d. The results showed that treatment with 2400 mg/kg MCT significantly increased the weaning survival rate and crude fat digestibility (p < 0.05) and dramatically raised the levels of serum immunoglobulin (Ig)A, IgG, IgM, catalase, superoxide dismutase, and total antioxidant capability (p < 0.05). The villus height and crypt depth in 1800 mg/kg MCT group were observably enhanced (p < 0.05). The abundance of Bacteroidetes was significantly increased in 1800 and 2400 mg/kg MCT groups (p < 0.05). In conclusion, 1800 and 2400 mg/kg MCT substituting soybean oil in the diet of weaned rabbits can improve the growth performance and intestinal barrier function of weaned rabbits.

Ultrasonic-assisted extraction of polyphenolic compounds from Paederia scandens (Lour.) Merr. Using deep eutectic solvent: optimization, identification, and comparison with traditional methods.

Ultrasonic-assisted extraction (UAE) coupled with deep eutectic solvent (DES) is a novel, efficient and green extraction method for phytochemicals. In this study, the effects of 16 DESs coupled with UAE on the extraction rate of polyphenols from Paederia scandens (Lour.) Merr. (P. scandens), an edible and medicinal herb, were investigated. DES synthesised with choline chloride and ethylene glycol at a 1:2 M ratio resulted in the highest extractability. Moreover, the effects of extraction parameters were investigated by using a two-level factorial experiment followed by response surface methodology The optimal parameters (water content in DES of 49.2%, the actual ultrasonic power of 72.4 W, and ultrasonic time of 9.7 min) resulted in the optimal total flavonoid content (TFC) (27.04 mg CE/g DW), ferric-reducing antioxidant power (FRAP) value (373.27 µmol Fe(Ⅱ)E/g DW) and 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS+) value (48.64 µmol TE/g DW), closely matching the experimental results. Furthermore, a comparison study demonstrated that DES-UAE afforded the higher TFC and FRAP value than traditional extraction methods. 36 individual polyphenolic compounds were identified and quantified by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) in P. scandens extracts, and of which 30 were found in the extracts obtained by DES-UAE. Additionally, DES-UAE afforded the highest sum of individual polyphenolic compound content. These results revealed that DES-UAE enhanced the extraction efficiency for polyphenols and provided a scientific basis for further processing and utilization of P. scandens.

Deep eutectic solvent-based ultrasonic-assisted extraction of phenolic compounds from different potato genotypes: Comparison of free and bound phenolic profiles and antioxidant activity.

Potato phenolics exhibit health-promoting effects. Studies on bound phenolics are scarce. Here, significant differences in total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity in free and bound forms were found among 19 potato genotypes. 7 free and 24 bound phenolics were characterized and quantified using ultrahigh-performance liquid chromatograph-mass spectrometry, among which 22 bound phenolics are reported for the first time in potato. The number and content of identified free and bound phenolics changed considerably among the genotypes. Chlorogenic acid, cryptochlorogenic acid and rutin in free form, and benzoic and caftaric acids in bound form were predominant. Heijingang showed the highest free and total TPC and antioxidant activity, and the largest number of phenolic compounds, whereas S17-1-1 contained the highest free and total TFC and Longshu 7 contained the highest bound phenolic content. Cluster analysis segregated the genotypes into 6 groups. This study provides useful information on benefits of potato in human health.

Effects of different extraction methods on contents, profiles, and antioxidant abilities of free and bound phenolics of Sargassum polycystum from the South China Sea.

Total phenolic content (TPC), phenolic profiles, and antioxidant activity of free and bound extracts of Sargassum polycystum, obtained by different extraction solvents and hydrolysis methods, were investigated. Aqueous acetone afforded the highest free TPC and antioxidant ability, followed by aqueous ethanol and aqueous methanol. Twelve free phenolic compounds were identified by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), including two hydroxycinnamic acids, seven flavonoids, one stilbene, and two phlorotannins. Three to nine different free phenolic compounds were extracted by these solvents with different compositions, including nine by 70% acetone and eight by 70% methanol, 70% ethanol, and 50% ethanol. The highest total content of free phenolic compounds determined by high-performance liquid chromatography-diode array detection was obtained from 70% ethanol. Alkaline hydrolysis afforded higher bound TPC (274.27 mg GAE/100 g DW) and antioxidant ability than acid hydrolysis. Five bound phenolic compounds were characterized by UHPLC-MS and five were released from alkaline hydrolysis, whereas two were released from acid hydrolysis. Total content of bound phenolic compounds released by alkaline hydrolysis was 14.68-fold higher than that by acid hydrolysis. The free and bound TPC, phenolic profiles, and antioxidant activities depended on the extraction solvent used. These results indicate that S. polycystum is a potentially useful antioxidant source and contribute to the development of seaweed-based functional foods. PRACTICAL APPLICATION: Phenolics are usually divided into free and bound forms based on their extractability and interaction with cell wall components. The nutritional effects of bound phenolics in algae have long been neglected. These topics contribute to the development of seaweed-based functional foods.

Maternal oxidized soybean oil exposure in rats during lactation damages offspring kidneys via Nrf2/HO-1 and NF-κB signaling pathway.

BACKGROUND: Cooking oil is an indispensable component of the human diet. However, oils usually undergo thermal oxidation. Oxidized soybean oil (OSO) has been shown to have detrimental effects on humans and has emerged as a root cause of many chronic diseases. The objective of this work was to evaluate the effects of puerpera exposure to OSO on kidney damage in the mother and offspring using lactating rats as an experimental model. RESULTS: Pathological sections and ultrastructure showed that OSO exposure resulted in various levels of damage to lactating rats and their offspring. OSO induced oxidative stress in the kidneys of lactating rats, as evidenced by increased levels of hydrogen peroxide, interleukin (IL)-1ß, and IL-8. OSO increased the activities of glutathione peroxidase and superoxide dismutase. OSO upregulated the expression of apoptosis-related genes, nuclear factor-erythroid 2-related factor 2 (Nrf2), and nuclear factor κB-related inflammatory factor genes. In the offspring of the OSO-exposed mothers, hydrogen peroxide, malondialdehyde, IL-6, and tumor necrosis factor-alpha contents were increased. Furthermore, OSO enhanced the levels of Nrf2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, and p65 and decreased B-cell lymphoma 2. CONCLUSION: These findings indicated that the kidneys of two generations of rats were compromised by oxidative damage when fed OSO during lactation. This study provides evidence for increasing the genes expression of the Nrf2/heme oxygenase 1 pathway to alleviate the kidney damage caused by OSO in the mother and offspring. © 2021 Society of Chemical Industry.

Dietary Trivalent Chromium Exposure Up-Regulates Lipid Metabolism in Coral Trout: The Evidence From Transcriptome Analysis.

Diet quality greatly affects an animal's performance and metabolism. Despite the fact that trivalent chromium [Cr(III)] is considered an essential element and is widely used in nutritional supplements for animals and humans, the potential toxicity of Cr(III) is unclear. Here, liver transcriptome sequencing was performed on coral trout (Plectropomus leopardus) exposed to 200 mg kg-1 of dietary organic Cr(III) [as chromium picolinate (CrPic)] for 8 weeks. One-hundred-and thirteen differentially expressed genes (DEGs) were identified in response to Cr(III) stress, in comparison to the control, including 31 up-regulated and 82 down-regulated DEGs. Clusters of Orthologous Groups of proteins (COG) classifies DEGs into 15 functional categories, with the predominant category being related to lipid transport and metabolism (9.73%). The Kyoto Encyclopedia of Genes and Genomes (KEGG) assigned DEGs to six major categories with robust DEGs as part of the lipid metabolism pathway (18.58%). Moreover, KEGG functional enrichment analysis showed that these DEGs are primarily related to steroid biosynthesis, terpenoid backbone biosynthesis, and steroid hormone biosynthesis pathways, of which steroid biosynthesis was the most significant pathway, and 12 key up-regulated DEGs (dhcr7, dhcr24, ebp, lss, msmo1, sqle, cyp51, tm7sf2, sc5dl, fdft1, nsdhl, and hsd17b7) were found for steroid biosynthesis pathways. To validate the RNA sequencing data using quantitative real-time PCR (qRT-PCR), qRT-PCR results indicate that the expression of genes encoding HMGCR, TM7SF2, TRYP2, CTRL, EBP, LSS, and CYP51 were induced, while those encoding THRSP, LCE, and MCM5 were reduced, consistent with RNA-seq results. This findings provides the first evidence that a long-term high dose of Cr(III) intake causes lipid metabolism disorder and potential toxicity in fish. Cautious health risk assessment of dietary Cr(III) intake is therefore highly recommended for the commercial and/or natural diets of aquatic animals, which has previously largely been ignored.

Rice Bran Phenolic Extract Confers Protective Effects against Alcoholic Liver Disease in Mice by Alleviating Mitochondrial Dysfunction via the PGC-1α-TFAM Pathway Mediated by microRNA-494-3p.

The initiation and development of alcoholic liver disease (ALD) is mediated, at least partly, by mitochondria dysfunction, which is regulated by PPARγ coactivator-1α (PGC-1α) via mitochondria transcription factor A (TFAM). Then, PGC-1α expression was regulated by several microRNAs. This research investigated the hepatoprotective effects of the rice bran phenolic extract (RBPE) on mice fed with an ethanol-containing diet via the microRNAs-PGC-1α-TFAM signal pathway. RBPE treatment protected against alcoholic liver injury, as indicated by decreased serum aminotransferase activities and hepatic triglyceride accumulation, together with alleviated oxidative stress in serum and the liver. RBPE treatment alleviated ethanol-induced mitochondrial dysfunction through altering the membrane potential, mtDNA content, and respiratory chain complex enzyme activities in mitochondria, resulting in increased hepatic ATP production. Decreased cytoplasmic cytochrome c contents, caspase-3 activity, and Bax/Bcl-2 ratio were detected in the liver of RBPE-treated mice, indicating that the RBPE might inhibit ethanol-induced hepatocellular apoptosis. Furthermore, ethanol-induced decreases in the mRNA and protein expression of PGC-1α and TFAM were remarkably alleviated in RBPE-treated mice. RBPE treatment to ethanol-fed mice could also downregulate the expression of microRNA-494-3p, which regulates PGC-1α expression directly. Therefore, the RBPE might exert protection against ALD by alleviating mitochondrial dysfunction and the resulting hepatocyte apoptosis via the PGC-1α-TFAM signal pathway mediated by microRNA-494-3p.

Association of in-hospital intensive statins dosage and death in arteriosclerotic cardiovascular disease with percutaneous coronary intervention: insights of multicentre cohort from China.

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.

Synthesis of amino-functionalized biochar/spinel ferrite magnetic composites for low-cost and efficient elimination of Ni(II) from wastewater.

Novel amino-modified rice bran biochar/MgFeAlO4 (RB@MgFeAlO4-NH2) magnetic composites were synthesized via a simple one-step solvothermal approach and applied for removing toxic Ni(II) from wastewater. The elimination process and sorption performance of Ni(II) on RB@MgFeAlO4-NH2 were analyzed by combining batch experiments and spectral techniques. The sorption isotherms and kinetic data indicated that Ni(II) sorption on RB@MgFeAlO4-NH2 was monolayer and rapid. The experimental results confirmed that the obtained RB@MgFeAlO4-NH2 magnetic composite had high sorption capacity for Ni(II). The maximum sorption capacity of Ni(II) on RB@MgFeAlO4-NH2 was 201.62 mg g-1. The researches based on the sorption mechanism showed that the ion exchange mechanism accounted for 76.51% of Ni(II) sorption. In addition, the amino, carboxyl and hydroxyl functional groups were also involved in the complexation with Ni(II). In view of its multiple advantages of environmental friendliness, low cost, easy magnetic separation and high sorption capacity, RB@MgFeAlO4-NH2 will be an excellent adsorbent for low-cost and efficient elimination of Ni(II) from aqueous solutions.

Cerebellar contribution to auditory feedback control of speech production: Evidence from patients with spinocerebellar ataxia.

The cerebellum has been implicated in the feedforward control of speech production. However, the role of the cerebellum in the feedback control of speech production remains unclear. To address this question, the present event-related potential study examined the behavioral and neural correlates of auditory feedback control of vocal production in patients with spinocerebellar ataxia (SCA) and healthy controls. All participants were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted -200 or -500 cents. The behavioral results revealed significantly larger vocal compensations for pitch perturbations in patients with SCA relative to healthy controls. At the cortical level, patients with SCA exhibited significantly smaller cortical P2 responses that were source localized in the right superior temporal gyrus, primary auditory cortex, and supramarginal gyrus than healthy controls. These findings indicate that reduced brain activity in the right temporal and parietal regions are significant neural contributors to abnormal auditory-motor processing of vocal pitch regulation as a consequence of cerebellar degeneration, which may be related to disrupted reciprocal interactions between the cerebellum and cortical regions that support the top-down modulation of auditory-vocal integration. These differences in behavior and cortical activity between healthy controls and patients with SCA demonstrate that the cerebellum is not only essential for feedforward control but also plays a crucial role in the feedback-based control of speech production.

Top-Down Modulation of Auditory-Motor Integration during Speech Production: The Role of Working Memory.

Although working memory (WM) is considered as an emergent property of the speech perception and production systems, the role of WM in sensorimotor integration during speech processing is largely unknown. We conducted two event-related potential experiments with female and male young adults to investigate the contribution of WM to the neurobehavioural processing of altered auditory feedback during vocal production. A delayed match-to-sample task that required participants to indicate whether the pitch feedback perturbations they heard during vocalizations in test and sample sequences matched, elicited significantly larger vocal compensations, larger N1 responses in the left middle and superior temporal gyrus, and smaller P2 responses in the left middle and superior temporal gyrus, inferior parietal lobule, somatosensory cortex, right inferior frontal gyrus, and insula compared with a control task that did not require memory retention of the sequence of pitch perturbations. On the other hand, participants who underwent extensive auditory WM training produced suppressed vocal compensations that were correlated with improved auditory WM capacity, and enhanced P2 responses in the left middle frontal gyrus, inferior parietal lobule, right inferior frontal gyrus, and insula that were predicted by pretraining auditory WM capacity. These findings indicate that WM can enhance the perception of voice auditory feedback errors while inhibiting compensatory vocal behavior to prevent voice control from being excessively influenced by auditory feedback. This study provides the first evidence that auditory-motor integration for voice control can be modulated by top-down influences arising from WM, rather than modulated exclusively by bottom-up and automatic processes.SIGNIFICANCE STATEMENT One outstanding question that remains unsolved in speech motor control is how the mismatch between predicted and actual voice auditory feedback is detected and corrected. The present study provides two lines of converging evidence, for the first time, that working memory cannot only enhance the perception of vocal feedback errors but also exert inhibitory control over vocal motor behavior. These findings represent a major advance in our understanding of the top-down modulatory mechanisms that support the detection and correction of prediction-feedback mismatches during sensorimotor control of speech production driven by working memory. Rather than being an exclusively bottom-up and automatic process, auditory-motor integration for voice control can be modulated by top-down influences arising from working memory.

Temporal Lobe Epilepsy Alters Auditory-motor Integration For Voice Control.

Temporal lobe epilepsy (TLE) is the most common drug-refractory focal epilepsy in adults. Previous research has shown that patients with TLE exhibit decreased performance in listening to speech sounds and deficits in the cortical processing of auditory information. Whether TLE compromises auditory-motor integration for voice control, however, remains largely unknown. To address this question, event-related potentials (ERPs) and vocal responses to vocal pitch errors (1/2 or 2 semitones upward) heard in auditory feedback were compared across 28 patients with TLE and 28 healthy controls. Patients with TLE produced significantly larger vocal responses but smaller P2 responses than healthy controls. Moreover, patients with TLE exhibited a positive correlation between vocal response magnitude and baseline voice variability and a negative correlation between P2 amplitude and disease duration. Graphical network analyses revealed a disrupted neuronal network for patients with TLE with a significant increase of clustering coefficients and path lengths as compared to healthy controls. These findings provide strong evidence that TLE is associated with an atypical integration of the auditory and motor systems for vocal pitch regulation, and that the functional networks that support the auditory-motor processing of pitch feedback errors differ between patients with TLE and healthy controls.

Feeding reduces waterborne Cu bioaccumulation in a marine rabbitfish Siganus oramin.

Waterborne metal uptake has been extensively studied and dietary metal assimilation is increasingly recognized in fish, whilst the interaction between the two uptake routes is largely overlooked. This study compared the waterborne Cu bioaccumulation ((65)Cu as tracer) in a juvenile rabbitfish at different feeding regimes (starvation (SG), feeding normal diet (NDG) or diet supplemented with extra Cu (DCG)) to test the hypothesis that feeding can influence waterborne metal uptake in marine fish. NDG and DCG diet was fed as a single meal and then all fish were exposed to waterborne (65)Cu for 48 h, during which the time course sampling was conducted to determine (65)Cu bioaccumulation, chyme flow and dietary Cu assimilation. The results revealed that SG fish accumulated the highest (65)Cu, followed by NDG (61% of SG), whilst DCG fish accumulated the lowest (65)Cu (34% of SG). These results suggested a protective effect of feeding against waterborne Cu bioaccumulation. This effect was most notable between 10 min and 16 h when there was chyme in gastrointestinal tract (GT). Dietary Cu assimilation mainly occurred before 16 h after feeding. Waterborne (65)Cu influx rate in the GT was positively correlated with (65)Cu contents of chyme in NDG, whereas it was largely negatively correlated with (65)Cu contents of chyme in DCG. The waterborne Cu uptake in the GT was mainly influenced by the chyme flow and dietary Cu assimilation. Overall, our findings suggested that feeding has an important effect on waterborne metal uptake and that both the feeding status of the fish and the relative metal exposure through water and food should be considered in prediction of the metal bioaccumulation and biomonitoring programs.

The removal of U(VI) from aqueous solution by oxidized multiwalled carbon nanotubes.

Multiwalled carbon nanotubes (MWCNTs) have exhibited high sorption capacity for radionuclides due to the unique hollow structure and large surface area. In this study, surface properties of oxidized MWCNTs were characterized by using XRD, SEM, FTIR and potentiometric acid-base titration. The sorption of U(VI) on oxidized MWCNTs as a function of contact time, U(VI) concentration, pH, ionic strength, humic acid/fulvic acid (HA/FA) and carbonate was investigated by using batch technique. The removal of U(VI) by oxidized MWCNTs was strongly dependent on pH and ionic strength. The presence of HA/FA enhanced U(VI) removal on oxidized MWCNTs at low pH while inhibited U(VI) sorption at high pH. The mechanism of U(VI) sorption on oxidized MWCNTs was assumed to be cation exchange/outer-sphere surface complexation in acidic pH and to form precipitation under circum neutral conditions. The oxidized MWCNTs exhibit higher sorption capacity and stronger chemical affinity than pristine MWCNTs.

Impact of water quality parameters on the sorption of U(VI) onto hematite.

In this study, the sorption of U(VI) from aqueous solution on hematite was studied as a function of various water quality parameters such as contact time, pH, ionic strength, soil humic acid (HA) or fulvic acid (FA), solid content and temperature by using a batch technique. The results demonstrated that the sorption of U(VI) was strongly dependent on ionic strength at pH<6.0, and outer-sphere surface complexation may be the main sorption mechanism. The sorption was independent of ionic strength at pH>6.0 and the sorption was mainly dominated by inner-sphere surface complexation. The presence of HA/FA increases U(VI) sorption at low pH, whereas decreases U(VI) sorption at high pH. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) were calculated from the temperature dependent sorption isotherms, and the results suggested that U(VI) sorption was a spontaneous and endothermic process. The results might be important for the application of hematite in U(VI) pollution management.

Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor.

The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.

Structure-activity relationships of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists.

SAR studies of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists resulted in potent compounds. The best compound from the series had a binding affinity of 2 nM.