Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.

BACKGROUND: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 µmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Mindfulness mediates the relationship between positive parenting and aggression, depression, and suicidal ideation: A longitudinal study in middle school students.

Previous research has indicated that parenting factors affect the risk of maladaptive psychological outcomes (e.g., aggression, depression, or suicidal ideation), and that positive parenting is a prospective risk factor for maladaptive psychological outcomes. However, the mechanisms underlying the relationships between positive parenting, mindfulness, and maladaptive psychological outcomes remain unknown, as do the processes that mediate the effect of positive parenting on maladaptive psychological outcomes in adolescents. The objective of the present study was to investigate the longitudinal relationship between positive parenting, mindfulness, and maladaptive psychological outcomes in middle school students, as well as the mediating effect of mindfulness in the relationships between positive parenting and depression, aggression, and suicidal ideation. In this study, 386 middle school children (aged 12-16) were tested three times over a period of 6 months. Positive parenting was assessed at Time 1, mindfulness at Time 2, and depression, aggression, and suicidal ideation at Time 3. Using structural equation modeling, positive parenting was revealed to be longitudinally associated with mindfulness and negatively associated with maladaptive psychological outcomes. More crucially, mindfulness mediated the relationship between positive parenting and maladaptive psychological outcomes. This research provides important insights into how to effectively decrease adolescent maladaptive psychological outcomes and highlights the importance of teaching mindfulness to youths.

The Role of Mindfulness in Mitigating the Detrimental Effects of Harsh Parenting among Chinese Adolescents: Testing a Moderated Mediation Model in a Three-Wave Study.

Based on the conservation of resources theory, this study aimed to investigate the mediating role of depressive symptoms and the moderating role of mindfulness in the association between harsh parenting and adolescent suicidal ideation in the Chinese cultural context. Using a three-wave (i.e., three months apart) data collection among 371 Chinese adolescents, this study found that depressive symptoms mediated the relationship between harsh parenting and adolescent suicidal ideation. Moreover, adolescent mindfulness mitigated the effects of harsh parenting on suicidal ideation, as well as the indirect effect of harsh parenting on suicidal ideation via depressive symptoms. The theoretical and practical implications are discussed.

Amidoxime Group-Anchored Single Cobalt Atoms for Anti-Biofouling during Uranium Extraction from Seawater.

Marine biofouling is one of the most significant challenges hindering practical uranium extraction from seawater. Single atoms have been widely used in catalytic applications because of their remarkable redox property, implying that the single atom is highly capable of catalyzing the generation of reactive oxygen species (ROS) and acts as an anti-biofouling substance for controlling biofouling. In this study, the Co single atom loaded polyacrylamidoxime (PAO) material, PAO-Co, is fabricated based on the binding ability of the amidoxime group to uranyl and cobalt ions. Nitrogen and oxygen atoms from the amidoxime group stabilize the Co single atom. The fabricated PAO-Co exhibits a broad range of antimicrobial activity against diverse marine microorganisms by producing ROS, with an inhibition rate up to 93.4%. The present study is the first to apply the single atom for controlling biofouling. The adsorbent achieves an ultrahigh uranium adsorption capacity of 9.7 mg g-1 in biofouling-containing natural seawater, which decreased only by 11% compared with that in biofouling-removed natural seawater. These findings indicate that applying single atoms would be a promising strategy for designing biofouling-resistant adsorbents for uranium extraction from seawater.

Ultrasensitive Detection of Aqueous Uranyl Based on Uranyl-Triggered Protein Photocleavage.

The detection of environmental uranyl is attracting increasing attention. However, the available detection strategies mainly depend on the selective recognition of uranyl, which is subject to severe interference by coexisting metal ions. Herein, based on the unique uranyl-triggered photocleavage property, the protein BSA is labelled with fluorescent molecules that exhibit an aggregation-induced emission effect for uranyl detection. Uranyl-triggered photocleavage causes the separation of the fluorescent-molecule-labelled protein fragments, leading to attenuation of the emission fluorescence, which is used as a signal for uranyl detection. This detection strategy shows high selectivity for uranyl and an ultralow detection limit of 24 pM with a broad detection range covering five orders of magnitude. The detection method also shows high reliability and stability, making it a promising technique for practical applications in diverse environments.

Guishaozichuan granules can attenuate asthma in rats via the MUC5AC/EGFR signaling pathway.

Background: Guishaozichuan (GSZC) granules are a traditional Chinese medicine formulation created by Professor Li (Chinese-Japanese Friendship Hospital, Beijing, China) we studied the effect of GSZC granules in rats suffering from asthma. Methods: Specific pathogen-free Sprague-Dawley rats were divided randomly into seven groups. Ovalbumin (OVA) and Al (OH)3 gel were used to create an asthma model. On day 1, rats were injected with OVA (10 mg) and an Al(OH)3 gel suspension (100 mg). One week later, rats were sensitized again. On day 15, rats were given aerosolized OVA (1%) for 30 min/day for 10 days. Gastric administration of OVA was 1 h before nebulization. At 24 h after the last stimulation, changes in airway resistance (RI) and dynamic compliance (Cdyn) in rat lungs were measured after challenge with methacholine at increasing concentrations. The contents of immunoglobulin (Ig)E, interleukin (IL)-4, IL-5, IL-13, and IL-17 in serum were measured by enzyme-linked immunosorbent assays. The percentage of eosinophils (EOS) and the white blood cell (WBC) count in bronchoalveolar lavage fluid (BALF) were counted under an optical microscope. Pathologic alterations in lung tissue were evaluated by optical microscopy, and lung injury score calculated. Expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) and epidermal growth factor receptor (EGFR) in lung tissue was measured by immunohistochemistry. mRNA expression of MUC5AC and EGFR in lung tissue was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: GSZC granules reduced RI markedly and improved Cdyn, decreased serum levels of IgE, IL-4, IL-5, IL-13, IL-17, %EOS and the WBC count in BALF. GSZC granules alleviated lung-tissue damage, diminished the Inflammation Score, and reduced mRNA and protein expression of MUC5AC and EGFR in lung tissue. Conclusion: GSZC granules could improve bronchial hyperresponsiveness, bronchial inflammation, and histopathologic damage in the lungs of rats suffering from asthma. This phenomenon may be related to its regulation of cytokine levels and the MUC5AC/EGFR signaling pathway.

Highly efficient immobilization of environmental uranium contamination with Pseudomonas stutzeri by biosorption, biomineralization, and bioreduction.

Uranium is a heavy metal with both chemotoxicity and radiotoxicity. Due to the increasing consumption of uranium, the remediation of uranium contamination and recovery of uranium from non-conventional approach is highly needed. Microorganism exhibits high potential for immobilization of uranium. This study for the first time isolated a marine Pseudomonas stutzeri strain MRU-UE1 with high uranium immobilization capacity of 308.72 mg/g, which is attributed to the synergetic mechanisms of biosorption, biomineralization, and bioreduction. The uranium is found to be immobilized in forms of tetragonal chernikovite (H2(UO2)2(PO4)2·8H2O) by biomineralization and CaU(PO4)2 by bioreduction under aerobic environment, which is rarely observed and would broaden the application of this strain in aerobic condition. The protein, phosphate group, and carboxyl group are found to be essential for the biosorption of uranium. In response to the stress of uranium, the strain produces inorganic phosphate group, which transformed soluble uranyl ion to insoluble uranium-containing precipitates, and poly-ß-hydroxybutyrate (PHB), which is observed for the first time during the interaction between microorganism and uranium. In summary, P. stutzeri strain MRU-UE1 would be a promising alternative for environmental uranium contamination remediation and uranium extraction from seawater.

Exploring the Active Components of Simotang Oral Liquid and Their Potential Mechanism of Action on Gastrointestinal Disorders by Integrating Ultrahigh-Pressure Liquid Chromatography Coupled with Linear Ion Trap-Orbitrap Analysis and Network Pharmacology.

Simotang oral liquid (SMT), a well-known traditional Chinese medicine formula composed of four medicinal and edible plants, has been extensively used for treating gastrointestinal disorders (GIDs) since ancient times. However, the major active constituents and the underlying molecular mechanism of SMT on GIDs are still partially understood. Herein, the preliminary chemical profile of SMT was first identified by ultrahigh-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). In total, 70 components were identified. Then, a network pharmacology approach integrating target prediction, pathway enrichment analysis, and network construction was adopted to explore the therapeutic mechanism of SMT. As a result, 170 main targets were screened out and considered as effective players in ameliorating GIDs. More importantly, the major hubs were found to be highly enriched in a calcium signaling pathway. Furthermore, 26 core SMT-related genes were identified, which may play key roles in ameliorating gastrointestinal motility. In conclusion, this work would provide valuable information for further development and clinical application of SMT.

Excess Folic Acid Supplementation before and during Pregnancy and Lactation Alters Behaviors and Brain Gene Expression in Female Mouse Offspring.

Use of folic acid (FA) during early pregnancy protects against birth defects. However, excess FA has shown gender-specific neurodevelopmental toxicity. Previously, we fed the mice with 2.5 times the recommended amount of FA one week prior to mating and during the pregnancy and lactation periods, and detected the activated expression of Fos and related genes in the brains of weaning male offspring, as well as behavioral abnormalities in the adults. Here, we studied whether female offspring were affected by the same dosage of FA. An open field test, three-chamber social approach and social novelty test, an elevated plus-maze, rotarod test and the Morris water maze task were used to evaluate their behaviors. RNA sequencing was performed to identify differentially expressed genes in the brains. Quantitative real time-PCR (qRT-PCR) and Western blots were applied to verify the changes in gene expression. We found increased anxiety and impaired exploratory behavior, motor coordination and spatial memory in FA-exposed females. The brain transcriptome revealed 36 up-regulated and 79 down-regulated genes in their brains at weaning. The increase of Tlr1; Sult1a1; Tph2; Acacb; Etnppl; Angptl4 and Apold1, as well as a decrease of Ppara mRNA were confirmed by qRT-PCR. Among these genes; the mRNA levels of Etnppl; Angptl4andApold1 were increased in the both FA-exposed female and male brains. The elevation of Sult1a1 protein was confirmed by Western blots. Our data suggest that excess FA alteres brain gene expression and behaviors in female offspring, of which certain genes show apparent gender specificity.

Study on the Mechanism of Sarsasapogenin in Treating Precocious Puberty by Regulating the HPG Axis.

The present study aims to investigate the effects and mechanisms of sarsasapogenin resistance to precocious puberty. Female Sprague Dawley rats were divided into a normal (N) group, model (M) group, leuprolide (L) group, and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. The development of the uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) were determined by radioimmunoassay. Also, the expressions of the hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54), and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. The results showed that compared with the model group, sarsasapogenin could significantly delay the opening time of vaginal, decreased uterine and ovarian coefficients, and reduced uterine wall thickness. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH-R, and kiss-1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss-1/GPR54 system for therapeutic precocious puberty.

The study on polymorphisms of Sep15 and TrxR2 and the expression of AP-1 signaling pathway in Kashin-Beck disease.

The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway in KBD subjects and in vitro. 208 KBD and 206 control subjects were included. PCR-Restriction Fragment Length Polymorphism (RFLP), Amplification Refractory Mutation Specific-PCR (ARMS-PCR) and Western Blotting were conducted. The results showed the minor A-allele frequency of rs5859 in KBD was statistically significantly higher than that in the control group (P < 0.05). The cases carrying A-allele had a 2-fold (95%CI: 1.064-3.956) increased risk of developing KBD compared with the G-allele carriers. There was no significant difference in genotype and allele distribution of rs1139793 between KBD patients and controls (P > 0.05). The frequency of the minor A allele of rs5859 was significantly different in Chinese healthy population compared with European, African and American. The frequency of the minor A allele of rs1139793 showed significant difference when compared with African and American. The levels of JunB, JunD, P65 proteins in KBD group were higher than those in control group (P < 0.0001). The expression of JunB, JunD, P65 proteins all increased in tBHP-induced C28/I2 oxidative damage model compared with control group (P < 0.05) and decreased after Se supplementation. Our finding indicated Sep15 is a possible candidate susceptibility gene for KBD. Combined with the in vitro study, our studies reveal novel insights into the mechanism of Se supplementation as an antioxidant via inhibiting the AP-1 signaling pathway in patients with KBD.

The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis.

OBJECTIVE: Selenium deficiency is a risk factor for Kashin-Beck Disease (KBD), an endemic osteoarthropathy. Although promoter hypermethylation of glutathione peroxidase 3 (GPX3) (a selenoprotein) has been identified in several cancers, little is known about promoter methylation and expression of GPX3 and their relation to selenium in KBD. The present study was thus conducted to investigate this research question. METHODS: Methylation and expressions of GPX3 in whole blood drawn from 288 KBD patients and 362 healthy controls and in chondrocyte cell line were evaluated using methylation-specific PCR and qRT-PCR, respectively. The protein levels of PI3K/Akt/c-fos signaling in the whole blood and chondrocyte cell line were determined with Western blotting. Chondrocytes apoptosis were detected by Hoechst 33342 and Annexin V-FITC/PI staining. RESULTS: GPX3 methylation was increased, GPX3 mRNA was decreased, and protein levels in the PI3K/Akt/c-fos signaling pathway were up-regulated in the whole blood collected from KBD patients as compared with healthy controls. Similar results were obtained for chondrocytes injured by oxidative stress. There was a significant, decreasing trend in GPX3 expression across groups of unmethylation, partial methylation, and complete methylation for GPX3, in sequence. Compared with unmethylation group, protein levels in PI3K/Akt/c-fos pathway were enhanced in partial and complete methylation groups. Treatment of chondrocytes with sodium selenite resulted in reduced methylation and increased expression of GPX3 as well as down-regulated level of PI3K/Akt/c-fos proteins. CONCLUSIONS: The methylation and expression of GPX3 and expression of PI3K/Akt/c-fos pathway are altered in KBD and these changes are reversible by selenium supplementation.

[Discussion on efficacy evaluation thought and method for innovation medicine of Chinese herbal compound formula based on clinical application characteristics].

The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including： ①the endpoint criteria should meet the clinical attribution of new drugs; ②the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; ③during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula.

Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.

Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus.

High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1ß, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1ß, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension.

Pomegranate extract and exercise provide additive benefits on improvement of immune function by inhibiting inflammation and oxidative stress in high-fat-diet-induced obesity in rats.

BACKGROUND: Obesity is reported to be associated with immune dysfunction and a state of low-grade, chronic inflammation. Either pomegranate extract (PomE) or exercise (Ex) has been shown to have antiobesity, anti-inflammatory and antioxidant effects. Nevertheless, no study has addressed the additive benefits of PomE and Ex on the restoration of obesity-induced immune defects. OBJECTIVE: The present work aims to study the effect of PomE and Ex as a combined intervention on immune function and the underlying mechanism involved in inflammation and oxidative stress in rats with high-fat-diet (HFD)-induced obesity. RESULTS: Our results demonstrate that the combination of PomE and Ex showed additive benefits on inhibition of HFD-induced body weight increase and improvement of HFD-induced immune dysfunction, including (a) attenuating the abnormality of histomorphology of the spleen, (b) increasing the ratio of the CD4+:CD8+ T cell subpopulations in splenocytes and peripheral blood mononuclear cells (PBMC), (c) inhibition of apoptosis in splenocytes and PBMC, (d) normalizing peritoneal macrophage phenotypes and (e) restoring immunomodulating factors in serum. We also find that immune dysfunction in HFD-fed rats was associated with increased inflammatory cytokine secretion and oxidative stress biomarkers, and that the combination of PomE and Ex effectively inhibited the inflammatory response and decreased oxidative damage. CONCLUSIONS: The effect of PomE and Ex as a combined intervention is greater than the effect of either PomE or Ex alone, showing that PomE and Ex may be additively effective in improving immune function in HFD-fed rats by inhibiting inflammation and decreasing oxidative stress.

Protective Effect of Ethanol Extracts of the Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes), on the Experimental Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) Model.

In this study, we investigated the effects of ethanol extracts of Ophiocordyceps sinensis (EEOS) on neuroprotective efficacy in a rat model of focal cerebral ischemia/reperfusion (IR). The effects of EEOS on mortality rate, neurobehavior, grip strength, polymorphonuclear (PMN) cells, interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, intracellular adhesion molecule 1 (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by enzyme-linked immunosorbent assay and immunohistochemistry. The cerebral infarction was examined through tetrazolium chloride staining. EEOS significantly inhibited IR-induced brain production of IL-1ß, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, EEOS suppressed infiltration of PMN cells. EEOS caused a significant reduction in the infarct size compared with the middle cerebral artery occlusion group. The study demonstrates the neuroprotective potential of EEOS inhibition of IR through anti-inflammatory activity in a rat model of IR.

Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin.

AIMS: Punicalagin (PU) is one of the major ellagitannins found in the pomegranate (Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD. RESULTS: PE administration at a dosage of 150 mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance. INNOVATION: Our work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component. CONCLUSIONS: By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.

[Current situation of toxicity classification of Chinese materia medica and its research thoughts].

Toxicity of Chinese materia medica (CMM) is an important part of Chinese herbal nature theory. In clinical application, the dosage, time limitation and compatibility of CMM is mainly determined by toxicity. At present, there is no uniform toxicity classification standard for the evaluation of Chinese herbal toxicity. Therefore, it is significant to research toxicity classification of CMM. The current situation of toxicity classification of CMM is reviewed in this paper, and proposed research thoughts are as follows: the measurement of toxicity parameters, the confirmation of poisoning target organs, the investigation on toxic mechanism by serum pharmacology and toxicokinetics, the comprehensive evaluation on toxicity based on quantitative theory.