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1.
Foods ; 13(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38611353

ABSTRACT

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

2.
Theriogenology ; 209: 170-177, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37393747

ABSTRACT

As a functional fatty acid, α-linolenic acid (ALA) is essential in promoting animal testosterone biosynthesis. This study investigated the effects of ALA on testosterone biosynthesis and the possible mechanism underlying the signaling pathway in primary Leydig cells of the rooster. METHODS: Primary rooster Leydig cells were treated with ALA (0, 20, 40, or 80 µmol/L) or pretreated with a p38 inhibitor (50 µmol/L), a c-Jun NH2-terminal kinase (JNK) inhibitor (20 µmol/L), or an extracellular signal-regulated kinase (ERK) inhibitor (20 µmol/L) before ALA treatment. Testosterone content in the conditioned culture medium was detected using an enzyme-linked immunosorbent assay (ELISA). The expression of steroidogenic enzymes and JNK-SF-1 signaling pathway factors was detected using real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Supplementation with ALA significantly increased testosterone secretion within culture media (P < 0.05), and the optimized dose was 40 µmol/L. Compared with the control group, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA expression significantly increased (P < 0.05) in the 40 µmol/L ALA group; 17-hydroxylase/c17-20 lyase (P450c17) and p38 mRNA expressions were not significantly different in the 40 µmol/L ALA group; ERK and JNK mRNA expressions were significantly upregulated (P < 0.05) in 40 µmol/L ALA group. In the inhibitor group, testosterone levels were significantly downregulated (P < 0.05). Compared with the 40 µmol/L ALA group, StAR, P450scc, and P450c17 mRNA expressions were significantly decreased (P < 0.05), and 3ß-HSD mRNA expression in the p38 inhibitor group did not change; StAR, P450scc, and 3ß-HSD mRNA expressions were significantly decreased (P < 0.05), and P450c17 mRNA expression in ERK inhibitor group did not change; StAR, P450scc, 3ß-HSD, and P450c17 mRNA expressions were significantly decreased (P < 0.05) in JNK inhibitor group. Additionally, the increased steroidogenic factor 1 (SF-1) gene expression levels induced by ALA were reversed when the cells were pre-incubated with JNK and ERK inhibitors. The levels in the JNK inhibitor group were significantly lower than those in the control group (P < 0.05). CONCLUSION: ALA may promote testosterone biosynthesis by activating the JNK-SF-1 signaling pathway to upregulate StAR, P450scc, 3ß-HSD, and P450c17 expression in primary rooster Leydig cells.


Subject(s)
Leydig Cells , alpha-Linolenic Acid , Male , Animals , Leydig Cells/metabolism , Steroidogenic Factor 1/metabolism , Steroidogenic Factor 1/pharmacology , alpha-Linolenic Acid/pharmacology , Chickens/genetics , 3-Hydroxysteroid Dehydrogenases/metabolism , RNA, Messenger/metabolism , Testosterone/metabolism , Signal Transduction , Cholesterol Side-Chain Cleavage Enzyme/genetics , Cholesterol Side-Chain Cleavage Enzyme/metabolism
3.
Front Physiol ; 14: 1110301, 2023.
Article in English | MEDLINE | ID: mdl-36744028

ABSTRACT

Aims: The study aimed to evaluate the effects of pretreated Chinese herbal medicine (PCHM) on egg quality, production performance, histopathological changes in the uterus, antiox idant capacity, and antioxidant gene expression in late-phase layers. Methods: Jinghong No.1 layers (n = 360, 68 weeks old) were assigned randomly to one of f our dietary interventions. Each treatment was replicated six times. Repeat 15 chickens per g roup. All birds were fed a diet composed of a corn-soybean meal-based diet supplemented with 0, 0.2, 0.4, or 0.8% PCHM for 6 weeks. Results: Dietary PCHM supplementation had no significant effects on laying rate, feed con sumption, yolk color, and shape index. With increasing PCHM level the Haugh unit linearly increased (P < 0.05). Supplementation of 0.8% PCHM increased egg weight, compared with the control (P < 0.05). PCHM can effectively alleviated the pathological changes caused by aging in the uterus including hemorrhage, and many inflammatory cell infiltrations. Supplementation of 0.4% PCHM increased glutathione peroxidase (GSHPx) in liver, magnum, and plasm considerably, compared with the control (P < 0.05). Supplementation of PCHM decr ease in the liver, magnum, and uterus on malondialdehyde (MDA) content, compared with the control (P < 0.05). Compared with the control group, mRNA expressions of glutathione peroxidase 1 (GPX1), peroxidase 4 (GPX4), catalase (CAT), and nuclear factor E2-related factor 2 (Nrf2) in the magnum, liver, and uterus were dramatically rose in the 0.4% PCHM supplementation group (P < 0.05). In summary, dietary supplementation after PCHM increased egg weight and quality in late-phase laying hens. Conclusion: Dietary PCHM increased the antioxidative capacity of late-phase laying hens, which could be associated with increased mRNA expression of antioxidant enzymes and Nrf2. These findings provide potential for using PCHM to increase the production performance in late-phase laying hens.

4.
Poult Sci ; 101(11): 102113, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36087443

ABSTRACT

This study's objective was to investigate the effects of dietary Se (in the form of selenomethionine) on the antioxidant activity and selenoprotein gene expressions in layer breeder roosters. One hundred and eighty, 36-wk-old Jingfen layer breeder roosters were randomly allocated to one of 5 dietary treatments (0, 0.25, 0.5, 1, or 2 mg/kg Se) for 6 wk on a corn-soybean meal-based diet. Antioxidant parameters and selenoprotein gene expressions were assessed at the end of the experiment. The results showed that Se supplementation significantly increased the activity of T-SOD, CAT, GSH-Px, and superoxide anion scavenging ability in plasma (P ≤ 0.05), and activities of T-SOD, CAT, GSH-Px, superoxide anion scavenging ability, and hydroxyl radical scavenging ability in the liver, kidney, and testis (P < 0.05). Moreover, MDA levels were significantly reduced in plasma, liver, kidney, and testis (P < 0.01), compared to the control group. Furthermore, the dietary administration of Se significantly increased TrxR2 and GPx4 mRNA levels in kidney and testis, and ID1 mRNA levels in liver and kidney. Most of the antioxidant parameters and selenoprotein-related gene expressions significantly increased, and MDA significantly decreased at dietary supplementation with 0.5 mg/kg Se. Whereas a higher dose of Se level (1 or 2 mg/kg) inhibited the activities of some of the antioxidant enzymes and selenoprotein-related gene expressions in selected tissues. In conclusion, dietary Se supplementation with 0.5 mg/kg significantly improved roosters' antioxidant status and selenoprotein-related gene expression in liver, kidney, and testis, while higher doses led to inhibit these; dietary Se might increase reproductive performance by enhancing their antioxidant status in roosters.


Subject(s)
Selenium , Selenomethionine , Animals , Male , Selenomethionine/metabolism , Antioxidants/metabolism , Chickens/metabolism , Animal Feed/analysis , Dietary Supplements , Superoxides/metabolism , Selenoproteins/genetics , Selenoproteins/metabolism , Diet/veterinary , RNA, Messenger/metabolism , Gene Expression , Superoxide Dismutase/metabolism , Selenium/metabolism
5.
Pharm Biol ; 60(1): 1331-1340, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35819372

ABSTRACT

CONTEXT: Qiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia. OBJECTIVE: To clarify the mechanisms of QLWH in treating pneumonia. MATERIALS AND METHODS: The potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH. RESULTS: Nine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1ß (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05). DISCUSSION AND CONCLUSIONS: This study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.


Subject(s)
NF-kappa B , Pneumonia , Animals , Lipopolysaccharides/toxicity , Male , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Network Pharmacology , Signal Transduction , Toll-Like Receptor 4/metabolism
6.
Molecules ; 27(11)2022 May 31.
Article in English | MEDLINE | ID: mdl-35684492

ABSTRACT

In this work, the extraction procedure of a natural pigment from the flower of Ceiba speciosa (A. St.-Hil.) was optimized by response surface methodology. It is the first time that the extraction of the flower pigment of C. speciosa (FPCS) has been reported, along with an evaluation of its stability and biological activity under various conditions, and an exploration of its potential use as a food additive and in medicine. Specifically, the effects of ethanol concentration, solid-liquid ratio, temperature and time on the extraction rate of FPCS were determined using a Box-Behnken design. The optimum extraction conditions for FPCS were 75% ethanol with a solid-liquid ratio of 1:75 mg/mL) at 66 °C for 39 min. The purification of FPCS using different macroporous resins showed that D101 performed best when the initial mass concentration of the injection solution was 1.50 mg/mL, resulting in a three-fold increase in color value. The yield of dry flowers was 9.75% of fresh petals and the FPCS extraction efficiency was 43.2%. The effects of light, solubility, pH, temperature, sweeteners, edible acids, redox agents, preservatives and metal ions on FPCS were also investigated. Furthermore, the characteristics of FPCS were determined by spectrophotometry at a specific wavelength using the Lambert-Beer law to correlate the mass of FPCS with its absorbance value. An acute toxicological test performed according to Horne's method showed that FPCS is a non-toxic extract and thus may be used as a food additive or in other ingestible forms. Finally, western blotting showed that FPCS prevents lipopolysaccharide-induced hippocampal oxidative stress in mice. The study suggests that FPCS may function as an antioxidant with applications in the food, cosmetics and polymer industries.


Subject(s)
Ceiba , Animals , Antioxidants/pharmacology , Ethanol , Flowers , Food Additives , Mice , Plant Extracts/pharmacology
7.
Poult Sci ; 101(5): 101812, 2022 May.
Article in English | MEDLINE | ID: mdl-35325831

ABSTRACT

As the antioxidant capacity of sperm declines with age in roosters, the objective of the present study was to determine the effects of different levels of pyrroloquinoline quinone disodium (PQQ.Na2) on antioxidative and sperm quality parameters of aging layer breeder roosters. A total of ninety-six 63-wk-old Jinghong No. 1 layer breeder roosters were randomly assigned to 4 treatments (0, 0.5, 1, 2 mg/kg PQQ.Na2) for 6 wk. Antioxidant activity and semen parameters were assessed biweekly. The dietary administration of PQQ.Na2 significantly increased semen quality (semen volume, sperm motility, straightness, progressive motility, curvilinear velocity, straight-line velocity, and amplitude of lateral head displacement) and antioxidant capacity (T-SOD, GSH-Px, hydroxyl radical scavenging ability, and/or superoxide scavenging capacity) in seminal plasma in aging layer breeder roosters. Whereas, PQQ.Na2 supplementations significantly decreased malondialdehyde (MDA) concentration in seminal plasma in aging layer breeder roosters. Supplementation with 1 mg/kg dietary PQQ.Na2 as an antioxidant supplement could increase sperm quality and antioxidant activity of aging layer breeder roosters, while a higher dose (2 mg/kg) did not result in further increment.


Subject(s)
PQQ Cofactor , Semen Analysis , Aging , Animal Feed/analysis , Animals , Antioxidants/metabolism , Chickens/metabolism , Dietary Supplements , Male , Oxidative Stress , PQQ Cofactor/pharmacology , Semen , Semen Analysis/veterinary , Sperm Motility
8.
Article in Chinese | WPRIM | ID: wpr-943107

ABSTRACT

The incidence of diabetes has been on the rise as the result of lifestyle changes, especially the high-fat diet and reduced exercise. Thus, it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β (TGF-β) signaling pathways with diabetes complications and tumors, but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors, directly or indirectly leading to the apoptosis of islet β cells and insulin resistance (IR), and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase (AMPK), protooncogene (c-Myc), Ski-relatednovel protein N (SnoN), Smad ubiquitination regulatory factor 1 (Smurf1), miR-335-5p, and other signaling molecules. They participate in the occurrence and development of IR, apoptosis of islet β cells, insulin secretion disorder, fibrosis of adipocytes, and metabolic disorder of adipocytes, and inhibit the browning of white adipose tissue, playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine (TCM), the pathogenesis of diabetes is the deficiency of Qi and Yin, and the late stage is characterized by the syndrome of Qi deficiency, and Yang deficiency and blood stasis, which should be treated according to the principle of replenishing Qi and nourishing Yin, warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways, elucidating the roles of them in pathogenesis of diabetes, and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

9.
Chin J Nat Med ; 19(7): 540-544, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34247778

ABSTRACT

A large number of protease inhibitors have been found from leeches, which are essential in various physiological and biological processes. In the curret study, a novel elastase inhibitor was purified and characterized from the leech of Hirudinaria manillensis, which was named HMEI-A. Primary structure analysis showed that HMEI-A belonged to a new family of proteins. HMEI-A exerted inhibitory effects on elastase and showed potent abilities to inhibit elastase with an inhibition constant (Ki) of 1.69 × 10-8 mol·L-1. Further study showed that HMEI-A inhibited the formation of neutrophil extracellular trap (NET). These results suggested that HMEI-A from the leech of H. manillensis is a novel elastase inhibitor which can suppress NET formation. It may play a significant role in blood-sucking of leeches and is a potential candidate as an anti-inflammatory agent.


Subject(s)
Leeches , Pancreatic Elastase/antagonists & inhibitors , Protease Inhibitors/pharmacology , Amino Acid Sequence , Animals , Leeches/chemistry , Proteins
10.
Journal of Forensic Medicine ; (6): 813-816, 2021.
Article in English | WPRIM | ID: wpr-984079

ABSTRACT

OBJECTIVES@#To explore the relationship between the frequency characteristics and response threshold of auditory steady-state response (ASSR), auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP), and their application values in forensic medicine.@*METHODS@#Thirty volunteers with normal hearing (60 ears) were selected to perform pure tone audiometry (PTA) threshold and ASSR, ABR and 40 Hz AERP response threshold tests in the standard sound insulation shielding room, and the results were statistically analyzed by SPSS 22.0 software.@*RESULTS@#At 0.5 kHz and 1.0 kHz frequencies, the correlation between 40 Hz AERP response threshold and PTA threshold was good, which was better than that of ASSR and ABR response threshold. At 2.0 kHz and 4.0 kHz frequencies, the correlation between ASSR and ABR response thresholds and PTA threshold was good, which was better than that of 40 Hz AERP response threshold.@*CONCLUSIONS@#To evaluate the hearing at 0.5 kHz and 1.0 kHz frequencies, it is recommended to use 40 Hz AERP and ASSR to comprehensively assess the PTA threshold of the subjects. To evaluate the hearing at 2.0 kHz and 4.0 kHz frequencies, ABR and ASSR are recommended to assess the PTA threshold of subjects comprehensively. The combination of ASSR, ABR and 40 Hz AERP can improve the accuracy of hearing function evaluation.


Subject(s)
Humans , Acoustic Stimulation/methods , Audiometry, Evoked Response , Audiometry, Pure-Tone , Auditory Threshold/physiology , Evoked Potentials, Auditory, Brain Stem/physiology , Forensic Medicine , Hearing/physiology
11.
Taiwan J Obstet Gynecol ; 59(6): 865-871, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33218403

ABSTRACT

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.


Subject(s)
Adenomyosis/surgery , High-Intensity Focused Ultrasound Ablation/methods , Leiomyoma/surgery , Uterine Neoplasms/surgery , Adult , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Imaging , Patient Satisfaction , Pregnancy , Pregnancy Rate , Quality of Life , Reproducibility of Results , Retrospective Studies , Treatment Outcome
12.
J Ethnopharmacol ; 244: 112137, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31381955

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Veratrum taliense is traditionally used TCMs in Yunnan province of China for pain and inflammation. Previous research and clinical applications have shown that V. taliense had significant analgesic activity. Jevine-type alkaloids were shown to be one of the anti-inflammatory and analgesic agents from V. taliense. However, other types of compounds from V. taliense related to its traditional use remains unknown. AIM OF THE STUDY: To identify veratramine-type steroidal alkaloids with analgesic effects from the roots and rhizomes of V. taliense. MATERIALS AND METHODS: Compounds were isolated from the roots and rhizomes of V. taliense by chromatographic separation. Their structures were elucidated based on UV, IR, NMR and MS spectra data. Analgesic activity was assessed with acetic acid-induced writhing in mice model. RESULTS: Seven new veratramine-type alkaloids were isolated from the roots and rhizomes of V. taliense. They all exhibited significant analgesic activity, of which alkaloids 1 and 4 were more potent antalgic than the well-known analgesic drug, pethidine. CONCLUSIONS: The veratramine-type alkaloids from V. taliense may serve as new leads for the discovery of analgesic drugs.


Subject(s)
Alkaloids/therapeutic use , Analgesics/therapeutic use , Pain/drug therapy , Veratrum , Acetic Acid , Alkaloids/analysis , Analgesics/chemistry , Animals , Female , Male , Mice, Inbred ICR , Pain/chemically induced , Phytochemicals/analysis , Phytochemicals/therapeutic use , Plant Roots
13.
Phytother Res ; 33(9): 2347-2359, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31273855

ABSTRACT

As yet, there was no effective pharmacological therapy approved for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to evaluate the therapeutic potential of puerarin against NAFLD and explored the underlying mechanisms. C57BL/6J mice were fed with a high-fat high-sucrose (HFHS) diet with or without puerarin coadministration intragastrically. The levels of hepatocellular injury, steatosis, fibrosis, and mitochondrial and metabolism alteration were detected. First, puerarin ameliorated histopathologic abnormalities due to HFHS. We observed a marked increase in hepatic lipid content, inflammation, and fibrosis level, which were attenuated by puerarin. Possible mechanisms were related to puerarin-mediated activation of PI3K/AKT pathway and further improvement in fatty acid metabolism. Puerarin restored the NAD+ content and beneficially affected the hepatic mitochondrial function, which attenuated HFHS-induced steatosis and metabolic disturbances. Finally, hepatic PARP-1 was activated due to excessive fat intake. Puerarin attenuated the PARP-1 expression in HFHS-fed mice, and PJ34, the PARP inhibitor, could mimic these protections of puerarin. However, pharmacological inhibition of PI3K disabled the protection of puerarin or PJ34 toward NAD+ refilling and mitochondrial homeostasis. In conclusion, our findings indicated that puerarin could be a promising and practical therapeutic strategy in NAFLD through modulating PARP-1/PI3K/AKT signaling pathway and further facilitating mitochondrial function.


Subject(s)
Diet, High-Fat/adverse effects , Isoflavones/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Sucrose/adverse effects , Vasodilator Agents/therapeutic use , Animals , Humans , Isoflavones/pharmacology , Male , Mice , Mice, Inbred C57BL , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Vasodilator Agents/pharmacology
14.
Cancer Med ; 7(8): 3848-3861, 2018 08.
Article in English | MEDLINE | ID: mdl-29956500

ABSTRACT

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.


Subject(s)
DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Immunomodulation/genetics , Mutation , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/immunology , Alleles , Case-Control Studies , Cell Line, Tumor , Female , Gene Expression Profiling , Genotype , High-Throughput Nucleotide Sequencing , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Nasopharyngeal Carcinoma/pathology , Neoplasm Staging , Polymorphism, Single Nucleotide , Tripartite Motif Proteins , Ubiquitin-Protein Ligases
15.
Neuromolecular Med ; 20(1): 97-111, 2018 03.
Article in English | MEDLINE | ID: mdl-29411248

ABSTRACT

Our previous studies demonstrated that the multifunctional agent TBN, a derivative of tetramethylpyrazine armed with a nitrone moiety, displayed high therapeutic efficacy in experimental ischemic stroke models. However, its molecular mechanisms of action underlying the neuroprotective effect need further exploration. In the present study, we found that TBN had significant activities scavenging free radicals such as ·OH, O 2·- and ONOO-, inhibiting Ca2+ overload, maintaining mitochondrial function and preventing neuronal damage in primary cortical cultures. Further, TBN was effective in reducing brain infarction and ameliorating impairment of behavioral functions in the permanent middle cerebral artery occlusion (p-MCAo) rat model. TBN down-regulated the expression of pro-apoptotic factors Bax, while up-regulated the expression of anti-apoptotic factor Bcl-2 and increased the expression of pro-survival factors including p-Akt and p-GSK3ß in the peri-infarct cortex of p-MCAo rats. In addition, LY-294002 (a PI3K inhibitor) and MK2206 (an Akt inhibitor) significantly blocked the protective effect of TBN against OGD-induced death of cortical neurons. Taken together, the multifunctional mechanisms including scavenging free radicals, blocking calcium overload, maintaining mitochondrial function and activating the PI3K/Akt/p-GSK3ß cell survival pathway were possibly involved in the neuroprotective effects of TBN, making it a promising clinical candidate for the treatment of ischemic stroke.


Subject(s)
Infarction, Middle Cerebral Artery/drug therapy , Neuroprotective Agents/therapeutic use , Nitrogen Oxides/therapeutic use , Pyrazines/therapeutic use , Animals , Apoptosis Regulatory Proteins/biosynthesis , Apoptosis Regulatory Proteins/genetics , Calcium/metabolism , Cell Hypoxia , Cells, Cultured , Drug Evaluation, Preclinical , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Glucose/pharmacology , Glutamic Acid/toxicity , Infarction, Middle Cerebral Artery/prevention & control , Lipid Peroxidation/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Motor Activity/drug effects , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Neuroprotective Agents/pharmacology , Nitrogen Oxides/pharmacology , Patch-Clamp Techniques , Protein Kinase Inhibitors/pharmacology , Pyrazines/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
16.
Article in Chinese | WPRIM | ID: wpr-775359

ABSTRACT

With the rapid development of traditional Chinese medicine (TCM) in China as well as the implementation of the four most strict requirements, the quality of Chinese medicinal materials and decoction pieces had beem improved in recent years, however new problems and challenges were occurred. All the data of Chinese medicinal materials and decoction piece in special inspection,supervision test and evaluation inspection of drug administration department to were summarized and analyzed evaluate and analyze of the quality of Chinese medicinal materials and decoction pieces in 2017. On this basis, the relevant quality control strategies and suggestions were put forward for the relevant departments of China Food and Drug Administration to formulate and implement regulatory measures, furthermore to improve drug standards, and ensure the safety of medication.


Subject(s)
China , Drugs, Chinese Herbal , Reference Standards , Medicine, Chinese Traditional , Product Surveillance, Postmarketing , Quality Control
17.
Acta Pharmaceutica Sinica ; (12): 505-509, 2017.
Article in Chinese | WPRIM | ID: wpr-779621

ABSTRACT

This paper was prepared to analyze and discuss the main content of the Botanical Drug Development Guidance for Industry by United States FDA's (the draft version of the 2015), especially focused on the guidelines for clinical research (mainly in late-stage clinical studies) recommendations and requirements sectiones. The key and difficult issues in the late clinic study were analyzed and discussed, and a series of countermeasures were proposed in this paper. At the same time, combined with the case of approved botanical drug products, analysis of the guidelines for the development of plant drug regulations, the enlightenment were presented in the last part, to guide the research and development of traditional Chinese medicine and the internationalization of Chinese medicine.

18.
Acta Pharmaceutica Sinica ; (12): 951-8, 2015.
Article in Chinese | WPRIM | ID: wpr-483401

ABSTRACT

The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.

19.
Acta Pharmaceutica Sinica ; (12): 951-958, 2015.
Article in Chinese | WPRIM | ID: wpr-257042

ABSTRACT

The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.


Subject(s)
Animals , Humans , China , Diabetes Mellitus , Drug Therapy , Disease Models, Animal , Drug Discovery , Hypoglycemic Agents , Medicine, Chinese Traditional
20.
Article in Chinese | WPRIM | ID: wpr-321316

ABSTRACT

By literature survey searching references and parsing prescriptions, the auther has analyze the clinical advantage of Miao medicine in the treatment of symptom heat stranguria. Guizhou Miao medicine Polygonum capitatum has many advantages such as resources and clinical. After companying with Phellodendri Cortex, the compound prescription plays the pharmacological activity of antipyretic and diuretic, especially for the symptom heat stranguria, damp and hot junction based in the bladder. Miao medicine Kelintong capsule showed clinical advantage in the treatment of symptom heat stranguria, having a clinical advantage in improving the overall effectiveness and improve the overall aspects of the patient's symptoms.


Subject(s)
Animals , Humans , Capsules , Chemistry , Therapeutic Uses , Drug Prescriptions , Drugs, Chinese Herbal , Chemistry , Therapeutic Uses , Medicine, Chinese Traditional , Polygonum , Chemistry , Urination Disorders , Drug Therapy
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