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1.
Sci Rep ; 13(1): 19550, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37945746

ABSTRACT

China has became the world's second largest pharmaceutical market, and the number of her registered clinical trials exceeded 3000 in 2021. Although thousands of healthy volunteers are participating in a large number of clinical trials in this country, there is no report about the characteristics, recognition, attitude of Chinese healthy volunteers and their concerns of clinical trials. A questionnaire survey was designed and given to 324 healthy volunteers participating in clinical trials in Wuhan, China. Four important findings emerged from our data. First, young, single and less educated men constituted the majority of Chinese healthy volunteers. Second, differences between the male and female healthy volunteers were observed. Female healthy volunteers are supposed to face more challenges and pressure in life, be more cautious about the clinical trials and more concerned about their health and feelings than the male. Third, no sociodemographic characteristic was associated with poorly understanding of the protocol research content, which was subjectively evaluated. Fourth, more support from society/family and more positive media reports about the participation of healthy volunteers in clinical trials are badly needed. These findings would help us to get a better understanding of Chinese healthy volunteers as a group for protecting them and promoting drug development.


Subject(s)
Attitude , Emotions , Female , Humans , Male , China , Healthy Volunteers , Surveys and Questionnaires , Clinical Trials as Topic
2.
Clin Pharmacol Drug Dev ; 10(12): 1495-1502, 2021 12.
Article in English | MEDLINE | ID: mdl-34288578

ABSTRACT

This bioequivalence study was conducted to determine the pharmacokinetics and safety profiles of an originator and a generic avanafil formulation in Chinese male subjects under fed and fasting conditions. Each eligible subject was initially randomly given avanafil (200 mg) in a test-reference or reference-test order, before being switched to another study drug sequence after 7 drug-free days. The bioequivalence of test and reference avanafil were determined if the 90%CIs of the geometric mean ratio (GMR) for the area under plasma concentration-time curve (AUC) from time 0 to infinity (AUC0-∞ ), AUC from time 0 to the last detectable concentration (AUC0-t ), and the maximum plasma concentration (Cmax ) fell within the range 80%-125%. Under fasting/fed conditions, the 90%CIs of GMR for AUC0-∞ , AUC0-t , and Cmax were 98.9% to 109.5%/96.0% to 101.2%, 99.6% to 110.3%/96.6% to 102.4%, and 99.3% to 116.8%/94.3% to 106.7%, respectively, which were all within the 80%-125% range. Adverse events (AEs) occurred in 20.8% of subjects under fasting conditions and 20.7% of subjects under fed conditions, with a severity of grade 1. No significant difference was found in the rate of occurrence of AEs and drug-related AEs in the test and reference-avanafil groups (all P > .05). We concluded that the test and reference avanafil were bioequivalent in healthy Chinese male subjects under fasting and fed conditions.


Subject(s)
Fasting , Area Under Curve , China , Cross-Over Studies , Healthy Volunteers , Humans , Male , Pyrimidines , Tablets , Therapeutic Equivalency
3.
Toxicol Appl Pharmacol ; 411: 115384, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33359661

ABSTRACT

Benign prostatic hyperplasia (BPH) is an age-related disease in men. Mesenchymal /stromal and epithelial cells interactions are essential to prostate functions. In this study, human nonmalignant prostate epithelial RWPE-1 cells were cocultured with testosterone (TE) -exposed prostate stromal fibroblasts WPMY-1 cells (TE-WPMY-1). The survival rate, epithelial-mesenchymal transition (EMT) and collagen deposition of RWPE-1 were observed. The expression profiles of circRNAs, lncRNAs and mRNAs in WPMY-1-derived exosome-like vesicles (WPMY-1-exo) were explored by high-throughput RNA sequencing. Firstly, both TE-WPMY-1 and TE-WPMY-1-exo significantly promoted RWPE-1 cells proliferation. Secondly, 41 circRNAs, 132 lncRNAs and 1057 mRNAs were differentially expressed (DE) between TE-WPMY-1-exo and the control. Functional enrichment analyses, co-expression analyses and quantitative real-time PCR verification showed that the DE RNAs played important roles in cell proliferation, structure, phenotype and fibrosis. Lastly, blocking WPMY-1-exo biogenesis/release by GW4869 can attenuate TE-WPMY-1-stimulated RWPE-1 cells EMT and collagen deposition. Taken together, our results indicated that WPMY-1-exo modulated the phenotypes changes and collagen deposition of prostate epithelial cells. It provided a novel basis for understanding the underlying mechanisms of RWPE-1 cells EMT and fibrosis induced by WPMY-1 in BPH.


Subject(s)
Cell Proliferation , Epithelial Cells/metabolism , Epithelial-Mesenchymal Transition , Exosomes/metabolism , Paracrine Communication , Prostate/metabolism , Prostatic Hyperplasia/metabolism , Stromal Cells/metabolism , Cell Line , Coculture Techniques , Collagen/metabolism , Epithelial Cells/pathology , Exosomes/drug effects , Exosomes/genetics , Exosomes/pathology , Fibrosis , Gene Regulatory Networks , Humans , Male , Phenotype , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/pathology , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stromal Cells/drug effects , Stromal Cells/pathology , Testosterone/pharmacology , Transcriptome
4.
Int J Antimicrob Agents ; 57(2): 106260, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33309765

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. However, the hazard to newborns in pregnancy remains controversial. The aim of this study was to investigate the vertical transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mother to child and developmental toxicity in the fetus. METHODS: All clinical information was recorded on 22 neonates born to mothers with confirmed COVID-19 pneumonia in Tongji Hospital. RESULTS: The average birth weight of the 22 newborns (16 males and 6 females) was 2980 g, and the mean gestational week was 37W+3. The birth weight of three babies was <2500 g, and the gestational week of all three low-birth-weight neonates was less than 36W. Three newborns had minor lesions of infection in the lungs as shown by computed tomography (CT) scans. Furthermore, three newborns had elevated SARS-CoV-2-related immunoglobin M (IgM) antibodies, and 11 newborns (52.4%) had positive immunoglobin G (IgG) antibodies. Notably, both cystatin C and ß2-microglobulin were increased in all newborns. Five of the 21 tested newborns had leukocytosis, and 11 had increased neutrophil levels. In addition, the aspartate aminotransferase of 18 newborns and the γ-glutamyl transpeptidase of 19 newborns were increased. Total bilirubin was elevated in all newborns and serum albumin was reduced in 20 of 22 newborns. CONCLUSIONS: This study was the first to discover that COVID-19 infection in the third trimester of pregnancy could cause fetal kidney developmental injury, as indicated by increased cystatin C and ß2-microglobulin in all neonates. Furthermore, there is the possibility of maternal-fetal transmission of SARS-CoV-2.


Subject(s)
COVID-19/transmission , Kidney Diseases/virology , Pregnancy Complications, Infectious/virology , Aspartate Aminotransferases/blood , Bilirubin/blood , COVID-19/etiology , COVID-19/immunology , Female , Humans , Immunoglobulin M/blood , Infant, Newborn , Infectious Disease Transmission, Vertical , Kidney Diseases/embryology , Male , Neutrophils , Pregnancy , Pregnancy Complications, Infectious/etiology , Pregnancy Trimester, Third , Retrospective Studies , gamma-Glutamyltransferase/blood
5.
Ecotoxicol Environ Saf ; 191: 110202, 2020 Mar 15.
Article in English | MEDLINE | ID: mdl-31945511

ABSTRACT

The environmental pollution caused by cigarette smoke (CS) seriously endangers people's health. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea. In this study, rats were exposed to CS for 90 days. Kidney function was evaluated by detecting the levels of serum creatinine and blood urea nitrogen. Liver function was evaluated by detecting the activities of alanine aminotransferase and aspartate transaminase. The renal and hepatic oxidative stress and inflammation were assessed by detecting the levels of malondialdehyde, reduced glutathione, antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and proinflammatory cytokines. Organ fibrosis was evaluated by observing collagen deposition via masson staining, by examining the hydroxyproline level, by measuring the mRNA levels of fibrosis-associated genes collagen (Col)-1A1 and Col-3A1, as well as by assessing the activity of profibrotic TGF-ß1 pathway. Additionally, renal and hepatic epithelial-mesenchymal transition (EMT) were evaluated. It was observed that EGCG ameliorated the renal and hepatic oxidative stress, inflammation, EMT, as well as inhibited the activation of TGF-ß1 signaling pathway induced by CS. These results showed that EGCG could attenuate CS-induced renal and hepatic fibrosis.


Subject(s)
Catechin/analogs & derivatives , Kidney/drug effects , Liver/drug effects , Tobacco Smoke Pollution/adverse effects , Animals , Catechin/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Fibrosis , Inflammation/chemically induced , Kidney/metabolism , Kidney/pathology , Liver/enzymology , Liver/pathology , Liver Cirrhosis/chemically induced , Male , Oxidative Stress/drug effects , Rats , Transforming Growth Factor beta1/physiology
6.
Aging (Albany NY) ; 11(22): 10409-10421, 2019 11 17.
Article in English | MEDLINE | ID: mdl-31739286

ABSTRACT

Chronic cigarette smoke (CS) exposure induces prostate deficits. We previously found that swertiamarin had prostatic protective potential. This study was to investigate the possible protective effect of swertiamarin against CS-induced prostate dysfunction on human prostate epithelial cells, stromal cells and rats. Rat prostate collagen deposition and fibrosis were assessed by sirius red staining and measuring hydroxyproline content, as well as by qPCR and western blot analysis for fibrotic extracellular matrix components. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. In order to explore its underling mechanisms, the activities of Hedgehog signaling pathway and epithelial-mesenchymal transition of human prostate cells and rat prostate tissue were estimated. It was found that swertiamarin ameliorated CS-induced prostatic collagen deposition, relieved oxidative stress and local inflammation, inhibited the activation of Hedgehog signaling pathway and attenuated epithelial-mesenchymal transition. It indicated that swertiamarin could ameliorate CS-induced prostatic fibrosis by inhibiting epithelial-mesenchymal transition and Hedgehog pathway.


Subject(s)
Iridoid Glucosides/pharmacology , Prostate/drug effects , Prostate/pathology , Pyrones/pharmacology , Tobacco Smoke Pollution/adverse effects , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cell Line , Epithelial-Mesenchymal Transition/drug effects , Fibrosis/chemically induced , Hedgehog Proteins/metabolism , Humans , Male , Prostate/metabolism , Rats , Rats, Wistar , Tobacco Products/adverse effects
7.
Int Immunopharmacol ; 64: 162-169, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30179845

ABSTRACT

Green tea is among the most popular beverages in the world and is an important source of phytoestrogens. Epigallocatechin­3­gallate (EGCG) is the major polyphenol in green tea. The aim of this study was to investigate the anti-benign prostatic hyperplasia (BPH) activity and underling mechanisms of EGCG in testosterone-induced BPH rats and in BPH-1 cells. Prostatic levels of oxidative stress and inflammation makers, as well as angiogenesis related growth factors were measured. Additionally, the prostatic levels of sex hormonal mediators (androgen receptor (AR), estrogen receptor (ER)-α and ER-ß), hypoxia-inducible factor (HIF)-1α, transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad3, phosphorylation-Smad3 (p-Smad3), epithelial-mesenchymal transition (EMT) markers (E-cadherin, collagen-I, fibronectin and α-SMA) and microRNA (miR)-133a/b were analyzed by immunohistochemistry assay, western blot and/or quantitative RT-PCR. It was observed that EGCG attenuated the prostatic oxidative stress and inflammatory microenvironment, ameliorated prostatic hyperplasia and collagen deposition, reduced the levels of angiogenesis related growth factors, inhibited the over-expression of AR, ER-α, HIF-1α, TGF-ß1, TGF-ßRI and p-Smad3, enhanced the expression of ER-ß, increased the levels of miR-133a/b, as well as relieved prostatic EMT in rats. Both HIF-1α inhibitor and EGCG decreased the expression of HIF-1α and TGF-ß1, as well as attenuated EMT in BPH-1 cells. It indicated that EGCG could attenuate testosterone-induced BPH and fibrosis.


Subject(s)
Catechin/analogs & derivatives , Prostate/drug effects , Prostatic Hyperplasia/drug therapy , Testosterone/toxicity , Animals , Catechin/pharmacology , Collagen/metabolism , Epithelial-Mesenchymal Transition/drug effects , Fibrosis , Male , MicroRNAs/analysis , Oxidative Stress , Prostate/metabolism , Prostate/pathology , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/metabolism , Rats , Rats, Wistar , Receptors, Androgen/analysis , Receptors, Estrogen/analysis , Smad3 Protein/analysis , Transforming Growth Factor beta1/analysis
8.
Cell Physiol Biochem ; 43(4): 1359-1368, 2017.
Article in English | MEDLINE | ID: mdl-28992620

ABSTRACT

BACKGROUND/AIMS: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. METHOD: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. RESULTS: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-ß1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. CONCLUSION: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-ß1/Smad pathways.


Subject(s)
Cadmium/adverse effects , Drugs, Chinese Herbal/therapeutic use , Oxidative Stress/drug effects , Prostate/drug effects , Prostatic Diseases/chemically induced , Prostatic Diseases/drug therapy , Signal Transduction/drug effects , Animals , Epithelial-Mesenchymal Transition/drug effects , Heme Oxygenase-1/metabolism , Male , NF-E2-Related Factor 2/metabolism , Prostate/metabolism , Prostate/pathology , Prostatic Diseases/metabolism , Prostatic Diseases/pathology , Rats , Rats, Wistar , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism
9.
Biomed Pharmacother ; 91: 707-713, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28499242

ABSTRACT

Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl2. GSP also inhibited the over-generation of TGF-ß1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits.


Subject(s)
Cadmium/toxicity , Polyphenols/pharmacology , Prostate/pathology , Seeds/chemistry , Vitis/chemistry , Actins/metabolism , Animals , Body Weight/drug effects , Cadherins/metabolism , Collagen/metabolism , Epithelial-Mesenchymal Transition/drug effects , Fibronectins/metabolism , Glutamate-Cysteine Ligase/metabolism , Heme Oxygenase-1/metabolism , Male , MicroRNAs/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Prostate/drug effects , Prostate/metabolism , Protein Serine-Threonine Kinases/metabolism , Rats, Wistar , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/metabolism , Smad Proteins/metabolism
10.
Behav Brain Res ; 328: 81-86, 2017 06 15.
Article in English | MEDLINE | ID: mdl-28411149

ABSTRACT

This study was conducted to elucidate the neuroprotective effect of caffeic acid phenethyl ester (CAPE), (R)-2-Hydroxy-3-(3,4-dihydroxyphenyl) propionic acid (Danshensu) and Curcumin, three caffeic acid derivatives which are contained in fruits, grains and certain dietary supplements. Our results showed that these compounds significantly attenuated H2O2-induced toxicity in PC12 cells in a dose-dependent manner. Furthermore, these compounds significantly improved the behavioral performance of d-gal-treated mice in both step-down avoidance test and Morris water maze test. Biochemical examination and western blot analysis showed that these compounds could ameliorate oxidative stress and facilitate activation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway. Its beneficial effects may partly relate to enhancing the activity of endogenous antioxidant enzymes and modulating the PKA/CREB signaling pathway. Furthermore, our results also indicated that the presence of 3, 4-dihydroxyphenyl groups in A ring may enhance their neuroprotective activity.


Subject(s)
Caffeic Acids/pharmacology , Curcumin/pharmacology , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Lactates/pharmacology , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Phenylethyl Alcohol/analogs & derivatives , Animals , Avoidance Learning/drug effects , Avoidance Learning/physiology , Caffeic Acids/chemistry , Cell Survival/drug effects , Cell Survival/physiology , Curcumin/chemistry , Dose-Response Relationship, Drug , Galactose , Hydrogen Peroxide , Lactates/chemistry , Maze Learning/drug effects , Maze Learning/physiology , Mice , Neuroprotective Agents/chemistry , Oxidative Stress/physiology , PC12 Cells , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/pharmacology , Random Allocation , Rats , Signal Transduction/drug effects , Spatial Memory/drug effects , Spatial Memory/physiology
11.
Pharm Biol ; 2013 Nov 21.
Article in English | MEDLINE | ID: mdl-24256126

ABSTRACT

Abstract Context: Cyclosorus acuminatus (Houtt.) Nakai (Thelypteridaceae) is used in Chinese traditional medicine for inflammation and pyretic stranguria. Objective: This study investigates the prostatic protective potential of the flavonoid-rich [(2S)-5,7,5'-trihydroxyflavanone glycosides] fraction from C. acuminatus (FCA). Materials and methods: Chronic non-bacterial prostatitis (CNBP) was induced by injecting 20 µl of 1% carrageenan into the rat prostate. Subsequently, FCA (150 or 300 mg/kg/d) was orally given once a day for 4 weeks. Finally, the levels of proinflammatory cytokines and the prostatic expression of peroxisome proliferator activated receptor-γ (PPAR-γ) were evaluated. Results: Treatment with 300 mg/kg/d FCA ameliorated the carrageenan-induced higher prostatic index (PI) state and proinflammatory cytokines levels (NFκB from 2602 ± 588 to 1348 ± 300 pg/ml, TNF-α from 151.6 ± 10.4 to 126.0 ± 3.52 pg/ml, IL-1ß from 153.7 ± 14.8 to 63.9 ± 6.7 pg/ml, COX-2 from 313.3 ± 16.5 to 263.1 ± 15.1 pg/ml, PGE from 1532 ± 130 to 864 ± 126 pg/ml, NOS from 33.7 ± 3.0 to 23.6 ± 1.6 U/mg protein, and NO from 40.3 ± 2.9 to 27.1 ± 2.9 µmol/g protein) as well as regulated the prostatic expression of PPAR-γ (increased about 3.50-fold) when compared to the rat model of prostatitis. Discussion and conclusion: FCA could exert a prostatic protective response via modulating the prostatic expression of PPAR-γ and eventually alleviating the NFκB dependent inflammatory response.

12.
Neurochem Res ; 38(8): 1686-94, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23670091

ABSTRACT

The aim of this study was to investigate the neuroprotective effects of (2S)-5, 2', 5'-trihydroxy-7-methoxyflavanone (TMF), a natural product from Abacopteris penangiana (Hook.) Ching, in oxidative stress-induced neurodegeneration models in vitro and in vivo. In PC12 cells, preincubation of TMF (3-20 µM) for 24 h decreased the dopamine-induced toxicity and attenuated the redox imbalance in PC12 cells through regulating the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG), which is a sensitive marker of oxidative stress. Additionally, long-term intraperitoneal (i.p.) injection of TMF (4 or 8 mg/kg/day) for 2 weeks significantly improved the behavioral performance of D-galactose (D-gal) treated mice in a Morris water maze test. Biochemical analysis revealed that TMF inhibited the activation of AP-1 (activator protein-1) and upregulated the level of BDNF (brain derived neurophic factor) as well as the ratio of GSH/GSSG in the hippocampus of D-gal treated mice. Furthermore, western blotting analysis indicated that TMF increased phosphorylation of cAMP-response element-binding protein (CREB). Therefore, the natural product TMF possessed a potential for the treatment of neurodegenerative diseases.


Subject(s)
Flavones/pharmacology , Neuroprotective Agents/pharmacology , Pteridaceae/chemistry , Animals , Behavior, Animal/drug effects , Dopamine/metabolism , Enzyme-Linked Immunosorbent Assay , Flavones/isolation & purification , Glutathione/metabolism , Glutathione Disulfide/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , In Vitro Techniques , Maze Learning/drug effects , Mice , Nerve Tissue Proteins/metabolism , Neuroprotective Agents/isolation & purification , PC12 Cells , Rats
13.
Food Chem ; 135(4): 2702-7, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-22980861

ABSTRACT

The potential of three natural flavonols (galangin, kaempferol and myricetin) to protect against D-galactose-induced cognitive impairment in mice was investigated. After 8 weeks treatment, the mice were assessed by behavioural tests. The levels of oxidative stress, the amount of Na(+),K(+)-ATPase and extracellular signal-regulated kinases (ERK)-cyclic AMP response element binding protein (CREB) signaling pathway in hippocampus were also analysed. It was found that all the three dietary flavonols could ameliorate the oxidative stress, enhance the activity of Na(+),K(+)-ATPase and regulate the expression of ERK-CREB pathway in mice. However, only kaempferol and myricetin could significantly improve the learning and memory capability when compared with D-galactose model. Our results suggest that the presence of hydroxyl groups in the B ring of flavonols may have contribution to the neuroprotective activity.


Subject(s)
Cognition Disorders/drug therapy , Cognition Disorders/metabolism , Flavonoids/administration & dosage , Kaempferols/administration & dosage , Neuroprotective Agents/administration & dosage , Oxidative Stress/drug effects , Animals , Behavior, Animal/drug effects , Cognition Disorders/chemically induced , Cognition Disorders/psychology , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Extracellular Signal-Regulated MAP Kinases/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Galactose/adverse effects , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Male , Mice , Signal Transduction/drug effects
14.
Food Chem ; 134(4): 1959-66, 2012 Oct 15.
Article in English | MEDLINE | ID: mdl-23442644

ABSTRACT

This study was conducted to characterise the flavonoid components of total flavan glycoside from Abacopteris penangiana rhizomes (TFA) and its acid hydrolysate (AHT) through HPLC-DAD-ESI-MS/MS analysis, and to investigate the hypothesis that TFA and AHT exhibit anti-benign prostatic hyperplasia (BPH) potential in castrated rats with testosterone-induced BPH. HPLC-MS/MS analysis indicated that TFA is rich in flavan-4-ol glycosides and AHT mainly contains 3-deoxygenated anthocyanidin. After 4 weeks of administration, TFA and AHT successfully decreased the prostate index and prostate specific antigen plasma concentrations in the rats. Histoarchitectural improvement in the prostate gland was also observed. Reduced dihydrotestosterone, VEGF, bFGF, EGF, and KGF levels were observed both in TFA- and AHT-treated rats. Furthermore, the prostatic expression of Blc-2 was inhibited, whereas that of Bax and p53 was activated by TFA and AHT. In conclusion, TFA and AHT have anti-BPH properties. Hence, plants with flavan glycosides have potential use in the treatment of BPH.


Subject(s)
Ferns/chemistry , Flavonoids/administration & dosage , Glycosides/administration & dosage , Plant Extracts/administration & dosage , Prostatic Hyperplasia/drug therapy , Rhizome/chemistry , Animals , Chromatography, High Pressure Liquid , Epidermal Growth Factor/genetics , Epidermal Growth Factor/metabolism , Flavonoids/chemistry , Glycosides/chemistry , Humans , Male , Mass Spectrometry , Plant Extracts/chemistry , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/metabolism , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
15.
J Ethnopharmacol ; 139(1): 207-13, 2012 Jan 06.
Article in English | MEDLINE | ID: mdl-22101083

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Macrothelypteris torresiana is traditionally used in Chinese folk medicine for the treatment of edema for patients suffering from kidney/bladder problems due to its satisfactory therapeutic effectiveness. AIM OF THE STUDY: The aim of this study was to investigate the renoprotective nature of the total polyphenols fraction from Macrothelypteris torresiana (PMT). MATERIALS AND METHODS: The biochemical criterions of plasma and kidney tissues were evaluated to study the effects of PMT on puromycin aminonucleoside-induced chronic nephrotic syndrome (NS) in hyperlipidemic mice. RESULTS: In this study, the NS and hyperlipidemia were ameliorated after 9 weeks administration of PMT. Besides, PMT was able to modulate the level of renal oxidative stress and vascular endothelial growth factor-nitric oxide (VEGF-NO) pathway. CONCLUSIONS: It represented a potential resource of PMT for the treatment of NS involved in metabolic syndrome.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Ferns , Hyperlipidemias/drug therapy , Nephrotic Syndrome/drug therapy , Polyphenols/therapeutic use , Protective Agents/therapeutic use , Animals , Blood Glucose/analysis , Blood Urea Nitrogen , Creatinine/blood , Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Hyperlipidemias/etiology , Hyperlipidemias/metabolism , Kidney/drug effects , Kidney/metabolism , Lipid Peroxidation/drug effects , Lipids/blood , Male , Mice , Nephrotic Syndrome/chemically induced , Nephrotic Syndrome/metabolism , Nitric Oxide/blood , Nitric Oxide Synthase Type II/blood , Oxidative Stress/drug effects , Phytotherapy , Polyphenols/pharmacology , Potassium Dichromate , Protective Agents/pharmacology , Puromycin Aminonucleoside , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/metabolism
16.
Food Chem Toxicol ; 49(12): 3206-10, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21963953

ABSTRACT

This study was to investigate the hypolipidemic and anti-inflammatory properties of Abacopterin A (APA), a flavonoid compound isolated from Abacopteris penangiana (Hook.) Ching. Male C57BL/6J mice were divided randomly and equally into five groups: the normal control group (N), the model group (M), the positive control group (P), the high and low doses of APA treated groups (H and L). All the animals except that in N group were fed with high-fat diet for 8 weeks. In the last 4 weeks, the mice in P, H and L groups were orally administered with simvastatin (at the dose of 20mg/kg/day) and APA (at the dose of 40 or 20mg/kg/day), respectively. Then the lipid profiles and related biochemical criterions of the studied mice were determined. The effects of high-fat diet on activating nuclear transcription factor-κB (NFκB) expression, elevating inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and increasing triacylglycerol (TG) and total cholesterol (TC) levels were abolished on daily supplementation with APA. APA also enhanced lipoprotein lipase (LPL) and hepatic lipase (HL) activities. These results suggested that APA had hypolipidemic and anti-inflammatory properties through inhibiting NFκB expression, and reducing inflammatory response.


Subject(s)
Anthocyanins/pharmacology , Anti-Inflammatory Agents/pharmacology , Diet, High-Fat , Glycosides/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Plant Extracts/pharmacology , Animals , Cholesterol/blood , Dietary Fats/administration & dosage , Ferns/chemistry , Gene Expression Regulation , Hyperlipidemias/chemically induced , Interleukin-6/blood , Lipoprotein Lipase/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/metabolism , Phytotherapy , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood
17.
J Asian Nat Prod Res ; 13(8): 707-13, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21751838

ABSTRACT

Two neuropective compounds were isolated from the rhizomes of Abacopteris penangiana, one was a new flavone and the other was a flavanone. Both compounds were firstly separated from natural plant. The isolation work was guided by the antioxidant activity. Both the compounds showed a significant antioxidant activity in vitro and a protective effect on dopamine-induced neurotoxicity in PC12 cells.


Subject(s)
Antioxidants/isolation & purification , Antioxidants/pharmacology , Ferns/chemistry , Flavanones/isolation & purification , Flavanones/pharmacology , Flavones/isolation & purification , Flavones/pharmacology , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Animals , Antioxidants/chemistry , Dopamine/pharmacology , Flavanones/chemistry , Flavones/chemistry , Molecular Structure , Neuroprotective Agents/chemistry , PC12 Cells , Rats , Rhizome/chemistry
18.
J Ethnopharmacol ; 136(1): 217-23, 2011 Jun 14.
Article in English | MEDLINE | ID: mdl-21549824

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: "Sanxuelian", the rhizome of Abacopteris penangiana (AP), is traditionally used in Chinese medicine for the treatment of blood circulation stasis, hemorheology barriers, edema and inflammation for patients of metabolic syndrome. This study was to investigate the protective effect of the total flavanol glycosides from AP (FAP) on diabetic vascular impairments by measuring the extents of oxidative stress and inflammatory response in mice. MATERIALS AND METHODS: The experimental aortic pathology in diabetic mice was induced by fed on high-fat diet and injected with streptozotocin. The activities of FAP on attenuating aortas injuries, hypoglycemic, hypolipidemic, inhibiting oxidative stress and anti-inflammation were investigated. Additionally, the aortic expressions of nuclear transcription factor-κB (NFκB) were determined by western blot and immunohistochemistry analysis. Furthermore, the effects of FAP on human umbilical vein endothelia cells (HUVECs) were studied. RESULTS: In animal study, the results showed that FAP enhanced the activities of antioxidant enzymes and attenuated the levels of proinflammatory cytokines. The plasma lipid profiles and glucose level in FAP treated groups were significantly decreased along with the vascular impairments were alleviated. Moreover, the aortic expression of NFκB was decreased. In cellular experiment, FAP could inhibit the apoptosis of HUVECs induced by H(2)O(2). CONCLUSIONS: The results indicated that FAP had hypolipidemic, hypoglycemic and vascular protective activities and represented a potential herb for the treatment of aortic pathology involved with metabolic syndrome.


Subject(s)
Diabetes Complications/prevention & control , Ferns/chemistry , Flavonols/therapeutic use , NF-kappa B/metabolism , Oxidative Stress/drug effects , Phytotherapy , Vascular Diseases/prevention & control , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Aorta/metabolism , Aorta/pathology , Apoptosis/drug effects , Blood Glucose/metabolism , Cytokines/metabolism , Diabetes Complications/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Dietary Fats/adverse effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flavonols/pharmacology , Glycosides/pharmacology , Glycosides/therapeutic use , Humans , Lipids/blood , Male , Mice , Mice, Inbred Strains , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rhizome , Signal Transduction/drug effects , Transcription Factors/metabolism , Umbilical Veins/cytology , Vascular Diseases/etiology , Vascular Diseases/metabolism
20.
J Ethnopharmacol ; 134(2): 275-80, 2011 Mar 24.
Article in English | MEDLINE | ID: mdl-21167928

ABSTRACT

AIM OF THE STUDY: Abacopterin E (AE) was isolated from Abacopteris penangiana (Hook.) Ching. This study was to elucidate its neuroprotective effects against hydrogen peroxide (H(2)O(2)) induced oxidative damage in PC12 cells and d-galactose (d-Gal) induced neurotoxicity in mice brain. MATERIALS AND METHODS: In vitro, the protective effect of AE against H(2)O(2)-induced oxidative damage in the PC12 was investigated by the method of MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide). In vivo, the protective effect of AE against d-Gal-induced neurotoxicity in mice was studied. The mice in the model group and the AE treatment groups were injected with the d-Gal 150 mg/(kg d) for 7 weeks while the mice in the control group were injected with the same volume of saline (0.9%). From the sixth week, the treatment groups were subcutaneously injected 4 or 8 mg/(kg d) of AE. In order to explore the potential mechanism of AE's action, the mice were assessed by behavioral and electrophysiological tests at the end of the administration. Then the mice brain tissues were measured for the levels of superoxide dismutases (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). RESULTS: This study showed that AE lowered the H(2)O(2)-induced cytotoxicity, and AE significantly improved the learning and memory ability in behavioral performance. The biochemical examination revealed that AE restored the activities of SOD and GSH-Px, and attenuated the increase of MDA. Moreover, the electrophysiological analysis evidently showed that AE ameliorated the long-term potentiation (LTP). CONCLUSIONS: These results suggested that AE had neuroprotective effects, and its beneficial effects may be linked with inhibiting the generation of free radical and enhancing the activities of endogenous antioxidant enzymes.


Subject(s)
Anthocyanins/therapeutic use , Antioxidants/therapeutic use , Ferns/chemistry , Glycosides/therapeutic use , Memory/drug effects , Neurotoxicity Syndromes/drug therapy , Oxidative Stress/drug effects , Phytotherapy , Animals , Anthocyanins/isolation & purification , Anthocyanins/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Galactose , Glutathione Peroxidase/metabolism , Glycosides/isolation & purification , Glycosides/pharmacology , Hydrogen Peroxide , Long-Term Potentiation/drug effects , Malondialdehyde/metabolism , Mice , Mice, Inbred Strains , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neurotoxicity Syndromes/metabolism , PC12 Cells , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Superoxide Dismutase/metabolism
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