Publications by authors named "Chun-Feng Zhang"

73 Publications

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration.

Chin Med J (Engl) 2021 Sep 20;134(19):2322-2332. Epub 2021 Sep 20.

Department of Ophthalmology, Peking University First Hospital, Beijing 100034, China.

Background: Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD.

Methods: The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed.

Results: Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE.

Conclusions: Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CM9.0000000000001773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510006PMC
September 2021

Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation.

Front Pharmacol 2021 14;12:698981. Epub 2021 Jul 14.

Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, United States.

SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.698981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316858PMC
July 2021

Screen of anti-migraine active compounds from Duijinsan by spectrum-effect relationship analysis and molecular docking.

J Ethnopharmacol 2021 Oct 20;279:114352. Epub 2021 Jun 20.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA. Electronic address:

Ethnopharmacological Relevance: Duijinsan (DJS) is a famous Chinese medicine prescription composed of Radix scutellariae (RS) and Rhei Radix (RRR), which has been mainly used for treating migraine.

Aim Of The Study: This study aimed to uncover the anti-migraine active compounds from DJS and preliminary predicted the pharmacological mechanism by evaluating the spectrum-effect relationship between high-performance liquid chromatography (HPLC) fingerprints and anti-migraine effects of Duijinsan (DJS) extract combined with molecular docking.

Materials And Methods: HPLC and LC-MS were applied for chemical analyses of DJS extracts in different proportions. Inhibition of DJS extracts on trigeminal nerve cell releasing calcitonin gene related peptide (CGRP) experiment was performed. The active compounds were screened by spectrum-effect relationship analysis and confirmed by molecular docking and the activities of major predicted compounds were validated in vitro.

Results: Twenty-six common peaks were assigned and identified from the fingerprints of different proportions DJS extracts. In vitro experimental results showed that DJS extracts inhibited inflammation and release of CGRP from trigeminal nerve cells. Five predicted active compounds, Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide were sorted out according to spectrum-effect relationship analysis and molecular docking comprehensively. In vitro validation experiments showed that all the predicted compounds inhibited the CGRP releasing and the activation of TRPV1 channel. Baicalin, chrysin-7-O-β-D-glucuronide and Oroxylin A-7-glucoronide significantly inhibited the activation of TRPV1 channel.

Conclusion: Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide which can inhibit the CGRP releasing and the activation of TRPV1 channel were screened as the anti-migraine active compounds by spectrum-effect relationship analysis and molecular docking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114352DOI Listing
October 2021

Sirtuin 3 Ameliorates Lung Senescence and Improves Type II Alveolar Epithelial Cell Function by Enhancing the FoxO3a-Dependent Antioxidant Defense Mechanism.

Stem Cells Dev 2021 Sep 16;30(17):843-855. Epub 2021 Jul 16.

Department of Cardiovascular Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/scd.2021.0099DOI Listing
September 2021

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer.

Drug Des Devel Ther 2021 12;15:557-576. Epub 2021 Feb 12.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, People's Republic of China.

Purpose: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA.

Methods: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model.

Results: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model.

Conclusion: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S292417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886095PMC
October 2021

Comprehensive evaluation on anti-inflammatory and anti-angiogenic activities in vitro of fourteen flavonoids from Daphne Genkwa based on the combination of efficacy coefficient method and principal component analysis.

J Ethnopharmacol 2021 Mar 8;268:113683. Epub 2020 Dec 8.

Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, 60637, USA. Electronic address:

Ethnopharmacological Relevance: Genkwa flos, as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema.

Aim Of The Study: The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions.

Materials And Methods: The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation.

Results: Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-β-D-glucoside), H2 (apigenin-7-O-β-D-glucoside), H3 (kaempferol-3-O-β-D-glucoside), H4 (hydroxygenkwanin-5-O-β-D-primeveroside), H5 (apigenin-5-O-β-D-primeveroside), H6 (apigenin-7-O-β-D-glucuronide), H7 (luteolin-5-O-β-D-glucopyranoside), H8 (genkwain-5-O-β-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3'- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14.

Conclusion: Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113683DOI Listing
March 2021

Chinese medicine GeGen-DanShen extract protects from myocardial ischemic injury through promoting angiogenesis via up-regulation of VEGF/VEGFR2 signaling pathway.

J Ethnopharmacol 2021 Mar 14;267:113475. Epub 2020 Oct 14.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA.

Headings Ethnopharmacological Relevance: Coronary heart disease (CHD) usually refers to myocardial ischemia or myocardial necrosis caused by coronary artery stenosis. GeGen and DanShen (GD) are popular Chinese herbs for the treatment of angina pectoris and myocardial infarction (MI). This sentence needs to be a separate paragraph.

Aim Of The Study: This study was to investigate the role of GD extract in promoting ischemic myocardial angiogenesis, and to explore its signaling mechanism, so as to provide a more reliable scientific basis for the clinical treatment of ischemic cardiovascular disease.

Materials And Methods: GD extract was initially analyzed by HPLC-Q-TOF MS. In vitro, migration assay and tube formation assay were subsequently used to detect the angiogenesis activity of GD extract in human umbilical vein endothelial cells (HUVECs). Following the in vitro study, an MI rat model was established by ligating the left anterior descending coronary artery (LAD), immediately followed by a 4-week daily GD extract treatment by intragastric administration. After the animal sacrifice, hematoxylin-eosin (HE) staining was conducted to observe the pathological changes of the infarct margin. Besides, the MI area was measured by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The microvascular density (MVD) was also quantified through CD31 immunohistochemistry. Moreover, the levels of VEGF, TXB2 and 6-keto-PGF1α in serum were detected by enzyme-linked immunosorbent assay. The expression of VEGFR2 and ERK were detected by immunohistochemistry as well.

Results: In vitro study, GD extract was found to induce significant angiogenesis in HUVECs. In vivo, smaller infarct size was found in treatment groups than that of the model group, and the protein expression of VEGFR2 as well as ERK in the marginal zone of MI in treatment groups were significantly increased. The morphological changes of myocardium were observed with a significant growth in the number of new blood vessels. Regarding the effect of GD extract, the serum levels of CK, LDH and TXB2 were consequently reduced, whereas the levels of VEGF, 6-keto-PGF1α were significantly increased.

Conclusions: Based on the findings of this study, GD extract had a protective effect against MI in rats. The possible mechanism is to promote angiogenesis by regulating the VEGF/VEGFR2 signaling pathway after MI occurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113475DOI Listing
March 2021

Evidence for the existence of CD34 angiogenic stem cells in human first-trimester decidua and their therapeutic for ischaemic heart disease.

J Cell Mol Med 2020 10 8;24(20):11837-11848. Epub 2020 Sep 8.

Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Stem cell transplantation is nearly available for clinical application in the treatment of ischaemic heart disease (IHD), where it may be joined traditional methods (intervention and surgery). The angiogenic ability of seed cells is essential for this applicability. The aim of this study was to reveal the presence of CD34 angiogenic stem cells in human decidua at the first trimester and to use their strong angiogenic capacity in the treatment of IHD. In vitro, human decidual CD34 (dCD34 ) cells from the first trimester have strong proliferation and clonality abilities. After ruling out the possibility that they were vascular endothelial cells and mesenchymal stem cells (MSCs), dCD34 cells were found to be able to form tube structures after differentiation. Their angiogenic capacity was obviously superior to that of bone marrow mesenchymal stem cells (BMSCs). At the same time, these cells had immunogenicity similar to that of BMSCs. Following induction of myocardial infarction (MI) in adult rats, infarct size decreased and cardiac function was significantly enhanced after dCD34 cell transplantation. The survival rate of cells increased, and more neovasculature was found following dCD34 cell transplantation. Therefore, this study confirms the existence of CD34 stem cells with strong angiogenic ability in human decidua from the first trimester, which can provide a new option for cell-based therapies for ischaemic diseases, especially IHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578869PMC
October 2020

Anti-migraine effect of wine-processed Radix scutellariae: Pharmacodynamic verification in nitroglycerin-induced rats and correlation study between compounds dissolution and the fractal dimension.

J Ethnopharmacol 2020 Dec 28;263:113131. Epub 2020 Jul 28.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA.

Ethnopharmacological Relevance: Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear.

Aim Of The Study: To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory.

Materials And Methods: In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV-Vis spectrophotometry and HPLC separately.

Results: The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution.

Conclusions: Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113131DOI Listing
December 2020

Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.

Biomed Chromatogr 2020 Oct 1;34(10):e4911. Epub 2020 Jul 1.

Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.

Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.4911DOI Listing
October 2020

Effect of liquiritin on neuroendocrine-immune network in menopausal rat model.

Phytother Res 2020 Oct 12;34(10):2665-2674. Epub 2020 Apr 12.

Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, USA.

Purpose: The aim of the study was to investigate the effect of liquiritin on neuroendocrine-immune network in menopausal rat model.

Methods: Liquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E ) and follicle-stimulating hormone (FSH) in the serum and 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin-eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining.

Results: For the nervous system, liquiritin relieved menopausal depression and up-regulated the levels of 5-HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen.

Conclusions: Liquiritin improved menopausal syndrome in multiple ways by affecting the neuro-endocrine-immune network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.6696DOI Listing
October 2020

Transfection of Aged Human Bone Marrow-Derived Mesenchymal Stem Cells Improves Cell Therapy-Mediated Myocardial Repair.

Rejuvenation Res 2020 Dec 28;23(6):453-464. Epub 2020 Apr 28.

Future Medical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Sirtuin 3 (SIRT3) is a deacetylase important for antioxidant protection, cell longevity, and aging. We hypothesized that SIRT3 improve oxidative resistance of aged cells and improve cell therapy in aged patients. , the proliferation and oxidative resistance of human mesenchymal stem cells (hMSCs) significantly declined with age. The expression and activity of antioxidant enzymes, including catalase (CAT) and manganese superoxide dismutase (MnSOD), increased after transfection of in hMSCs from older donors (O-hMSCs). The protein level of Forkhead box O3a (FOXO3a) in nucleus increased after SIRT3 overexpression. The antioxidant capacity of O-hMSCs increased after SIRT3 overexpression. 3-Amino-1,2,4-triazole (3-AT, CAT inhibitor) or diethyldithiocarbamate (DETC, SOD inhibitor) that was used to inhibit CAT or SOD activity significantly blocked the antioxidant function of SIRT3. When two inhibitors were used together, the antioxidant function of SIRT3 almost disappeared. Following myocardial infarction and intramyocardial injections of O-hMSCs in rats , the survival rate of O-hMSCs increased by transfection. The cardiac function of rats was improved after SIRT3-overexpressed O-hMSC transplantation. The infarct size, collagen content, and expression levels of matrix metalloproteinase 2 (MMP2) and MMP9 decreased. Besides, the protein level of vascular endothelial growth factor A and vascular density increased after cell transplantation with SIRT3-modified O-hMSCs. These results indicate that damage resistance of hMSCs decline with age and SIRT3 might protect O-hMSCs against oxidative damage by activating CAT and MnSOD through transferring FOXO3a into nucleus. Meanwhile, the therapeutic effect of aged hMSC transplantation can be improved by SIRT3 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/rej.2019.2260DOI Listing
December 2020

Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa.

Int Immunopharmacol 2020 Jun 18;83:106384. Epub 2020 Mar 18.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.

Objective: This study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism.

Methods: The anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs).

Results: TF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-α, IL-6, IFN-γ and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-κB (NF-κB) pathway by decreasing the phosphorylation levels of IKK, IκB and NF-κB, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6.

Conclusion: The most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-κB pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.106384DOI Listing
June 2020

Ginseng berry polysaccharides on inflammation-associated colon cancer: inhibiting T-cell differentiation, promoting apoptosis, and enhancing the effects of 5-fluorouracil.

J Ginseng Res 2020 Mar 2;44(2):282-290. Epub 2019 Jan 2.

Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, USA.

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms.

Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation.

Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4IFN-γ cell (Th1) differentiation, and decreased CD4FoxP3 cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil.

Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgr.2018.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031751PMC
March 2020

Chinese Medicine , Containing , and , Protects from Myocardial Ischemia Injury via Angiogenesis.

Am J Chin Med 2020 14;48(1):107-126. Epub 2020 Jan 14.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China.

The Chinese patent medicine (SXXTN) is a clinical medication for coronary heart disease (CHD) and angina pectoris. This study aimed to investigate pharmacological effects of SXXTN and elucidate the role in angiogenesis on human umbilical vein endothelial cells (HUVECs) and acute myocardial ischemia (AMI) rats. We prepared SXXTN to treat the cells to reveal their effects on oxidative stress-damaged cell viability, as well as cell proliferation, migration, and tube formation processes. SXXTN was also used to treat coronary artery ligation-induced acute myocardial ischemia rats to confirm whether it had positive effect on myocardial issues by hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining. We measured the levels of peroxidative damage-related enzymes in cytoplasm and serum by biochemical kits and detected vascular endothelial growth factor (VEGF), angiotensin II (Ang II), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1) levels in cells and rats by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that SXXTN protects HUVECs against oxidative stress damage and reversed the decrease of superoxide dismutase (SOD), glutathione (GSH) and increase of creatine kinase (CK), lactate dehydrogenase (LDH) caused by oxidative stress. SXXTN promoted angiogenesis through stimulating cell migration, tube formation, and activating VEGF/VEGFR2 and ERK1/2 pathways. Furthermore, SXXTN reduced infarct size and inhibited PGI2/TXA2 imbalance, preventing atherosclerosis plaque rupture leading to worsening coronary heart disease. Taken together, we report the first and evidence that SXXTN reduced oxidative stress-mediated damage and enhanced angiogenesis, which might be useful in treatment of myocardial infarction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1142/S0192415X20500068DOI Listing
September 2020

Optimization of Low-Dimensional Components of Quasi-2D Perovskite Films for Deep-Blue Light-Emitting Diodes.

Adv Mater 2019 Nov 18;31(44):e1904319. Epub 2019 Sep 18.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.

Compared to efficient green and near-infrared light-emitting diodes (LEDs), less progress has been made on deep-blue perovskite LEDs. They suffer from inefficient domain [various number of PbX layers (n)] control, resulting in a series of unfavorable issues such as unstable color, multipeak profile, and poor fluorescence yield. Here, a strategy involving a delicate spacer modulation for quasi-2D perovskite films via an introduction of aromatic polyamine molecules into the perovskite precursor is reported. With low-dimensional component engineering, the n domain, which shows nonradiative recombination and retarded exciton transfer, is significantly suppressed. Also, the n domain, which represents the population of emission species, is remarkably increased. The optimized quasi-2D perovskite film presents blue emission from the n domain (peak at 465 nm) with a photoluminescence quantum yield (PLQY) as high as 77%. It enables the corresponding perovskite LEDs to deliver stable deep-blue emission (CIE (0.145, 0.05)) with an external quantum efficiency (EQE) of 2.6%. The findings in this work provide further understanding on the structural and emission properties of quasi-2D perovskites, which pave a new route to design deep-blue-emissive perovskite materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.201904319DOI Listing
November 2019

Identification of the metabolites in normal and AA rat plasma, urine and feces after oral administration of Daphne genkwa flavonoids by LC-Q-TOF-MS spectrometry.

J Pharm Biomed Anal 2020 Jan 4;177:112856. Epub 2019 Sep 4.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA.

Daphne genkwa Sieb. et Zucc., as a traditional oriental herb, has been widely distributed and employed in China. The major bioactive components in D. genkwa are flavonoid compounds, which showed pharmacological activities such as anti-inflammatory, analgesic, anti-tumor and immunomodulatory activities. In this study, we analyzed total flavonoids in D. genkwa and their metabolites in normal and adjuvant arthritis (AA) rat plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). A total of 4 metabolites in plasma, 9 metabolites in urine and 15 metabolites in feces were characterized respectively by LC-Q-TOF-MS technology in normal rat. And 9 of the metabolites were observed in the AA rat urine, while there was no prototype drug or its metabolites detected in plasma and fecal samples. The metabolic pathway mainly involves hydroxylation, methylation, glucuronide, sulfate conjugation, oxidation and reduction, during the phase I and phase II biotransformation pathway. All the information gained here will be greatly helpful in elucidating the potential biological and pharmacological mechanism of flavonoid in D. genkwa, thus providing new ideas for drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2019.112856DOI Listing
January 2020

Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-κB signaling pathways.

Phytomedicine 2019 Oct 1;63:153036. Epub 2019 Aug 1.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, United States.

Background: Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA.

Purpose: This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms.

Methods: The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis.

Results: Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats.

Conclusion: Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2019.153036DOI Listing
October 2019

Red American ginseng enhances the effect of fluorouracil on human colon cancer cells via both paraptosis and apoptosis pathways.

J Appl Biomed 2018 Nov 31;16(4):311-319. Epub 2018 May 31.

Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.

Introduction: As a commonly used chemotherapeutic agent, fluorouracil (5-FU) has serious dose-limiting side effects. In this study, we evaluated the synergy between red American ginseng (RAG) and 5-FU on human colorectal cancer cells, and explored the potential mechanisms.

Methods: Ginsenoside contents of white American ginseng (WAG) and RAG were determined by HPLC. Cell proliferation was evaluated by MTS assay. Combination Index (CI) analysis was executed using CompuSyn software. Paraptotic events were observed after crystal violet staining. Cell cycle distribution, cyclin A expression and apoptotic induction were analyzed using flow cytometry.

Results: We observed the heat treatment remarkably increased levels of ginsenoside Rg3, 20-Rg3, Rk1 and Rg5. When the combinations of 5-FU and RAG were applied, cell proliferation inhibition rates were notably increased, indicating that RAG significantly enhanced 5-FU's effect. Additionally, CI analysis suggested that there was a synergistic action of 5-FU and RAG when combined. The cell cycle data indicated 5-FU induced S phase arrest, and the combination of 5-FU and RAG increased G1 phase. Further, the RAG's ability to enhance the anti-cancer effects of 5-FU was linked to both paraptosis and apoptosis inductions.

Conclusion: RAG may have clinical utility to decrease the dosage of 5-FU in colorectal cancer therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456072PMC
November 2018

Fecal metabolomic dataset of American ginseng-treated DSS mice: Correlation between ginseng enteric inflammation inhibition and its biological signatures.

Data Brief 2018 Dec 29;21:1403-1408. Epub 2018 Oct 29.

Department of Anesthesia & Critical Care, and Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.

Although anti-inflammatory effects of American ginseng metabolites have been investigated at systemic and cellular levels, the biological signatures of ginseng microbial metabolite-induced bioactivities are still unknown. To fill this knowledge gap and to support the findings published in the companion research article entitled "American ginseng microbial metabolites attenuated DSS-induced colitis and abdominal pain" (Wang et al., 2018), we are here to provide datasets of enteric microbiome biotransformation and fecal metabolomics. For the microbiome biotransformation study, data were obtained from C57BL6 mice treated with a broad-spectrum antibiotic metronidazole. After oral administration of ginseng extract, we observed that compound K (CK) was undetectable in metronidazole-treated mouse stools but was detected in stools from vehicle-treated mice, suggesting biotransformation of CK is gut microbial dependent. In the fecal metabolomic study, three small molecules which were associated with gut inflammation were identified. In the DSS mice, the levels of lactate, linoleic acid, and malic acid increased significantly in the model group. After ginseng treatment, the expressions of these metabolites reduced significantly. Thus, the selective fecal endogenous metabolites could be used as biological signatures reflecting severity of enteric inflammation and ginseng treatment outcomes. Our results showed the enteric microbiome plays a key role for CK conversion, and the effects of CK on enteric inflammation can be demonstrated by the metabolomics data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2018.10.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234249PMC
December 2018

Deglycosylation of wogonoside enhances its anticancer potential.

J Cancer Res Ther 2018 Sep;14(Supplement):S594-S599

Tang Center for Herbal Medicine Research, University of Chicago; Department of Anesthesia and Critical Care, University of Chicago; Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA.

Introduction: Scutellaria baicalensis is commonly used in Asia as an herbal medicine to treat a variety of ailments, including cancer. Wogonoside, one major constituent of S. baicalensis, can be primarily converted to wogonin through deglycosylation via enteric microbiome metabolism.

Materials And Methods: The antiproliferative effects of the glycoside (wogonoside) and its deglycosylated compound (wogonin) on a panel of human cancer cell lines from the most common solid tumors were evaluated using the MTS colorimetric assay. Cell cycle and apoptosis were determined using flow cytometry. Enzymatic activities of caspases were measured, and the interactions of wogonin and caspases were explored by a docking analysis.

Results: Wogonoside did not have obvious antiproliferative effects on the cancer cells. In contrast, wogonin showed significant antiproliferative activities on all the tested cancer cells. Wogonin arrested the cells in the G1 phase and significantly induced cell apoptosis. The compound also activated the expression of caspases 3 and 9. The docking results suggest that the compound forms hydrogen bonds with Phe250 and Ser251, and π-π interactions with Phe256 in caspase 3, and with Asp228 in caspase 9.

Conclusions: After wogonoside deglycosylation, wogonin significantly enhanced its anticancer potential as a potent anticancer compound derived from S. baicalensis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0973-1482.183218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159225PMC
September 2018

Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model.

Biomed Pharmacother 2018 Dec 15;108:309-315. Epub 2018 Sep 15.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.

Smilax glabra Roxb. (Tufuling) and Bolbostemma paniculatum (Maxim.) Franquet (Tubeimu) are used as couplet medicine in traditional Chinese medicine for the treatment of arthritis. This study is conducted to provide evidence on their therapeutic effects on rheumatoid arthritis (RA) and to explore its possible mechanisms of action. The identification and quantification of representative components (Astilbin and Tubeimoside I) in the n-butyl alcohol fraction of this couplet medicine (BFCM) were carried out by HPLC-UV assays. The contents of Astilbin and Tubeimoside I in BFCM were 13.13% (15.434 min) and 3.4% (18.619 min) respectively. For the assessment of anti-RA and anti-inflammatory activities, a carrageenan-induced paw edema model in rats was used. The swelling rates of paws and levels of IL-1β, IL-6 and TNF-α in the swelling tissue were determined. We observed that the BFCM exhibited significant inhibitory activity on carrageenan-induced paw edema model (p<0.01). The down regulated levels of IL-1β, IL-6 and TNF-α (all p<0.05) were reported. The results indicate that BFCM possesses significant anti-RA and anti-inflammatory effects, and it has a potential to be developed as a new therapeutic agent against RA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.09.004DOI Listing
December 2018

American ginseng microbial metabolites attenuate DSS-induced colitis and abdominal pain.

Int Immunopharmacol 2018 Nov 10;64:246-251. Epub 2018 Sep 10.

Department of Anesthesia & Critical Care, and Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA.

Inflammatory bowel disease (IBD) is a significant public health problem in the United States. Abdominal pain is a major complaint among individuals with IBD. Successful IBD management not only controls enteric inflammation, but also reduces abdominal discomfort. Recently, increased attention has been focused on alternative strategies for IBD management. HPLC/Q-TOF-MS analysis was employed to evaluate the intestinal microbiome's biotransformation of parent American ginseng compounds into their metabolites. Using a DSS mouse model, the effects of American ginseng microbial metabolites on chemically induced colitis was investigated with disease activity index and histological assessment. Expressions of inflammatory cytokines were determined using real-time PCR and ELISA. Abdominal pain was evaluated using the von Frey filament test. After the gut microbiome's biotransformation, the major metabolites were found to be the compound K and ginsenoside Rg3. Compared with the DSS animal group, American ginseng treatment significantly attenuated experimental colitis, as supported by the histological assessment. The enteric microbiome-derived metabolites of ginseng significantly attenuated the abdominal pain. American ginseng treatment significantly reduced gut inflammation, consistent with pro-inflammatory cytokine level changes. The gut microbial metabolite compound K showed significant anti-inflammatory effects even at low concentrations, compared to its parent ginsenoside Rb1. American ginseng intestinal microbial metabolites significantly reduced chemically-induced colitis and abdominal pain, as mediated by the inhibition of pro-inflammatory cytokine expression. Intestinal microbial metabolism plays a critical role in American ginseng mediated colitis management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2018.09.005DOI Listing
November 2018

Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases.

J Cell Mol Med 2018 11 9;22(11):5504-5517. Epub 2018 Aug 9.

Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.13821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201360PMC
November 2018

Anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenes from Daphne genkwa based on hierarchical cluster and principal component analysis.

J Nat Med 2018 Jun 21;72(3):675-685. Epub 2018 Apr 21.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA.

Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory and angiogenic diseases. The aim of this study was to evaluate the anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenoids isolated from Daphne genkwa. LC-MS was used to identify diterpenes isolated from D. genkwa. The anti-inflammatory and anti-angiogenic activities of eight diterpenoids were evaluated on LPS-induced macrophage RAW264.7 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) using hierarchical cluster analysis (HCA) and principal component analysis (PCA). The eight diterpenes isolated from D. genkwa were identified as yuanhuaphnin, isoyuanhuacine, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuagine, isoyuanhuadine, yuanhuadine, yuanhuaoate C and yuanhuacine. All the eight diterpenes significantly down-regulated the excessive secretion of TNF-α, IL-6, IL-1β and NO in LPS-induced RAW264.7 macrophages. However, only 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl markedly reduced production of VEGF, MMP-3, ICAM and VCAM in TNF-α-stimulated HUVECs. HCA obtained 4 clusters, containing 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, isoyuanhuacine, isoyuanhuadine and five other compounds. PCA showed that the ranking of diterpenes sorted by efficacy from highest to lowest was 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuaphnin, isoyuanhuacine, yuanhuacine, yuanhuaoate C, yuanhuagine, isoyuanhuadine, yuanhuadine. In conclusion, eight diterpenes isolated from D. genkwa showed different levels of activity in LPS-induced RAW264.7 cells and TNF-α-stimulated HUVECs. The comprehensive evaluation of activity by HCA and PCA indicated that of the eight diterpenes, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl was the best, and can be developed as a new drug for RA therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11418-018-1202-1DOI Listing
June 2018

Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat.

Am J Chin Med 2017 9;45(8):1745-1759. Epub 2017 Nov 9.

† State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, JS 210009, P. R. China.

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1142/S0192415X1750094XDOI Listing
February 2018

Relationship between the UPLC-Q-TOF-MS fingerprinted constituents from Daphne genkwa and their anti-inflammatory, anti-oxidant activities.

Biomed Chromatogr 2017 Dec 20;31(12). Epub 2017 Jun 20.

Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, USA.

Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to apply the ultra-high performance liquid chromatography system to establish a quality control method for D. genkwa. Data revealed that there were 15 common peaks in 10 batches of D. genkwa Sieb. Et Zucc. (Thymelaeaceae) from different provinces of China. On this basis, the fingerprint chromatogram was established to provide references for quality control. Afterwards, the chemical constitutions of these common peaks were analyzed using the UPLC-Q-TOF-MS system and nine of them were identified. In addition, LPS-stimulated RAW264.7 murine macrophages and DPPH assay were used to study the anti-inflammatory and anti-oxidation effects of D. genkwa. Then the fingerprint-efficacy relationships between UPLC fingerprints and pharmacodynamic data were studied with canonical correlation analysis. Analysis results indicated that the anti-inflammatory and anti-oxidation effects differed among the 10 D. genkwa samples owing to their inherent differences of chemical compositions. Taken together, this research established a fingerprint-efficacy relationship model of D. genkwa plant by combining the UPLC analytic technique and pharmacological research, which provided references for the detection of the principal components of traditional Chinese medicine on bioactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.4012DOI Listing
December 2017

Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the Trigeminovascular System.

Phytother Res 2017 Jun 10;31(6):899-905. Epub 2017 May 10.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL, 60637, USA.

Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.5811DOI Listing
June 2017

The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced migraine rats.

Biomed Pharmacother 2017 Jul 27;91:138-146. Epub 2017 Apr 27.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, JS 210009, China; Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA. Electronic address:

To elucidate the increasing dissolution and enhancement mechanism of wine-processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20% (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron microscope were employed to explore the internal structure of RS and the components dissolution of RS was analyzed by HPLC. Rats were randomly allocated into following groups and orally given different solutions for 10days: normal group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU, 1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR. Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and endothelin-ET) and c-fos positive cells were measured with commercial kits and immunohistochemical method, separately. Total surface area significantly increased in wine-processed RS (p<0.05) while fractal dimension markedly decreased (p<0.05) compared with crude RS. Additionally, S3 owned the highest increase of dissolution including the percentage increase of total extract, total flavonoids and main compounds (all p<0.05 vs S1 and S2). Pharmacodynamic data showed c-fos positive cells significantly decreased (p<0.05) in WP compared with MOD and the level of NO, CGRP, ET in WP was better than that of CRU. Wine-processed RS could be a promising candidate medicine for migraine treatment due to its increased component dissolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2017.04.067DOI Listing
July 2017

Analgesia effect of baicalein against NTG-induced migraine in rats.

Biomed Pharmacother 2017 Jun 24;90:116-121. Epub 2017 Mar 24.

Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.

Background: Migraine is a complex nervous system disease characterized by typical throbbing and unilateral headache, which causes severe healthy and social issues worldwide. The purpose of this study was to investigate the effect of baicalein (BAI) on the treatment of migraine.

Material And Methods: Twenty-four rats were randomly divided equally into four groups, including a blank group, model group, positive group (ibuprofen tablets 82mg/kg), and BAI group (60mg/kg). All rats were intragastrically treated with the corresponding treatment for 10 consecutive days, and they were subcutaneously injected with NTG (10mg/kg) 1h after the last treatment, except in the blank group. After model establishment, the behaviors of all rats, including scratching head and shaking body were observed continuously for 100min. Four hours after NTG treatment, all rats were anaesthetized and the blood was collected. Thereafter, nitric oxide (NO) in plasma was determined by colorimetric method, the level of calcitonin gene-related peptide (CGRP) and endothelin (ET) were detected by radioimmunoassay method. In addition, immunohistochemistry was applied to detect c-Fos neuronal activity in trigeminal nucleus caudalis (TNC).

Results: Behavioral research showed that BAI administration alleviated the hyperalgesia in migraine rats. Compared with the model group, the levels of NO and CGRP in BAI administration groups were markedly decreased (p<0.01), and the levels of ET was significantly increased (p<0.01). Meanwhile, immunohistochemistry results showed that NTG treatment significantly activated c-Fos neurons while BAI treatment inhibited the expression of c-Fos.

Conclusions: BAI could alleviate the migraine-like headache induced by NTG, which is related to the regulation of vasoactive substances. These findings may contribute to the further study of BAI as a potential drug for migraine pharmacotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2017.03.052DOI Listing
June 2017
-->