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1.
Phytother Res ; 38(1): 82-97, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37807970

ABSTRACT

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1ß, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.


Subject(s)
Inflammasomes , Prostatitis , Humans , Male , Rats , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Ursolic Acid , Pyroptosis/physiology , Caspase 1/metabolism , Prostatitis/drug therapy , Molecular Docking Simulation , Gasdermins , Phosphate-Binding Proteins/metabolism , Phosphate-Binding Proteins/pharmacology
2.
Mater Horiz ; 10(7): 2554-2567, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37078123

ABSTRACT

Enhanced joint synergistic lubrication combined with anti-inflammatory therapy is an effective strategy to delay the progression of early osteoarthritis (OA) but has been rarely reported. The hydration lubrication of zwitterions and inherent super-lubrication properties of the cyclic brush, as well as the enhancement of the steric stability of the cyclic topology, can effectively improve the drug loading and utilization; herein we report a pH-responsive cyclic brush zwitterionic polymer (CB) with SBMA and DMAEMA as brushes and a cyclic polymer (c-P(HEMA)) as the core template, possessing a low coefficient of friction (0.017). After loading with hydrophobic curcumin and hydrophilic loxoprofen sodium it demonstrates high drug-loading efficiency. In vitro and in vivo experiments confirmed the triple function of the CB on superlubrication, sequence controlled release and anti-inflammatory effects demonstrated by Micro CT, histological analysis and qRT-PCR. Overall, the CB is a promising long-acting lubricating therapeutic agent, with potential for OA treatment or other diseases.


Subject(s)
Osteoarthritis , Polymers , Humans , Lubrication , Polymers/chemistry , Osteoarthritis/drug therapy , Drug Delivery Systems , Hydrogen-Ion Concentration
3.
Chin J Integr Med ; 29(3): 224-232, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35809177

ABSTRACT

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION: CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Cell Line, Tumor , HeLa Cells , Neoplastic Stem Cells/metabolism , RNA, Small Interfering/metabolism , Uterine Cervical Neoplasms/metabolism
4.
Mol Pain ; 18: 17448069221121562, 2022 04.
Article in English | MEDLINE | ID: mdl-35976914

ABSTRACT

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.


Subject(s)
Hyperalgesia , Neuralgia , Analgesics/metabolism , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Enzyme Activation , Extracellular Signal-Regulated MAP Kinases/metabolism , Hyperalgesia/complications , Hyperalgesia/drug therapy , Hyperalgesia/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , Rats , Rats, Sprague-Dawley , Sesquiterpenes , Spinal Cord/metabolism , Spinal Cord Dorsal Horn/metabolism , Superoxide Dismutase/metabolism
5.
Mol Med Rep ; 24(5)2021 11.
Article in English | MEDLINE | ID: mdl-34523697

ABSTRACT

α­rhamnrtin­3­α­rhamnoside (ARR) is the principal compound extracted from Loranthus tanakae Franch. & Sav. However, its underlying pharmacological properties remain undetermined. Inflammation is a defense mechanism of the body; however, the excessive activation of the inflammatory response can result in physical injury. The present study aimed to investigate the effects of ARR on lipopolysaccharide (LPS)­induced RAW264.7 macrophages and to determine the underlying molecular mechanism. A Cell Counting Kit­8 assay was performed to assess cytotoxicity. Nitric oxide (NO) production was measured via a NO colorimetric kit. Levels of prostaglandin E2 (PGE2) and proinflammatory cytokines, IL­1ß and IL­6, were detected using ELISAs. Reverse transcription­quantitative (RT­q)PCR analysis was performed to detect the mRNA expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase­2 (COX­2), IL­6 and IL­1ß in LPS­induced RAW246.7 cells. Western blotting, immunofluorescence and immunohistochemistry analyses were performed to measure the expression levels of NF­κB and nuclear factor­erythroid 2­related factor 2 (Nrf2) signaling pathway­related proteins to elucidate the molecular mechanisms of the inflammatory response. The results of the cytotoxicity assay revealed that doses of ARR ≤200 µg/ml exhibited no significant effect on the viability of RAW264.7 cells. The results of the Griess assay demonstrated that ARR inhibited the production of NO. In addition, the results of the ELISAs and RT­qPCR analysis discovered that ARR reduced the production of the proinflammatory cytokines, IL­1ß and IL­6, as well as the proinflammatory mediators, PGE2, iNOS and COX­2, in LPS­induced RAW264.7 cells. Immunohistochemical analysis demonstrated that ARR inhibited LPS­induced activation of TNF­associated factor 6 (TRAF6) and NF­κB p65 signaling molecules, while reversing the downregulation of the NOD­like receptor family CARD domain containing 3 (NLRC3) signaling molecule, which was consistent with the results of the western blotting analysis. Immunofluorescence results indicated that ARR reduced the increase of NF­κB p65 nuclear expression induced by LPS. Furthermore, the results of the western blotting experiments also revealed that ARR upregulated heme oxygenase­1, NAD(P)H quinone dehydrogenase 1 and Nrf2 pathway molecules. In conclusion, the results of the present study suggested that ARR may exert anti­inflammatory effects by downregulating NF­κB and activating Nrf2­mediated inflammatory responses, suggesting that ARR may be an attractive anti­inflammatory candidate drug.


Subject(s)
Loranthaceae/metabolism , Quercetin/analogs & derivatives , Animals , Anti-Inflammatory Agents/pharmacology , China , Cyclooxygenase 2/metabolism , Heme Oxygenase-1/metabolism , Lipopolysaccharides/pharmacology , Mice , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/pharmacology , Quercetin/chemistry , Quercetin/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effects , Transcription Factor RelA/metabolism
6.
Food Chem ; 353: 129439, 2021 Aug 15.
Article in English | MEDLINE | ID: mdl-33743430

ABSTRACT

Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This "components - function - indicators" clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.


Subject(s)
Gastrointestinal Microbiome , Tea/chemistry , Animals , Colitis/microbiology , Colitis/pathology , Flavonoids/chemistry , Flavonoids/metabolism , Flavonoids/pharmacology , Gastrointestinal Microbiome/drug effects , Humans , Obesity/microbiology , Obesity/pathology , Polysaccharides/metabolism , Polysaccharides/pharmacology , Tannins/metabolism , Tannins/pharmacology
7.
Chin J Integr Med ; 27(3): 229-240, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31502185

ABSTRACT

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.


Subject(s)
Drugs, Chinese Herbal , Astragalus propinquus , Ethnopharmacology , Medicine, Chinese Traditional , Phytochemicals/toxicity , Phytotherapy
8.
BioData Min ; 13: 2, 2020.
Article in English | MEDLINE | ID: mdl-32351618

ABSTRACT

BACKGROUND AND OBJECTIVE: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. METHODS: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. RESULTS: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. CONCLUSION: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

9.
Front Pharmacol ; 10: 1400, 2019.
Article in English | MEDLINE | ID: mdl-31849659

ABSTRACT

Siraitia grosvenorii (Swingle) C. Jeffrey, a member of the family Cucurbitaceae, is a unique economic and medicinal plant grown in China. For more than 300 years, S. grosvenorii has been used as a natural sweetener and as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an anti-tussive remedy in China. It is one of the first approved medicine food homology species in China. It has been widely studied as a natural product with high development potential. Therefore, the present paper provides a review of the botanical characterization, traditional uses and ethnopharmacology, food and nutritional values, chemical constituents, pharmacological effects, toxicology, and development direction for the future of S. grosvenorii. Phytochemical studies have revealed that the chemical composition of this plant mainly includes iridoid and phenylpropanoid glycosides. Several compounds such as triterpenoids, flavonoids, and amino acids have been isolated from the plant. S. grosvenorii and its active constituents possess broad pharmacological properties, such as antioxidant, hypoglycemic, immunologic, anti-tussive and sputum-reducing, hepatoprotective, and antimicrobial activities, etc. By documenting the comprehensive information of S. grosvenorii, we hope to establishes the groundwork for further research on the mechanism of action of S. grosvenorii and its development as a new health food in the future.

10.
Phytochem Anal ; 30(4): 447-455, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30916852

ABSTRACT

INTRODUCTION: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect. OBJECTIVE: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction. METHODS: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment. RESULTS: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively. CONCLUSION: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.


Subject(s)
Berberine Alkaloids/chemistry , Cevanes/chemistry , Drugs, Chinese Herbal/chemistry , Leiomyoma/drug therapy , Phytochemicals/chemistry , Berberine Alkaloids/isolation & purification , Cevanes/isolation & purification , Chromatography, High Pressure Liquid , Humans , Limit of Detection , Phytochemicals/isolation & purification , Tandem Mass Spectrometry
11.
Biomed Res Int ; 2019: 2692970, 2019.
Article in English | MEDLINE | ID: mdl-30800665

ABSTRACT

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 µM), BSO (10 µM), and brusatol (10 µM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.


Subject(s)
Gentianella/chemistry , Hydrogen Peroxide/pharmacology , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Apoptosis/drug effects , Cell Line , Glutamate-Cysteine Ligase/metabolism , Heme Oxygenase-1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Rats , Transcription, Genetic/drug effects , Xanthenes/pharmacology , Xanthones/pharmacology
12.
Front Pharmacol ; 10: 1627, 2019.
Article in English | MEDLINE | ID: mdl-32082153

ABSTRACT

[This corrects the article DOI: 10.3389/fphar.2019.01400.].

13.
J Mater Chem B ; 6(48): 8170-8179, 2018 Dec 28.
Article in English | MEDLINE | ID: mdl-32254936

ABSTRACT

Bilayer-type hydrogel composites that respond to multiple stimuli provide a useful approach for manufacturing soft actuators and intelligent sensors. In this study, we propose two types of bilayer hydrogel composites (referred to as "N" type and "D" type). The "N" type and the "D" type separately consist of poly(N-isopropylacrylamide) (PNIPAM) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) bilayer hydrogels, with acrylamide (AM) as the co-monomer. The "N" type hydrogel composite exhibits oriented bending as temperature increases or as environmental salt concentration increases. The "D" type also presents oriented bending as temperature increases. Additionally, it demonstrates bending and changes color based on the pH of the surrounding solution, since it is doped with an acid-based pH-indicator. In a demonstration, we present several straight rods composed of a mixture of "N" and "D" type hydrogel composites that are able to morph into the letters "SOS" under environmental changes (temperature or pH). This can be used as a visual environmental indicator, or as an alarm. Furthermore, we show structures composed of a mixture of "N" and "D" composites imitating the flexible motions of a ballet dancer or a Tai Chi master. These mixed bilayer polymer composites may be used for applications in soft robotics, biomimetic devices, and environmental sensors.

14.
Chem Biol Interact ; 275: 210-217, 2017 Sep 25.
Article in English | MEDLINE | ID: mdl-28811126

ABSTRACT

Persimmon (Diospyros kaki L.) leaves are extensively used in Chinese medicine and are also excellent source of dietary polyphenols. Here we investigated the antiproliferative and pro-apoptotic activity of the total flavonoids extracted from persimmon leaves (FPL) in PC-3 cells. After treating cells with different concentration of FPL, Quercetin or Rutin for 24 h, MTT and flow cytometry were used to measure the cytotoxicity, apoptotic rate and cell cycle arrest. Compared with Quercetin and Rutin, FPL showed higher cytotoxicity at 12.5 and 25 µg/ml concentrations and also presented lower IC50 in PC-3 cells. In addition, FPL induced PC-3 cells apoptosis by activation of oxidative stress, as detected by ROS, MDA, nitrite and iNOS activity, and increased mitochondrial membrane permeability. Morphological changes, inactivation of Bcl-2, upregulation of BAX, release of cytochrome c and activation of downstream apoptotic signaling in FPL-treated PC-3 cells also suggested apoptotic death. Meanwhile, FPL significantly inhibited migration of PC-3 cells. Therefore, FPL inhibited proliferation, migration and induced apoptosis of PC-3 cells by activation of oxidative stress and mitochondrial-related apoptosis.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Diospyros/chemistry , Flavonoids/pharmacology , Mitochondria/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cytochromes c/metabolism , Diospyros/metabolism , Flavonoids/chemistry , Flavonoids/isolation & purification , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Leaves/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolism
15.
J Pineal Res ; 63(3)2017 Oct.
Article in English | MEDLINE | ID: mdl-28708271

ABSTRACT

Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload-induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8-week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α-myosin heavy chain, downregulated the expression level of ß-myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator-activated receptor-gamma co-activator-1 beta (PGC-1ß) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II-induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC-1ß using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC-1ß.


Subject(s)
Antioxidants/therapeutic use , Cardiomegaly/prevention & control , Melatonin/therapeutic use , Myocytes, Cardiac/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Angiotensin II , Animals , Antioxidants/pharmacology , Cardiomegaly/metabolism , Cardiomegaly/pathology , Disease Models, Animal , Drug Evaluation, Preclinical , Fibrosis , Heart/drug effects , Lung Diseases/prevention & control , Male , Melatonin/pharmacology , Mice, Inbred C57BL , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Primary Cell Culture , Transcriptional Activation/drug effects
16.
BMC Biotechnol ; 16(1): 87, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-27908283

ABSTRACT

BACKGROUND: Manganese peroxidase (MnP) from Irpex lacteus F17 has been shown to have a strong ability to degrade recalcitrant aromatic pollutants. In this study, a recombinant MnP from I. lacteus F17 was expressed in Escherichia coli Rosetta (DE3) in the form of inclusion bodies, which were refolded to achieve an active enzyme. Further, we optimized the in vitro refolding conditions to increase the recovery yield of the recombinant protein production. Additionally, we attempted to express recombinant MnP in soluble form in E. coli, and compared its activity with that of refolded MnP. RESULTS: Refolded MnP was obtained by optimizing the in vitro refolding conditions, and soluble MnP was produced in the presence of four additives, TritonX-100, Tween-80, ethanol, and glycerol, through incubation at 16 °C. Hemin and Ca2+ supplementation was crucial for the activity of the recombinant protein. Compared with refolded MnP, soluble MnP showed low catalytic efficiencies for Mn2+ and H2O2 substrates, but the two enzymes had an identical, broad range substrate specificity, and the ability to decolorize azo dyes. Furthermore, their enzymatic spectral characteristics were analysed by circular dichroism (CD), electronic absorption spectrum (UV-VIS), fluorescence and Raman spectra, indicating the differences in protein conformation between soluble and refolded MnP. Subsequently, size exclusion chromatography (SEC) and dynamic light scattering (DLS) analyses demonstrated that refolded MnP was a good monomer in solution, while soluble MnP predominantly existed in the oligomeric status. CONCLUSIONS: Our results showed that two forms of recombinant MnP could be expressed in E. coli by varying the culture conditions during protein expression.


Subject(s)
Basidiomycota/enzymology , Basidiomycota/genetics , Escherichia coli/enzymology , Escherichia coli/genetics , Peroxidases/chemistry , Peroxidases/metabolism , Enzyme Activation , Enzyme Stability , Peroxidases/genetics , Protein Conformation , Protein Refolding , Solubility
17.
Eur J Pharmacol ; 766: 91-8, 2015 Nov 05.
Article in English | MEDLINE | ID: mdl-26420356

ABSTRACT

Recent studies uncovered that glutamate accumulation following cerebral ischemia-reperfusion (I/R) was related to the dysfunction of miR-107/glutamate transporter-1(GLT-1) pathway and magnesium lithospermate B (MLB) possesses the pharmacological activity of anti-excitotoxicity. This study aims to explore whether MLB is able to protect rat brain from excitatory neurotoxicity during I/R by modulating miR-107/GLT-1 pathway. Rats were subjected to 2h of cerebral ischemia following by 24h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score, infarct volume and cellular apoptosis concomitant with glutamate accumulation, miR-107 elevation and GLT-1 down-regulation. Administration of MLB reduced I/R-induced cerebral injury accompanied by a reverse in glutamate accumulation, miR-107 and GLT-1 expression. Next, we examined the association of MLB with miR-107/GLT-1 pathway in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased the nerve cells apoptosis concomitant with glutamate accumulation and miR-107 elevation, and suppressed GLT-1 expression, mimicking our in vivo findings. All these effects were reversed in the presence of MLB, confirming a strong correlation between MLB and miR-107/GLT-1 pathway. Based on these observations, we conclude that MLB is able to protect the rat brain from excitatory neurotoxicity during I/R through the regulation of miR-107/GLT-1 pathway.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Excitatory Amino Acid Transporter 2/metabolism , Infarction, Middle Cerebral Artery/metabolism , MicroRNAs/metabolism , Neuroprotective Agents/pharmacology , Reperfusion Injury/drug therapy , Animals , Apoptosis/drug effects , Brain/drug effects , Brain/metabolism , Brain/pathology , Cell Line , Drugs, Chinese Herbal/therapeutic use , Excitatory Amino Acid Transporter 2/genetics , Glutamic Acid/metabolism , Hypoxia/drug therapy , Hypoxia/metabolism , Hypoxia/pathology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Male , Neurons/drug effects , Neurons/pathology , Neuroprotective Agents/therapeutic use , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology
18.
Planta Med ; 81(15): 1361-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26252829

ABSTRACT

Salviaolate is a group of depside salts isolated from Danshen (a traditional Chinese herbal medicine), with ≥ 85 % of magnesium lithospermate B. This study aims to investigate whether salviaolate is able to protect the rat brain from ischemia/reperfusion injury and the underlying mechanisms. Rats were subjected to 2 h of cerebral ischemia and 24 h of reperfusion to establish an ischemia/reperfusion injury model. The neuroprotective effects of salviaolate at different dosages were evaluated. A dosage (25 mg/kg) was chosen to explore the neuroprotective mechanisms of salviaolate. Neurological function, infarct volume, cellular apoptosis, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were measured. In a nerve cell model of hypoxia/reoxygenation injury, magnesium lithospermate B was applied. Cellular apoptosis, lactate dehydrogenase, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were examined. Ischemia/reperfusion treatment significantly increased the neurological deficit score, infarct volume, and cellular apoptosis accompanied by the elevated nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content in the rat brains. Administration of salviaolate reduced ischemia/reperfusion-induced cerebral injury in a dose-dependent manner concomitant with a decrease in nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 production. Magnesium lithospermate B (20 mg/kg) and edaravone (6 mg/kg, the positive control) achieved the same beneficial effects as salviaolate did. In the cell experiments, the injury (indicated by apoptosis ratio and lactate dehydrogenase release), nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content were dramatically increased following hypoxia/reoxygenation, which were attenuated in the presence of magnesium lithospermate B (10(-5) M), VAS2870 (nicotinamide adenine dinucleotide phosphate-oxidase inhibitor), or edaravone (10(-5) M). The results suggest that salviaolate is able to protect the brain from ischemia/reperfusion oxidative injury, which is related to the inhibition of nicotinamide adenine dinucleotide phosphate-oxidase and a reduction of reactive oxygen species production.


Subject(s)
Benzofurans/therapeutic use , Brain Ischemia/prevention & control , Cinnamates/therapeutic use , Depsides/therapeutic use , Drugs, Chinese Herbal/therapeutic use , NADPH Oxidases/antagonists & inhibitors , Neuroprotective Agents/therapeutic use , Reperfusion Injury/prevention & control , Salvia miltiorrhiza/chemistry , Animals , Antioxidants/therapeutic use , Benzoxazoles/pharmacology , Brain/drug effects , Brain/enzymology , Cells, Cultured , China , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Male , Rats , Rats, Sprague-Dawley , Triazoles/pharmacology , Rosmarinic Acid
19.
Zhongguo Zhong Yao Za Zhi ; 40(5): 785-92, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-26087534

ABSTRACT

The distribution information of Cistanche deserticola was collected by interview investigation and field survey, and 55 related environmental factors were collected, the habitat suitability study was conducted based on geographic information system (GIS) and Maximum entropy model. The AUCs of ROC curve were both above 0.9, indicating that the predictive results with the maxent model were highly precise. The results showed that 14 major environmental factors have obvious influence on ecology suitability distributions of C. deserticola, including vegetation type et al, the suitable distribution areas are mainly concentrated in the central of Alxa Youqi, the north of Alxa Zouqi and the south-east of Ejin Banner, including Tamusu towns, Alateng towns et al, The zoning results basically coincide with the genuine producing areas, and further afford new suitable distribution areas, which can provide reference for the siting of introduction and cultivation of C. deserticola.


Subject(s)
Cistanche/growth & development , Ecosystem , China , Environment , Geographic Information Systems , Rain , Soil/chemistry , Temperature
20.
Int J Syst Evol Microbiol ; 64(Pt 10): 3492-3495, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25052398

ABSTRACT

An endophytic actinomycete strain, IXS4(T), was isolated from the root of Artemisia argyi, a medicinal plant collected from Yesanpo located in Laishui county, Hebei province, China. The 16S rRNA gene sequence of strain IXS(T) showed most similarity to Glycomyces mayteni YIM 61331(T) (98.23% 16S rRNA gene sequence similarity), Glycomyces scopariae YIM 56256(T) (98.00%), Glycomyces sambucus E71(T) (97.90%) and Glycomyces algeriensis NRRL B-16327(T) (97.10%). DNA-DNA hybridization values between strain IXS4(T) and the closely related type strains were well below 70%. The strain also showed a number of physiological and biochemical characteristics that were distinct from the closely related species. The strain contained MK-10(H2) and MK-11(H0) as the detected menaquinones. The peptidoglycan was mainly meso-diaminopimelic acid and the whole-cell sugars contained galactose, glucose, mannose, xylose and ribose. The major cellular fatty acids were iso-C14:0, iso-C15:0, iso-C16:0, anteiso-C15:0 and anteiso-C17:0. Based on the genetic and phenotypic properties, it is proposed that strain IXS4(T) represents a novel species of the genus Glycomyces, with the name http://dx.doi.org/10.1601/nm.7671Glycomyces artemisiae sp. nov. The type strain is IXS4(T) ( = HBUM178000(T) = CGMCC 4.7067(T) = NBRC 109773(T)).


Subject(s)
Actinomycetales/classification , Artemisia/microbiology , Phylogeny , Plant Roots/microbiology , Actinomycetales/genetics , Actinomycetales/isolation & purification , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Diaminopimelic Acid/chemistry , Fatty Acids/chemistry , Molecular Sequence Data , Nucleic Acid Hybridization , Peptidoglycan/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/chemistry
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