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1.
Chin J Nat Med ; 18(6): 460-471, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503737

RESUMO

The quality of Astragali Radix (AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years' wild Astragali Radix (WAR) and transplanted Astragali Radix (TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1-6 growth years root through the methods. The contents of flavonoids and saponins in 2-6 growth years' WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR (4-year-old) and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters (EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.

2.
Acta Pharmacol Sin ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451414

RESUMO

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, but there is no effective drug available for GBM. Avasimibe is a potent inhibitor of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), which was used to treat atherosclerosis. Experimental evidence and bioinformatics have shown that avasimibe has anticancer activity. In this study we investigated the anticancer effects of avasimibe on human glioblastoma cells and the underlying mechanisms. Our results showed that avasimibe dose-dependently inhibited the proliferation of U251 and U87 human glioblastoma cells with IC50 values of 20.29 and 28.27 µM, respectively, at 48 h. Avasimibe (7.5, 15, 30 µM) decreased the DNA synthesis, and inhibited the colony formation of the tumor cells. Treatment of avasimibe also dose-dependently increased the apoptotic rate of tumor cells, decreased the mitochondrial membrane potential, induced the activity of caspase-3/7, and increased the protein expression of cleaved caspase-9, cleaved PARP and Bax in U251 and U87 cells. RNA-sequencing analyses revealed that avasimibe suppressed the expression of CDK2, cyclin E1, CDK4, cyclin D, CDK1, cyclin B1, Aurora A, and PLK1, while induced the expression of p53, p21, p27, and GADD45A, which was validated by Western blot analysis. These results demonstrated that avasimibe induced mitochondria-dependent apoptosis in glioblastoma cells, which was associated with arresting the cell cycle at G0/G1 phase and G2/M phase by regulating the p53/p21 pathway, p53/GADD45A and Aurora A/PLK1 signaling pathways. In U87 xenograft nude mice model, administration of avasimibe (15, 30 mg·kg-1·d-1, ip, for 18 days) dose-dependently inhibit the tumor growth. Taken together, our results demonstrated that avasimibe might be a promising chemotherapy drug in the treatment of GBM.

3.
Biomed Pharmacother ; 128: 110262, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447214

RESUMO

Chemotherapy-induced intestinal mucositis (CIM) is a principal reason for reduced living quality of patients undergoing chemotherapy. Growing evidence showed gut microbiota played an important role in the development of intestinal mucositis. Dihydrotanshinone I (DHTS) is a liposoluble extract of Salvia miltiorrhiza Bunge with many bioactivities. Here we investigated the effect of DHTS on intestinal mucositis induced by 5-fluorouracil and irinotecan in mice. We detected the degree of intestinal mucosal damage and inflammatory response in CIM mice with or without DHTS administration. The body weight and disease activity index (DAI) of mice were monitored each day. H&E staining was used to evaluate pathological damage. The contents of interleukin 6 (IL-6), tumor necrosis factor (TNFα), diacylglycerol (DAO) and triglyceride (TG) in serum were determined by commercial kits. We also investigated the changes of fecal microbiota by 16S rRNA high-throughput sequencing. Spearman correlation analysis was used to evaluate the correlation between fecal microbiota and inflammatory factors. Tax4Funwas performed to infer the potential function of the microbial community. Results showed DHTS significantly reduced DAI, intestinal mucosal damage and inflammatory response in CIM mice by decreasing serum IL-6 and TNFα. In addition, there is an intense correlation between fecal microbiota and inflammatory factors. DHTS efficiently reversed disordered fecal microflora close to normal and increased the abundance of g__Akkermansia. DHTS also enriched bacterial species which promote butyric acid metabolism or negatively correlated with inflammatory factors. Besides, species enriched by DHTS in fecal microbiota were probably involved in glutamine production and ammonia oxidation. In conclusion, our study provides evidence that DHTS effectively attenuates CIM induced by 5-fluorouracil and irinotecan in mice. Regulation of the composition and function of fecal microbiota probably plays a critical role in the therapeutic effect of DHTS in CIM mice.

4.
Nat Prod Bioprospect ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415420

RESUMO

Betulin (BE) has exceedingly become a potential natural product, providing multiple pharmacological and biological activities, including anti-cancer, anti-viral, and anti-inflammatory benefits. Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents. This property of BE can directly affect its extraction, isolation, and preparation process. In this study, a system of thermogravimetry (TG)-differential thermal analysis (DTA) coupled with mass spectrometry (MS) with electron ionization (EI) and photoionization (PI) capability, equipped with the skimmer-type interface (i.e., skimmer-type interfaced TG-DTA-EI/PI-MS system), as a real-time and onsite analysis technique, was employed. Then, four solvatomorphs of BE, namely, with pyridine and water (A), sec-butanol (B), n,n-dimethylformamide (DMF) (C), and isopropanol (V), were analyzed for the first time. Finally, five kinds of the main volatile gaseous species, including H2O, pyridine, sec-butanol, DMF, and isopropanol, were identified clearly. Furthermore, the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time. This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products.

5.
Apoptosis ; 25(5-6): 354-369, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32338336

RESUMO

It is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baicalein treatment at dose of 100 mg/kg for 7 days significantly inhibited the release of cytokines, activation of PARP-1, nuclear translocation of apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor (MIF) in cerebral I/R rats, therefore decreased cerebral infarct volume and neurological scores. Then, we further investigated the signal transduction mechanisms of ischemic tissue protection by baicalein in vitro. Following oxygen and glucose deprivation (OGD) in SH-SY5Y cells, the mitochondrial AIF was translocated into nucleus after 12 h. The co-immunoprecipitation analysis showed that the interaction between AIF and MIF was activated by OGD and subsequently resulted in MIF nuclear translocation. Also, the baicalein inhibited apoptosis, reduced oxidative stress, protected mitochondrial function and restored mitochondrial membrane potential in OGD cells. The results obtained from both in vivo and in vitro study demonstrated the PARP-1/AIF pathway involved in mechanisms of baicalein to protect the cerebral tissues from ischemic injury.

6.
Biol Sex Differ ; 11(1): 9, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156311

RESUMO

Fibroblast growth factors (FGFs) belong to a large family comprising 22 FGF polypeptides that are widely expressed in tissues. Most of the FGFs can be secreted and involved in the regulation of skeletal muscle function and structure. However, the role of fasting on FGF expression pattern in skeletal muscles remains unknown. In this study, we combined bioinformatics analysis and in vivo studies to explore the effect of 24-h fasting on the expression of Fgfs in slow-twitch soleus and fast-twitch tibialis anterior (TA) muscle from male and female C57BL/6 mice. We found that fasting significantly affected the expression of many Fgfs in mouse skeletal muscle. Furthermore, skeletal muscle fibre type and sex also influenced Fgf expression and response to fasting. We observed that in both male and female mice fasting reduced Fgf6 and Fgf11 in the TA muscle rather than the soleus. Moreover, fasting reduced Fgf8 expression in the soleus and TA muscles in female mice rather than in male mice. Fasting also increased Fgf21 expression in female soleus muscle and female and male plasma. Fasting reduced Fgf2 and Fgf18 expression levels without fibre-type and sex-dependent effects in mice. We further found that fasting decreased the expression of an FGF activation marker gene-Flrt2 in the TA muscle but not in the soleus muscle in both male and female mice. This study revealed the expression profile of Fgfs in different skeletal muscle fibre types and different sexes and provides clues to the interaction between the skeletal muscle and other organs, which deserves future investigations.

7.
Biochem Biophys Res Commun ; 525(3): 759-766, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145915

RESUMO

Formononetin (FN), a methoxy isoflavone abundant in many plants and herbs, has been evidently proven to possess multiple medicinal properties. Our study aimed to clarify the impact of FN on myocardial ischemia/reperfusion (I/R) injury (MIRI) and the involved mechanism. A rat model of MIRI was produced by ligation and loosening of the left anterior descending (LAD) branch of the coronary artery. Rats received 10 and 30 mg/kg of FN when the reperfusion started. At 24 h after surgery, cardiac function, infarct size, and sera levels of the cardiac markers and inflammatory mediators were measured. To mimic the inflammasome activation in cardiomyocytes, neonatal rat cardiomyocytes (NRCMs) were cultured and treated with lipopolysaccharide (LPS) plus nigericin. Cell death and reactive oxygen species (ROS) were determined. Myocardial expression and activation of the nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome in rats were examined by western blotting. The level of thioredoxin interacting protein (TXNIP)-NLRP3 interaction was assessed. FN notably attenuated cardiac dysfunction, infarct size, release of cardiac markers, and elevation of TNF-α, IL-1ß, and IL-6. FN alleviated LPS plus nigericin-induced injury and ROS increase in NRCMs. Western blotting revealed that FN suppressed the activation of NLRP3 inflammasome and TXNIP-NLRP3 interaction in rats. These findings indicate that FN ameliorated MIRI in rats and inhibited the activation of the NLRP3 inflammasome, at least partially, attributable to suppression of the ROS-TXNIP-NLRP3 pathway.

8.
Life Sci ; 248: 117471, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112868

RESUMO

AIMS: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aß25-35-induced toxicity. MAIN METHODS: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aß25-35 aggregation in vitro. PC12 cells were stimulated with Aß25-35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aß25-35-injured PC12 cells. KEY FINDINGS: The results showed that baicalein could inhibit the aggregation of Aß25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aß25-35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. SIGNIFICANCE: Our study revealed that baicalein has a protective effect on Aß25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Flavanonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Trifosfato de Adenosina/biossíntese , Peptídeos beta-Amiloides/toxicidade , Animais , Arginina/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacina/metabolismo , Niacinamida/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fragmentos de Peptídeos/toxicidade , Prolina/metabolismo , Agregados Proteicos/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
9.
Acta Pharmacol Sin ; 41(4): 516-522, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32047262

RESUMO

Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125-2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 µM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 µM) significantly improved GA A protection in PC12 cells. The addition of ß1-adrenergic receptor antagonist metoprolol (10 µM) or ß2-adrenergic receptor antagonist ICI 118551 (0.1 µM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 µM) did not affect GA A protection in SH-SY5Y cells. These results suggest that ß-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.

10.
Exp Gerontol ; 134: 110843, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045633

RESUMO

Scutellaria baicalensis Georgi flowers is rich in flavonoids resources but not effectively exploited. This study aimed to investigate the anti-aging effects and potential mechanism of Scutellaria baicalensis Georgi flowers extract (SFE). The chemical components of the SFE were analyzed by UPLC-MS and the anti-aging effects of SFE were investigated in d-galactose (d-gal) induced aging rats by behavior examination and biochemical indexes, and the potential anti-aging mechanism of SFE were explored by 1H NMR-based liver metabolomics. Chemical composition research showed that 19 flavonoids were identified in SFE, and pharmacological research showed that SFE could significantly ameliorate spatial learning and memory ability. SFE could significantly regulate malondialdehyde (MDA), superoxide dismutase (SOD) and advanced glycation end products (AGEs). It also ameliorated the pathological abnormalities in liver. Additionally, anti-aging mechanism of SFE showed that total of 10 potential biomarkers were found by metabolomics techniques, which involved in 6 metabolic pathways. Among them, SFE could significantly increased the levels of d-glutamine and d-glutamate. Furthermore, the levels of glutamine and glutamate, and the levels of the key amino acids, enzymes and final product in the synthesis process of glutathione (GSH) were quantitatively determined in the liver by commercial kits and enzyme-linked immunosorbent assay. These results indicated that regulation of the glutamine-glutamate metabolic pathway is involved in the anti-aging effect of SFE in d-gal induced aging rats.

11.
J Mol Neurosci ; 70(5): 667-676, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31907865

RESUMO

Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.

12.
Rejuvenation Res ; 23(2): 138-149, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30982406

RESUMO

Guilingji (GLJ), a traditional Chinese medicine, is of wide concern because of its remarkable antiaging effect with a long application history. It mainly consists of traditional Chinese herbs, that is, Ginseng radix et rhizoma rubra. This study focused on the anti-aging effects of GLJ on natural aging rats and its underlying mechanisms. Morris water maze was used to determine the learning and memory ability of rats. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), acetylcholine (ACh), and acetylcholinesterase (AChE) in serum were determined. Furthermore, a 1H-NMR-based serum metabolomics coupled with multivariate data analysis was used to identify potential biomarkers and corresponding metabolic pathways. The results showed that GLJ significantly improved the learning and memorial dysfunctions of natural aging rats. The mechanisms of the anti-aging and memory ameliorative effects of GLJ related to balancing oxidative stress, improving cholinergic system. Its specific mechanism of action may be through regulating pyruvate metabolism and arginine and proline metabolism.

13.
Acta Pharmacol Sin ; 41(5): 599-611, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31685977

RESUMO

At present, few available drugs can be used to either improve pathological features or prevent the progression of Alzheimer's disease (AD). DL0410 ((1,1'-([1,1'-biphenyl]-4,4'-diyl) bis (3-(piperidin-1-yl) propan-1-one) dihydrochloride) is a multiple-target small molecule that has been found to reverse cognitive impairment in different animal models of AD. In this study we evaluated the cognition-improving effects of DL0410 in APP/PS1 transgenic mice and explored the underlying mechanisms. APP/PS1 transgenic mice were administered DL0410 (3, 10, 30 mg· kg-1· d-1, ig) for 2 months. We found that DL0410 administration significantly ameliorated cognitive deficits in both the nest-building and Morris water maze tests. In electrophysiological analysis of hippocampal slices, we showed that DL0410 administration significantly enhanced the field EPSP slope and HFS-induced LTP in CA1 area. Furthermore, we revealed that DL0410 administration significantly increased the phosphorylation of AKT and the activity of GSK-3ß in the hippocampus and cortex. Moreover, DL0410 administration dose-dependently increased the expression level of phosphorylated ERK1/2 in the hippocampus and cortex. In addition, DL0410 dose-dependently decreased the neuronal loss by decreasing the production of Aß deposition, inhibited glial overactivation, and the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. We conclude that DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission via activating the AKT/GSK-3ß and MAPK/ERK signaling pathway and reducing neuronal loss. DL0410 may be an effective agent for AD treatment in the future.

14.
Hypertension ; 75(1): 150-162, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31735085

RESUMO

Endothelial dysfunction is an early step to the progression of cardiovascular diseases in diabetes. Apart from their anti-diabetic action, DPP-4 (dipeptidyl peptidase-4) inhibitors also reduce cardiovascular events in diabetic patients. However, the underlying mechanism of the beneficial effect of DPP-4 inhibitor on endothelial function is still obscure. In this study, we intervened type 1 or 2 diabetic model mice with vildagliptin for 4 weeks and measured the vascular reactivity. We found that vildagliptin improved endothelium-dependent vasodilation in diabetic mice independent of GLP-1 (glucagonlike peptide-1), but this effect was blocked by a SIRT1 (Sirtuin 1) inhibitor, Ex527. Mechanistically, vildagliptin-activated Transient Receptor Potential Channel Vanilloid 4 (TRPV4) to promote extracellular calcium uptake in endothelial cells, which activated AMPK (AMP-activated protein kinase)/SIRT1 pathway to counteract hyperglycemia-induced endothelial reactive oxygen species generation and senescence. Vildagliptin directly binds to TRPV4 by forming a hydrogen bond, which is critical to vildagliptin-evoked endothelial calcium intake. Knockout or inhibition of TRPV4 erased the beneficial role of vildagliptin. In addition, activation of SIRT1 by SRT1720 improved endothelial function independent of TRPV4 and reduced TRPV4 transcription to maintain an appropriate calcium level. In summary, our findings prove that vildagliptin protects against hyperglycemia-induced endothelial dysfunction by activating TRPV4-meditaed Ca2+ uptake, which helps to re-understand the mechanism of DPP-4 inhibitors and expand the therapeutic scope.

15.
Int Immunopharmacol ; 79: 106092, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31863920

RESUMO

Baicalein (5,6,7-trihydroxyflavone), isolated from the root of traditional Chinese herb Scutellaria baicalensis Georgi, has anti-inflammatory and anti-oxidative activities. This study explored the protective and modulatory mechanisms of baicalein on neuroinflammation, oxidative stress and metabolic abnormality in lipopolysaccharide (LPS)-activated BV-2 cells. Our results demonstrated that treatment with baicalein remarkably restrained the production of pro-inflammatory factors including nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in LPS-activated BV-2 cells. Moreover, baicalein significantly inhibited reactive oxygen species (ROS) production, decreased cyclooxygenase-2 (COX-2) and nuclear factor-b (NF-κB)/p65 expression. 1H NMR metabolomics analysis revealed that 12 differential metabolites were regulated by baicalein, implicated in alanine, aspartate and glutamate metabolism, glutathione metabolism, arginine and proline metabolism, D-glutamine and D-glutamate metabolism. In conclusion, these results indicated that baicalein has protective and modulatory effects on neuroinflammation and oxidative stress in LPS-activated BV-2 cells.

16.
Brain Res Bull ; 156: 33-42, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31877338

RESUMO

Numerous studies have shown that local excessive inflammatory response in brain tissue was an important pathogenesis of secondary injury following cerebral ischemia-reperfusion (I/R). However, the inflammatory-related targets and pathways after cerebral I/R injury are still unclear. This study was to investigate possible targets and mechanisms after cerebral I/R injury. Rats were subjected to transient or permanent middle cerebral artery occlusion (MCAO). Neurological deficit scores test was used to evaluate neurological function. Cerebral infarction was evaluated by MRI, TTC staining and Nissl staining. Microglia activation was detected by immunofluorescence using Iba-1 antibody. Inflammatory factors were detected by ELISA assay. RNA-sequencing transcriptome analysis was processed and the differential genes were verified by real-time quantitative PCR (qPCR) and western blotting. The results showed that neurological function of rats in I/R group was more severe than that in I group on the 7th after cerebral I/R. Therefore, the differences between cerebral ischemia and cerebral I/R for 7 days were studied in further study. The results showed that the levels of pro-inflammatory factors in I/R group were higher and the levels of anti-inflammatory factors were lower than those in I group. KEGG pathway and gene network enrichment analysis revealed that some common differential up- and down-regulated genes were involved in most of significant pathways. These common differential up-regulated genes belonged to TLR4/MYD88 inflammatory signaling pathway and common differential down-regulated genes belonged to HRAS/RAF1 neurotrophic signaling pathway. Interestingly, according to the genetic interaction analysis of string database, these up-regulated differential genes might promote the development of inflammation, while the down-regulated differential genes might inhibit the development of inflammation. Furthermore, qPCR and WB results verified that these pro-inflammatory genes in the I/R group were higher than those in the I group, while possible anti-inflammatory genes in the I/R group were lower than those in the I group. It is concluded that TLR4/MYD88 inflammatory signaling pathway and HRAS/RAF1 neurotrophic signaling pathway may play different roles after cerebral I or I/R and may be therapeutic targets for stroke recovery.

17.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.


Assuntos
Antialérgicos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artemisia , Extratos Vegetais/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Sinusite/tratamento farmacológico , Alérgenos , Animais , Antialérgicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/crescimento & desenvolvimento , Citocinas/imunologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cobaias , Masculino , Medicina Tradicional Chinesa , Medicina Tradicional da Mongólia , Camundongos , Simulação de Acoplamento Molecular , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Ovalbumina , Extratos Vegetais/farmacologia , Receptores Histamínicos H1/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Sinusite/imunologia , Sinusite/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Xilenos
18.
J Asian Nat Prod Res ; : 1-9, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31838892

RESUMO

A new polycyclic polyprenylated acylphloroglucinol (PPAP), hypermonin C (1), along with nine known PPAPs (2-10) were obtained from the leaves and twigs of Hypericum monogynum. The structures of the isolates were determined on the basis of extensive spectroscopic analysis. The neuroprotective effects of the isolates against several chemical-induced injuries in SH-SY5Y and PC12 cells were assessed, and most of the compounds exhibited significant protective effects at 10 µg/ml. Especially, three compounds (1, 3, and 7) showed excellent neuroprotective activity with a cell viability of 92.4% ∼ 95.8% in KCl-induced SH-SY5Y cell injury. Their preliminary structure-activity relationship was also discussed and the configuration of substituent in furohyperforin may be critical for the neuroprotective activity of PPAP derivatives.

19.
J Neuroimmunol ; 337: 577049, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31526918

RESUMO

Myricitrin, a bioactive and natural flavonoids, is well known for its anti-inflammatory and antioxidant properties. However, the anti-neuroinflammation and possible mechanism has not been fully elucidated. Therefore, the present study was to investigate the possible mechanism of its neuroprotection and anti-neuroinflammation in the nigrostriatum of LPS-stimulated mice. The results showed that myricitrin improved neuron injury and raised the expressions of PSD-95 protein and TH protein in the nigrostriatum of LPS-stimulated mice. In addition, myricitrin decreased the production of pro-inflammatory factors including IL-1ß, IL-6 and TNFα, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS. Meanwhile, myricitrin suppressed HMGB1, TLR4, and MyD88 expression in the nigrostriatum of LPS-stimulated mice. Furthermore, myricitrin inhibited NF-κB and MAPK signaling pathways activated by LPS. In conclusion, our studies suggest that myricitrin blocks activation of protects NF-κB and MAPK signaling pathways to nigrostiatum neuron from injury in LPS-stimulated mice and is beneficial to treatment nigrostriatum inflammation of PD.

20.
Brain Res ; 1722: 146361, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377105

RESUMO

Kaempferol has been reported to act as an anti-inflammatory agent in LPS-induced neuroinflammation in vitro and in vivo, but its role in the inflammation after cerebral ischemia/reperfusion (I/R) is unclear. The present study was to investigate the effect of kaempferol on inflammation in ischemic brain tissue and explore its mechanisms in cerebral I/R rats. Cerebral I/R rat model was established by middle cerebral artery occlusion for 60 min and following reperfusion. Kaempferol at doses of 25, 50 and 100 mg/kg was administered for 7 days after cerebral I/R. Kaempferol treatment significantly reduced cerebral infarct volume, attenuated inflammation and blood-brain barrier (BBB) disruption after cerebral I/R, thus improved neurological outcomes at the day 7 after cerebral I/R. Furthermore, the results also showed kaempferol treatment decreased the phosphorylation and nuclear transposition of transcription factor NF-κB p65, thus inhibited expression of various pro-inflammatory proteins. In conclusion, kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral I/R rats, its mechanism is related to NF-κB pathway.

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