Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by t...Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by the discovery of anticancer agents bearing critical mechanisms of action. Baicalein is a flavonoid with promising anticancer activity, among other pharmacological benefits, and has therefore been of high clinical interest. We tested baicalein in vitro for its effect on several CRC hallmarks, including the suppression of metastasis (the spread of cancer cells from their initial site), the ability to induce apoptosis (cell death), and the inhibition of proliferation (the growth of cells). The suppression of the metastasis of CRC cells was recorded via two studies: the cell migration assay and the in silico docking of baicalein with toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9). Results from the cell migration assay showed that baicalein inhibited metastasis by up to 25.76% (p 0.01) in a concentration-dependent manner. We then reinforced these results by docking baicalein with TLR4 (binding affinity: -8.4 kcal/mol) and docking baicalein with MMP-9 (binding affinity: -7.9 kcal/mol), classifying strong binding affinities as those less than -6.0 kcal/mol. The induction of cell death was measured using a caspase activity assay. Again, a docking study was done to reinforce the findings from the primary in vitro experiment, though this time between baicalein and caspase-3 (binding affinity: -7.1 kcal/mol). Despite mixed observations in concentration dependence, caspase activity, relative to control, reached a maximal increase of 88.6% (p 0.01), and results from the MTT assay demonstrated a survival rate, relative to control, of as low as 59.64%. Considerations for future studies include the testing of baicalein in vivo and on more aberrative CRC cell lines.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility...Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.展开更多
AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrogra...AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P < 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P > 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.展开更多
OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremor...OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.展开更多
Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic...Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic Classification System(BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro. Physiologically based pharmacokinetic(PBPK) model commercial software GastroPlus~(TM) was used to predict oral absorption of baicalein in vivo.Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling(IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug(C_(max)) and area under the curve(AUC)fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug.Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.展开更多
The in vitro effects of baicalein,wogonin,baicalin and Na<sub>2</sub>MoO<sub>4</sub> on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of...The in vitro effects of baicalein,wogonin,baicalin and Na<sub>2</sub>MoO<sub>4</sub> on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of dimethylnitrosamine（DMN） and diethylnitrosamine（DEN） produced using the UV-photclysis spectrophotometric and pyrolysis gas chromatography test. Baicalein,wogonin and Na<sub>2</sub>MoO<sub>4</sub> showed varing extents of inhibition of the formation of DMN and DEN. Baicalin promoted the formation of DMN and DEN under the condition of simulating gastric Juices. It is also found that E. coli showed a remarkable promoting effect on the formation of DMN and DEN,but this promoting effect could be blocked to some extent by baicalein,wogonin,baicalin and Na<sub>2</sub>MoO<sub>4</sub>. Besides, Na<sub>2</sub>MoO<sub>4</sub> and wogonin have shown synergic effect on the blocking of N-nitrosation reaction.展开更多
Aim To study the effects of baicalein （BC）, a phenolic flavonoid extracted mainly from Scutellaria ba- icalensis Georgi, on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice and the molecular mech...Aim To study the effects of baicalein （BC）, a phenolic flavonoid extracted mainly from Scutellaria ba- icalensis Georgi, on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice and the molecular mecha- nisms underlying. Methods Mice were administrated intranasally with LPS （20 mg · kg^-1/body weight） to estab- lish the ALI model. Then the mice were treated twice with BC （50,100 and 200 mg · kg^-1, p. o. ） 0. 5 hour and 12 hours after LPS stimulation, following another 12 hours, the lungs were collected for histological study. Results LPS caused marked inflammatory cell infiltration and myeloperoxidase activation in lungs, accompanied by significantly in- creased lung W/D ratio, from 7.97±0. 60 in normal group to 12. 49 ± 1.49 in the model. 77.88% reduction in the lung W/D ratio was observed in 200 mg· kg^-1 dose of baicalein. The myeloperoxidase activity was reduced to 40. 14% in mice treated with 200 mg · kg^-1. The number of total cells, neutrophils, and macrophages in BALF de- creased with increasing concentration of baicalein. Inflammatory cytokines level in serum declined significantly while insignificant changes of the same in BALF was observed in mice treated with 50,100 and 200 mg · kg^-1 doses of ba- icalein. Furthermore, LPS induced markedly the expression of inflammasomes and other inflammation-related genes in lung tissue. Treatment of LPS-exposed mice with BC significantly reduced the expression levels of these genes and al- leviated the pathological changes in lungs. Moreover, 1 μmol · L^-1 and 10 μmol · L^-1 BC inhibited remarkably the nuclear translocation of NF-kappaB p65 in Raw264.7 cells. Conclusion Baicalein alleviates LPS-induced acute lung injury in mice by suppressing NF-KB-mediated inflammatory responses and downregulation of inflammasomes.展开更多
Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The pu...Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The put- pose of this study was to investigate the role of baicalein in modulating dopamine （DA） metabolism in PC12 cells and to explore possible mechanisms of its actions. Methods The intracellular content and extracellular release of DA in both rotenone-treated and untreated PC12 cells were examined. Second, PC12 cells were first pretreated with baicalein （ 10 μmol · L^-1 ） for 10 rain, and then incubated with or without ionomycin （5 μmol · L^-1 ） for 10 rain to test whether short-term exposure to baicalein affected calcium-dependent or spontaneous DA release. Third, the intracellular and extracellular contents of DA and its related metabolites were examined. After treatment with baica- lein for 24 h, the The tyrosine hydroxylase （TH）, monoamine oxidase B （MAOB）, catechol-O-methyltransferase （COMT） and dopamine transporter （DAT） were detected by immunoblot analysis. Results The results showed that baicalein prevented rotenone-induced cytotoxicity and significantly increased the DA content in both rotenone- treated and untreated PC12 cells. Furthermore, it had no effect on ionomycin-induced or spontaneous DA release after short-term exposure but significantly increased DA content in a time- and dose-dependent manner after treat- ment for 6 h. Baicalein also significantly decreased the intracellular and extracellular homovanillic acid （HVA） content but increased the intracellular 3,4-dihydroxy phenylacetic acid （DOPAC） content. Finally, baicalein sig- nificantly decreased the expression of COMT and DAT, but it had no effect on the expression of TH and MAOB. Conclusion These data suggest that bacalein has the ability to increase DA content and modulate DA metabolism by inhibiting the expression of COMT and DAT. Our study provides evidence that baicalein may be a potential anti- PD drug that merits further study.展开更多
Oxidative damage and redox metal homeostasis loss are two contributing factors in brain aging and widely distributed neurodegenerative diseases. Oxidative species in company with excessive amounts of intracellular fre...Oxidative damage and redox metal homeostasis loss are two contributing factors in brain aging and widely distributed neurodegenerative diseases. Oxidative species in company with excessive amounts of intracellular free iron result in Fenton-type reaction with subsequent production of highly reactive hydroxyl radicals which initiate peroxidation of biomolecules and further formation of non-degradable toxic pigments called lipofuscin that amasses in long-lived postmitotic cells such as neurons. Dietary flavonoid baicalein can counteract the detrimental consequences through exertion of a multiplicity of protective actions within the brain including direct ROS scavenging activity and iron chelation. In this study, we evaluated the neuroprotective effects of baicalein in menadione (superoxide radical generator)-treated SK-N-MC neuroblastoma cell line. Our results showed that treatment of cells with menadione led to lipofuscin formation due to elevated intracellular iron contents and accumulation of oxidative products such as MDA and PCO. Also, menadione caused apoptotic cell death in SK-N-MC cells. However, pretreatment with baicalein (40 μM) reversed the harmful effects by chelating free iron and preventing biomolecules peroxidations. Moreover, baicalein prevented cell death through modulation of key molecules in apoptotic pathways including suppression of Bax and caspase-9 activities and induction of bcl2 expression. Key structural features such as presence of hydroxyl groups and iron-binding motifs in baicalein make it the appropriate candidate in antioxidant-based therapy in age-related neurodegenerative diseases.展开更多
Objective:To investigate the role of baicalein in phenotypic transformation of vascularsmooth muscle cells induced by high glucose.Methods:Rat vascular smooth muscle cellexperiments were divided into control group,bai...Objective:To investigate the role of baicalein in phenotypic transformation of vascularsmooth muscle cells induced by high glucose.Methods:Rat vascular smooth muscle cellexperiments were divided into control group,baicalein group,high glucose group,highglucose plus baicalein group,real time quantitative PCR were used for mRNA analysis of-SMA,SM22-αnd OPN,Western blot were used for protein analysis of α-SMA,SM22-αand OPN.Results:Comparing the high glucose group and the high glucose plus baicaleingroup,the level of α-SMA mRNA in high glucose group was 0.419±0.090,the level ofα-SMA mRNA in high glucose plus baicalein group was 0.699±0.079,the latter was 66.8%higher than the former.The level of α-SMA protein in high glucose group was 0.213±0.034,the level of α-SMA protein in high glucose plus baicalein group was 0.393±0.062,the latterwas 84.5%higher than the former.Baicalein could significantly inhibit the down-regulationof α-SMA gene expression induced by high glucose(P<0.05).Comparing the high glucosegroup and the high glucose plus baicalein group,the level of SM22-mRNA in high glucosegroup was 0.369±0.063,the level of SM22-α mRNA in high glucose plus baicalein groupwas 0.583±0.049,the latter was 58.0%higher than the former.The level of SM22-α proteinin high glucose group was 0.343±0.047,the level of SM22-protein in high glucose plusbaicalein group was 0.486±0.051,the latter was 41.7%higher than the former.Baicaleincould significantly inhibit the down-regulation of SM22-α gene expression induced by highglucose(P<0.05).Comparing the high glucose group and the high glucose plus baicaleingroup,the level of OPN mRNA in high glucose group was 2.023±0.281,the level of OPNmRNA in high glucose plus baicalein group was 1.511±0.091,the latter was 25.3%lowerthan the former.The level of OPN protein in high glucose group was 1.063±0.132,the levelof OPN protein in high glucose plus baicalein group was 0.761±0.089,the latter was 28.4%lower than the former.Baicalein could significantly inhibit the up-regulation of OPN geneexpression induced by high glucose(P<0.05).Conclusion:Baicalein can significantly inhibitthe high glucose-induced phenotypic transformation of vascular smooth muscle cells fromcontractile phenotype to synthetic phenotype.展开更多
Background:To confirm whether baicalein improves the sensitivity of carbapenem-resistant Escherichia coli(CREC)to fosfomycin by increasing the permeability of bacterial outer membrane in vitro experiments.Methods:The ...Background:To confirm whether baicalein improves the sensitivity of carbapenem-resistant Escherichia coli(CREC)to fosfomycin by increasing the permeability of bacterial outer membrane in vitro experiments.Methods:The clinically isolated CREC strains were amplified and then divided into three groups including baicalein monotherapy groups,fosfomycin monotherapy groups,and baicalein plus fosfomycin groups,and their minimum inhibitory concentrations(MICs)measurement and interpretation were performed according to CLSI interpretive criteria.To determine bacterial permeability after contact with baicalein,CREC were incubated with fluorescein isothiocyanate(FITC)after pretreatment with blank control without baicalein,with 0.25 MIC of baicalein,and with 0.125 MIC of baicalein,followed by observation of the intrabacterial fluorescence intensity of FITC.In addition,CREC were pretreated with 0.125 MIC of baicalein and with blank control without baicalein followed by measurement of alkaline phosphatase(AKP)leak to determine the change of bacterial permeability.Results:The MIC range in baicalein monotherapy groups was from 128 mg/L to 256 mg/L,and the MIC range in fosfomycin monotherapy groups was from 16 mg/L to 1,024 mg/L,but the MIC range in both combination therapy groups was reduced to 4 mg/L to 64 mg/L.The combination use reduced the MIC of each therapy by 75%-96.88%in all strains,and the fractional inhibitory concentration index(FICI)values less than or equal to 0.5.In the permeability assay,no permeabilization of FITC was observed in the blank groups without baicalein,but the intrabacterial FITC aggregation was observed in the groups of pretreatment with 0.25 MIC of baicalein or 0.25 MIC of baicalein.In the AKP leak assay,the AKP leak was more severe at the groups of coincubation with 0.25 MIC of baicalein than those blank groups without baicalein within the first 6 hours.Conclusion:Our study suggests that baicalein may synergistically enhance the antibacterial effect of fosfomycin by increasing the permeability of CREC outer membrane.展开更多
AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic b...AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.展开更多
This paper aimed to study the ability of baicalein to block human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) and its effect on the vasoactive intestinal peptide (VIP) expression in HCMV-in...This paper aimed to study the ability of baicalein to block human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) and its effect on the vasoactive intestinal peptide (VIP) expression in HCMV-infected EVT in vitro. A human trophoblast cell line (HPT-8) was chosen in this study. HCMV with 100 TCID50 was added into culture medium to infect HPT-8 cells, and then HCMV pp65 antigen was assayed by immunofluorescence staining. The infection status was determined by virus titration. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect virus DNA load in the infected cells. The expression of VIP mRNA and protein in the infected cells was measured by qRT-PCR, immunocytochemistry and Western blotting. Concentration of VIP secreted in supernatants was determined by ELISA. Red-stained HCMV pp65 antigens were found in infected HPT-8 cells 48 h after infection. HCMV replicated in large quantity in infected HPT-8 cells 4 days after infection, reaching a peak at day 6 post-infection. After treatment with baicalein, virus DNA load in infected HPT-8 cells was decreased (P<0.05), and the levels of VIP mRNA and protein, and the concentration were raised to the normal (P>0.05). Our study suggested that baicalein exerts a positive effect on the VIP expression in HCMV-infected EVT at maternal-fetal interface.展开更多
Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor sym...Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel.opment new drugs.Baicalein is a flavonoid isolated from traditional Chinese herb,Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxydopamine(6-OHDA) and promote the differentiation of PC12 cells through high throughput drug screen.ing at the cellularlevel.In vivo studies have shown that baicalein exerts significant therapeutic effect,particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory,we could consider neuroprotec.tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation.Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function,inhibition of collapse of mitochondrial membrane potential,increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia,as well as the production of cathepsin B and cytokines.Additionally,promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu) and gamma-aminobutyric acid(GABA).Overall,baica.lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody.namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.展开更多
The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 1...The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^(-1) from fluorescence quenching studies.Negative ΔH°(-5.66 + 0.14 kJ/mol) and positive(ΔS°)(+ 79.96 + 0.65J/mol K) indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate(SDS) due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°(-40.65 + 0.87 J/mol K).Matrix-assisted laser desorption ionization/time of flight(MALDI-TOF) experiments indicate a 1:1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions(Ag^+,Mg^(2+),Ni^(2+),Mn^(2+),Co^(2+) and Zn^(2+)) increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism(CD) and Fourier transform infrared(FT-IR) spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1(subdomain MA) of BSA.展开更多
文摘Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by the discovery of anticancer agents bearing critical mechanisms of action. Baicalein is a flavonoid with promising anticancer activity, among other pharmacological benefits, and has therefore been of high clinical interest. We tested baicalein in vitro for its effect on several CRC hallmarks, including the suppression of metastasis (the spread of cancer cells from their initial site), the ability to induce apoptosis (cell death), and the inhibition of proliferation (the growth of cells). The suppression of the metastasis of CRC cells was recorded via two studies: the cell migration assay and the in silico docking of baicalein with toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9). Results from the cell migration assay showed that baicalein inhibited metastasis by up to 25.76% (p 0.01) in a concentration-dependent manner. We then reinforced these results by docking baicalein with TLR4 (binding affinity: -8.4 kcal/mol) and docking baicalein with MMP-9 (binding affinity: -7.9 kcal/mol), classifying strong binding affinities as those less than -6.0 kcal/mol. The induction of cell death was measured using a caspase activity assay. Again, a docking study was done to reinforce the findings from the primary in vitro experiment, though this time between baicalein and caspase-3 (binding affinity: -7.1 kcal/mol). Despite mixed observations in concentration dependence, caspase activity, relative to control, reached a maximal increase of 88.6% (p 0.01), and results from the MTT assay demonstrated a survival rate, relative to control, of as low as 59.64%. Considerations for future studies include the testing of baicalein in vivo and on more aberrative CRC cell lines.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
基金Supported by National Natural Science Foundation of China,No.30901945Science Research Foundation of Shaanxi Administration of Traditional Chinese Medicine,No.15-ZY029Science Research Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.RC(XM)201602
文摘AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P < 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P > 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.
文摘OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.
基金supported by the National Natural Science Foundation of China (81473362)。
文摘Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic Classification System(BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro. Physiologically based pharmacokinetic(PBPK) model commercial software GastroPlus~(TM) was used to predict oral absorption of baicalein in vivo.Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling(IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug(C_(max)) and area under the curve(AUC)fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug.Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.
文摘The in vitro effects of baicalein,wogonin,baicalin and Na<sub>2</sub>MoO<sub>4</sub> on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of dimethylnitrosamine（DMN） and diethylnitrosamine（DEN） produced using the UV-photclysis spectrophotometric and pyrolysis gas chromatography test. Baicalein,wogonin and Na<sub>2</sub>MoO<sub>4</sub> showed varing extents of inhibition of the formation of DMN and DEN. Baicalin promoted the formation of DMN and DEN under the condition of simulating gastric Juices. It is also found that E. coli showed a remarkable promoting effect on the formation of DMN and DEN,but this promoting effect could be blocked to some extent by baicalein,wogonin,baicalin and Na<sub>2</sub>MoO<sub>4</sub>. Besides, Na<sub>2</sub>MoO<sub>4</sub> and wogonin have shown synergic effect on the blocking of N-nitrosation reaction.
文摘Aim To study the effects of baicalein （BC）, a phenolic flavonoid extracted mainly from Scutellaria ba- icalensis Georgi, on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice and the molecular mecha- nisms underlying. Methods Mice were administrated intranasally with LPS （20 mg · kg^-1/body weight） to estab- lish the ALI model. Then the mice were treated twice with BC （50,100 and 200 mg · kg^-1, p. o. ） 0. 5 hour and 12 hours after LPS stimulation, following another 12 hours, the lungs were collected for histological study. Results LPS caused marked inflammatory cell infiltration and myeloperoxidase activation in lungs, accompanied by significantly in- creased lung W/D ratio, from 7.97±0. 60 in normal group to 12. 49 ± 1.49 in the model. 77.88% reduction in the lung W/D ratio was observed in 200 mg· kg^-1 dose of baicalein. The myeloperoxidase activity was reduced to 40. 14% in mice treated with 200 mg · kg^-1. The number of total cells, neutrophils, and macrophages in BALF de- creased with increasing concentration of baicalein. Inflammatory cytokines level in serum declined significantly while insignificant changes of the same in BALF was observed in mice treated with 50,100 and 200 mg · kg^-1 doses of ba- icalein. Furthermore, LPS induced markedly the expression of inflammasomes and other inflammation-related genes in lung tissue. Treatment of LPS-exposed mice with BC significantly reduced the expression levels of these genes and al- leviated the pathological changes in lungs. Moreover, 1 μmol · L^-1 and 10 μmol · L^-1 BC inhibited remarkably the nuclear translocation of NF-kappaB p65 in Raw264.7 cells. Conclusion Baicalein alleviates LPS-induced acute lung injury in mice by suppressing NF-KB-mediated inflammatory responses and downregulation of inflammasomes.
文摘Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The put- pose of this study was to investigate the role of baicalein in modulating dopamine （DA） metabolism in PC12 cells and to explore possible mechanisms of its actions. Methods The intracellular content and extracellular release of DA in both rotenone-treated and untreated PC12 cells were examined. Second, PC12 cells were first pretreated with baicalein （ 10 μmol · L^-1 ） for 10 rain, and then incubated with or without ionomycin （5 μmol · L^-1 ） for 10 rain to test whether short-term exposure to baicalein affected calcium-dependent or spontaneous DA release. Third, the intracellular and extracellular contents of DA and its related metabolites were examined. After treatment with baica- lein for 24 h, the The tyrosine hydroxylase （TH）, monoamine oxidase B （MAOB）, catechol-O-methyltransferase （COMT） and dopamine transporter （DAT） were detected by immunoblot analysis. Results The results showed that baicalein prevented rotenone-induced cytotoxicity and significantly increased the DA content in both rotenone- treated and untreated PC12 cells. Furthermore, it had no effect on ionomycin-induced or spontaneous DA release after short-term exposure but significantly increased DA content in a time- and dose-dependent manner after treat- ment for 6 h. Baicalein also significantly decreased the intracellular and extracellular homovanillic acid （HVA） content but increased the intracellular 3,4-dihydroxy phenylacetic acid （DOPAC） content. Finally, baicalein sig- nificantly decreased the expression of COMT and DAT, but it had no effect on the expression of TH and MAOB. Conclusion These data suggest that bacalein has the ability to increase DA content and modulate DA metabolism by inhibiting the expression of COMT and DAT. Our study provides evidence that baicalein may be a potential anti- PD drug that merits further study.
文摘Oxidative damage and redox metal homeostasis loss are two contributing factors in brain aging and widely distributed neurodegenerative diseases. Oxidative species in company with excessive amounts of intracellular free iron result in Fenton-type reaction with subsequent production of highly reactive hydroxyl radicals which initiate peroxidation of biomolecules and further formation of non-degradable toxic pigments called lipofuscin that amasses in long-lived postmitotic cells such as neurons. Dietary flavonoid baicalein can counteract the detrimental consequences through exertion of a multiplicity of protective actions within the brain including direct ROS scavenging activity and iron chelation. In this study, we evaluated the neuroprotective effects of baicalein in menadione (superoxide radical generator)-treated SK-N-MC neuroblastoma cell line. Our results showed that treatment of cells with menadione led to lipofuscin formation due to elevated intracellular iron contents and accumulation of oxidative products such as MDA and PCO. Also, menadione caused apoptotic cell death in SK-N-MC cells. However, pretreatment with baicalein (40 μM) reversed the harmful effects by chelating free iron and preventing biomolecules peroxidations. Moreover, baicalein prevented cell death through modulation of key molecules in apoptotic pathways including suppression of Bax and caspase-9 activities and induction of bcl2 expression. Key structural features such as presence of hydroxyl groups and iron-binding motifs in baicalein make it the appropriate candidate in antioxidant-based therapy in age-related neurodegenerative diseases.
基金Hainan Provincial Natural Science Foundation of China(No.817141)National Natural Science Foundation of China(No.81460043).
文摘Objective:To investigate the role of baicalein in phenotypic transformation of vascularsmooth muscle cells induced by high glucose.Methods:Rat vascular smooth muscle cellexperiments were divided into control group,baicalein group,high glucose group,highglucose plus baicalein group,real time quantitative PCR were used for mRNA analysis of-SMA,SM22-αnd OPN,Western blot were used for protein analysis of α-SMA,SM22-αand OPN.Results:Comparing the high glucose group and the high glucose plus baicaleingroup,the level of α-SMA mRNA in high glucose group was 0.419±0.090,the level ofα-SMA mRNA in high glucose plus baicalein group was 0.699±0.079,the latter was 66.8%higher than the former.The level of α-SMA protein in high glucose group was 0.213±0.034,the level of α-SMA protein in high glucose plus baicalein group was 0.393±0.062,the latterwas 84.5%higher than the former.Baicalein could significantly inhibit the down-regulationof α-SMA gene expression induced by high glucose(P<0.05).Comparing the high glucosegroup and the high glucose plus baicalein group,the level of SM22-mRNA in high glucosegroup was 0.369±0.063,the level of SM22-α mRNA in high glucose plus baicalein groupwas 0.583±0.049,the latter was 58.0%higher than the former.The level of SM22-α proteinin high glucose group was 0.343±0.047,the level of SM22-protein in high glucose plusbaicalein group was 0.486±0.051,the latter was 41.7%higher than the former.Baicaleincould significantly inhibit the down-regulation of SM22-α gene expression induced by highglucose(P<0.05).Comparing the high glucose group and the high glucose plus baicaleingroup,the level of OPN mRNA in high glucose group was 2.023±0.281,the level of OPNmRNA in high glucose plus baicalein group was 1.511±0.091,the latter was 25.3%lowerthan the former.The level of OPN protein in high glucose group was 1.063±0.132,the levelof OPN protein in high glucose plus baicalein group was 0.761±0.089,the latter was 28.4%lower than the former.Baicalein could significantly inhibit the up-regulation of OPN geneexpression induced by high glucose(P<0.05).Conclusion:Baicalein can significantly inhibitthe high glucose-induced phenotypic transformation of vascular smooth muscle cells fromcontractile phenotype to synthetic phenotype.
基金This work was supported by Wenling Science and Technology Bureau for Youth Scholars(No.2021S00058).
文摘Background:To confirm whether baicalein improves the sensitivity of carbapenem-resistant Escherichia coli(CREC)to fosfomycin by increasing the permeability of bacterial outer membrane in vitro experiments.Methods:The clinically isolated CREC strains were amplified and then divided into three groups including baicalein monotherapy groups,fosfomycin monotherapy groups,and baicalein plus fosfomycin groups,and their minimum inhibitory concentrations(MICs)measurement and interpretation were performed according to CLSI interpretive criteria.To determine bacterial permeability after contact with baicalein,CREC were incubated with fluorescein isothiocyanate(FITC)after pretreatment with blank control without baicalein,with 0.25 MIC of baicalein,and with 0.125 MIC of baicalein,followed by observation of the intrabacterial fluorescence intensity of FITC.In addition,CREC were pretreated with 0.125 MIC of baicalein and with blank control without baicalein followed by measurement of alkaline phosphatase(AKP)leak to determine the change of bacterial permeability.Results:The MIC range in baicalein monotherapy groups was from 128 mg/L to 256 mg/L,and the MIC range in fosfomycin monotherapy groups was from 16 mg/L to 1,024 mg/L,but the MIC range in both combination therapy groups was reduced to 4 mg/L to 64 mg/L.The combination use reduced the MIC of each therapy by 75%-96.88%in all strains,and the fractional inhibitory concentration index(FICI)values less than or equal to 0.5.In the permeability assay,no permeabilization of FITC was observed in the blank groups without baicalein,but the intrabacterial FITC aggregation was observed in the groups of pretreatment with 0.25 MIC of baicalein or 0.25 MIC of baicalein.In the AKP leak assay,the AKP leak was more severe at the groups of coincubation with 0.25 MIC of baicalein than those blank groups without baicalein within the first 6 hours.Conclusion:Our study suggests that baicalein may synergistically enhance the antibacterial effect of fosfomycin by increasing the permeability of CREC outer membrane.
基金Supported by The Fundamental Research Funds for the Central Universities No.JKQ2011008,JKQ2011010Postdoctoral Science Foundation of Jiangsu Province,China,No.1101029C
文摘AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.
基金supported by grants from the National Natural Science Foundation of China (Nos. 39970769, 30371488,30672243, and 81200354)the Natural Science Foundation of Hubei Province (No. 2009CDD216)
文摘This paper aimed to study the ability of baicalein to block human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) and its effect on the vasoactive intestinal peptide (VIP) expression in HCMV-infected EVT in vitro. A human trophoblast cell line (HPT-8) was chosen in this study. HCMV with 100 TCID50 was added into culture medium to infect HPT-8 cells, and then HCMV pp65 antigen was assayed by immunofluorescence staining. The infection status was determined by virus titration. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect virus DNA load in the infected cells. The expression of VIP mRNA and protein in the infected cells was measured by qRT-PCR, immunocytochemistry and Western blotting. Concentration of VIP secreted in supernatants was determined by ELISA. Red-stained HCMV pp65 antigens were found in infected HPT-8 cells 48 h after infection. HCMV replicated in large quantity in infected HPT-8 cells 4 days after infection, reaching a peak at day 6 post-infection. After treatment with baicalein, virus DNA load in infected HPT-8 cells was decreased (P<0.05), and the levels of VIP mRNA and protein, and the concentration were raised to the normal (P>0.05). Our study suggested that baicalein exerts a positive effect on the VIP expression in HCMV-infected EVT at maternal-fetal interface.
基金supported by National Key R＆D Plan(2016YFC1000905)
文摘Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel.opment new drugs.Baicalein is a flavonoid isolated from traditional Chinese herb,Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxydopamine(6-OHDA) and promote the differentiation of PC12 cells through high throughput drug screen.ing at the cellularlevel.In vivo studies have shown that baicalein exerts significant therapeutic effect,particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory,we could consider neuroprotec.tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation.Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function,inhibition of collapse of mitochondrial membrane potential,increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia,as well as the production of cathepsin B and cytokines.Additionally,promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu) and gamma-aminobutyric acid(GABA).Overall,baica.lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody.namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.
基金Department of Science and Technology(DST,Project no.SR/SO/BB-54/2007),Government of India for financial support
文摘The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^(-1) from fluorescence quenching studies.Negative ΔH°(-5.66 + 0.14 kJ/mol) and positive(ΔS°)(+ 79.96 + 0.65J/mol K) indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate(SDS) due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°(-40.65 + 0.87 J/mol K).Matrix-assisted laser desorption ionization/time of flight(MALDI-TOF) experiments indicate a 1:1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions(Ag^+,Mg^(2+),Ni^(2+),Mn^(2+),Co^(2+) and Zn^(2+)) increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism(CD) and Fourier transform infrared(FT-IR) spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1(subdomain MA) of BSA.
