To enhance the anesthetic efficacy of propofol while mitigating its systemic toxicity and irreversible developmental neurotoxicity, we developed a strategy leveraging the neuroprotective effects of baicalin in combina...To enhance the anesthetic efficacy of propofol while mitigating its systemic toxicity and irreversible developmental neurotoxicity, we developed a strategy leveraging the neuroprotective effects of baicalin in combination with propofol anesthesia via baicalinbased nanocomposites. High propofol-loaded porous Baicalin-Fe(Ⅲ) infinite coordination polymer@propofol nanocomposites were synthesized, wherein baicalin coordinates with Fe3+ ions to form porous nanoparticles that encapsulate propofol within a core-shell structure. These nanocomposites exhibited an average diameter of 92.3 ± 10.2 nm and a pore volume of 0.322 cm^(3)/g, achieving ultra-high propofol loading(~62%) with no detectable leakage over 100 d, attributed to their large surface area and strong molecular interactions.When combined with focused ultrasound(FUS) and microbubbles, the effective dose(ED_(50))of propofol decreased from 10 to 4.3 mg/kg, doubling the duration of anesthesia and extending the therapeutic window by 200%. Importantly, the therapeutic index improved1.66-fold while vital physiological parameters remained stable. Histological analyses revealed an 80% reduction in neuronal injury compared to free propofol, and behavioral tests demonstrated significant enhancements in motor and cognitive performance, alongside recovery from propofol-induced irreversible developmental neurotoxicity, indicating effective neuroprotection. Collectively, this baicalin-propofol nanocomposite, coupled with FUS-mediated delivery, represents a promising approach for safe and long-term anesthesia in clinical applications.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory sym...Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.展开更多
Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,t...Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear.To investigate this,we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes,and added baicalin(Ba)to further explore its protective effects.Results The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes,while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes.Furthermore,Cu exposure significantly upregulated mRNA and protein levels related to ER stress,autophagy,and lysosomal membrane factors.It also markedly increased ER-lysosomal co-localization.Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes.Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba;in vitro experiments demonstrated that Ba could effectively alleviate Cuinduced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B;additionally,in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks.Conclusions In summary,the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver,leading to ER-lysosomal damage and subsequent hepatocyte injury.In contrast,Ba alleviates this injury by selectively targeting LAPTM4B,ultimately attenuating Cu-induced hepatotoxicity.展开更多
Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant...Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant research interest for its hepatoprotective properties.Nevertheless,the clinical application of BAI is constrained by its limited water solubility and poor bioavailability.To address these challenges,BAI-nanoliposome(BAI-NL)has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes.Methods:We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the pro-tective effect of BAI and BAI-NL on liver inflammation,oxidative stress,and mitochondrial function.The parameters included histological,biochemical,and molecular biological analyses.Results:In the diquat-induced model,both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation.Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mito-chondrial membrane potential,reducing oxidative stress,and modulating the phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin RBR E3 ubiquitin-protein ligase(Parkin)signaling pathway.These findings enhanced mitophagy and facilitated the removal of damaged mitochondria.Conclusions:BAI-NL exhibited superior hepatoprotective effects compared to free BAI,possibly by re-ducing inflammation,preserving mitochondrial homeostasis,and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway.These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.展开更多
Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease in...Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.展开更多
[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods...[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods]The chromatographic separation was performed on a GL Sciences(19H0044724)-C_(18)column(4.6 mm×250 mm,5μm)with a mobile phase of acetonitrile-0.05%formic acid solution at a flow rate of 1 mL/min.The injection volume was 10μL,detection wavelength was set at 280 nm,and column temperature was maintained at 25℃.[Results]The linear ranges of forsythin,baicalin,and chlorogenic acid were 10.5-52.5,20.6-103,and 14.2-71μg/mL,respectively,with good linear relationships between concentration and peak area(R^(2)=0.9999).The relative standard deviations(RSD s)for precision and repeatability tests were all≤1.0%.The average recoveries were 98.51%,98.48%,and 97.71%for the three components,with RSD s of 0.96%,0.97%,and 0.73%,respectively.[Conclusions]This method demonstrates strong specificity,high precision,excellent accuracy,and simplicity of operation,making it suitable for the simultaneous quantification of forsythin,baicalin,and chlorogenic acid in traditional Chinese medicine spray disinfectants.It provides a reliable basis for quality control and practical applications in animal breeding environments.展开更多
Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe inters...Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe interstitial pneumonia and liver dysfunction.Importantly,the hepatotoxicity induced by Scutellaria root can be controlled by the baicalin content,one of its major constituents.This study aimed to clarify the role of MRP2 in modulating baicalin-induced cytotoxicity in HepG2 cells,providing insights that inform safer use and assessment of baicalin.Methods:Cytotoxicity of HepG2 and MDCK cells was assessed using a cell counting kit-8 assay in the presence and absence of MK571,an MRP2 inhibitor.MRP2 expression levels were confirmed using agarose gel electrophoresis,and intracellular baicalin concentrations were measured using LC/MS.Results:Baicalin exhibited concentration-dependent cytotoxicity,with higher toxicity observed in MRP2-negative MDCK cells than in MRP2-positive HepG2 cells.Pre-treatment with MK571 increased baicalin-induced cytotoxicity in HepG2 cells and doubled the intracellular baicalin concentration.Conclusion:Our results indicated that MRP2 plays an important role in reducing baicalin-induced hepatocyte toxicity by decreasing intracellular baicalin levels.Monitoring MRP2 activity could serve as a critical predictive biomarker to identify individuals at higher risk of baicalin-induced hepatotoxicity,enabling personalized dosing strategies and minimizing adverse effects associated with Scutellaria root-containing formulae.展开更多
Baicalin,a major flavonoid compound found in Scutellariae radix,is the first SARS-CoV-23CLpro virus inhibitor.Therefore,developing an accurate and reliable strategy to detect baicalin in biological systems is vital.He...Baicalin,a major flavonoid compound found in Scutellariae radix,is the first SARS-CoV-23CLpro virus inhibitor.Therefore,developing an accurate and reliable strategy to detect baicalin in biological systems is vital.Herein,we report the first indolyl-lanthanide metal-organic framework(MOF)materials and their application as baicalin sensors.The results of this study indicate that the new crystal structure has good stability and luminous performance.The detection limits of baicalin in serum and urine are 0.05 and 0.04μmol/L,respectively,suggesting high sensitivity and selectivity.Various background substances present in practical samples,such as anions,cations,and amino acids,do not interfere with the photoluminescence analytical signal of Eu^(3+).We identified that the quenching of the Eu-MOF is due to the inner filter effect,absorption energy competition,and photoinduced electron transfer among the baicalin,ligand,and MOF through powder X-ray diffraction analysis,Fourier transform infrared spectroscopy,luminescence lifetimes,ultraviolet studies,and computational analysis.Thus,we designed a convenient,sensitive,and facile detection method using the Eu-MOF and demonstrate that Eu^(3+)-based materials are promising sensors for baicalin detection in actual serum and urine.Additionally,the prepared Eu-MOF@polyvinyl alcohol composite matrix membrane test film has considerable practical application value for the portable detection of baicalin.展开更多
Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weigh...Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weight gain,and significant economic losses.Results In this study,we isolated an E.coli strain,SKLAN202302,from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin.Piglets infected with E.coli exhibited significant reductions in body weight,feed intake,small intestine length,and ileal goblet cell count(P<0.05),along with deteriorated ileal morphology.However,baicalin supplementation resulted in body weights,feed intake,and intestinal morphology similar to those of the control group.Notably,there was a significant increase in the colonization of Lactobacillus species,particularly Lactobacillus_reuteri,Lactobacillus_amylovorus,and Lactobacillus_johnii,compared to the E.coli group(P<0.05).At the metabolic and transcriptional levels,E.coli infection increased inflammatory mediators,including eicosanoids(leukotriene F4,prostaglandin F1a,leukotriene E4,thromboxane B2,prostaglandin G2,and PGH2),monosaccharides,and TCA cycle intermediates(oxoglutaric acid,glutaric acid,adipic acid,citric acid,and isocitric acid)in the ileum.It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway(CTLA4,IFN-ALPHA-8,IL12RB2,TRAV3,TRAV16,FOS,and VEGFA),as well as inflammatory factors.Conversely,baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids[including lyso PC(P-18:1(9Z)/0:0),PC(17:0/0:0),lyso PC(16:1(9Z)/0:0),PC(18:0/0:0),lyso PC(18:0/0:0),PA(10:0/i-16:0),and PA(10:0/8:0)]and amino acids.It also regulated genes within the IL-17 signaling pathway(IL4,CCL17,CXCL10,IFNG,and CXCL2),suggesting a mechanism by which baicalin mitigates E.coli-induced intestinal and microbial disturbances.Subsequent flow cytometry analysis showed that E.coli infection increased the numbers of CD3+and Foxp3+cells,decreased IL-17A+cells,and reduced Th17/Treg ratios.Baicalin supplementation restored these parameters to control levels.Conclusions Baicalin supplementation effectively alleviates E.coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization,counteracting inflammatory mediators,and regulating immune-related gene expression and the Th17/Treg balance.These findings highlight baicalin's potential in alleviating intestinal inflammation.展开更多
目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC...目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)定量分析单药(斑蝥素6μg/mL、黄芩苷30μg/mL)及配伍组(斑蝥素6μg/mL+黄芩苷30μg/mL)给药后12 h内,整体细胞及细胞核、线粒体、内质网和溶酶体各细胞器中药物浓度的动态变化,并应用Phoenix WinNonlin软件非房室模型计算药动学参数。结果在整体细胞水平,配伍使斑蝥素的胞内药时曲线下面积(area under the curve,AUC_(0~t))增加48.9%,清除率降低(P<0.05),但未显著影响黄芩苷的药动学行为。在亚细胞层面,配伍使斑蝥素与黄芩苷在细胞核、溶酶体、线粒体、内质网内的AUC_(0~t)分别增加了93.5%、46.4%、38.3%、52.3%和68.4%、40.0%、41.0%、46.7%(P<0.05、0.01)。此外,配伍后2种药物在线粒体内达峰时间(t_(max))提前,且斑蝥素在内质网中的平均驻留时间(mean residence time,MRT_(0~t))显著延长(P<0.01),表明两者配伍实现了时空协同的药物递送。结论斑蝥素/黄芩苷配伍可通过协同优化药物在细胞核、线粒体、内质网及溶酶体等关键亚细胞结构的分布,进而可能通过诱导DNA损伤、加速线粒体介导细胞凋亡及促进内质网应激等途径,增强抗肝癌效果,为基于细胞器靶向的中药配伍设计提供了理论依据。展开更多
Aim In the present study a RP-HPLC method was developed and validated toinvestigate the stability of baicalin aqueous solution. Methods The influences of temperature and pHon the stability of baicalin aqueous solution...Aim In the present study a RP-HPLC method was developed and validated toinvestigate the stability of baicalin aqueous solution. Methods The influences of temperature and pHon the stability of baicalin aqueous solution were investigated by classic homoiothermicacceleration test, and the pH for the most stable solution was determined. Results The time whenbaicalin suffered 10% loss was found to be 18.1 h, and the degradation activation energy of baicalinwas 79.1 kJ·moL^(-1) . The pH at which baicalin is most stable is 4.28. Conclusion The temperatureshould be kept at a lower level and the pH should be adjusted to near that for the most stablesolution in the production of baicalin preparations.展开更多
Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was perform...Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.展开更多
基金funded by the National Natural Science Foundation of China (No. 82271572)The Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University (No. XJTU1AF2021CRF-008) and (No. XTJU1AF-CRF2023-025)。
文摘To enhance the anesthetic efficacy of propofol while mitigating its systemic toxicity and irreversible developmental neurotoxicity, we developed a strategy leveraging the neuroprotective effects of baicalin in combination with propofol anesthesia via baicalinbased nanocomposites. High propofol-loaded porous Baicalin-Fe(Ⅲ) infinite coordination polymer@propofol nanocomposites were synthesized, wherein baicalin coordinates with Fe3+ ions to form porous nanoparticles that encapsulate propofol within a core-shell structure. These nanocomposites exhibited an average diameter of 92.3 ± 10.2 nm and a pore volume of 0.322 cm^(3)/g, achieving ultra-high propofol loading(~62%) with no detectable leakage over 100 d, attributed to their large surface area and strong molecular interactions.When combined with focused ultrasound(FUS) and microbubbles, the effective dose(ED_(50))of propofol decreased from 10 to 4.3 mg/kg, doubling the duration of anesthesia and extending the therapeutic window by 200%. Importantly, the therapeutic index improved1.66-fold while vital physiological parameters remained stable. Histological analyses revealed an 80% reduction in neuronal injury compared to free propofol, and behavioral tests demonstrated significant enhancements in motor and cognitive performance, alongside recovery from propofol-induced irreversible developmental neurotoxicity, indicating effective neuroprotection. Collectively, this baicalin-propofol nanocomposite, coupled with FUS-mediated delivery, represents a promising approach for safe and long-term anesthesia in clinical applications.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
基金supported by the National Natural Science Foundation of China(Grant No.:82474195)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:021093002882)+2 种基金the Youth Medical Innovation Research Project of China(Grant No.:P24021887623)Taizhou Science and Technology Support Project,China(Grant No.:TS202420)grants from Nanjing Medical University,China(Grant Nos.:TZKY20230104 and 2024KF0292).
文摘Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
基金supported by the program of Introduce and cultivate high-level innovative and entrepreneurial personnel:Thousand Talents Program of Jiangxi province(jxsg2023201121)the National Natural Science Foundation of China(32460908)Natural Science Foundation of Jiangxi province(20232ACB215004).
文摘Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear.To investigate this,we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes,and added baicalin(Ba)to further explore its protective effects.Results The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes,while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes.Furthermore,Cu exposure significantly upregulated mRNA and protein levels related to ER stress,autophagy,and lysosomal membrane factors.It also markedly increased ER-lysosomal co-localization.Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes.Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba;in vitro experiments demonstrated that Ba could effectively alleviate Cuinduced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B;additionally,in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks.Conclusions In summary,the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver,leading to ER-lysosomal damage and subsequent hepatocyte injury.In contrast,Ba alleviates this injury by selectively targeting LAPTM4B,ultimately attenuating Cu-induced hepatotoxicity.
基金supported by grants from the National Key Re-search and Development Program of China(2023YFC3603100 and 2023YFC3603105)“Leading Goose”R&D Program of Zhejiang Province(2022C03076-4).
文摘Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant research interest for its hepatoprotective properties.Nevertheless,the clinical application of BAI is constrained by its limited water solubility and poor bioavailability.To address these challenges,BAI-nanoliposome(BAI-NL)has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes.Methods:We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the pro-tective effect of BAI and BAI-NL on liver inflammation,oxidative stress,and mitochondrial function.The parameters included histological,biochemical,and molecular biological analyses.Results:In the diquat-induced model,both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation.Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mito-chondrial membrane potential,reducing oxidative stress,and modulating the phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin RBR E3 ubiquitin-protein ligase(Parkin)signaling pathway.These findings enhanced mitophagy and facilitated the removal of damaged mitochondria.Conclusions:BAI-NL exhibited superior hepatoprotective effects compared to free BAI,possibly by re-ducing inflammation,preserving mitochondrial homeostasis,and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway.These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.
基金supported by grants from the National Natural Science Foundation of China(U21A20400,81973789,82004327).
文摘Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.
基金Supported by Shandong Province Major Agricultural Technologies Collaborative Promotion Project(SDNYXTTG-2024-04)National Key Laboratory for Quality Control of Chinese Medicinal Materials and Decoction Pieces Project(2024GSMPA-KL16)Weifang Municipal Science and Technology Bureau Project(2021GX031).
文摘[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods]The chromatographic separation was performed on a GL Sciences(19H0044724)-C_(18)column(4.6 mm×250 mm,5μm)with a mobile phase of acetonitrile-0.05%formic acid solution at a flow rate of 1 mL/min.The injection volume was 10μL,detection wavelength was set at 280 nm,and column temperature was maintained at 25℃.[Results]The linear ranges of forsythin,baicalin,and chlorogenic acid were 10.5-52.5,20.6-103,and 14.2-71μg/mL,respectively,with good linear relationships between concentration and peak area(R^(2)=0.9999).The relative standard deviations(RSD s)for precision and repeatability tests were all≤1.0%.The average recoveries were 98.51%,98.48%,and 97.71%for the three components,with RSD s of 0.96%,0.97%,and 0.73%,respectively.[Conclusions]This method demonstrates strong specificity,high precision,excellent accuracy,and simplicity of operation,making it suitable for the simultaneous quantification of forsythin,baicalin,and chlorogenic acid in traditional Chinese medicine spray disinfectants.It provides a reliable basis for quality control and practical applications in animal breeding environments.
基金supported by the JSPS KAKENHI(Grant Number:JP22K06676)。
文摘Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe interstitial pneumonia and liver dysfunction.Importantly,the hepatotoxicity induced by Scutellaria root can be controlled by the baicalin content,one of its major constituents.This study aimed to clarify the role of MRP2 in modulating baicalin-induced cytotoxicity in HepG2 cells,providing insights that inform safer use and assessment of baicalin.Methods:Cytotoxicity of HepG2 and MDCK cells was assessed using a cell counting kit-8 assay in the presence and absence of MK571,an MRP2 inhibitor.MRP2 expression levels were confirmed using agarose gel electrophoresis,and intracellular baicalin concentrations were measured using LC/MS.Results:Baicalin exhibited concentration-dependent cytotoxicity,with higher toxicity observed in MRP2-negative MDCK cells than in MRP2-positive HepG2 cells.Pre-treatment with MK571 increased baicalin-induced cytotoxicity in HepG2 cells and doubled the intracellular baicalin concentration.Conclusion:Our results indicated that MRP2 plays an important role in reducing baicalin-induced hepatocyte toxicity by decreasing intracellular baicalin levels.Monitoring MRP2 activity could serve as a critical predictive biomarker to identify individuals at higher risk of baicalin-induced hepatotoxicity,enabling personalized dosing strategies and minimizing adverse effects associated with Scutellaria root-containing formulae.
基金Project supported by Jilin Province Science and Technology Development Plan Project(20210201061GX)。
文摘Baicalin,a major flavonoid compound found in Scutellariae radix,is the first SARS-CoV-23CLpro virus inhibitor.Therefore,developing an accurate and reliable strategy to detect baicalin in biological systems is vital.Herein,we report the first indolyl-lanthanide metal-organic framework(MOF)materials and their application as baicalin sensors.The results of this study indicate that the new crystal structure has good stability and luminous performance.The detection limits of baicalin in serum and urine are 0.05 and 0.04μmol/L,respectively,suggesting high sensitivity and selectivity.Various background substances present in practical samples,such as anions,cations,and amino acids,do not interfere with the photoluminescence analytical signal of Eu^(3+).We identified that the quenching of the Eu-MOF is due to the inner filter effect,absorption energy competition,and photoinduced electron transfer among the baicalin,ligand,and MOF through powder X-ray diffraction analysis,Fourier transform infrared spectroscopy,luminescence lifetimes,ultraviolet studies,and computational analysis.Thus,we designed a convenient,sensitive,and facile detection method using the Eu-MOF and demonstrate that Eu^(3+)-based materials are promising sensors for baicalin detection in actual serum and urine.Additionally,the prepared Eu-MOF@polyvinyl alcohol composite matrix membrane test film has considerable practical application value for the portable detection of baicalin.
基金supported by the National Natural Science Foundation of China(32102582)the Youth innovation of Chinese Academy of Agricultural Sciences(Y2023QC09)+1 种基金Zhejiang Province Traditional Chinese Medicine Science and technology Project(2022ZB270)the Agricultural Science and Technology Innovation Program(ASTIPIAS07,cxgc-ias-16)。
文摘Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weight gain,and significant economic losses.Results In this study,we isolated an E.coli strain,SKLAN202302,from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin.Piglets infected with E.coli exhibited significant reductions in body weight,feed intake,small intestine length,and ileal goblet cell count(P<0.05),along with deteriorated ileal morphology.However,baicalin supplementation resulted in body weights,feed intake,and intestinal morphology similar to those of the control group.Notably,there was a significant increase in the colonization of Lactobacillus species,particularly Lactobacillus_reuteri,Lactobacillus_amylovorus,and Lactobacillus_johnii,compared to the E.coli group(P<0.05).At the metabolic and transcriptional levels,E.coli infection increased inflammatory mediators,including eicosanoids(leukotriene F4,prostaglandin F1a,leukotriene E4,thromboxane B2,prostaglandin G2,and PGH2),monosaccharides,and TCA cycle intermediates(oxoglutaric acid,glutaric acid,adipic acid,citric acid,and isocitric acid)in the ileum.It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway(CTLA4,IFN-ALPHA-8,IL12RB2,TRAV3,TRAV16,FOS,and VEGFA),as well as inflammatory factors.Conversely,baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids[including lyso PC(P-18:1(9Z)/0:0),PC(17:0/0:0),lyso PC(16:1(9Z)/0:0),PC(18:0/0:0),lyso PC(18:0/0:0),PA(10:0/i-16:0),and PA(10:0/8:0)]and amino acids.It also regulated genes within the IL-17 signaling pathway(IL4,CCL17,CXCL10,IFNG,and CXCL2),suggesting a mechanism by which baicalin mitigates E.coli-induced intestinal and microbial disturbances.Subsequent flow cytometry analysis showed that E.coli infection increased the numbers of CD3+and Foxp3+cells,decreased IL-17A+cells,and reduced Th17/Treg ratios.Baicalin supplementation restored these parameters to control levels.Conclusions Baicalin supplementation effectively alleviates E.coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization,counteracting inflammatory mediators,and regulating immune-related gene expression and the Th17/Treg balance.These findings highlight baicalin's potential in alleviating intestinal inflammation.
文摘目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)定量分析单药(斑蝥素6μg/mL、黄芩苷30μg/mL)及配伍组(斑蝥素6μg/mL+黄芩苷30μg/mL)给药后12 h内,整体细胞及细胞核、线粒体、内质网和溶酶体各细胞器中药物浓度的动态变化,并应用Phoenix WinNonlin软件非房室模型计算药动学参数。结果在整体细胞水平,配伍使斑蝥素的胞内药时曲线下面积(area under the curve,AUC_(0~t))增加48.9%,清除率降低(P<0.05),但未显著影响黄芩苷的药动学行为。在亚细胞层面,配伍使斑蝥素与黄芩苷在细胞核、溶酶体、线粒体、内质网内的AUC_(0~t)分别增加了93.5%、46.4%、38.3%、52.3%和68.4%、40.0%、41.0%、46.7%(P<0.05、0.01)。此外,配伍后2种药物在线粒体内达峰时间(t_(max))提前,且斑蝥素在内质网中的平均驻留时间(mean residence time,MRT_(0~t))显著延长(P<0.01),表明两者配伍实现了时空协同的药物递送。结论斑蝥素/黄芩苷配伍可通过协同优化药物在细胞核、线粒体、内质网及溶酶体等关键亚细胞结构的分布,进而可能通过诱导DNA损伤、加速线粒体介导细胞凋亡及促进内质网应激等途径,增强抗肝癌效果,为基于细胞器靶向的中药配伍设计提供了理论依据。
文摘Aim In the present study a RP-HPLC method was developed and validated toinvestigate the stability of baicalin aqueous solution. Methods The influences of temperature and pHon the stability of baicalin aqueous solution were investigated by classic homoiothermicacceleration test, and the pH for the most stable solution was determined. Results The time whenbaicalin suffered 10% loss was found to be 18.1 h, and the degradation activation energy of baicalinwas 79.1 kJ·moL^(-1) . The pH at which baicalin is most stable is 4.28. Conclusion The temperatureshould be kept at a lower level and the pH should be adjusted to near that for the most stablesolution in the production of baicalin preparations.
基金Innovation Fund of Chinese Academy of Sciences(KGCX2 SW 213 05)
文摘Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.
