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1.
Article in Chinese | WPRIM | ID: wpr-940589

ABSTRACT

ObjectiveTo investigate the effects and mechanism of baicalin (BA) on lipopolysaccharide (LPS)-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group, model group, low-dose BA (BA-L) group, medium-dose BA (BA-M) group, high-dose BA (BA-H) group, dexamethasone (DEX) group, SB203580 group, and BA + SB203580 group, with 10 rats in each group. The rats in the BA-L, BA-M, and BA-H groups were injected intraperitoneally with different doses (10, 50, 100 mg·kg-1) of BA solution, the ones in the DEX group with 5 mg·kg-1 DEX solution, the ones in the SB203580 group with 0.5 mg·kg-1 SB203580 solution, the ones in the BA + SB203580 group with 100 mg·kg-1 BA solution and 0.5 mg·kg-1 SB203580, and those in both the control group and model group with the same volume of normal saline, once per day, for seven successive days. One hour after the last administration, rats in all groups except for the control group were given 5 mg·kg-1 LPS via intratracheal instillation for inducing the acute lung injury, whereas those in the control group received the same volume of normal saline solution. Twelve hours later, the lung tissues were sampled and stained with htoxylin-eosin (HE) for observing the pathological changes, followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid (BALF). The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. The activity of reactive oxygen species (ROS) in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in BALF by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase (MAPK) and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK, thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific protease-1 (Caspase-1) in the lung tissue. ResultCompared with the control group, the model group displayed inflammatory pathological changes in lung tissue, elevated wet/dry weight ratio, total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.01), decreased SOD activity (P<0.01), and up-regulated IL-1, IL-18, IL-6, TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 expression (P<0.01). Compared with the model group, BA at different doses, SB203580, and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS, reduce the lung wet/dry weight ratio, the total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.05,P<0.01), enhanced the activity of SOD (P<0.05,P<0.01), and down-regulated the expression of IL-1β, IL-18, IL-6,TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 in lung tissue (P<0.05,P<0.01). ConclusionBA has a protective effect against LPS-induced acute lung injury, which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.

2.
Article in Chinese | WPRIM | ID: wpr-940492

ABSTRACT

ObjectiveTo establish a high performance liquid chromatography (HPLC) for simultaneous determination of baicalin magnesium and baicalein in rat plasma and tissues, and to investigate the effect of acute liver injury on pharmacokinetics and tissue distribution of baicalin magnesium in rats. MethodAcute liver injury rat model was induced by carbon tetrachloride (CCl4). Normal rats and acute liver injury model rats were given an equal dose (287.31 mg·kg-1) of baicalin magnesium aqueous solution by intragastric administration, the orbital blood was collected at different time points, and HPLC was used to simultaneously determine the concentrations of baicalin magnesium and baicalein in rat plasma at each time point, the concentration-time curves were drawn, the pharmacokinetic parameters were calculated with DAS 3.0, and SPSS 23.0 was used for statistical analysis. After oral administration of baicalin magnesium aqueous solution, HPLC was used to simultaneously determine the contents of baicalin magnesium and baicalein in rat liver, lung, kidney, stomach, brain and small intestine at different time points, the mobile phase was 0.1% phosphoric acid aqueous solution-methanol, and the detection wavelength was 278 nm. ResultIn the acute liver injury model group, the peak concentration (Cmax) of baicalin magnesium was 0.58 times that of the normal group, the area under concentration-time curve (AUC0-t) was 0.5 times that of the normal group (P<0.05), the apparent volume of distribution (Vd) was 2.3 times that of the normal group (P<0.05), and baicalein is almost undetectable in plasma. The content of baicalin magnesium in liver, stomach and brain of the acute liver injury model group was higher than that of the normal group at each time point, while the content of baicalin magnesium in the samples of lung at 8 h, kidney at 8 h and 12 h, and small intestine at 0.333 h was lower than that of the normal group. The content of baicalein in lung, stomach and small intestine of the model group was higher than that of the normal group at each time point, while the content of baicalein in the tissue samples of liver at 6, 8 h and kidney at 0.333, 4, 6 h was lower than that in the normal group, and baicalein could hardly be detected in the brain. ConclusionAfter intragastric administration of the same dose of baicalin magnesium aqueous solution, acute liver injury induced by CCl4 can affect the pharmacokinetics and tissue distribution characteristics of baicalin magnesium in rats, and there is biotransformation of baicalin magnesium and baicalein in liver, lung, kidney, stomach and small intestine.

3.
Article in Chinese | WPRIM | ID: wpr-928090

ABSTRACT

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.


Subject(s)
Animals , Flavonoids , Inflammation/genetics , Interferon-gamma , Lipopolysaccharides/adverse effects , Mice , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism
4.
Article in Chinese | WPRIM | ID: wpr-928023

ABSTRACT

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.


Subject(s)
Animals , Aquaporin 4/genetics , Astrocytes , Brain Edema/drug therapy , Brain Ischemia/metabolism , Flavonoids , Infarction, Middle Cerebral Artery/drug therapy , Rats , Rats, Sprague-Dawley , Reperfusion , TRPV Cation Channels/therapeutic use
5.
China Pharmacy ; (12): 943-949, 2022.
Article in Chinese | WPRIM | ID: wpr-923596

ABSTRACT

OBJECTIVE To optimize the pr eparation technology of the baicalin lipid nano foam aerosol (BC-LN-FA). METHODS Baicalin lipid nanoparticle (BC-LN)and BC-LN-FA were prepared by the thin film dispersion method and homogeneous emulsification method ,respectively,using baicalin (BC) as the model drug. The preparation technology was optimized by Box-Behnken design-response surface methodology using particle size and encapsulation efficiency (EE)as indexes ,with dosage , emulsifier dosage ,co-emulsifier dosage and homogenization time as factors. The morphology ,particle size ,polymerdispersity index(PDI),EE,the viscosity ,the foam dissolution rate and in vitro transdermal release of BC-LN-FA were characterized. RESULTS The optimal technology included 25 mg BC ,40 mg emulsifier (mass ratio of stearic acid-soybean lecithin-glycerol was 1∶1∶1),30 mg co-emulsifier (mass ratio of octadecanol-lactic acid was 1∶1),homogenization time of 20 min. Results of 3 times of validation tests showed that particle size of prepared BC-LN-FA was (151.70±2.40)nm,EE was (68.62±1.16)%;the deviation of them from the predicted value (particle size of 150.80 nm,EE of 67.02%)were 0.60% and 2.39% respectively. The BC-LN-FA prepared by the optimal process was light yellow opalescence ,uniform in particle size and round-like in shape. The viscosity,the foam dissolution rate ,the content of BC and PDI were (122.92±5.09)mPa·s,(65.32±3.22)%,(7.01±0.12)% and(0.199±0.006),respectively. At 48 h,the cumulative release rates of BC-LN-FA in phosphate buffer saline (PBS)at pH 7.4, 6.8,5.0 were(54.12±2.69)%,(57.85±4.25)% and(59.47±1.83)%,respectively;those of free BC in PBS at pH 7.4 was only (15.04±1.43)%. CONCLUSIONS The optimized technology is stable and feasible. Prepared BC-LN-FA has a uniform particle size,high digestion rate and certain viscosity.

6.
Braz. J. Pharm. Sci. (Online) ; 58: e19791, 2022. tab, graf
Article in English | LILACS | ID: biblio-1383988

ABSTRACT

Abstract In China, Scutellaria is used for treating inflammatory-related diseases. Baicalin is the main active component of Scutellaria and has protective effects on acute pancreatitis. However, the mechanism of Baicalin is still unclear. In this study, the protective effects of baicalin on acute pancreatitis induced by taurocholate and its mechanism are investigated. In this study, mice were randomly divided into three groups: sham operation, model, and treatment groups. Acute pancreatitis in mice was induced by intraperitoneal injection of taurocholate (35 mg/kg). The treatment group was given baicalin (100 mg/kg) 2 h before acute pancreatitis induction. The mRNA expression levels of miR-429, nuclear factor kappa B65(NF-kB65), toll-like receptor 4(TLR4), TNF receptor associated factor6 (TRAF6), NF-kappa-B inhibitor(IkB), Follistatin-like 1 (FSTL1), and interleukin-1 receptor-associated kinase (IRAK) in the liver tissues 24 h after intraperitoneal injection were detected by RT-PCR. Then, the expression levels of NF-kB65, p-NF-κB65, TLR4, TRAF6, IkB, FSTL1, IRAK, p- IRAK, and p- IkB-а proteins were detected by Western blot. IL-6, TNF-α and IL-1 ß in plasma were measured by ELISA, and histopathological changes in the pancreases of the mice were observed. The results showed that after baicalin treatment, miR-429 expression in the pancreatic tissues and the expression levels of NF-kB65, TLR4, TRAF6, p-IkB-а, FSTL1, and p-IRAK decreased. Similarly, pancreatic myeloperoxidase (MPO) activity and the plasma levels of IL-6, TNF-а, IL-12, IL-1ß1, endotoxin, serum amylase, and lipase were reduced. Thus, the pancreatic injury induced by taurocholate was alleviated. The present study indicates that pretreatment with Baicalin can alleviate acute pancreatic injury induced by taurocholate in mice. The mechanism may be associated with the decreased miR-429 expression, reduced FSTL1 signaling pathway activity, TLR4 and TLR4/MyD88 signaling pathway inhibition, and reduced pancreatic inflammation. FSTL1 is the regulatory target for miR-429


Subject(s)
Animals , Male , Mice , HMGB1 Protein/adverse effects , Scutellaria/adverse effects , Injections/classification , Pancreatitis/pathology , Enzyme-Linked Immunosorbent Assay/instrumentation , Blotting, Western , Receptors, Tumor Necrosis Factor , Follistatin/administration & dosage , Liver/abnormalities
7.
Article in Chinese | WPRIM | ID: wpr-909505

ABSTRACT

Objective:To explore the regulation effects of baicalin on the behavior as well as extracellular regulated protein kinase(ERK)and cAMP-response element binding protein(CREB) in chronic unpredictable mild stimulus(CUMS) model mice.Methods:Thirty ICR mice were randomly assigned to control(CON) group, model(CUMS) group, fluoxetine(FLU) group, baicalin high-dose(BA-H) group and baicalin low-dose(BA-L) group with 6 mice in each group.In addition to the CON group, the mice in the other four groups were modeled by CUMS method.The modeling was carried out for 42 days, and intragastric administration was carried out according to groups from the 21st day to the completion of modeling.After administration, the depression like behavior of mice was measured by sugar water preference test and water maze test.Western blot (WB) and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the protein level and mRNA level of ERK and CREB in mouse hippocampus respectively.SPSS 21.0 was used for statistical analysis.After normal test and variance homogeneity test, one-way ANOVA was used for multi group comparison, and Tukey test was used for pairwise comparison.Results:Results from the sugar preference experiment showed that compared with CON group, the sugar preference rate of CUMS group was decreased ((82.88±2.00)%, (64.49±1.24)%, t=19.11, P<0.05). Compared with CUMS group, sugar preference rate in FLU group ((81.90±1.19) %), BA-H group (77.86±2.51)%) and BA-L group ((67.98±2.56)%) increased ( t=24.83, 11.68, 3.00, all P<0.05). The results of water maze test showed that compared with CON group, the number of crossing platform ((6.33±0.82), (1.83±0.75), t=9.93, P<0.05) and the target quadrant residence time ((46.83±4.78)s, (24.25±6.12)s, t=7.13, P<0.05) of mice in CUMS group were decreased, but the the escape latency was prolonged ((14.88±3.00) s, (70.70±4.77) s, t=24.26, P<0.05). Compared with CUMS group, the number of crossing platform ((5.00±0.89)times, (5.17±0.75)times and (3.33±0.82) times, t=6.64, 7.67, 3.31, all P<0.05), and the residence time in the target quadrant ((36.80±2.66) s, (36.82±5.62) s, (33.28±3.56) s, t=4.61, 3.71, 3.13, all P<0.05) in FLU group, BA-H group and BA-L group increased, but the escape latencies were shortened ((23.37±4.86) s, (34.83±4.72) s, (62.15±5.30) s, t=17.02, 13.10, 2.94, all P<0.05). WB results showed that compared with CON group, the expression of ERK protein ((1.00±0.15), (0.36±0.10), t= 6.26, P<0.05) and CREB protein((1.00±0.12), (0.29±0.03), t=10.32, P<0.05) in hippocampus of mice in CUMS group decreased.Compared with CUMS group, ERK protein in hippocampus of mice in FLU, BA-H and BA-L groups increased ((0.87±0.05), (0.77±0.08), (0.67±0.03), t=8.25, 5.7, 5.39, all P<0.05), and CREB protein in FLU, BA-H and BA-L groups were also increased ((0.90±0.12), (0.84±0.14), (0.62±0.04), t=8.94, 6.59, 12.25, all P<0.05). qPCR results showed that compared with CON group, ERK mRNA ((1.00±0.03), (0.41±0.10), t=9.78, P<0.05) and CREB mRNA ((1.00±0.08), (0.61±0.12), t=4.62, P<0.05) were decreased in CUMS group.Compared with CUMS group, ERK mRNA in hippocampus of mice in FLU, BA-H and BA-L groups were increased ((0.71±0.08), (0.69±0.03), (0.59±0.04), t=4.15, 4.65, 2.84, all P<0.05), CREB mRNA in FLU group and BA-H group were increased ((0.87±0.08), (0.86±0.07), t=3.14, 3.19, all P<0.05). Conclusion:BA can improve the depression-like behavior of CUMS model mice.The mechanism of action may be related to the regulation of ERK and CREB proteins.

8.
Chinese Critical Care Medicine ; (12): 866-870, 2021.
Article in Chinese | WPRIM | ID: wpr-909419

ABSTRACT

Objective:To observe the protective effect and mechanism of different doses of Baicalin (BAI) on acute kidney injury (AKI) in septic mice.Methods:According to the random number table, 100 mice were divided into sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis model group (CLP group) and BAI pretreatment groups. The mice in BAI pretreatment groups were divided into low-, medium- and high-dose groups (BAI-L+CLP, BAI-M+CLP, BAI-H+CLP groups), with 20 mice in each group. A murine sepsis associated-acute kidney injury (SA-AKI) model was reproduced using CLP. The mice in the Sham group were only opened and closed the abdomen, without ligating or perforating the cecum. The mice in the BAI pretreatment groups were given BAI 25, 50 and 100 mg/kg daily for 3 days, and CLP was performed at 6 hours after administration of BAI at the 3rd day to reproduce sepsis model. The mice in the Sham group and CLP group were given the same amount of distilled water as control. Ten mice were sacrificed at 24 hours after operation to collect orbital blood for renal function determination [serum creatinine (SCr), blood urea nitrogen (BUN), plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1)] by enzyme linked immunosorbent assay (ELISA). The kidney tissue was collected to observe the kidney tissue injury under light microscope after hematoxylin-eosin (HE) staining. The TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect the apoptosis of renal tubular epithelial cells. Western blotting was used to detect the expression of cell FLICE like inhibitory protein (c-FLIP) in renal tissue. The remaining 10 mice in each group were used to calculate the survival rate of 7 days after operation.Results:The renal tubular epithelial cells in the CLP group were massively degenerated with necrosis, the renal tubular lumen was significantly expanded, and inflammatory cells were widely infiltrated in the renal interstitium. Furthermore, the renal function deteriorated rapidly. Compared with the CLP group, the renal function of mice pretreated with low dose of BAI was improved, but the difference was not significant. Compared with the CLP group, the renal function in the mice pretreated with medium and high doses of BAI was significantly improved, the SCr, BUN, pNGAL and pKIM-1 were significantly reduced [SCr (μmol/L): 135.16±5.18, 125.70±5.26 vs. 170.42±5.42; BUN (mmol/L): 33.59±1.77, 27.29±1.61 vs. 45.68±1.39; pNGAL (μg/L): 91.29±4.68, 73.40±3.77 vs. 131.50±6.55; pKIM-1 (μg/L): 6.34±0.30, 5.51±0.35 vs. 8.03±0.29; all P < 0.01], the pathological injury of renal tissue was significantly decreased, the apoptotic number of renal tubular epithelial cells was significantly reduced (cells/HP: 16.20±0.49, 13.10±0.66 vs. 29.60±0.49, both P < 0.01), and the expression of c-FLIP protein in renal tissue was significantly increased [c-FLIP protein (c-FLIP/GAPDH): 0.35±0.02, 0.46±0.02 vs. 0.21±0.01, both P < 0.01]. No mouse in the Sham group died within 7 days. Compared with the CLP group, the average survival time of the mice within 7 days in the BAI-L+CLP, BAI-M+CLP and BAI-H+CLP groups was significantly prolonged with a dose-dependent manner (days: 3.5±2.5, 5.4±2.2, 5.9±1.9 vs. 2.1±1.2; Log-Rank test: χ2 = 73.410, P < 0.001). Conclusion:Pretreatment with medium and high doses of BAI can significantly improve the renal function in mice with SA-AKI, decrease the pathological damage and increase the survival of mice, and its mechanism may be related to promoting the increase of c-FLIP protein expression and inhibiting cell apoptosis.

9.
Article in Chinese | WPRIM | ID: wpr-905937

ABSTRACT

Objective:To investigate the effects of polyethylene glycol 400 (PEG400) on the pharmacokinetics and anti-inflammatory effect of baicalin, and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucuronide (B6G) by molecular docking. Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix, and rats were administrated the equal dose of baicalin aqueous solution (baicalin+water group) and baicalin PEG400 solution (baicalin+PEG400 group). After the plasma samples were processed at different time periods, the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group (normal saline, 20 mL·kg<sup>-1</sup>), aspirin group (dose of 0.2 g·kg<sup>-1</sup>), baicalin/baicalin+PEG400 high and low dose (3.0, 1.5 g·kg<sup>-1</sup>) groups, after continuous administration for 7 days, the mouse ear swelling and foot swelling models were established, and the swelling degree and swelling inhibition rate were calculated. Result:The pharmacokinetic study showed that compared with baicalin+water group, the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution, and the area under the curve (AUC<sub>0-</sub><italic><sub>t</sub></italic>) increased by 2.36, 1.97 times, and the peak concentration (<italic>C</italic><sub>max</sub>) increased by 2.12, 1.65 times, respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition, molecular docking results showed that baicalin and B6G could site bind to multiple target proteins [tumor necrosis factor (TNF)-<italic>α</italic>, interleukin (IL)-6, IL-1<italic>β</italic>, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and nuclear transcription factor-<italic>κ</italic>B (NF-<italic>κ</italic>B)] with higher affinity, which was superior to the positive drug aspirin. Conclusion:PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G, and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors, it is speculated that baicalin and B6G jointly play an anti-inflammatory role.

10.
Article in Chinese | WPRIM | ID: wpr-876394

ABSTRACT

Objective @# To investigate the inhibitory effect of baicalin on Streptococcus mutans UA159 in vitro.@*Methods @#The minimum inhibitory concentration (MIC) of baicalin on Streptococcus mutans UA159 was determined by the liquid multiple dilution method combined with the OD600 value measured by microplate. The OD600 value of Streptococcus mutans UA159 in different concentrations of baicalin was measured by an enzyme mapping instrument. A growth curve was drawn, and the adhesion rate and adhesion inhibition rate were calculated. The effect of baicalin on the formation of Streptococcus mutans UA159 biofilms was observed by the crystal violet quantitative method and scanning electron microscopy. The effect of baicalin on the total number of Streptococcus mutans UA159 bacteria was observed by scanning electron microscopy.@*Results@#The MIC of baicalin on Streptococcus mutans UA159 was 12 mg/mL. With increasing baicalin concentration, the growth rate of Streptococcus mutans UA159 was slowed, the adhesion rate of Streptococcus mutans UA159 decreased and the adhesion inhibition rate increased(P < 0.05). The results of crystal violet quantitative method showed that compared with the bacterial control group, the biofilm formation of Streptococcus mutans UA159 was significantly reduced after adding baicalin at 0 h, 6 h and 12 h (P < 0.001). Under a scanning electron microscope, the total number of bacteria decreased significantly after adding baicalin at 0 h, 6 h and 12 h.@*Conclusion@# baicalin ; natural medicine ; Streptococcus mutans UA159 ; caries ; minimum inhibitory concentration ; growth curve ; adhesion rate ; adhesion inhibition rate ; biofilm formation ; in vitro study

11.
China Pharmacy ; (12): 225-230, 2021.
Article in Chinese | WPRIM | ID: wpr-862648

ABSTRACT

OBJECTIVE:To establish the method for content determination of 6 components in Fuzheng guben granules ,such as 2,3,5,4′-tetrahydroxystilbene glucoside ,baicalin,icariin,scutellarin,baicalein and wogonin. METHODS :HPLC method was adopted. The determination was performed on Dikma Diamonsil C 18 column with mobile phase consisted of acetonitrile- 0.1% phosphoric acid aqueous solution (gradient elution )at the flow rate of 1.0 mL/min. The detection wavelengths were set at 275 nm (0-8 min),320 nm(8-9 min)and 275 nm(9-33 min). The column temperature was set at 25 ℃,and sample size was 10 μL. With baicalin as reference material ,the relative corr ection factors (fk/s) of other five components were calculated by multi-point correction method and slope correction method ;the retention time difference method was used to locate the chromatographic peaks ; the calculation values obtained by above 2 QAMS were compared with measured values of external standard method. RESULTS : The linear range of 2,3,5,4′-tetrahydroxystilbene glucoside ,baicalin,icariin,scutellarin,baicalein and wogonin were 0.053-2.12, 0.163-6.52,0.059-2.36,0.021 6-0.864,0.03-1.2,0.021-0.84 μg(r>0.999),respectively. RSDs of precision ,stability(12 h)and reproducibility tests were all lower than 3%. Average recoveries were 98.72%-99.82%(RSDs were 0.89%-1.24%,n=9). Using baicalin as reference material ,fk/s of multi-point correction method for 2,3,5,4′-tetrahydroxystilbene glucoside ,icariin,scutellarin, baicalein and wogonin were 1.172,0.528,1.479,1.820 and 2.534,respectively;fk/s of slope correction method were 1.234, 0.550,1.559,1.939,2.664. RSDs of 6 components in 10 batches of Fuzheng guben granules by 3 methods were 0.29%-2.77% (n=10),respectively. Pearson correlation coefficient was not lower than 0.999 9(P<0.001)in measured values between QAMS and external standard method. CONCLUSIONS :QAMS method is established successfully for simultaneous determination of 6 components in Fuzheng guben granules.

12.
Acta Pharmaceutica Sinica ; (12): 1416-1423, 2021.
Article in Chinese | WPRIM | ID: wpr-887064

ABSTRACT

The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.

13.
Acta Pharmaceutica Sinica B ; (6): 4045-4054, 2021.
Article in English | WPRIM | ID: wpr-922459

ABSTRACT

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

14.
Acta Pharmaceutica Sinica ; (12): 1537-1543, 2021.
Article in Chinese | WPRIM | ID: wpr-881545

ABSTRACT

Flavonoids baicalin is the main bioactive component extracted from Scutellaria baicalensis Georgi. Baicalin has high medicinal value and shows extensive pharmacological effects including antitumor, antibiosis, anti-inflammatory, antioxidation, neuro-protection, and significant potential in tumor treatment. Recent studies have shown that baicalin suppresses the growth of many kinds of human cancer. The underlying mechanisms include induction of apoptosis, induction of cell cycle arrest, inhibition of tumor metastasis, suppression of angiogenesis, and so on. This article reviewed the research progress of baicalin on its antitumor pharmacology and possible mechanisms at home and abroad, and provided the basis for its further research.

15.
Article in Chinese | WPRIM | ID: wpr-879130

ABSTRACT

In the pharmacopoeia, many process parameters for the purification process of Scutellariae Radix are unclear. In this study, deterministic screening design combined with design space method was used to optimize the purification process of Scutellariae Radix extract. Nine method parameters such as mass fraction of solution(X_1), first acid precipitation pH(X_2) and first holding time(X_3) in the purification process were firstly studied by definitive screening design. The yield of baicalin was defined as the evaluation index. A stepwise regression method was used then to build quantitative models between evaluation index and method parameters and the three most critical impact parameters were determined. Probability-based design space was calculated and successfully verified with the experimental error simulation method. Finally, the second standing temperature, the first standing temperature and the pH value of the second acid precipitation were determined as the three most critical method parameters. The recommended operating space was as follows: the second standing temperature 5-7 ℃, the first standing temperature 13-15 ℃, and the pH of the second acid precipitation 1.5-1.7. Within this operating space, the baicalin yield in the purification process was over 80%, and the probability of reaching the standard was over 0.96. In this study, we optimized the effect of various parameters for the purification process of the Scutellariae Radix extract in the pharmacopoeia on the yield of baicalin and provided a reference for industrial production of the exact of Scutellariae Radix.


Subject(s)
Drugs, Chinese Herbal , Flavonoids , Plant Extracts , Scutellaria baicalensis
16.
Braz. j. med. biol. res ; 53(12): e9949, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132509

ABSTRACT

Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin (BA) possesses potential anti-inflammatory properties. In this study, we evaluated the anti-inflammatory activity of BA in vitro and in vivo. Heat-killed Propionibacterium acnes-induced THP-1 cells and live P. acnes-injected male Sprague Dawley rats were used for establishing the acne model. The rate of ear swelling was calculated, and the severity was determined by hematoxylin and eosin staining. The production of cytokines [interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF-α)] in the cell supernatant and ear tissue homogenates was measured by ELISA. Protein levels of JNK, ERK, P38, IκBα, P65, Nod-like receptor pyrin domain-containing 3 (NLRP3), pro-caspase-1, and IL-1β in THP-1 cells and ear tissues were detected by western blotting. NLRP3 and IL-1β were detected by immunohistochemistry, and the NLRP3, IL-1β and pro-caspase-1 mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that BA decreased the expression of pro-inflammatory cytokines in vitro and in vivo. Moreover, BA down-regulated the phosphorylation of JNK, ERK1/2, and κBα and inhibited the nuclear translocation of p65. Furthermore, BA inhibited the activation of NLRP3 inflammasome, at both the gene and protein levels. Taken together, the results demonstrated that BA might exert its anti-inflammatory activity by inhibiting NF-κB/MAPK signaling pathways and consequently suppressing the activation of the NLRP3 inflammasome both in vivo and in vitro.


Subject(s)
Animals , Male , Rats , Dermatitis/drug therapy , Inflammasomes , Propionibacterium acnes/metabolism , Flavonoids , Signal Transduction , NF-kappa B/metabolism , Rats, Sprague-Dawley , MAP Kinase Signaling System , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Inflammation/chemically induced , Inflammation/drug therapy
17.
Article in Chinese | WPRIM | ID: wpr-873254

ABSTRACT

Objective::To investigate the effect of polyethylene glycol 400 (PEG400) on rat bile excretion of baicalin and its main metabolite [baicalein 6-O-β-D-glucuronide (B6G)], and to analyze its mechanism of action. Method::Rats were randomly divided into baicalin+ water group and baicalin+ PEG400 group, the anesthesia was induced by intraperitoneal injection of 10% chloral hydrate (dose of 4 mL·kg-1) to prepare a rat bile duct intubation model. After the rats were fully awake, rats were given baicalin aqueous solution and baicalin PEG400 solution with dose of 168 mg·kg-1 for baicalin, respectively. And bile was collected from 0 h to 12 h after administration. UPLC-MS/MS was used to determine the concentration of drug excreted through bile at different time periods. Thermo Hypersil GOLD C18 column was used with acetonitrile (A)-0.1% formic acid solution (B) as the mobile phase for gradient elution (0-9 min, 90%-27%B; 9-10 min, 27%-90%B; 10-12 min, 90%B), the flow rate was 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 5 μL. The mass spectra were obtained in positive ion mode with electrospray ionization (ESI). The effects of PEG400 on the activities and expressions in rat liver of uridine diphosphate glucuronyltransferase (UGT) 1A8 and UGT1A9 were studied in vitro incubation assay and enzyme linked immunosorbent assay (ELISA). Result::Compared with the baicalin+ water group, in the baicalin+ PEG400 group, the bile cumulative excretions of baicalin and B6G increased by 1.8 times and 2.1 times within 12 h, respectively. PEG400 increased the enzyme activities of UGT1A8 and UGT1A9 by 2.0 times and 1.5 times, and their concentrations in liver were increased by 2.2 times and 1.3 times, respectively. Conclusion::PEG400 can significantly increase the bile excretion of baicalin and its main metabolite B6G by enhancing the activities and expressions of UGT1A8 and UGT1A9, and its promoting effect on bile excretion of B6G is greater than that of baicalin, which provides a basis for the rational clinical application of PEG400 and the design of new dosage forms of flavonoids such as baicalin.

18.
Article in Chinese | WPRIM | ID: wpr-873031

ABSTRACT

Objective:To investigate the effect of different angles of atomizer on the delivery rates and total delivery quantities of Tanreqing inhalation solution, so as to provide reference for the clinical use of this preparation. Method:Taking baicalin, ursodeoxycholic acid, caffeic acid as indexes, PARI Boy SX compression atomization inhaler (equipped with red core atomizing cup) and BRS2000 respiratory simulator were used, the effects of different angles of the atomizer (upper 15 degree, lower 15 degree, upper 30 degree, lower 30 degree, partial 15 degree, partial 30 degree, vertical) on the delivery rates and total delivery quantities of Tanreqing inhalation solution were investigated. The respiratory patterns of adults, children, infants and young children were selected to determine the delivery rates and total delivery quantities of three components in Tanreqing inhalation solution. Result:In the same atomization time, the delivery rates and the total delivery quantities of caffeic acid and ursodeoxycholic acid in Tanreqing inhalation solution were not significantly affected by the atomizer from different angles, but significantly affected baicalin. At the vertical angle, the delivery rate and total delivery quantity of baicalin were higher than the other angles. Under different respiratory modes, there were significant differences in the delivery rates and total delivery quantities of these three components in the inhalation solution. Compared with other respiratory modes, the delivery rates and total delivery quantities of baicalin, ursodeoxycholic acid and caffeic acid were the highest in the adult respiratory mode, with delivery rates of (555.5±16.61), (226.3±6.54), (26.1±0.32) μg·min-1 and total delivery quantities of (4 001.1±82.97), (1 754.9±63.73), (167.6±1.42) μg, respectively. Conclusion:The use angle of atomizer has a certain effect on the delivery rate and total delivery quantity of Tanreqing inhalation solution, so it is suggested that the vertical angle should be kept as far as possible in clinical use. Under the four respiratory patterns, the delivery rate and total delivery quantity of Tanreqing inhalation solution are different, suggesting that the atomization dose or atomization time should be adjusted according to the respiratory characteristics of the patients to ensure the safety and effectiveness of clinical medication.

19.
Article in Chinese | WPRIM | ID: wpr-872763

ABSTRACT

Objective:Quantitative analysis of anti-inflammatory synergistic pharmacodynamics mechanism of baicalin and wogonoside by medium efficiency principle. Method:inflammatory cell model was constructed by stimulating RAW264.7 cells by lipopolysaccharide (LPS) 100 μg·L-1 in vitro. The experiment was performed in the normal group, the model group, the andrographolide group (10 μmol·L-1), the baicalin group (2.06,4.13,8.25,16.5,33,66,132 μmol·L-1) and the wogonoside group (2.94,5.88,11.75,23.5,47,94,188 μmol·L-1) and the baicalin-wogonoside combination group [(2.06+2.94)(4.13+5.88)(8.25+11.75)(16.5+23.5)(33+47)(66+94)(132+188) μmol·L-1]. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the cell culture supernatants after drug intervention for 50 min and 4 h were detected by enzyme-linked immunosorbent assay (ELISA) method. The level of nitric oxide (NO) in the cell culture supernatant after drug intervention for 24 h were detected by Griess method. Western blot was used to detect the activation levels of phosphorylation of nuclear factor-κB p65(p-NF-κB p65) and inducible nitric oxide synthase(iNOS) in cells after drug intervention for 2 h and 12 h. The fa/fu-dose profile of each indicator was drawn to observe the increase or decrease of effect. Result:Compared with normal group, the expression of p-NF-кB p65, iNOS and cytokines including TNF-α, IL-6 and NO (P<0.05,P<0.01) in the model group were significantly up-regulated. Compared with the model group, each group at high doses could inhibit the phosphorylation of NF-кB p65 protein(P<0.05),the baicalin group and the combined group could down-regulate the expression of iNOS protein in a concentration-dependent manner(P<0.01) and the baicalin group had no obvious inhibitory effect. each administration group at high dose could significantly inhibit the production of NO(P<0.05),but each group had no inhibitory effect on IL-6 production. The baicalin group and the combined group could significantly Inhibit the production of TNF-α(P<0.05) and there was no significant difference between the baicalin group and the model group. At the experimental dose, the fa/fu-dose table showed that the fa/fu value of p-NF-кB p65 and IL-6 in the combined group was not greater than the baicalin group and the wogonoside group. The fa/fu value of iNOS, TNF-α and NO in the combined group is higher than the baicalin group and the wogonoside group. Conclusion:The baicalin and wogonoside have different effects on different targets in the NF-κB pathway. The wogonoside is the main pharmacological substance in this combination and the combination shows different degrees of synergy or antagonism effects on different targets.

20.
Chinese Pharmaceutical Journal ; (24): 465-472, 2020.
Article in Chinese | WPRIM | ID: wpr-857756

ABSTRACT

OBJECTIVE: To optimize and improve the quality standard of Qingkailing dropping pills. METHODS Lonicerae Japonicae Flos, geniposide in Gardeniae Fructus and baicalin in Scutellariae Radix of Qingkailing dropping pills were identified by TLC and HPLC respectively. Cholic acid and hydrodeoxycholic acid were determined by HPLC equipped with an ELSD and a column (4.6 mm×250 mm, 5 μm) packed with ODS bonded silica gel (5 μm particle size). The mobile phase was a mixture of methanol, acetonitrile and 0.1% formic acid (68∶17∶15, V/V/V) and the flow rate was 1.0 mL•min-1. Geniposide in Gardeniae Fructus of Qingkailing dropping pills was determined by HPLC equipped with a DAD (238 nm) and a column (4.6 mm×250 mm) packed with ODS bonded silica gel (5 μm particle size). The mobile phase was a mixture of acetonitrile and 0.05% phosphoric acid (10∶90, V/V) and the flow rate was 1.0 mL•min-1. Baicalin in Scutellariae Radix of Qingkailing dropping pills was determined by HPLC equipped with a DAD (275 nm) and a column (4.6 mm×150 mm) packed with ODS bonded silica gel (5 μm particle size), the mobile phase was a mixture of methnol, water and phosphoric acid (47∶53∶0.2, V/V/V), and the flow rate was 1.0 mL•min-1. RESULTS: The developed TLC spots were clear with good reproducibility. Hydrodeoxycholic acid, cholic acid, geniposide and baicalin showed good linear relationship in the ranges of 0.505 0-6.312 μg, 0.515-6.440 μg, 0.029 12-0.582 4 μg, and 0.109 2-1.092 μg, respectively. The average recoveries (n=6) were 101.5%, 101.6%, 98.61% and 99.77%, with RSDs of 1.7%, 1.5%, 1.42% and 0.79%, respectively. CONCLUSION: The method is simple, rapid, accurate, with low toxicity, and can be used to control the quality of Qingkailing dropping pills more effectively and comprehensively.

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