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Objective: To study the prescription and preparation technology of licorice flavonoids self-microemulsifying drug delivery system (LF-SMEDDS) and evaluate its quality. Methods: The optimal formulation of LF-SMEDDS was screened by test of solubility, compatibility of oil and emulsifier, and pseudo-ternary phase diagram. Simplex lattice method was applied to optimize formulation with average particle size, polydispersity index and drug loading as evaluation indexes, the physicochemical characteristics, in vitro dissolution and stability were also determined. Results: The optimal prescription composition of LF-SMEDDS was 10% of Cinnamomi Cortex oil, 55% of RH-40, and 35% of 1,2-propanediol. The LF-SMEDDS exhibited uniform and transparent appearance, with the average particle size of (16.30 ± 0.22) nm, polydispersity index of 0.155 ± 0.008, Zeta pontential of (-20.11 ± 0.50) mV and drug loading of (86.03 ± 0.37) mg/g. The results of in vitro dissolution test indicated that the accumulative dissolution of LF was 90.65% at 30 min. The stability experiment showed that LF-SMEDDS was affected by high temperature and illumination, indicating that it should be stored at low temperature and protected from light. Conclusion: The LF-SMEDDS is simple in preparation and stable in quality, significantly increasing the solubility of LF and improving its oral bioavailability, which can provide reference for further research and development about the related preparations of the active fraction.
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This study aimed to study the inhibitory activities of flavonoids on cell cycle-dependent protein kinase (CDK1)and hepatoma cells BEL-7402.The CDK1 inhibitory activity of licorice flavonoids was evaluated by CDK1 reagent kit,and antiproliferaty activity in vitro was investgated by CCK-8 assay.Subcutaneous tumor model of liver cancer Bel-7402 was established in nude mice,which were then randomly divided into drug group,posi-tive drug group and blank control group.The mice in drug group were orally administrated with licorice flavonoids for continuous 18 days. The body weight and tumor size of mice were recorded every other day.The results demonstrated that these licorice flavonoids displayed potent efficacy against CDK1,specifically,isoliquiritigenin exhibited the most potent CDK1 inhibitory activity(IC50=0.05 ± 0.005 μmol/L),which was about 6-fold more potent than positive control flavopiridol(IC50=0.29 ± 0.230 μmol/L).Molecular docking studies revealed that isoliquiritigenin engaged in six hydrogen bonds with K33,E81,L83,S84,D86,D149 in CDK1,while flavopiridol only engaged in five hydrogen bonds with E81,L83,S84,Q132,D149.In vitro biological evaluation indicated that these licorice flavonoids displayed significant antiproliferative effects on Bel-7402 cancer cells.Among them, isoliquiritigenin showed the greatest potency against Bel-7402(IC50=0.7 ± 0.11 mol/L),which was 3-fold more potent than flavopiridol(2.4 ± 0.34 mol/L).In vivo biological evaluation showed that the LD50of isoliquiritigenin was 4.38 mg/kg,and could effectively inhibit the cell growth of liver cancer Bel-7402 in mice.
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Objective Licorice (Glycyrrhizae Radix or Liquiritiae Radix) is traditionally used to treat various diseases including inflammation and gastric ulcers. Licorice is rich in flavonoid compounds and possesses anti-inflammatory activities. To investigate the protective effects of licorice flavonoids (LFs) in both acetic acid-induced and dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mouse model and its underlying mechanism. Acute UC was induced by intra-rectal acetic acid (4% v/v) after pretreatment with LFs (100, 200, and 400 mg/kg, p.o.), 0.9% saline (20 mL/kg, p.o.) or Sulfasalazine (SASP) (600 mg/kg, p.o.) for 10 d. Quantitative analysis of chemical components of LFs was also conducted by HPLC. Our results showed that pre-treatment with LFs significantly reduced the wet weight/length ratio of colon, percentage of affected area, macroscopic and histological damage scores in acid-induced UC mice. LFs also significantly decreased the oxidative stress and pro-inflammatory cytokines, upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and downregulated nuclear transcription factor kappa B (NF-κB) pathway. At last, LFs also showed obvious antiulcer effect on the DSS-induced UC model. The major components of LFs were licochalcone A, glabrone, licoflavone, and licoflavone B. This study demonstrates that the protective effect of LFs may at least in part be due to its anti-oxidant activity through Nrf2 pathway and anti-inflammatory activity through NF-κB pathway.
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As a medicine and food homology plant, licorice has received extensive attention from many pharmacologists and biologists. The authors reviewed the new biotechnologies applied to licorice in recent years, including the research on the key enzyme genes involved in the biological synthetic pathway of the active constituents, the formation mechanism of genuineness based on genes, the gene regulation of the biosynthesis of active components, and DNA identification of licorice, aiming to bring up some ideas for deeper studies of licorice.
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Objective: To multi-objectively optimize the purification process parameters of licorice flavonoids using entropy-weight method, Plackett-Burman design (PBD), and Box-Behnken design (BBD). Methods: On the basis of HPLC fingerprints of licorice, the macroporous resin type was chosen using the recovery rates of six components (liquiritin apioside, liquiritigenin, isoliquiritin apioside, licuraside, isoliquiritin, and neoisoiiquiritin) as detection indexes. Weights of the recovery rates of six components were determined by entropy-weight method, in order to obtain the comprehensive index. The significantly influencing factors were firstly evaluated by PBD, then purification conditions were optimized by BBD. Results: ADS-7 type resin showed a high selectivity for six components. The optimized purification technology was as follows: pH value was 4.5, sample concentration was 0.20 g/mL, ratio of sample to resin was 1.0 g/g, flow rate was 0.6 mL/min, elution dosage was 6.7 BV, ethanol concentration was 83% of eluting agent, and elution rate was 1.0 mL/min. Under the conditions, the recovery rates of six components were 86%-97%, the theoretical and actual comprehensive indexes were 93.32% and 93.05%, respectively, with a relative error of 1.17%. Conclusion: Entropy-weight method combined with PBD and BBD-RSM used to optimize the purification process for the licorice flavonoids in this study is scientific and feasible, providing a new reference to realize the multi-objective optimization of the purification technology for active constituents in Chinese materia medica.
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Glabridin (Glab) is an isoflavonoid originally isolated from the roots of Glycyrrhiza glabra L. (Fabaceae). Glab is widely considered to be a phytoestrogen and has been associated with numerous biological properties ranging from antioxidant, anti-inflammatory, neuroprotective, anti-atherogenic effects, to the regulation of energy metabolism. In this paper, a review on its biological activity was reviewed.
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Objective To study the mechanism of anti-inflammatory effects of licorice flavonoids(LF) isolated from the roots of Glycyrrhiza uralensis(licorice) on lipopolysaccharide(LPS)-induced lung inflammation in mice.Methods Mice were intratracheally instillated with either LPS(4 mg/kg) or saline.At 6 or 24 h after LPS intratracheal instillation,pathological examination and bronchoalveolar lavage were performed and the lung wet/dry weight ratio as an index of acute lung injury was assessed.Then,the numbers of total leukocytes,neutrophils and the activity of superoxide dismutase(SOD) and TNF-? protein in bronchoalveolar lavage fluid(BALF) were measured.LPS-induced myeloporoxidase(MPO) activity and expressions of TNF-? and IL-1? at the mRNA levels and TNF-? at the protein level in lung tissues were determined by RT-PCR and ELISA.Results LPS caused a severe lung inflammation,as indicated by the pathological findings and the lung wet/dry weight ratio.However,oral LF could attenuate these LPS-induced abnormalities.LF could decrease the numbers of total leukocyte cells and neutrophils,and increase the levels of SOD and TNF? BALF.In addition,LF significantly suppressed the MPO activity,TNF-? and IL-1? mRNA expression levels,and TNF-? protein level in the lung tissues.Conclusion Inhibition of inflammatory cytokines expressions and regulation of oxidation/antioxidation of LF may be its anti-inflammatory mechanism in LPS-induced lung inflammation in mice.