Beverages ; Exercise ; Female ; Glycyrrhizic Acid ; pharmacology ; Humans ; Physical Endurance ; Students

This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.
Antineoplastic Agents ; pharmacology ; Diterpenes ; pharmacology ; Drug Carriers ; chemistry ; Glycyrrhizic Acid ; chemistry ; Micelles ; Particle Size ; Polymers

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

AIM: This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate (GLN) on the pharmacokinetics of entecavir (ETV) in rats. METHODS: Male SD rats were randomized into short-term and long-term experimental groups, respectively. In the short-term experiment, the control group received saline, the low dose group received GLN 13.5 mg·kg(-1) and the high dose group received GLN 40.5 mg·kg(-1). ETV (0.09 mg·kg(-1)) was given i.g. 0.5 h after saline/GLN administration. For the long-term experiment, rats were allocated into two experimental designs. The control group received saline/ETV (0.09 mg·kg(-1)), the low dose group received GLN 13.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 13.5 mg·kg(-1), while the high dose group received GLN 40.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 40.5 mg·kg(-1); all administration was continued for 15 days. On the 16(th) day, 0.09 mg·kg(-1) ETV was administrated to all groups. Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations. RESULTS: Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments. CONCLUSION Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats.
Animals ; Drug Interactions ; Glycyrrhizic Acid ; pharmacology ; Guanine ; analogs & derivatives ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.
Mice ; Animals ; Imiquimod ; Drugs, Chinese Herbal/pharmacology* ; Glycyrrhizic Acid ; Chromatography, High Pressure Liquid/methods*

Glycyrrhizin acid and licorice flavonoids are the component of Glycyrrhiza uralensis Fisch root that has been used for various medicinal purposes in traditional oriental medicine for thousands of years. Macrophages as a principal component of immune system play an important role in the initiation, modulation and final activation of immune response against pathogens. In the present study, glycyrrhizin acid and licorice flavonoids was investigated the anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophage cell line of RAW264.7. Well-grown RAW264.7 cells were collected and randomly divided into the blank control group, the LPS(1 mg x L(-1)) group, the dexamethasone (5 mg x L(-1)) with LPS group, the glycyrrhizin acid (400, 80, 16 mg x L(-1)) with LPS group and the licorice flavonoids (200, 40, 8 mg x L(-1)) with LPS group. RAW264.7 cells were cultured in 24-well plates, pre-incubated for 4 h with different concentrations of dexamethasone, glycyrrhizin acid, or licorice flavonoids. Then cells were stimulated for 20 h with LPS. The supernatant of culture medium was collected from each well and determinated the concentrations of cytokines by means of BioPlex mouse cytokines assay. Compared with the control group, the LPS group could significantly induced relatively high levels of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor( GM-CSF), macrophage inflammatory protein-1 alpha (MIP-1α), macrophage inflammatory protein-1 beta (MIP-1β), regulated upon activation normal T cell expressed and secreted factor (RANTES), tumor necrosis factor alpha ( TNF-α), monocyte chemotactic protein 1 (MCP-1), chemokine (C-X-C motif) ligand 1 (KC), eotaxin, interleukin(IL)-1α, IL-1β, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, and IL-17 secretion (P < 0.05). The glycyrrhizin acid significantly inhibited IL-1β, IL-3, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, Eotaxin and TNF-α secreted by LPS-stimulated RAW264.7 cells (P < 0.05). The expression levels of IL-6 and Eotaxin were observably decreased in the licorice flavonoids with LPS group (P < 0.05). The data presented here suggested that the glycyrrhizin acid and licorice flavonoids modulate various cytokines secreted by macrophages and were important anti-inflammatory constituent of Licorice.
Animals ; Cell Line ; Cytokines ; genetics ; immunology ; Flavonoids ; pharmacology ; Glycyrrhiza ; chemistry ; Glycyrrhizic Acid ; pharmacology ; Lipopolysaccharides ; immunology ; Macrophages ; drug effects ; immunology ; Mice

OBJECTIVESTo investigate the role of glycyrrhizin on TGFbeta1 stimulated signaling transduction in rat hepatic stellate cells (HSCs).

METHODSThe mice HSCs were isolated and cultured with or without glycyrrhizin (1 micromol/L-1000 micromol/L) in vitro after TGFbeta1 stimulation. The mRNA level of Smad2, 3, 7 were measured with RT-PCR; protein expression level of Smad2, 3, 7 and collagen I, III were analyzed with Western blot.

RESULTSTGFbeta1 increased the mRNA level and protein expression of Smad2, 3, 7 in HSC; it also increased protein expression of collagen I and III. 1 micromol/L-1000 micromol/L glycyrrhizin decreased the mRNA level and protein expression of Smad2, 3, 7; it also inhibited protein expression of collagen I and III gradually.

CONCLUSIONInterventing the TGFbeta signaling pathway and decreasing the synthesis of collagen, might be involved in the anti-fibrosis mechanism of glycyrrhizin.

Animals ; Glycyrrhizic Acid ; pharmacology ; Hepatocytes ; metabolism ; Male ; Rats ; Signal Transduction ; Smad Proteins ; metabolism ; Transforming Growth Factor beta ; pharmacology

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line ; Glycyrrhizic Acid ; pharmacology ; Humans ; Lipopolysaccharides ; toxicity ; Liver ; drug effects ; pathology

To study the anti-inflammatory activity of glycyrrhizin acid, ligustrazine and puerarin. In the study, the liquichip-based high-throughput synchronous detection technique for 23 inflammatory factors, uniform design, comprehensive weight method were adopted to study the effect of different combined administration of glycyrrhizin acid, ligustrazine and puerarin in inhibiting the expression of lipopolysaccharide (LPS)-induced RAW264. 7 cells and multiple inflammatory cytokines. In the study, the uniform design table U₉ (9³) was adopted to design doses of glycyrrhizin acid, ligustrazine and puerarin. The liquichip technique was used to detect the effect of different combined administration of glycyrrhizin acid, ligustrazine and puerarin on the 23 cytokines expressed in LPS-induced mouse macrophage RAW264. 7 inflammation model. The traditional Chinese medicine component optimization software and the improved least angle regression algorithm were used to analyze the dose-effect relationship among the three components and the cytokine inhibition rate and produce the regression equation. The comprehensive weight method was applied to get the optimal dose ratio of glycyrrhizic acid, ligustrazine and puerarin with highest efficacy of 25:2:13 and verify the optimal dose ratio. The verification results were consistent with the prediction trend, indicating the accuracy of the mathematical model for predicting the experiment. The experimental results showed the multi-target and multi-level efficacies of glycyrrhizic acid, ligustrazine and puerarin and the high anti-inflammatory activity of their combined administration, which provides powerful basis for subsequent drug development.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Cytokines ; Glycyrrhizic Acid ; pharmacology ; Isoflavones ; pharmacology ; Lipopolysaccharides ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; NF-kappa B ; genetics ; immunology ; Pyrazines ; pharmacology ; RAW 264.7 Cells

An experiment was conducted using cultivated Glycyrrhiza uralensis in age of one year to study the effects of abscisic acid (ABA) on chemical components content and color of G. uralensis. By using different concentrations of ABA spraying on leaves, the change of the chemical component content was analyzed within 45 d after ABA stimulation, and the effects on quality were studied combined with colorimetric analysis data. It turned out that in some sense the content of glycyrrhizic acid and liquiritin had increased within 45 d, especially for liquiritin. After high concentrations of ABA (3.96 mg · L(-1)) stimulating, the content of glycyrrhizic acid rose 52% while liquiritin up 392% within 30 d. Then they both showed a decline in the content of glycyrrhizic acid and liquiritin on 45 d. Color index values of a* and b* were all significantly higher than that of the control group within 45 d, which meant the color of powders turned toward red and yellow. The conclusion was that ABA (3.96 mg · L(-1)) stimulating could not only improve the quality in the traditional sense through the color of G. uralensis, but also in the modern sense by improving the content of glycyrrhizic acid and liquiritin.
Abscisic Acid ; pharmacology ; Color ; Drugs, Chinese Herbal ; chemistry ; Flavanones ; analysis ; Glucosides ; analysis ; Glycyrrhiza uralensis ; chemistry ; drug effects ; growth & development ; Glycyrrhizic Acid ; analysis ; Plant Growth Regulators ; pharmacology