MOLECULES
·
2022
·Vol. 27
·期 20
·6851
·
IF 4.927
Rui Fan,Yanxiang Gao
Nowadays, subcritical water extraction (SWE) techniques are extensively investigated worldwide, while the thermal reactions that inevitably occur under subcritical water conditions are rarely studied. In order to investigate the behaviors of the different reactions during SWE of bioactive compounds from licorice, the Maillard reaction process was accessed via their products and the hydrolytic reaction was analyzed according to the kinetic parameters. In addition, the contents of total phenolics and flavonoids in the extracts obtained at the different temperatures were determined and total antioxidant capacities were evaluated by HPLC-ABTS+. The results showed that flavonoids and phenolics from licorice as well as new compounds generated via the Maillard reaction contributed to the antioxidant activity of the extracts. The fluorescence, color and absorbance of the extracts showed that the degree of the Maillard reaction increased with the rise of the extraction temperature. The kinetics of extraction for glycyrrhizic acid showed that it was firstly extracted by diffusion, and then was hydrolyzed into glycyrrhetinic acid 3-O-mono-β-D-glucuronide and glycyrrhetinic acid following a first-order mechanism. These findings could provide deep insights into the SWE process and a new method for producing glycyrrhetinic acid 3-O-mono-β-D-glucuronide and glycyrrhetinic acid.Keywords:glycyrrhizic acid;glycyrrhetinic acid;glycyrrhetinic acid 3-O-mono-β-D-glucuronide;antioxidant;Maillard reaction
研究领域:
植物化学
·
食品科学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Juan Sun,Han-Yu Liu,Cheng-Zhi Lv,Jie Qin,Yuan-Feng Wu
Licorice is a traditional Chinese medicine, which is often used as sweetener and cosmetic ingredients in food and pharmaceutical industries. Among them, glycyrrhetic acid is one of the most important agents. Studies have shown that glycyrrhetic acid exhibited antitumor activities as PPARγ agonist. However, the limited number of PPARγ glycyrrhetinic agonists and their high toxicity greatly limit the design based on the structure. Therefore, clarifying the binding mode between PPARγ and small molecules, we focused on the introduction of a natural active piperazine skeleton in the position of glycyrrhetinic acid C-3. According to the Combination Principle and the Structure-Based Drug Design, 19 glycyrrhetic acid derivatives were designed and synthesized as potential PPARγ agonists. Compounds 4c and 4q were screened as high-efficiency and low-toxicity lead compounds.
研究领域:
药理学
·
药物化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Hongqing Cheng,Xiaoshun Jia,Dandan Yuan,Huaning Li,Lingchong Wang,Tingming Fu,Hongzhi Qiao,Jing Chen,Zengwu Wang,Xiaobing Cui,Jianming Cheng,Junsong Li
Natural aglycones, a major ingredient accompanied by glycosides in plants, have played an important role in the treatment of various diseases. However, their bioavailability is limited by their poor water solubility. In contrast to previous efforts that required the use of new exotic materials which may raise concerns about biocompatibility, we report the first case of excipient-free nanodispersions in which an insoluble glycyrrhetinic acid (GA) assembled with its amphiphilic parent drug diammonium glycyrrhizinate (DG) into water-dispersible nanodispersions (130.8 nm for particle size and 91.74% for encapsulation efficiency). This strategy largely increased GA's water apparent solubility by hundreds of times to 549.0 μg/mL with a high cumulative dissolution percentage in vitro greater than 80% in 5 min. The study on the formation mechanism showed that the OH, C-O and C=O group stretching peaks shifted in the FTIR spectra of GA-DG nanodispersions, while the COOH peak (δ COOH 12.19 ppm) disappeared in the 1 H NMR spectrum of GA-DG nanodispersions, indicating that carboxyl groups on GA may interact with the hydroxyl groups of DG in solution. Molecular dynamics simulations suggested that both hydrophobic interactions and hydrogen-bond interactions contribute to the coassembly of GA and DG molecules in aqueous solution. Oral pharmacokinetic studies in rats demonstrated that such nanodispersions have a significant increase in C max and AUC 0-t of 2.45- and 3.45-fold compared with those for GA, respectively. Therefore, this strategy, employing amphiphilic glycosides as excipients to prepare nanodispersions, not using new materials, paves the way for the further application of hydrophobic aglycone drugs.
研究领域:
药学
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纳米技术
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药物递送系统
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药代动力学
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产品关联
DOI
PubMed
高影响因子
3 Biotech
·
2022
·Vol. 12
·期 3
·1-11
·
IF 2.893
Xiao Yiwen,Zhang Zhibin,Liang Weizhong,Gao Boliang,Wang Ya,Chang Jun,Zhu Du
Endophytic fungi inhabiting niche environments are novel biocatalyst resources that need to be exploited urgently. In this study, 63 endophytic fungi isolated from Dongxiang wild rice ( Oryza rufipogon Griff.) were tested to assess their potentials to transform glycyrrhizin (GL) into glycyrrhetinic acid monoglucuronide (GAMG) or glycyrrhetinic acid (GA), of which 12 strains were shown to have β- d -glucuronidase activity. Based on morphological characteristics and rDNA ITS sequence analysis, the strains S59, L138, L55 and R57 with high GL molar conversion rates (55%, 45%, 65% and 89%) were further identified as Microsphaeropsis arundinis S59, Penicillium rubens L138, Aspergillus flavus L55 and Eupenicillium javanicum R57, respectively. These four strains with four different types of GL conversion processes were identified, i.e., (1) GL → GAMG in M. arundinis S59, (2) GL → GAMG and GA in A. flavus L55, (3) GL → GA in P. rubens L138, and (4) GL → GAMG → GA in E. javanicum R57, in which the bioconversion type (4) is reported for the first time. The study not only provided abundant and diverse β- d -glucuronidase resources that can be used for GL bioconversion, especially for GAMG biosynthesis from endophytic fungi, but also expanded our knowledge of potential roles of endophytes as new biocatalysts in biotransformation.
研究领域:
微生物学
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生物技术
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药理学
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植物科学
✓ 已验证
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2017
·
IF 5.605
Wenping Wang,Yaya Lei,Hong Sui,Wenping Zhang,Rongyue Zhu,Jun Feng,Hong Wang
The aim of the present study was to prepare and evaluate microparticle formulation encapsulated with glycyrrhetinic acid (GA) based on bovine serum albumin (BSA). The drug-loaded nanoparticles were firstly formed by a simple desolvation method, and were further assembled into microparticles using zinc chloride and glutaraldehyde as crosslinkers. The obtained microparticles contained approximately 30% (w/w) drug and showed as spherical particles with a size of about 2 μm. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that GA lost its crystallinity during the nano/microencapsulation process. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1% at the first 30 min, which fitted well by Higuchi model. After intravenous administration into mice, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h. These results suggested the potential benefit of using the prepared albumin microparticles as a promising vector for enhanced liver delivery of poorly water-soluble drug.
研究领域:
药剂学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Xiumei Zhu,Altansukh Tsend-Ayush,Zhongyue Yuan,Jing Wen,Jiaxin Cai,Shifu Luo,Jianxu Yao,Junxing Bian,Linfang Yin,Jianping Zhou,Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6 ± 1.2 nm with a low poly-dispersity index (0.224 ± 0.013) and negative zeta potential (−16.30 mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-8
·
IF 4.011
Zhou Neng,Zou Caiyuan,Qin Menglin,Li Yi,Huang Jiayi
A simple validated high performance liquid chromatography method was developed for the evaluation of the effect of three kinds of active ingredients in traditional Chinese medicine (TCM) on the pharmacokinetics of glycyrrhetinic acid (GA),a kind of active component from the most commonly used TCM licorice. Our results revealed that all of the calibration curves displayed good linearity. Intra- and inter-day precision for GA ranged from 2.54 to 3.98% and from 4.95 to 7.08%, respectively. The recovery rates for GA were determined to be 96.3–106.4%. All the samples showed satisfactory precision and accuracy in various stability tests. Plasma pharmacokinetic parameters including area under the concentration-time curve (AUC), elimination half-life (t 1/2 ), time to peak concentration(T max ) and peak concentration C max were calculated. No significant difference was found as compared the groups administrating GA with and without other ingredients from TCM.
研究领域:
药理学
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中药学
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 29
·5845-5853
·
IF 4.543
Ping Zhang,Yang Cao,Huali Chen,Bo Zhou,Wenjing Hu,Liangke Zhang
In this study, a multi-functional drug delivery system, which combines targeted tumor treatment with glycyrrhetinic acid-modified nanodroplets and ultrasound imaging with low-boiling-point phase-change perfluorocarbon, was proposed and validated. The obtained nanodroplets were spherical in shape with an average size of 324.8 ± 183.7 nm and a negative zeta-potential. Low-intensity focused ultrasound (LIFU) was introduced to perform targeted US imaging via acoustic droplet vaporization (ADV) both in vitro and in vivo. The in vitro cytotoxicity and cellular uptake studies conducted on HepG2 cells demonstrated that nanodroplets modified with glycyrrhetinic acid enhanced the selective delivery to cells expressing high levels of glycyrrhetinic acid receptors. Moreover, the glycyrrhetinic acid-modified nanodroplets showed significant antitumor efficacy in HepG2 cell-bearing mice with the assistance of both passive targeting via the EPR effects and active targeting ability of glycyrrhetinic acid. In conclusion, our fabricated multi-functional nanodroplets possess targeted antitumor activity and simultaneous US imaging, providing high potential for targeted tumor theranostics.
研究领域:
药剂学
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肿瘤学
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医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2014
·Vol. 33
·期 2
·375-388
·
IF 3.55
Huang Run-Yue,Chu Yong-Liang,Jiang Ze-Bo,Chen Xiu-Ming,Zhang Xian,Zeng Xing
Background/Aims: The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin. Methods: Lung adenocarcinoma A549 and NCI-H23 cell lines were used in this study. Cell growth was examined by MTS assays, while apoptosis and cell cycle were determined by flow cytometric analysis. Both real-time PCR and western blotting were used to examine the expression levels of thromboxane synthase (TxAS), and TxAS activity was measured using EIA detection of the biosynthesis of TxA2. TxAS was overexpressed in NCI-H23 cells by transfection with TxAS cDNA, while TxAS was inhibited by transfection with TxAS siRNA in A549 cells. For the mouse model of lung adenocarcinoma, the effects of glycyrrhizin on tumor growth were analyzed by western blot evaluation of TxAS, PTEN and survivin. TxAS activity was determined by EIA assay. Results: Glycyrrhizin suppressed cell growth in A549 cells, but not in NCI-H23 cells, by induction of apoptosis. TxAS was overexpressed in A549 cells, but the TxAS levels in NCI-H23 cells were minimal. Moreover, TxAS expression and activity were suppressed by glycyrrhizin. Glycyrrhizin had no additive effects with TxAS siRNA knockdown in suppressing A549 cell growth, whereas it completely suppressed cell growth of NCI-H23 cells transfected with TxAS cDNA. These results were further confirmed by the in vivo study. Conclusion: Our study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. Therefore, glycyrrhizin is a promising anti-cancer agent for the treatment of lung adenocarcinoma
研究领域:
肿瘤学
·
分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Xuan Ma,Hui Chen,Lixing Cao,Shuang Zhao,Chong Zhao,Shutao Yin,Lihong Fan,Hongbo Hu
Ferroptosis is a new form of iron-dependent cell death . A growing body of evidence suggests that abnormal ferroptosis is involved in developing neurodegenerative diseases. 18β-glycyrrhetinic acid (GA) is a major bioactive component of licorice with multiple biological activities including neuroprotection. Give the role of ferroptosis in the neurodegenerative diseases, we hypothesized that the neuroprotective effect of GA might be associated with its ability to protect neuro-cells from ferroptosis. Results demonstrated that GA was able to prevent a well-known ferroptosis inducer ferroptosis inducer 56 (FIN56)-triggered ferroptosis in HT22 mouse neuronal cell. Further mechanistic investigation revealed that the protection of GA on ferroptosis is attributed its inhibiting effect on cellular labile iron accumulation and up-regulating coenzyme Q10 (CoQ10) levels. The findings of the present study uncovered a novel mechanism involved in the neuroprotective effect of GA, and imply that GA could be developed as a novel agent to manage ferroptosis-related diseases.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY AND PHYSICS OF LIPIDS
·
2023
·
IF 3.4
Jie Hu,Yongsheng Zheng,Zhijie Wen,Hudie Fu,Xuedan Yang,Xuexin Ye,Shengpeng Zhu,Li Kang,Xiaojun Li,Xinzhou Yang,Yan Hu
The aim of this study was to construct a bifunctional liposome with hepatic-targeting capacity by modifying with a targeting ligand and an intracellular tumor reduction response functional group to deliver drugs precisely to focal liver tissues and release them in large quantities in hepatocellular carcinoma cells. This could improve drug efficacy and reduce toxic side effects at the same time. First, the bifunctional ligand for liposome was successfully obtained by chemically synthesizing it from the hepatic-targeting glycyrrhetinic acid (GA) molecule, cystamine , and the membrane component cholesterol. Then the ligand was used to modify the liposomes. The particle size, PDI and zeta potential of the liposomes were determined with a nanoparticle sizer, and the morphology was observed by transmission electron microscopy . The encapsulation efficiency and drug release behavior were also determined. Further, the stability in vitro of the liposomes and the changes in the simulated reducing environment were determined. Finally, the antitumor activity in vitro and cellular uptake efficiency of the drug-loaded liposomes were investigated by performing cellular assays. The results showed that the prepared liposomes had a uniform particle size of 143.6 ± 2.86 nm with good stability and an encapsulation rate of 84.3 ± 2.1 %. Moreover, the particle size of the liposomes significantly increased and the structure was destroyed in a DTT reducing environment. Cellular experiments showed that the modified liposoes had better cytotoxic effects on hepatocarcinoma cells than both normal liposomes and free drugs. This study has great potential for tumor therapy and provides novel ideas for the clinical use of oncology drugs in dosage forms.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Qingxia Guan,Yumeng Liu,Zhaorui Xia,Yue Zhang,Liping Wang,Yanhong Wang,Shujun Zou,Shaowa Lv,Xiaoying Zhou
Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3’-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.
研究领域:
药理学
·
纳米医学
·
病毒学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）