JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Wenxin Wang,Yinting Yu,Huixian Chen,Peijun Sun,Lujie Lu,Shuwei Yan,Xunhong Liu,Tulin Lu,Weidong Li,Jining Liu,Lihong Chen
Ethnopharmacological relevance Honey-processed licorice (HPL) is the roasted product of licorice. It is recorded in the “Shang Han Lun” that licorice has better protection on heart after honey-processed. However, researches regarding its protective effect on the heart and the distribution of HPL in vivo are still limited. Aim of the study To evaluate the cardio-protection of HPL and explore the law of ten main components distribution in vivo under physiological and pathological conditions for an attempt to clarify the pharmacological substance basis of HPL in treating arrhythmia . Materials and methods The adult zebrafish arrhythmia model was established by doxorubicin (DOX). Electrocardiogram (ECG) was used to detect the heart rate changes of zebrafish. SOD and MDA assays were used to evaluate oxidative stress levels in the myocardium. HE staining was used to observe the morphological change of myocardial tissues after HPL treatment. The UPLC-MS/MS was adapted to detect the content of ten main components of HPL in heart, liver, intestine, and brain under normal and heart injury conditions. Results Heart rate of zebrafish was decreased, the SOD activity was attenuated and MDA content was increased in myocardium after administration of DOX. Moreover, tissue vacuolation and inflammatory infiltration were detected in zebrafish myocardium induced by DOX. HPL could ameliorate heart injury and bradycardia induced by DOX to a certain extent by increasing SOD activity and reducing MDA content. In addition, the study of tissue distribution revealed that the content of liquiritin , isoliquiritin, and isoliquiritigenin in the heart was higher in the presence of arrhythmias than those in the normal condition. Under pathological conditions, the heart highly exposed to these three components could elicit anti-arrhythmic effects by regulating immunity and oxidation. Conclusion These findings indicate that the HPL is protective against heart injury induced by DOX, and its effect is associated with the alleviation of oxidative stress and tissue injury. And the cardioprotective effect of HPL under pathological conditions may be related to the high distribution of liquiritin, isoliquiritin, and isoliquiritigenin in heart tissue. This study provides an experimental basis for the cardioprotective effects and tissue distribution of HPL.
研究领域:
药理学
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心脏病学
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民族药理学
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斑马鱼模型
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氧化应激
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组织病理学
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组织分布
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Xiaojuan Jiang,Yihua Lin,Yunlong Wu,Caixia Yuan,Xuli Lang,Jiayun Chen,Chunyan Zhu,Xinyi Yang,Yu Huang,Hao Wang,Caisheng Wu
Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
研究领域:
药理学
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中药学
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质谱学
·
炎症
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分子动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
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食品科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Shangyun Lu,Jiali Xu,Yang Xu,Yang Liu,Dongxing Shi,Jia Wang,Fubin Qiu
Maintaining the integrity and stability of the gut tract is essential for the health of the body. Autophagy is a promising target for balancing gut homeostasis, and numerous studies have focused on regulating autophagy to improve gut health. In this study, we found that glycyrol (GC), a representative coumarin compound isolated from Glycyrrhiza uralensis Fisch (used for medicine and food), can attenuate colon injury by activating autophagy. Specifically, we demonstrated that GC can act on ubiquitin-specific protease 8 (USP8), inhibit the interaction between SQSTM1/p62 and USP8, promote the ubiquitination of p62, and activate autophagy. Collectively, the findings of the present study suggest that GC is a novel and promising colon protector and deserves further investigation.
研究领域:
药理学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 89
·86640-86649
·
IF 3.289
Mingyan Liao,Yudan Zhao,Lizi Huang,Biao Cheng,Kun Huang
Parkinson's disease (PD), with widespread aggregation of α-synuclein in the form of Lewy bodies as a neuropathological hallmark, is a rising threat for ageing society. Glycyrrhiza uralensis is an herbal medicine and sweets used for centuries in Asia and Europe, its major pharmacologically active ingredients include isoliquiritigenin (ILG), liquiritin (LT), liquiritigenin (LG) and glycyrrhizic acid (GA). Here, we investigated the effects of Glycyrrhiza uralensis ethanol extract (GUE) and the above four compounds, on the aggregation of α-synuclein in vitro and in a transgenic Caenorhabditis elegans PD model NL5901. In vitro, ILG, LT and GUE inhibit the amyloid formation of α-synuclein and alleviate the toxicity caused by aggregates; moreover, ILG could disaggregate preformed fibrils. In vivo, ILG, LT and GUE not only reduce amyloid formation in C. elegans NL5901, but also extend its life span. Together, these data suggest that ILG and LT may be further considered as candidates for PD treatment.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2015
·
IF 2.998
Lei Shi,Xiuling Tang,Xueliang Dang,Qinhui Wang,Xiangrui Wang,Ping He,Qingwei Wang,Linna Liu,XinYou Liu,Yan Zhang
Ethnopharmacological relevance Glycyrrhizae radix et rhizoma (Gancao) is often prescribed together with Sophorae flavescentis radix (Kushen) in traditional Chinese medicinal practice to increase the efficacy on the treatment of hepatitis and hepatic fibrosis . Meanwhile, long-term single used Gancao can cause adverse reactions, lead to pseudohypercorticosteroidism especially. But the side effects of Gancao are significantly reduced when combined with Kushen; the reasons are still unknown. The aim of this study was to elucidate potential pharmacokinetic interaction between Kushen and Gancao, and to provide guidance for clinical medicine safety. Materials and methods A specific and rapid HPLC–MS method was established to quantify the four main activity ingredients matrine (MT), oxymatrine (OMT), glycyrrhizin (GL) and glycyrrhetinic acid (GA) in rat plasma. In this study, the pharmacokinetic parameters and the pharmacokinetic differences of the four main activity ingredients MT, OMT, GL and GA in single herb and Kushen–Gancao couple were obtained. Results Compared with oral administration of Gancao extract, K 10 and T max of GA significantly increased to 0.43 h −1 and 30 h after giving Kushen–Gancao ( p <0.05), but T 1/2 and V d were reduced to 0.73 L kg −1 and 4.98 h ( p <0.05). In addition, the AUC of GA was increased, and the other three activity ingredients all decreased. Conclusion GA as the main factor leading to the sodium–water retention side effects of Gancao. The result found that the absorption of GA was significantly slowed down and the metabolism rate was accelerated in Kushen–Gancao than single herb. So the attenuated toxicity mechanism may be because the accumulation of GA reduced in vivo. The conclusion has important meaning to the compatibility of Chinese med.
研究领域:
中药学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 14
·4657
·
IF 4.927
Mengxin Cao,Jiawei Zuo,Jian-Guo Yang,Chenyao Wu,Yongan Yang,Wenjian Tang,Lili Zhu
To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellentCmax(2377.57 ng/mL),Tmax(5 min) and AUC0-T(6625.54 mg/L*h), which was much higher than theCmax(346.03 ng/mL),Tmax(2.00 h) and AUC0-T(459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.Keywords:GAMG;glycyrrhetic acid;glycyrrhizin;pharmacokinetics;pharmacodynamics;tissue distribution
研究领域:
药理学
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中药学
✓ 已验证
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
ULTRASONICS SONOCHEMISTRY
·
2022
·
IF 9.336
Chen Xing,Wen-Qiang Cui,Yue Zhang,Xin-Shu Zou,Jing-You Hao,Si-Di Zheng,Ting-Ting Wang,Xiao-Zhen Wang,Tong Wu,Yan-Yan Liu,Xue-Ying Chen,Shu-Guang Yuan,Zhi-Yun Zhang,Yan-Hua Li
Licorice ( Glycyrrhiza glabra ) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.
研究领域:
药学
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分析化学
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生物技术
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植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Jiehong He,Tian Wang,Yuanyuan Xie,Xianrui Liang
Gancao Ganjiang decoction (GGD) is one of the classic formulas in China known for its effective therapeutic effects in treating various diseases. Component research before and after the compatibility of Gancao and Ganjiang revealed that 6-gingerol content considerably changed. Compared with the decoction of Ganjiang, 6-gingerol in GGD demonstrated improved solubility. It was assumed that the partially hydrophilic glycyrrhizic acid and 6-gingerol self-assembled into nanoparticles, which then improved the solubility of 6-gingerol. The self-assembled nanoparticles in GGD were separated and characterized. Subsequently, 6-gingerol–glycyrrhizic acid nanoparticles (6-Gin-Gly NPs) were further prepared and characterized via dynamic light scattering (DLS) and transmission electron microscope (TEM). The formation mechanism of the self-assembled nanoparticles was examined using ultraviolet–visible spectroscopy (UV–vis), Fourier transform infrared spectroscopy (FTIR), electrospray ionization–mass spectrometry (ESI-MS), and molecular docking. The in vitro antioxidant activity of the 6-Gin-Gly NPs was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino bis(3-ethylbenzothiazoline-6- sulfonic acid) + (ABTS + ) free radical scavenging assays, which confirmed that the nanoparticles considerably enhanced their in vitro antioxidant capacity. In this study, the solubility of insoluble components was improved by the formation of self-assembled nanoparticles, which provided substantial reference data for the study of complicated multi-component interaction in herbal medicine decoction.
研究领域:
药学
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纳米技术
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中医药
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Molecular Catalysis
·
2025
·
IF 4.9
Shiyu Wei,Yali You,Zixuan Wang,Dantong Feng,Ci Song,Yali Wang,Jiaxing Zhao,Yan Yang,Yanli Zheng,Yin Li,Wangshan Zheng,Yan Leng,Yongqiang Tian
β-Glucuronidase (GUS) catalyzes the hydrolysis of the glucuronide group in glycyrrhizin (GL) to produce glycyrrhetinic acid (GA). However, the industrial application of β-glucuronidases (GUSs) is often limited by their poor stability, low hydrolytic activity, and particularly insufficient substrate specificity. In this work, a novel and thermostable β-glucuronidase from Thermobacillus composti ( Tc GUS) was identified through gene mining. Evolutionary relationship and sequence analyses revealed that Tc GUS belongs to the family of typical GUS enzymes. Tc GUS demonstrated specificity and efficiently transformed GL to generate GA, exhibiting maximum activity at 35 °C and pH 6.5, with a half-life of 5 days at 50 °C, indicating excellent thermostability. The K m and V max values of Tc GUS were 3.20 mM and 151.18 μM·mg⁻¹·min⁻¹, respectively, reflecting its high substrate selectivity and biotransformation efficiency. Therefore, Tc GUS is a promising biocatalyst for the synthesis of glycyrrhetinic acid.
研究领域:
酶学
·
分子生物学
·
生物催化
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天然产物化学
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药物代谢
✓ 已验证
DOI
高影响因子
ACS Sustainable Chemistry & Engineering
·
2024
·
IF 7.1
Bo Yang,Wentao Sun,Xinhe Liu,Ming-zhu Ding,Xudong Feng,Chun Li
Glycyrrhetinic acid 3-O-monoglucuronide (GAMG) and glycyrrhizin (GL) are typical pentacyclic triterpenoid saponins present in licorice roots that exhibit important pharmacological properties. GAMG and GL are sourced primarily from licorice, namely, “digging roots and extracting acid”, which results in ecological imbalance and environmental pollution. To overcome these issues, it is an eco-friendly and sustainable alternative to de novo synthesize GAMG and GL in Saccharomyces cerevisiae by coupling UDP-glucuronic acid and glycyrrhetinic acid (GA) under the catalysis of glycosyltransferases. However, the reported productivity is too low for industrial production. The primary limiting factors include insufficient supply of precursors, poor activity, and low specificity of the glycosyltransferases. In this study, we reconstructed the GA-producing platform strain in which GA was mainly accumulated intracellularly, making it suitable for subsequent glycosylation modifications. Different glycosyltransferases were tested and selected in the platform strain for achieving the efficient and specific synthesis of GAMG and GL. Protein engineering of rate-limiting enzyme cUGT73P12 was performed to further facilitate the conversion from GAMG to GL. The glycosylation capacity of this system was assessed in vivo, uncovering that the insufficient supply of precursor GA limited glycosylation modifications. Correspondingly, multiple metabolic engineering strategies were applied to optimize the carbon flux distribution, increasing the titers of GAMG and GL by 115.6 and 50.2%, respectively. Finally, 552.9 mg/L GAMG and 476.6 mg/L GL were produced in the 5 L fed-batch fermentation, which were 238- and 79-fold higher than previously reported values, respectively. The strategy described herein can serve as a reference for the glycosylation of triterpenoids in a cost-effective manner.
研究领域:
生物技术
·
药学
·
代谢工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）