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INDUSTRIAL CROPS AND PRODUCTS · 2024 · IF 5.6

Enhanced co-extraction of glycyrrhizic acid and glabridin from Glycyrrhiza glabra L. through enzyme-focused techniques

Mei-yuan Li,Zhi-peng Jia,De-min Li,Man-ping Luo,Ying-ying Meng,Kang- xu Wang,Bei Wang,Bing Liu,Xin-guo Zhang,Qin Li

Glycyrrhizic acid (GA) and glabridin (GD) are very important sweeteners and whitening agents present in Glycyrrhiza glabra L. This study investigates the cellulase and pectinase produced by endophytes in G. glabra to optimize and enhance the extraction of GA and GD from licorice using enzyme-assisted extraction (EAE) and microbial co-culture-assisted extraction (MCAE) approaches. Twelve strains with cellulase and pectinase activities were isolated from G. glabra. Notably, the strain G1–5, preliminarily identified as Penicillium sp., demonstrated superior performance in enzyme production and extraction efficiency of GA. Compared to the traditional extraction methods, the EAE process showed an obvious improvement of 32.21% and 56.37% in GA and GD extraction rates, respectively. Similarly, the MCAE process with the enzyme-producing strain G1–5 exhibited an increase of 25.52% and 38.45% in GA and GD extraction rates, respectively. These findings provide valuable guidance and innovative strategies for the extraction of active ingredients.

研究领域: 植物化学 · 生物技术 · 药用植物学
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Small · 2020 ·Vol. 16 ·期 13 ·1906206 · IF 11.459

Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

Ting Tong,Hongwei Hu,Junwei Zhou,Shuangfei Deng,Xiaotong Zhang,Wantao Tang,Liurong Fang,Shaobo Xiao,Jiangong Liang

With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.

CAS / MDL: 1405-86-3 6119-70-6
研究领域: 生物医学 · 病毒学 · 药理学
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Pharmaceuticals · 2025 ·Vol. 18 ·期 4 ·448 · IF 4.8

Preparation and Evaluation of Hepatoma-Targeting Glycyrrhetinic Acid Composite Micelles Loaded with Curcumin

Xueli Guo,Zhongyan Liu,Lina Wu,Pan Guo

Background : Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods : A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w / w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results : The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug ( p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls ( p < 0.001), leading to 58.7% tumor volume reduction ( p < 0.001). Conclusions : The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy.

CAS / MDL: 70-18-8
研究领域: 药剂学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD HYDROCOLLOIDS · 2024 · IF 11

Construction of oleogels based on emulsion gels stabilized by glycyrrhizic acid and chitosan

Qianzhu Lin,Chenxi Wang,Zhengyu Jin,Liming Jiang,Jinsheng Wen,David Julian McClements,Chao Qiu

Liquid oils can be converted into elastic solids by preparing oleogels using an emulsion-templated approach. In this study, we prepared emulsion gels using a layer-by-layer (LBL) electrostatic deposition approach. These emulsion gels were then used as templates to prepare oleogels. Initially, oil-in-water emulsion gels were formed using glycyrrhizic acid (GA) as a natural anionic surfactant to form and stabilize the oil droplets. Cationic chitosan (CS) was then added to these emulsions to form a biopolymer coating around the oil droplets. The GA/CS ratio in these emulsion gels played a critical role in determining the physical stability of the oleogels created from them. At a sufficiently high chitosan concentration (3% CS for samples with 1% GA, 2% CS for samples with 2% GA), the emulsion gels were resistant to destabilization during drying, which was attributed to the formation of a thick chitosan coating around the oil droplets. The oil loss from the optimized oleogels (GCOs1-3, GCOs2-2, GCOs2-3) during drying was relatively low (0.41%–1.08%), indicating their strong oil binding capacity. In contrast, non-optimized oleogels (2% GA, 1% CS) were prone to droplet coalescence and oil loss (74.2% ± 1.3%) during drying. The optimized oleogels (GCOs1-3, GCOs2-2, GCOs2-3) all had relatively high storage modulus (∼150 kPa) at a frequency of 1 rad/s. Overall, the interfacial engineering strategy used in this study may be useful for converting liquid oils into semi-solid materials, which may be useful for several applications in the food and other industries.

研究领域: 食品科学 · 材料科学
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RSC Advances · 2025 ·Vol. 15 ·期 18 ·14217-14226 · IF 4.6

Enhanced immunoregulation in traumatic urethral stricture repair utilizing a glycyrrhizic acid-infused antiswelling biogel scaffold

Zhihuan Zheng,Ziqiang Wu,Chao Li,Lei Zhou,Weibin Hou,Wei Xiong,Shuo Tan

As a prevalent complication following urinary system trauma, urethral stricture is characterized by progressive fibrosis and luminal narrowing often leading to recurrent dysuria and impaired renal function. Current treatments including surgical interventions face challenges such as high recurrence rates and secondary stenosis. Hydrogel-based drug delivery systems offer therapeutic potential but are limited by material swelling under urinary flow and insufficient modulation of inflammatory microenvironments. This study introduces an innovative anti-swelling carrageenan biogel scaffold (Car/Ga) functionalized with glycyrrhizic acid (Ga), a dual anti-inflammatory and immunoregulatory phytochemical. The Car matrix ensures structural stability in biological fluids by resisting swelling-induced obstruction while Ga targets trauma-induced inflammatory cascades through M1 macrophage polarization mitigation to reduce fibrotic progression. In vitro and in vivo evaluations demonstrate that the Car/Ga system synergistically combines urine stability with immunomodulatory bioactivity, significantly reducing pro-inflammatory cytokine levels (iNOS) and promoting M2 macrophage polarization (Arg1). Histological analyses reveal attenuated collagen deposition and enhanced epithelial regeneration in urethral stricture models, highlighting its capacity to disrupt the inflammation–fibrosis cycle. By addressing both urine stability and immunological dysregulation, this dual-functional biogel represents a transformative strategy for precise urethral repair, demonstrating potential for clinical translation in urethral repair applications.

CAS / MDL: 1405-86-3 9000-07-1
研究领域: 泌尿外科 · 生物材料学 · 药理学
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International Journal of Pharmaceutics-X · 2025 · IF 6.4

Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss

Huaan Li,Bohan Lin,Shuangwu Wang,Ying Zhang,Zeming Zhou,Dingsheng Wen,Zhifeng Zhang,Xiaohua Feng,Lu Wen,Jun He,Gang Chen

Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or diabetes. Glycyrrhizic acid (GA), derived from edible herb licorice, is widely utilized in traditional Chinese medicine and clinical treatments for liver diseases. However, its potential in preventing hearing loss remains largely unexplored. Herein, we propose GA as a novel otoprotective agent and demonstrate its capability to prevent hearing loss. Our results show that GA effectively reduces oxidative stress and inflammation induced by cisplatin, aminoglycosides, or even noise and diabetes, thereby protecting cochlear hair cells. In hearing loss models, two commonly used administration methods were compared, with tympanic injection providing better protective effects than oral administration of GA. To enhance oral bioavailability, GA is employed as both the medicine and excipient, and formulated into micelles with curcumin, another extensively used bioactive compound. Interestingly, formulation parameters such as feeding ratio and temperature have little impact on micelle size but significantly affect the drug loading efficiency. The carrier-free strategy can achieve a high drug loading capacity and significantly increase the drug concentration in blood, offering improved preventive efficacy. Notably, the micelles also exhibit protection on kidneys and liver, and do not compromise the antitumor activity of cisplatin. Therefore, GA holds promise as an otoprotective candidate, with potential clinical applications for oral prophylaxis of hearing loss using the micellar formulation.

研究领域: 药理学 · 耳科学 · 纳米医学
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FOOD RESEARCH INTERNATIONAL · 2021 · IF 6.475

Tailoring structure and properties of long-lived emulsion foams stabilized by a natural saponin glycyrrhizic acid: Role of oil phase

Qing Li,Mengyue Xu,Yunyi Yang,Jian Guo,Zhili Wan,Xiaoquan Yang

Novel supramolecular nanofibrils assembled from food-grade saponin glycyrrhizic acid (GA) are effective building blocks to make complex multiphase systems, e.g., emulsion foams. In this work, the effects of different oil phases (castor oil, sunflower oil, dodecane, and limonene) on the formation, stability and structural properties of long-lived emulsion foams prepared by GA nanofibrils (GNs) were investigated. The obtained results showed that soft-solid emulsion foams (4 wt% GNs) can be fabricated, independently of oil phase, and their structural properties, viscoelasticity, and tribological properties can be well tuned by oil phase polarity. Compared to the GNs aqueous foams, the presence of jammed emulsion droplets in the liquid channels and at the surfaces of bubbles can provide a higher bubble stability for emulsion foams. For more polar oil phase (castor oil), GNs showed a higher affinity to the oil–water interface with a lower interfacial tension, thus forming smaller oil droplets and bubbles, which leads to the higher mechanical strength, denser network microstructures, and lower friction coefficients of emulsion foams. However, the limonene foam exhibited weak storage stability and rheological properties, as well as the relatively low lubrication, which may be related to the formation of oil droplet aggregates and clusters induced by the volatility of limonene. GN-based emulsion foams are thermoresponsive, independently of oils, and the temperature-switchable process for the destabilization and regeneration of foams can be controlled and repeated. These emulsion foams based on natural saponin nanofibrils with tunable properties have potential sustainable applications in foods, pharmaceuticals, and personal care products.

研究领域: 食品科学 · 材料科学 · 界面化学
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FOOD AND CHEMICAL TOXICOLOGY · 2025 · IF 3.5

Glycyrrhizic acid alleviates gefitinib-induced liver injury by regulating the p53/p21 pathway and releasing cell cycle arrest

Min Li,Shuaijun Peng,Jingjing Bu,Siqi Quan,Liming Liu,Zhouli Yue,Linlin Wang,Yucheng Li

Gefitinib, a first-line tyrosine kinase inhibitor (TKI) target to non-small cell lung cancer (NSCLC) treatment, is known to cause hepatotoxicity, which seriously limiting its therapeutic application. This study investigated the underlying mechanisms of gefitinib-induced liver injury and the protective effects of glycyrrhizic acid (GL) in mice and AML12 cells. Sixty mice were randomly divided into six groups: control, gefitinib, glutathione (200 mg/kg), and three doses of GL (50, 100, and 200 mg/kg). Liver injury was induced in mice through daily oral administration of gefitinib (400 mg/kg) for 16 days, with hepatotoxicity was assessed through serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and hepatic histopathology. Hepatic mRNA profiles were analyzed using RNA sequencing, with differentially expressed genes (DEGs) confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Finally, the effect of GL on the anticancer efficacy of gefitinib was assessed in A549 and Lewis lung carcinoma (LLC) lung cancer cells, as well as in a urethane-induced lung cancer mouse model. GL treatment significantly reduced liver index and serum ALT and AST levels, while also improving hepatic histopathology. Transcriptomic analysis identified 114 DEGs linked to the p53 pathway and cell cycle regulation. Further study indicated that GL inhibited the expression of p53 and p21, thereby upregulated Cyclin D1 expression, thereby alleviating gefitinib-induced cell cycle arrest without impairing its anticancer activity in vivo and in vitro . These findings highlight the potential of GL as a safe adjunct therapy, effectively mitigating gefitinib-induced hepatotoxicity while preserving its anticancer efficacy.

CAS / MDL: 70-18-8 184475-35-2
研究领域: 药理学 · 肿瘤学 · 分子生物学
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CHINESE JOURNAL OF POLYMER SCIENCE · 2014 ·Vol. 32 ·期 5 ·540-550 · IF 1.42

Studies on antineoplastic effect by adjusting ratios of targeted-ligand and antitumor drug

Guo Hua,Yang Cheng-ling,Wang Wei,Wu Yu-kun,Lai Quan-yong,Yuan Zhi

A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid (GA) and doxorubicin (DOX) conjugates at different ratios. GA (a liver-targeting ligand) and DOX (an antitumor drug) were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate (ALG-mOEG) for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo . In addition, nanoparticles with a 1:1 ( W : W ) ratio of GA-ALG-mOEG and DOXALG-mOEG (NPs-3) showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and antitumor activity in vivo . Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC 0-∞ and t 1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth (88.37% reduction in tumor weight) 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.

CAS / MDL: 76-05-1 2052-49-5
研究领域: 药学 · 肿瘤学 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy

Tingsheng Yan,Dalong Li,Jiwei Li,Feng Cheng,Jinju Cheng,Yudong Huang,Jinmei He

A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110   nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro . In simulated body fluid with 10   mM glutathione, the release rate in 12   h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy.

研究领域: 药剂学 · 肿瘤学
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Frontiers in Oncology · 2025 · IF 3.3

Engineered celastrol liposomes with glycyrrhizic acid augment synergistic antitumor efficacy in breast cancer

Wei Zhang,Jiping Li,Xiuli Gao,Likun Liu,Hong Liang,Liling Yue

Background/Objectives Breast cancer treatment remains challenged by the non-specific distribution and systemic toxicity of conventional chemotherapeutics. Celastrol (CEL), a natural compound with antitumor efficacy, faces clinical limitations due to its toxicity and poor solubility. Glycyrrhizic acid (GA), known for tumor-suppressive and membrane-modifying properties, offers potential to enhance targeted drug delivery. This study aimed to develop GA-modified liposomes (GA/LIP-CEL) to synergistically improve CEL’s therapeutic specificity and safety. Methods GA/LIP-CEL nanoparticles were engineered via thin-film hydration, replacing cholesterol with GA. Physicochemical properties were characterized using TEM, DLS, and HPLC. In vitro evaluations included stability assays, cellular uptake (flow cytometry), cytotoxicity (MTT assay), mitochondrial membrane potential (JC-1 staining), apoptosis (Annexin V/PI), DNA damage (γ-H2AX immunofluorescence), and cell cycle analysis in BT549 breast cancer and MCF-10A normal cells. Results GA/LIP-CEL exhibited uniform spherical morphology (122.48 ± 5.37 nm), high drug loading (87.75 ± 2.61%), sustained release (70.13% cumulative release at 24 h), and colloidal stability (negligible size variation over 14 days). Compared to LIP-CEL, GA/LIP-CEL reduced IC50 in BT549 cells while lowering cytotoxicity in MCF-10A cells. Compared with the LIP-CEL group, GA/LIP-CEL treatment demonstrated a statistically significant increase in apoptotic cell proportion (P < 0.05). Enhanced mitochondrial dysfunction (P < 0.05) and DNA (P < 0.05) damage were observed. GA modification improved cellular uptake potentially via regulating membrane fluidity and receptor-mediated endocytosis effects, and induced S-phase arrest (31.66 ± 1.70% cells). Conclusions GA/LIP-CEL combines GA’s membrane-targeting capabilities with CEL’s therapeutic effects, improving stability, specificity, and safety. This platform represents a novel strategy for precision drug delivery, addressing limitations of conventional systems through natural component integration. Further validation of in vivo performance and pharmacokinetics is warranted to advance clinical translation.

研究领域: 药学 · 肿瘤学
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JOURNAL OF PHARMACY AND PHARMACOLOGY · 2024 · IF 2.8

Preparation of glycyrrhizic acid-modified BSA-nanoparticles and evaluation of their hepatic cellular distribution

Tang Hongping,Qiu Xinyu,Chen Yue,Yan Li,Zhao Jie,Cao Bing tao,He Yujing,Hao Jifu

ObjectivesOrientation to specific cells is an important topic in active targeting strategy for nanoparticle-based drug delivery systems. While these administered nanoparticles will be sequestrated within the liver, their cellular distribution behaviors in the liver are not clear. The aim of this study was to fabricate glycyrrhizic acid (GL) modified BSA nanoparticles and evaluate their hepatic cellular distribution.MethodsGL-modified BSA (GL-BSA) was tailored according to the periodate oxidation method, then GL-BSA nanoparticles loaded with paclitaxel (PTX@GL-BSA NPs) were prepared through self-assembly approach. In vitro cellular uptake was assessed by FITC-labeled BSA nanoparticles and immunofluorescent analysis was performed to track their relative distribution in the liver.Key findingsThe fabricated PTX@GL-BSA NPs were spherical structure with the particle size of 179 nm and a negative potential (−17.3 mV). Flow cytometry (FCM) studies exhibited that the accumulation of GL-BSA nanoparticles was 5.3-fold compared with BSA nanoparticles in HepG2 cells. The Nanoparticles were preferentially accumulated in the sinusoidal endothelial cells rather than the Kupffer cells.ConclusionsThis study provides useful information to understand the distribution of hepatic targeting nanoparticles when using GL-modified BSA nanoparticles, which helps to further use for effective treatment of liver disease.

CAS / MDL: 28969-60-0 7790-28-5
研究领域: 药剂学 · 肝脏病学
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