Recent advances in glycyrrhizin metabolism, health benefits, clinical effects and drug delivery systems for efficacy improvement; a comprehensive review

Bakr, Alaa F.; Shao, Ping; Farag, Mohamed A.

doi:10.1016/j.phymed.2022.153999

Cited by 23 publications

(8 citation statements)

References 159 publications

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“…Furthermore, the pharmacokinetic (PK) properties of Lf-GL were improved compared to free-GL (as shown in Table 2 ), which led us to anticipate that Lf-GL would be a suitable formulation to enhance tumor targeting by increasing bioavailability. In contrast, free-GL is rapidly eliminated from the body without being effectively metabolized [ 38 ], which may limit its efficacy as a therapeutic agent for tumor treatment.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy

et al. 2023

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Background High-mobility group box-1 (HMGB1) released from the tumor microenvironment plays a pivotal role in the tumor progression. HMGB1 serves as a damaged-associated molecular pattern (DAMP) that induces tumor angiogenesis and its development. Glycyrrhizin (GL) is an effective intracellular antagonist of tumor released HMGB1, but its pharmacokinetics (PK) and delivery to tumor site is deficient. To address this shortcoming, we developed lactoferrin-glycyrrhizin (Lf-GL) conjugate. Methods Biomolecular interaction between Lf-GL and HMGB1 was evaluated by surface plasmon resonance (SPR) binding affinity assay. Inhibition of tumor angiogenesis and development by Lf-GL attenuating HMGB1 action in the tumor microenvironment was comprehensively evaluated through in vitro, ex vivo, and in vivo. Pharmacokinetic study and anti-tumor effects of Lf-GL were investigated in orthotopic glioblastoma mice model. Results Lf-GL interacts with lactoferrin receptor (LfR) expressed on BBB and GBM, therefore, efficiently inhibits HMGB1 in both the cytoplasmic and extracellular regions of tumors. Regarding the tumor microenvironment, Lf-GL inhibits angiogenesis and tumor growth by blocking HMGB1 released from necrotic tumors and preventing recruitment of vascular endothelial cells. In addition, Lf-GL improved the PK properties of GL approximately tenfold in the GBM mouse model and reduced tumor growth by 32%. Concurrently, various biomarkers for tumor were radically diminished. Conclusion Collectively, our study demonstrates a close association between HMGB1 and tumor progression, suggesting Lf-GL as a potential strategy for coping with DAMP-related tumor microenvironment. Graphical Abstract HMGB1 is a tumor-promoting DAMP in the tumor microenvironment. The high binding capability of Lf-GL to HMGB1 inhibits tumor progression cascade such as tumor angiogenesis, development, and metastasis. Lf-GL targets GBM through interaction with LfR and allows to arrest HMGB1 released from the tumor microenvironment. Therefore, Lf-GL can be a GBM treatment by modulating HMGB1 activity.

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Section: Resultsmentioning

confidence: 99%

Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy

et al. 2023

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“…Glycyrrhizin has been used in China for more than 4,000 years. It is widely employed to treat a variety of diseases and conditions because it possesses multiple pharmacological properties, including anti-inflammation, antioxidative, immunomodulatory, antiviral, anticancer, and hepatoprotective effects (Chen et al, 2020;Rehman et al, 2020;Bakr et al, 2022).…”

Section: Glycyrrhizin and Its Potential Advantages In The Treatment O...mentioning

confidence: 99%

Glycyrrhizin for treatment of CRS caused by CAR T-cell therapy: A pharmacological perspective

Li²,

Luo³

2023

Front. Pharmacol.

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Chimeric antigen receptor T (CAR T)-cell therapy promises to revolutionize the management of hematologic malignancies and possibly other tumors. However, the main side effect of cytokine release syndrome (CRS) is a great challenge for its clinical application. Currently, treatment of CRS caused by CAR T-cell therapy is limited to tocilizumab (TCZ) and corticosteroids in clinical guidelines. However, the theoretical risks of these two agents may curb clinicians’ enthusiasm for their application, and the optimal treatment is still debated. CAR T-cell therapy induced-CRS treatment is a current research focus. Glycyrrhizin, which has diverse pharmacological effects, good tolerance, and affordability, is an ideal therapeutic alternative for CRS. It can also overcome the shortcoming of TCZ and corticosteroids. In this brief article, we discuss the therapeutic potential of glycyrrhizin for treating CRS caused by CAR T-cell therapy from the perspective of its pharmacological action.

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“…Saponins represent an important group of plant metabolites that are characterized by a wide range of pharmacological activities and clinical applicability. Among the many uses of saponin-rich plants, their expectorant, anti-inflammatory, and antihyaluronidase effects are most valued, with glycyrrhizin, asiaticoside, or escin being some prominent examples [ 29 , 30 , 31 ]. Triterpene saponins have also been reported in some of the Atriplex species, such as A. semibaccata [ 26 ], A.nummularia [ 32 ], A. glauca [ 25 ], A. lasiantha [ 24 ], A. tatarica [ 28 ], A. leucoclada and A. stilosa [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Antihyaluronidase and Antioxidant Potential of Atriplex sagittata Borkh. in Relation to Phenolic Compounds and Triterpene Saponins

et al. 2023

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The genus Atriplex provides species that are used as food and natural remedies. In this work, the levels of soluble phenolic acids (free and conjugated) and flavonoids in extracts from roots, stems, leaves and flowers of the unexplored Atriplex sagittata Borkh were investigated by LC-ESI-MS/MS, together with their antioxidant and antihyaluronidase activity. Phenolic acids were present in all parts of A. sagittata; and were most abundant in the leaves (225.24 μg/g dw.), whereas the highest content of flavonoids were found in the flowers (242.71 μg/g dw.). The most common phenolics were 4-hydroxybenzoic and salicylic acids, kaempferol-3-glucoside-7-rhamnoside, kaempferol-3-rutinoside and the rare narcissoside, which was present in almost all morphotic parts. The stem extract had the highest antioxidant activity and total phenolic content (611.86 mg/100 g dw.), whereas flower extract exerted the most potent antihyaluronidase effect (IC50 = 84.67 µg/mL; control—quercetin: IC50 = 514.28 μg/mL). Phytochemical analysis of the flower extract led to the isolation of two triterpene saponins that were shown to be strong hyaluronidase inhibitors (IC50 = 33.77 and 168.15 µg/mL; control—escin: IC50 = 307.38 µg/mL). This is the first report on the presence of phenolics and saponins in A. sagittata. The results suggest that both groups of metabolites may contribute to the overall activity of this plant species.

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Recent advances in glycyrrhizin metabolism, health benefits, clinical effects and drug delivery systems for efficacy improvement; a comprehensive review

Cited by 23 publications

References 159 publications

Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy

Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy

Glycyrrhizin for treatment of CRS caused by CAR T-cell therapy: A pharmacological perspective

Antihyaluronidase and Antioxidant Potential of Atriplex sagittata Borkh. in Relation to Phenolic Compounds and Triterpene Saponins

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