Characterization of lipid solubilization, bicelle formation, and magnetic-alignment induced by saponins.

Glycyrrhizin suppresses fatty infiltration following rotator cuff tear in mice.

Glycyrrhizic acid encapsulated in zein/Astragalus polysaccharides nanoparticle: enhanced stability, bioactivity and sustained release.

Co-assembly of glycyrrhizic acid and ferritin nanocage into an acidic-stable complex hydrogel with porous skeleton structure and their application for compartmentalized co-encapsulation of food nutrients.

Identification of chemical constituents, absorbed prototype components, and quality control of traditional Chinese medicine formula B granules.

Pre-harvest application of co-assembled Berberine-integrated herbal hydrogel for enhancing strawberry quality and shelf life.

A multidimensional strategy for exploring quality markers of Xue-Fu-Zhu-Yu decoction and its three processed products based on intestinal absorption and pharmacodynamics.

High-fat Diet-associated Digestive Cancers: Mechanisms, Natural Product-based Therapies, and Drug Development.

Single-cell-guided design of glycyrrhizic acid hydrogel for metabolic reprogramming and healing of infected diabetic wounds

High mobility group box 1 is a dynamic nuclear protein that acts as a damage-associated molecular pattern when released from cells and plays key roles in neurodegenerative diseases. This review comprehensively analyzes the related post-translational modifications that affect the dual functions of high mobility group box 1 in neuroinflammation and neuronal survival, including acetylation, phosphorylation, oxidation, S-nitrosylation, lactylation, and ubiquitination. Post-translational modifications play critical regulatory roles in high mobility group box 1 subcellular localization, release processes and the specificity of receptor binding. In Alzheimer's disease, high mobility group box 1 exacerbates the disease through the Toll-like receptor 4/nuclear factor kappa B signaling pathway. Inhibition of high mobility group box 1 acetylation can alleviate neuroinflammation. Parkinson's disease models indicate that the S-nitrosylation of Cys106 is essential for the secretion of high mobility group box 1, which contributes to dopaminergic degeneration through the activation of microglia. In multiple sclerosis, high mobility group box 1 obstructs remyelination by inhibiting the maturation of oligodendrocytes and activating pro-inflammatory pathways. In contrast, high mobility group box 1 can maintain autophagy and DNA repair functions, suggesting its protective role. Therapeutic strategies targeting high mobility group box 1 show potential benefits. Glycyrrhizic acid inhibits disulfide-linked high mobility group box 1, SIRT activators suppress acetylation, and anti-high mobility group box 1 antibodies neutralize extracellular isoforms, thereby improving the results of preclinical studies. However, the diverse functions of high mobility group box 1 and the lack of post-translational modification-specific biomarkers present challenges for clinical translation. Future research should aim to create selective inhibitors that can cross the blood-brain barrier to target harmful forms of high mobility group box 1, and establish post-translational modification-based biomarkers for early detection. This review emphasizes that accurately targeting of high mobility group box 1 post-translational modifications in neurodegenerative diseases could be a new approach that can interrupt neuroinflammatory cascades while maintaining neuroprotective functions.

A Dual-Network Injectable Hydrogel Scaffold Integrating Glycyrrhizic Acid and Acellular Fat Extracts for Synergistic Enhancement of Diabetic Wound Healing

Various natural drugs such as glycyrrhizic acid (GA), hesperidin (Hes), and baicalin (Bai) exhibit anti-SARS-CoV-2 potential but suffer from poor water solubility, short half-life, and low binding capacity to viral targets. Hence, a dual-targeted, long-circulating, ROS-responsive, and broad-spectrum antiviral inhibitor (mPAGHB) is designed through a strategy of "polymer-drug linkage". The mPAGHB suppresses SARS-CoV-2 through two "lines of defense", including extracellular inhibition of the "spike protein-angiotensin converting enzyme 2 (ACE2)" process and intracellular inhibition of the enzymatic activity of major protease. It exhibits higher affinity for spike protein (KD = 4.95 × 10-2 μM), excellent inhibition of Mpro activity (76.27 ± 5.94% inhibition), and improved inhibition for pseudovirus of SARS-CoV-2 and Omicron variants in cellular and animal assays. In addition, as an efficient generic strategy, the "polymer-drug linkage" strategy facilitates the rapid construction of antiviral inhibitors based on natural active ingredients for the outbreaks of viral public infections.

Case reports of adverse event and loss of efficacy in individuals are the primary source of natural product drug interactions (NPDIs). Given the fundamental constraints, there is clear need for prospective and systematic study as foolproof methodology to understand NPDIs. Although human trials are confirmatory, an integrative physiologically-based pharmacokinetic (PBPK) modelling approach can be considered, despite challenges associated with NP data availability, variability and complexity. To explore the applicability of this approach, glycyrrhizin (GL) and its active metabolite glycyrrhetinic acid (GA) were identified as an NP with numerous pharmacological benefits and a potential likelihood of concomitant administration with narrow therapeutic antipsychotic drug quetiapine. Numerous serious case reports of quetiapine toxicity in combination with NPs support the proposed hypothesis. Simcyp® simulator was used to develop and validate quetiapine PBPK model followed by its utilisation for the evaluation of NPDI risk. PBPK modelling data indicated ∼ three-fold increase in quetiapine area under the curve (AUC) and peak plasma concentration (Cmax) in the presence of GA, signifying moderate increase in exposure which implies the need for further clinical assessment. This study successfully demonstrated the translation of in vitro information into helpful risk predictions for in vivo NPDIs by PBPK modelling.

Triple-negative breast cancer (TNBC) shows limited therapeutic efficacy due to the absence of effective targeted treatment options, with its immunosuppressive tumor microenvironment further diminishing the effectiveness of immunotherapy. Intracellular Ca²⁺ homeostasis plays a critical role in cancer progression, yet the efficacy of traditional inorganic nanoparticles in inducing calcicoptosis through Ca²⁺ release is constrained by poor water solubility, stability, and delivery efficiency. To address these challenges, we developed novel nanoparticles (NPs) by coordinating Ca²⁺ with the natural bioactive compound glycyrrhizic acid to create a multifunctional carrier (GC NPs), which was further loaded with the therapeutic natural compound curcumin (CUR) to form GC@CUR NPs. Through synergistic effects of Ca²⁺ overload and CUR-mediated regulation, these NPs significantly promote Ca²⁺ accumulation in mitochondria, triggering mitochondrial dysfunction and efficiently inducing calcicoptosis. Additionally, low-intensity pulsed ultrasound (LIPUS)-mediated targeted release markedly improved antitumor effects. Importantly, this strategy effectively induces immunogenic cell death (ICD) in TNBC, thereby significantly boosting antitumor immune responses. This study provides an innovative and efficient strategy for integrating chemotherapy and immunotherapy to transform TNBC tumors into immunoresponsive ones, offering new possibilities for comprehensive TNBC treatment.

PurposePrevious studies have highlighted a strong association between programmed cell death and ulcerative colitis (UC). Banxia Xiexin decoction (BXD) is a thoroughly validated formula with an extensive history of clinical application for treating UC. However, it remains unclear whether BXD regulates pyroptosis and necroptosis in UC. This study focused on pyroptosis and necroptosis to investigate the underlying mechanisms of BXD on UC.Material and MethodsThe therapeutic effects of BXD were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. To identify key signaling pathways, transcriptomics and proteomics were performed, followed by the validation of these pathways using Western blotting, immunohistochemistry, and immunofluorescence in vivo and in vitro. The bioactive components of BXD were screened through pharmacodynamic experiments, molecular docking, and surface plasmon resonance (SPR) analysis.ResultsBXD significantly alleviated UC symptoms by reducing inflammatory levels and improving intestinal barrier function. Multi-omics analyses demonstrated a significant alteration in pyroptosis- and necroptosis-related signaling pathways following BXD intervention. BXD suppressed pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway in the colons of UC model mice and in LPS+TNF-α-induced NCM460 cells. The screening of active ingredients revealed that baicalin and glycyrrhizic acid significantly affected LDH release and IL-1β levels. Molecular docking and SPR analyses demonstrated that baicalin targeted P2RX7 with high affinity and that glycyrrhizic acid targeted TNFR1 with moderate affinity.ConclusionBXD ameliorates inflammation and intestinal barrier dysfunction in UC by suppressing pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway. Baicalin and glycyrrhizic acid are identified as the pharmacodynamic components responsible for these therapeutic effects. These findings can provide molecular mechanisms and a material basis for the clinical application of BXD in the treatment of UC.

Hydrogen peroxide (H2O2) is a versatile green oxidant, but its industrial application is plagued by safety risks due to impurity-induced exothermic decomposition and leakage. Conventional stabilizers compromise reactivity, creating a persistent safety-reactivity paradox. Herein, this challenge is resolved through a supramolecular gelation strategy using a glycyrrhizic acid (GA) and polyvinyl alcohol (PVA) binary system, transforming aqueous H2O2 into mechanically robust gels. The resulting gel exhibits exceptional mechanical strength (storage modulus >3600Pa), thixotropy, and long-term stability (>6 months), effectively eliminating leakage. Crucially, the gel matrix suppresses H2O2 decomposition by up to 212-fold in the presence of metal contaminants (e.g., Fe3+, Cu2+, MnO2) by slowing convective mixing and isolating impurities via a bubble barrier, thereby preventing thermal runaway. Remarkably, the shear-thinning properties of the gel enable the release of H2O2 with uncompromised reactivity, achieving efficient sulfoxidation and alcohol oxidation with yields comparable to those of liquid H2O2. This work establishes supramolecular gelation as a transformative platform for the safe utilization of H2O2 in industrial processes without sacrificing oxidative efficiency.

Introduction. Hepatoprotectors are one of the broad drug groups used in complex therapy at different stages of liver damage. In clinical practice, hepatoprotective agents are used in form of individual or combined drugs. A combined drug is defined as a preparation containing two or more active biological substances that act together in the human body to prevent and treat diseases or to restore and maintain health. Combined drugs are used to increase the treatment effectiveness, reduce side effects, simplify medication intake, or help to treat multiple symptoms at the same time. Often the following well-known hepatotropic agents are most studied and used in combinations: essential phospholipids, glycyrrhizic acid, ursodeoxycholic acid and silymarin. It should be noted that although the pharmacological action of ursodeoxycholic acid and milk thistle preparations has been well studied, no technological research has been conducted to create combined medicines based on them. Aim. Development of a technology for a combined hepatoprotective agent in form of solid enteric-soluble gelatin capsules with granules containing ursodeoxycholic acid and milk thistle dry extract in form of a solid dispersion system as active substances. Material and methods. Ursodeoxycholic acid and the solid dispersion system of milk thistle dry extract are included as substances in the formulation of the combined hepatoprotective drug. Solid intestinal-soluble gelatin capsules were filled with granules containing a solid dispersion system of milk thistle dry extract and ursodeoxycholic acid using a ProFiller 3600 desktop manual capsule filling machine, capsule size "2". 3 series of solid gelatin capsules with granules were developed. The capsules standardization was carried out in accordance with the State Pharmacopoeia of the Russian Federation XV edition. The following indicators were determined: description, authenticity, quantitative content of the amount of flavolignans in terms of silybin, quantitative content of ursodeoxycholic acid, mass uniformity of dosage forms, disintegration and dissolution. Results and discussion. The granules formulation was developed by wet granulation, microcrystalline cellulose as disintegrator, magnesium stearate as lubricant, and 5 % aqueous solution of potato starch were used as excipients. The obtained formulations were compared in terms of quality and technological properties. It was found that granules containing microcrystalline cellulose have the best technological properties, such as weight loss during drying, hygroscopicity, bulk density, Carr index, Hausner coefficient, flowability. For capsules with granules, quality indicators were determined and standardized according to the POA (pharmacopeia official article) "Capsules" in terms of quality indicators: description, authenticity, quantitative content of the amount of flavonoids in terms of silybin, quantitative content of ursodeoxycholic acid, mass uniformity of dosage forms, disintegration and dissolution. When performing the "Dissolution" test, the release of silybin and UDCA was determined in 30, 45 and 60 minutes. The release of silybin was monitored by spectroscopy at a wavelength of λ = 289 nm and the release of ursodeoxycholic acid by high–performance liquid chromatography (HPLC) in accordance with the US pharmacopoeia, USP 44 – NF 39. It was determined that 89.0 ± 0.5 % of silybin was released in 45 minutes, during which time 97.0 ± 0.3 % of ursodeoxycholic acid was released. Conclusion. The granules formulation with a solid dispersion system of milk thistle dry extract and ursodeoxycholic acid has been developed. Microcrystalline cellulose is used as disintegrant, magnesium stearate as lubricant, and 5% aqueous solution of potato starch as binder. The technological properties of the granules and quality indicators are determined. The technology of intestinal-soluble capsules filled with granules has been developed. The quality indicators were determined and standardized according to quality indicators: description, authenticity, quantitative content of the amount of flavonoids in terms of silybin (by UV spectroscopy), quantitative content of ursodeoxycholic acid (by HPLC), mass uniformity of dosage forms, disintegration and dissolution. The releasing profiles of the active pharmaceutical substance from enteric capsules were studied and it was found that 89.0 ± 0.5 % of the amount of flavolignans in terms of silybin and 97.0 ± 0.3 % of ursodeoxycholic acid were released by 45 minutes, respectively, which meets the requirements of the State Pharmacopoeia of the Russian Federation XV edition.

PurposeThe present study aimed to systematically compare the in vitro and in vivo characteristics of three nano-assemblies with different components derived from Shaoyao Gancao Decoction (SGD), with particular emphasis on their differential effects on oral absorption of paeoniflorin (Pae).MethodsThe self-assembled nanoparticles of SGD (SGD-SAN), glycyrrhizic acid self-assembled nanomicelles (GL-SNM), and Glycyrrhiza protein self-assembled nanoparticles (GP-SAN) were separated or prepared, and characterized in terms of particle size, zeta potential, morphology, drug loading, and in vitro release behavior. The single-pass intestinal perfusion and pharmacokinetic studies of SGD-SAN, GL-SNM, and GP-SAN following oral administration were performed to evaluate their absorption-enhancing effect. Chemical interference agents (NaCl, urea, and Tween 20) were added, followed by particle size detection, to identify the types of intermolecular forces in the self-assemblies.ResultsThree nano-assemblies exhibited significant differences in particle size (133 nm for SGD-SAN, 154 nm for GL-SNM, and 184 nm for GP-SAN) and drug loading (5.54% for SGD-SAN, 10.70% for Pae GL-SNM, and 21.52% for Pae GP-SAN). While hydrophobic interactions act as the common core force driving the formation of all nano-assemblies, their dependencies on other intermolecular forces vary remarkably. SGD-SAN, GL-SNM, and GP-SAN exhibited sustained Pae release (50–75% over 12 h vs 100% for the Pae solution in 2 h). In situ intestinal perfusion in rats showed significantly higher effective permeability coefficients (Peff) for all nano-assemblies than the Pae solution, with GP-SAN exhibiting the highest ileal absorption, which may be attributed to preferential M-cell uptake facilitated by its protein-rich composition. Pharmacokinetic studies confirmed superior performance of GP-SAN with the highest AUC0-t (11209.01 ± 2093.72 ng/mL·h) and Cmax (2896.04 ± 255.01 ng/mL), representing 2.0-fold and 3.0-fold increases over Pae solution (5676.14 ± 311.61 ng/mL·h & 964.89 ± 128.81 ng/mL), respectively. GL-SNM and SGD-SAN also significantly enhanced the bioavailability (AUC0-t increased by 65% and 45%, respectively).ConclusionThese results suggested that nano-assemblies, particularly protein-based GP-SAN, provide a structural foundation for SGD’s bioavailability-enhancing effect.

The self-assembly of glycyrrhizic acid into nanofibrils.

pH-responsive self-assembly of natural saponin glycyrrhizic acid.