Search Results (169)

Leucomisine is a major component of renewable plant raw material Artemisia leucodes Schrenk, a sesquiterpene γ-lactone exhibiting antioxidant, hypoglycemic, antiparasitic, and hepatoprotective activities. However, the use of leucomisine in pharmaceuticals is limited by its insufficient bioavailability associated with low aqueous solubility. Therefore, the effect of solid-state synthesis based on leucomisine using the methods of “solvent removal”, “simple mixing”, and “mixture heating”, with disodium glycyrrhizinate as a carrier, on the aqueous solubility of leucomisine was investigated. It was established that the synthesized solid dispersions exhibit increased solubility (7–19-fold) and dissolution rate (36–100-fold) of leucomisine released from the carrier. The most pronounced stimulation of the dissolution process was observed for samples obtained using the “simple mixing” method. Based on physicochemical studies (visible-range spectrophotometry, microcrystalloscopy, investigation of optical properties of solutions, and X-Ray phase analysis), it was determined that the enhancement of solubility is attributed to the loss of crystalline state, micronization, and the solubilization process of leucomisine by the carrier, as well as to the formation of a colloidal solution of leucomisine stabilized by disodium glycyrrhizinate. Full article

Shoseiryuto (SST) is a Kampo medicine widely used to treat respiratory diseases. We previously showed that SST attenuates lipopolysaccharide (LPS)-induced tight junction (TJ) barrier disruption in human bronchial epithelial (16HBE) cells. However, the underlying mechanisms remain unclear. This study aimed to clarify the mechanisms underlying the protective effects of SST. SST attenuated inflammatory responses (increased IL-6 protein and mRNA levels) and TJ disruption (decreased transepithelial electrical resistance, increased sodium fluorescein permeability, and decreased occludin mRNA and protein expression) induced by LPS, hydrogen peroxide (H₂O₂), tumor necrosis factor-α (TNF-α), and polyinosinic–polycytidylic acid (Poly I:C). Further analyses using the Poly I:C model confirmed that the effects of SST were comparable to those of the nuclear factor κB (NF-κB) inhibitors SC-514 and BAY11-7085. SST reduced the activation of NF-κB signaling (increased phosphorylation of NF-κB and IκB), similar to BAY11-7085. SST components, isoliquiritigenin (ILQG) and glycyrrhizin (GL), also attenuated inflammation, barrier dysfunction, and NF-κB signaling activity. These findings suggest that (1) activation of the NF-κB signaling pathway might be associated with both inflammatory responses and TJ barrier disruption; (2) SST could reduce these effects, potentially through modulation of NF-κB signaling; and (3) ILQG and GL may contribute, in part, to these activities. Overall, this study provides the first evidence suggesting that SST may exert anti-inflammatory and epithelial barrier-protective effects, possibly via the suppression of the NF-κB signaling pathway. Full article

Glycyrrhizic acid and its derivatives are a crucial class of glycoside terpenoids with significant pharmaceutical and food industry applications. The biotransformation of glycyrrhizin (GL) into glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) and glycyrrhetinic acid (GA) can enhance the production of these valuable compounds. This study aimed to develop strategies to improve the catalytic and operational stability of β-glucuronidase from wild-type Talaromyces pinophilus Li-93, previously known as Penicillium purpurogenum Li-3 (w-PGUS), for efficient GL hydrolysis. Whole cells of T. pinophilus Li-93 expressing w-PGUS were capable of directly converting GL into GAMG. To enhance enzyme stability and reusability, three polymeric supports including, polyurethane foam (PUF), loofah sponge (LS), and polyvinyl chloride (PVC), were evaluated for immobilization of w-PGUS from the fermentation medium. Among these, PUF was the most effective immobilization support, yielding higher immobilization efficiency, GAMG production, and biomass retention. Under optimized conditions (1% PUF, 1.5 g.L⁻¹ w-PGUS inoculum, pH 5.0, 36 °C, 180 rpm), the immobilized w-PGUS produced a final GAMG yield of 3.90 g.L⁻¹, achieving 67.10% immobilization efficiency within 72 h. The PUF-immobilized w-PGUS retained 37.51% of its initial activity after 10 repeated batch reactions, whereas free w-PGUS retained only 6.21%. Additionally, the storage stability of immobilized w-PGUS was significantly higher (40.22%) than that of free w-PGUS (14.74%) after 30 days. Immobilization slightly reduced the initial yield due to mass-transfer limits but enabled much higher cumulative GAMG production through improved stability and reusability. Full article

Glycyrrhiza glabra L. (Fabaceae) is a plant species with already demonstrated countless biological properties and many more still to be discovered. Here, root sample extracts from different geographical areas were compared based on their phytochemical profiles and biological activities. Both raw and hydrolysate extracts, as well as 18β-glycyrrhetinic acid, glycyrrhizin, and isoliquiritigenin, considered as the main licorice secondary metabolites, were screened for antiproliferative and anti-migration properties in MCF-7, MDA-MB-231, A2780, HeLa, SiHa, and C33A breast and gynecological cancer cell lines. Hydrolysate extracts showed higher cytotoxicity than the raw extracts at the same final concentrations, 30 and 60 µg/mL, respectively. Among the standards, isoliquiritigenin showed the most pronounced cytotoxic activity, with inhibitory percentages exceeding 70% in each of the investigated cell lines at the lowest tested dose of 30 µg/mL. Then, the most effective extracts in the MTT assay, LIT2-H and LMO-H, were screened in a wound-healing test, demonstrating efficacy against ovarian (A2780) and cervical (C33A) cancer cell lines after 24 and 48 h of exposure. Full article

Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article

Licorice (Glycyrrhiza uralensis) contains bioactive flavonoids and saponins, primarily liquiritin and glycyrrhizin, which exhibit pharmacological activities but also potential dose-dependent toxicity. This study aimed to establish an integrative workflow combining analytical chemistry, network pharmacology, and computational toxicology to evaluate the skin-related safety of these compounds. High-performance liquid chromatography (HPLC) was employed to quantify liquiritin and glycyrrhizin in licorice extract. Network pharmacology and molecular docking analyses were conducted to identify core toxicity-related targets. In silico toxicity and threshold of toxicological concern (TTC) assessments were performed using VEGA and database-driven prediction models to estimate dermal exposure risk. Liquiritin and glycyrrhizin were identified as major constituents of G. uralensis. Network analysis revealed three key targets—EGFR, STAT3, and SRC—linked to skin sensitivity and toxicological pathways, including TRP channel regulation and EGFR signaling. Molecular docking showed strong binding affinities to SRC. The threshold of toxicological concern evaluation indicated that liquiritin exposure remained below safety thresholds, while glycyrrhizin slightly exceeded but remained within acceptable limits. The proposed HPLC–network pharmacology–TTC workflow provides a novel, non-animal approach for early-stage cosmetic safety screening. Both compounds demonstrate acceptable safety margins, supporting their controlled use in dermal formulations. Full article

Chronic low-grade inflammation, or “inflammaging,” is a defining feature of aging and a key driver of functional decline. Among innate immune sensors, Toll-like receptors (TLRs) are central mediators linking cellular stress to sterile inflammation, yet their modulation in physiological aging remains largely overlooked. This review bridges that gap by integrating molecular and clinical evidence on age-associated TLR remodeling and summarizing preclinical data on natural compounds that suppress TLR signaling. Across diverse inflammatory models, phytochemicals such as curcumin, quercetin, resveratrol, baicalin, and glycyrrhizin consistently downregulate Toll-like receptor 2- (TLR2-), Toll-like receptor 4- (TLR4-), and Toll-like receptor 9- (TLR9-) dependent myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, lowering interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF-α) while enhancing IL-10. These mechanisms mirror the molecular signature of inflammaging, supporting TLRs as actionable targets for restoring immune balance. Collectively, the evidence positions natural TLR modulators as a promising, yet untapped, avenue for promoting healthy aging and extending healthspan. Full article

Glycyrrhiza glabra L. is a species widely spread all over the world, with a long tradition of use in folk medicine. Here, raw and hydrolyzed extracts obtained from roots collected in different geographical areas belonging to the Mediterranean basin were standardized as regards the amount of three main compounds: glycyrrhizin, the most abundant triterpene saponin of licorice, the 18β-glycyrrhetinic acid and the chalcone isoliquiritigenin. Raw and hydrolyzed extracts, as well as their pure single compounds, were investigated for their potential anti-inflammatory properties. The hydrolyzed extracts significantly reduced the production of pro-inflammatory cytokines such as TNF-α, IL-6, NO mediator in LPS-stimulated RAW 264.7 cells. Moreover, they were able to inhibit JAK2 and STAT3 phosphorylated proteins more than pure single standards tested at the same final concentrations, displaying a strength synergism of action. These findings suggest that G. glabra extracts and, more specifically, the hydrolyzed ones could represent interesting sources of potential anti-inflammatory agents able to inhibit the JAK/STAT signaling pathway. Full article

Treatment options for major depression are limited: only about one-third of patients achieve remission with first line treatments with no established predictive markers. Parameters associated with treatment refractory depression, including metabolic markers (increased BMI, increased triglyceride levels), inflammation markers (C-reactive protein, CRP), autonomic disturbances (reduced blood pressure, reduced heart rate variability), and brain morphology changes (increased volume of the choroid plexus and brain ventricle volumes), may serve such purpose. These features can be linked mechanistically to an increase in aldosterone plasma concentration due to a reduced mineralocorticoid receptor (MR) sensitivity. The primary CNS target of aldosterone is the nucleus of the solitary tract (NTS), which is also the entry point of the vagus nerve. This nucleus integrates signals from endocrine, inflammatory, chemoreceptive, and physiological parameters, including blood pressure. In search of a mechanism to overcome this pathology, we identified a molecule which is derived from the licorice plant glycyrrhiza glabra, namely glycyrrhizin and its biologically active metabolite enoxolone. These molecules potentially reverse the above-described pathology. They inhibit the enzyme 11beta hydroxysteroid-dehydrogenase type 2 (11betaHSD2) and the toll-like receptor 4 (TLR4). 11betaHSD2 regulates the activity of the mineralocorticoid receptor (MR) by degrading cortisol/corticosterone, which allows aldosterone to bind to the MR. TLR4 is the ligand for lipopolysaccharide (LPS, endotoxin) and trigger of innate immunity. Consequently, patients with increased inflammation markers, increased aldosterone, or low blood pressure may preferentially benefit from the treatment with glycyrrhizin/enoxolone. Importantly, these patients can be identified BEFORE treatment is initiated. Clinically, patients sharing these biological indicators are primarily young females or patients with a history of childhood trauma. A combination of enoxolone with standard antidepressants may therefore avoid a trial-and-error approach and allow to achieve recovery faster. Full article

Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on its molecular targets. Methods: Scientific literature was thoroughly retrieved from reputable databases, including Scopus, Web of Science, and PubMed, up to 30 July 2025. The keywords “glycyrrhizin” and “glycyrrhizic acid” were used to identify relevant references, with a focus on pharmacological applications. Studies on synthetic analogs, non-English publications, non-pharmacological applications, and GL containing crude extracts were largely excluded. Results: Glycyrrhizin, the major bioactive constituent of Glycyrrhiza glabra, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, hepatoprotective, antitumor, neuroprotective, and immunomodulatory effects. These actions are primarily mediated through the inhibition of high-mobility group box 1 (HMGB1) and the modulation of key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and various cytokine networks. As a result of its therapeutic potential, GL-based formulations, including Stronger Neo-Minophagen C, and GL-rich extracts of G. glabra are commercially available as pharmaceutical preparations and food additives. Conclusions: Despite its therapeutic potential, the clinical application of GL is limited by poor oral bioavailability, metabolic variability, and adverse effects such as pseudoaldosteronism. Hence, careful consideration of pharmacokinetics and safety is essential for translating its therapeutic potential into clinical practice. Full article

Background/Objectives: Bangkeehwangkee-tang (BHT) is a traditional herbal formula composed of six medicinal herbs: Sinomenii Caulis et Rhizoma, Astragali Radix, Atractylodis Rhizoma Alba, Zingiberis Rhizoma Recens, Zizyphi Fructus, and Glycyrrhizae Radix et Rhizoma. BHT has been widely used for its immunomodulatory and anti-inflammatory effects. This study aimed to develop a reliable analytical method for the simultaneous determination of 22 marker compounds to ensure consistent quality control and to ensure consistent efficacy in both clinical and non-clinical studies of BHT. Methods: An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method based on multiple reaction monitoring was developed and validated for the simultaneous determination of 22 marker compounds in BHT. The method was evaluated for selectivity, linearity (coefficient of determination, r²), sensitivity (limit of detection (LOD) and limit of quantification (LOQ)), accuracy (recovery), and precision (relative standard deviation (RSD)) in accordance with guidelines. Results: The developed method exhibited excellent selectivity and linearity (r² ≥ 0.9913) for all target compounds. The LOD and LOQ ranged from 0.09 μg/L to 326.58 μg/L and 0.28 μg/L to 979.75 μg/L, respectively. The recovery ranged from 90.36% to 113.74%, and precision (RSD) was ≤15%, confirming the method’s reliability. The application of the method to various BHT samples revealed substantial variations in the marker compound contents, particularly for sinomenine, magnoflorine, and glycyrrhizin. Conclusions: These findings highlight the necessity for standardized quality control of BHT and demonstrate that the developed UPLC–MS/MS method is a practical and reliable tool for performing quality assessment of traditional herbal formulas. Full article

Oral mucositis (stomatitis) is a painful condition that affects the mouth lining. Kampo medicines (e.g., Hangeshashinto [Chinese name, Ban-Xia-Xie-Xin-Tang], Orento, and Orengedokuto) have been widely used to treat stomatitis, such as gargling with Hangeshashinto. However, the mechanisms by which Kampo medicines work are not widely understood due to their oral administration and the subsequent digestion, absorption, and metabolization of their components. Stomatitis is associated with advanced glycation end-products (AGEs) in patients with lifestyle diseases, and can be induced by both intra- and extracellular AGEs (blood and dietary AGEs). Various natural products inhibit intracellular AGE generation and suppress cytotoxicity, such as inflammation caused by extracellular AGEs. This review summarizes 19 natural products identified in the Hangeshashinto water extract and 16 natural products identified in the crude drug extract. The data show that several natural products, such as glycyrrhizin, baicalin, 6-shogaol, quercetin, epigallocatechin-3-galate, and genistein, inhibit intracellular AGEs and suppress extracellular AGE inflammation. Furthermore, several natural products in the Hangeshashito water extract can suppress cytotoxicity in stomatitis. Full article

Background: High Mobility Group Box 1 is a mediator in inflammation, acting as a damage-associated molecular pattern molecule in various diseases. This review examines its role in nasal inflammatory disorders, such as chronic rhinosinusitis and allergic rhinitis. Methods: A comprehensive review of recent literature was conducted using a refined PubMed search strategy, focusing on studies published from 2015 onward and targeting HMGB1’s role in nasal inflammatory diseases. Results: HMGB1 emerges as a central factor in amplifying and modulating inflammatory responses through interactions with multiple receptors. It regulates cytokine production, epithelial–mesenchymal transition, and tissue remodeling, particularly in eosinophilic CRS. While discrepancies in the literature highlight its context-dependent activity, therapeutic strategies like glycyrrhetinic acid and PPAR-γ agonists demonstrate potential in modulating its effects. Conclusions: HMGB1 represents a promising diagnostic biomarker and therapeutic target in nasal inflammatory diseases. However, due to its intrinsic nature and multiple localizations, much remains to be understood. It is precisely by reflecting on its role as an “inflammatory crossroads” that we aim to underscore the need for targeted translational research to elucidate the molecular mechanisms and therapeutic applications of HMGB1. Full article

Glycyrrhizic acid (GA) and its derivatives have been reported to have potent pharmacological effects against viral infections, including SARS-CoV and SARS-CoV-2. However, their antiviral mechanisms against coronaviruses are not fully understood. In this study, we found that diammonium glycyrrhizinate (DG) can effectively reduce infections of several human coronaviruses, including HCoV-OC43, HCoV-229E, and SARS-CoV-2, as well as newly emerged variants, with EC₅₀ values ranging from 115 to 391 μg/mL being recorded. Time-of-addition and pseudotype virus infection studies indicated that DG treatment dramatically inhibits the process of virus entry into cells. Furthermore, we demonstrated that DG broadly binds to the RBD of human coronaviruses, thereby blocking spike-mediated cellular entry, by using TR-FRET-based receptor-binding domain (RBD)-ACE2 interaction assay, capillary electrophoresis (CE), and surface plasmon resonance (SPR) assay. In support of this notion, studies of molecular docking and amino acid mutation showed that DG may directly bind to a conserved hydrophobic pocket of the RBD of coronaviruses. Importantly, intranasal administration of DG had a significant protective effect against viral infection in a HCoV-OC43 mouse model. Finally, we found that combinations of DG and other coronavirus inhibitors exhibited antiviral synergy. In summary, our studies strongly reveal that DG exerts broad-spectrum antiviral activity against human coronaviruses by interrupting spike-mediated cellular entry, demonstrating the pharmacological feasibility of using DG as a candidate for alternative treatment and prevention of coronavirus infection. Full article