Search Results (345)

Flavanones retrieved in the leaves of Glycyrrhiza glabra (licorice), specifically glabranin (GLA), pinocembrin (PIN) and licoflavanone (LIC), represent a valuable source of bioactive natural products, although their isolation and handling are often complicated by their structural similarity and unfavorable physical properties. In this work, crystal engineering strategies were explored both to facilitate the selective separation of licorice flavanones and to improve their solid-state characteristics. Co-crystallization was investigated as a tool for the selective recognition of PIN from a GLA-rich chromatographic fraction. Guided by structural considerations and predictive analyses performed using the Co-Crystal Design and Hydrogen Bond Propensity (HBP) tools in CCDC Mercury (within CCDC-Materials), co-crystallization experiments were performed with pyridinic co-formers. 4,4′-Bipyridine (BPY) selectively formed a new co-crystal with PIN, enabling the capture of traces of this flavanone directly from the GLA-rich fraction. In contrast, nicotinic acid (NIC) did not form a co-crystal with PIN, consistently with the predicted preference for NIC self-association. In addition, a co-amorphous system between LIC and BPY was obtained by quench cooling, yielding a fully amorphous solid with improved handling properties compared to the waxy precursor. These results highlight the potential of crystal engineering approaches for the selective separation and solid-state modification of natural flavanones. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder driven by tightly interconnected metabolic, inflammatory, and lipid dysregulation pathways. Glycyrrhetinic acid, a pentacyclic triterpenoid derived from Glycyrrhiza species, has demonstrated anti-inflammatory and hepatoprotective activities in previous experimental studies. Objectives: This study aimed to systematically investigate the potential molecular targets and signaling pathways of glycyrrhetinic acid in MASLD using an integrated network pharmacology and molecular docking strategy. Methods: Predicted protein targets of glycyrrhetinic acid and MASLD-associated genes were collected from public databases. A protein–protein interaction (PPI) network was constructed, and hub genes were identified using the maximal clique centrality algorithm in Cytoscape. Functional annotation was performed through Gene Ontology and KEGG pathway enrichment analyses. Molecular docking simulations were subsequently conducted to assess the binding affinity of glycyrrhetinic acid with biologically prioritized targets derived from the network analysis. Results: Intersection analysis identified 26 shared targets between glycyrrhetinic acid and MASLD. PPI network analysis highlighted IL6, TNFα, AKT1, and PPARγ as central hub genes. Functional enrichment indicated that these targets were mainly involved in NF-κB, TNFα, and PI3K–Akt signaling pathways. Molecular docking results revealed favorable predicted binding affinities, with glycyrrhetinic acid exhibiting the strongest binding toward PPARγ among the evaluated targets. Conclusions: This integrative in silico analysis suggests that glycyrrhetinic acid may interact with multiple MASLD-related targets involved in inflammatory and metabolic regulation. These findings provide a computational framework for target prioritization and support further experimental investigations to elucidate the pharmacological relevance of glycyrrhetinic acid in MASLD. Full article

This study concurrently addressed the separation method for carbon dots derived from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (GRRPM) and the in vitro evaluation of their anti-allergic biological activity. Glycyrrhizae Radix et Rhizoma Praeparata cum Melle Carbon Dots (GRRPM-CDs) were prepared via decoction followed by dialysis, and their properties were characterized using High-Performance Liquid Chromatography (HPLC) and nanomaterial techniques. Anti-allergic activity was evaluated using a C48/80-induced RBL-2H3 mast cell degranulation model. Safety and efficacy were assessed using the CCK-8 assay, direct intervention, and drug-containing serum methods. The release of β-hexosaminidase (β-hex), histamine (HIS), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) was measured by ELISA, and key proteins in the MAPK signaling pathway were analyzed by Western blot. GRRPM-CDs inhibited mast cell degranulation and the release of allergic and inflammatory mediators in a dose-dependent manner. They also significantly downregulated the phosphorylation levels of the JNK, ERK, and p38 proteins in the MAPK signaling pathway. GRRPM-CDs exhibit significant anti-allergic activity, likely via suppression of the MAPK pathway. These findings provide new insights into the bioactive components of processed Glycyrrhiza and suggest potential avenues for developing novel therapies for allergic diseases. Full article

Plant polysaccharides, such as Astragalus polysaccharide (APS) and Glycyrrhiza polysaccharide (GPS), hold potential as feed additives, yet their individual and synergistic effects on squab meat quality remain unclear. In this study, 192 healthy, 15-day-old, early-weaned Silver King squabs were assigned to one of four dietary treatments for 28 days: a control group (CK), an APS group, a GPS group, and a combined APS + GPS group (AG). Slaughter traits, organ indices, liver antioxidant capacity, and meat quality were evaluated across the four groups. Results indicated that supplementation with APS, GPS, and AG enhanced several slaughter traits compared to CK, including live weight, carcass weight, full-eviscerated weight, half-eviscerated weight, and leg muscle weight. GPS and AG supplementation improved color parameters in both breast and leg muscles, with AG showing the most favorable tenderness-related outcomes. Additionally, AG supplementation enhanced liver antioxidant capacity, as evidenced by increased total antioxidant capacity and superoxide dismutase activity. Given AG’s superior overall performance, the ileal metabolomics analysis focused on comparing CK and AG. Metabolomics data revealed clear group separation and significant changes in amino acid-related pathways. In summary, while APS and GPS individually improved certain traits, their combined supplementation yielded the most favorable results, likely through enhanced antioxidant capacity and altered ileal amino acid metabolism. Full article

Gastric cancer remains a highly heterogeneous malignancy in which chemotherapy response is limited by intrinsic and acquired resistance, cumulative toxicity, and the restricted predictive value of conventional preclinical models. This review critically synthesizes evidence on selected medicinal plants and their bioactive phytocompounds as adjuncts to standard chemotherapy for gastric cancer, with an emphasis on mechanistic plausibility, preclinical synergy, and translational barriers. Across the reviewed literature, phytocompounds from Curcuma longa, Scutellaria baicalensis, Camellia sinensis, Syzygium aromaticum, Glycyrrhiza glabra, Allium sativum, Marsdenia tenacissima, and Rhus verniciflua showed anticancer or chemopreventive activity through multitarget effects on apoptosis, proliferation, invasion, inflammation, oxidative stress, and resistance-associated signaling. The most convincing chemosensitizing evidence involved curcumin, wogonin, baicalein, EGCG, which enhanced the activity of fluoropyrimidines, platinum agents, paclitaxel, doxorubicin, or related antitumor regimens in selected gastric cancer models. However, the evidence base remains heterogeneous and is constrained by variable extract standardization, incomplete dose reporting, poor bioavailability, insufficient pharmacokinetic/pharmacodynamic integration, and underuse of clinically relevant model systems. Overall, medicinal plant bioactives remain promising adjunct candidates in gastric cancer. Still, meaningful translation will require chemically defined interventions, rigorous synergy analysis, interaction-aware study design, and validation in advanced preclinical and clinical settings. Full article

Weaning impairs intestinal function and growth performance in piglets. This study evaluated a fermented herbal formulation (FHF) composed of five bioactive herbal ingredients—Radix isatidis, Folium isatidis, Radix scutellariae, Fructus forsythiae, and Radix glycyrrhizae—fermented with Enterococcus faecium and Saccharomyces cerevisiae and characterized by flavonoids, phenolic acids, and hydroxylated fatty acids, using the porcine intestinal epithelial cell line (IPEC-J2) and weaned piglets. In vitro, IPEC-J2 cells were pretreated with FHF extract (100–1000 μg/mL) for 3 h prior to lipopolysaccharide (LPS) challenge. In vivo, 72 piglets were weaned at 32 days of age and, after a 3-day post-weaning adaptation period, entered a 35-day feeding trial. The piglets were then randomly assigned to three treatment groups: control (basal diet), A1 (basal diet + 0.4% FHF), and A2 (basal diet + 0.6% FHF during days 1–18, followed by 0.3% FHF during days 19–35). FHF dose-dependently alleviated the LPS-induced decrease in cell viability and suppressed IL-6, IL-8, IL-1β, and TNF-α expression. In piglets, the A2 group showed higher final body weight, average daily gain (ADG), and average daily feed intake (ADFI), lower feed conversion ratio (FCR), and a lower diarrhea rate than the control group. FHF also improved intestinal morphology, reduced serum TNF-α and diamine oxidase (DAO) levels, increased jejunal tight junction protein expression, enriched Limosilactobacillus and Lactobacillus, and elevated acetic and butyric acids. FHF improved intestinal health and growth performance in weaned piglets, with the A2 group showing the best overall efficacy. Full article

Traditional Chinese prescriptions are characterized by complex chemical constituents and wide variations in constituent content, which pose a substantial challenge to their comprehensive characterization. As a classic traditional Chinese prescription known for its heat-clearing and detoxifying properties, Huangqintang Decoction (HQD) is composed of Scutellariae Radix, Paeoniae Radix Rubra, Glycyrrhizae Radix et Rhizoma, and Jujubae Fructus. In this study, we developed an off-line two-dimensional liquid chromatography that addressed the limitations of traditional analysis of unfractionated extracts, such as restricted peak capacity, which often obscured trace components. By coupling with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), this study successfully performed rapid identification or characterization of the complete chemical profile of HQD. Notably, beyond high-throughput identification, this approach leveraged characteristic fragment ions and reversed-phase chromatographic behaviors to differentiate some isomers of flavonoid glycosides and triterpenoid saponins, demonstrating its depth in structural identification. Flavonoid glycoside isomers were distinguished by diagnostic neutral losses, while flavanones and chalcones were characterized by retro-Diels–Alder (RDA) and β-rearrangement, respectively. Isomers of triterpenoid saponins were inferred from aglycone-specific pathways alongside RDA cleavages. Ultimately, a total of 192 compounds were identified, including 88 flavonoids, 80 triterpenoids, 7 monoterpene glycosides, 3 fatty acid amides, 3 phenylethanoid glycosides, 4 coumarins, 3 saccharides, 1 organic acid, and 3 others. This study demonstrated that the off-line two-dimensional liquid chromatography analysis strategy significantly enhanced chromatographic resolution and expanded the coverage of trace components. It presented an effective strategy for comprehensive compound identification in complex traditional Chinese medicine prescriptions. Full article

Soil salinization is one of the main stress factors limiting plant growth and ecosystem restoration in arid regions. Arbuscular mycorrhizal fungi (AMF) can form common mycorrhizal networks (CMNs) that potentially facilitate resource and signal exchange between plants. In this study, we investigated whether such processes associated with AMF connectivity might contribute to salt tolerance in different plant combinations, using Glycyrrhiza inflata and Lycium ruthenicum. However, under salt stress, it remains unclear how different plant combinations (conspecific vs. heterospecific) may differentially benefit from CMN-mediated processes under salt stress, and whether such processes involve coordinated stress signaling and nitrogen transfer. This study used Glycyrrhiza inflata (a leguminous N-fixing plant with a “N-input” strategy) and Lycium ruthenicum (a deep-rooted desert shrub with a “resource-use efficiency” strategy) as materials to construct conspecific and heterospecific plant combinations: G-G (G. inflata-G. inflata), L-L (L. ruthenicum-L. ruthenicum), G-L (G. inflata-L. ruthenicum), and L-G (L. ruthenicum-G. inflata). Four salt stress levels were set (NaCl concentrations of 0, 150, 250, and 350 mmol·L⁻¹), along with AMF inoculation treatments. The study evaluated responses in AMF colonization, nitrogen transfer, biomass, root structure, photosynthetic characteristics, antioxidant capacity, osmotic regulation, and hormone levels. The results show that: (1) AMF colonization rates in all inoculated groups significantly decreased with increasing salt concentration, with the G-L combination showing a smaller decline; (2) The G-G combination maintained strong root activity and photosystem stability under high salt stress, exhibiting higher salt tolerance; (3) In conspecific combinations, the JA-Pro signaling pathway was dominant, whereas in heterospecific combinations, the ABA-SOD pathway prevailed, indicating differences in hormone regulation mechanisms among different combinations; (4) ¹⁵N transfer efficiency was significantly higher in conspecific combinations than in heterospecific combinations (p < 0.05), and increasing salt concentrations limited the resource-sharing ability of heterospecific combinations. In summary, our results revealed distinct physiological and hormonal responses in conspecific versus heterospecific plant combinations under salt stress when grown in an AMF-colonized system that permits hyphal connections. These patterns were consistent with a potential role of CMNs in signal coordination and resource sharing, although further experiments with disrupted hyphal connections would be required to confirm this mechanism. Full article

Background: Glabridin, a natural compound derived from Glycyrrhiza glabra L., possesses skin-lightening effects. This study aims to further elucidate the depigmentation mechanism of glabridin by investigating its effects on melanogenesis and melanin transfer. Methods: We initially confirmed the anti-melanogenic effects of glabridin in MNT-1 human melanoma cells. Then, we investigated the mechanism of its anti-melanogenic effect by evaluating the protein expression of β-catenin and MITF via Western blot. To investigate melanin transfer, we compared glabridin’s efficacy with that of niacinamide, a recognized inhibitor of melanosome transfer and employed two complementary experimental models: (1) α-melanocyte-stimulating hormone (α-MSH)-stimulated MNT-1 cells to analyze dendrite formation, and (2) a UVB-irradiated co-culture system of MNT-1 cells and HaCaT keratinocytes to evaluate melanin transfer. Results: By measuring glabridin’s effects on melanin content, tyrosinase activity, and melanogenesis-related protein expression confirmed its inhibition of melanin synthesis. Further investigation demonstrated that glabridin suppresses melanogenesis by downregulating β-catenin and MITF, indicating inhibition of the Wnt/β-catenin pathway. Furthermore, in α-MSH-treated MNT-1 cells, both glabridin and niacinamide were found to suppress dendrite formation and elongation. In a UVB-exposed co-culture system, both glabridin and niacinamide inhibited melanin transfer to keratinocytes. Mechanistically, these effects were linked to the regulation of Rho GTPases (Rac1, RhoA, Cdc42) and suppression of F-actin reorganization. Conclusions: This study provides, for the first time, evidence that the skin-lightening effect of glabridin involves two complementary mechanisms: inhibition of melanogenesis through suppression of the Wnt/β-catenin pathway, and attenuation of both dendricity and melanin transfer via the influence of Rho family GTPases expression. Full article

Toxoplasmosis is a zoonotic disease with limited therapeutic options, which are further hampered by significant toxicity and suboptimal efficacy. Effective interventions for chronic infection remain insufficient, and thus, natural product-derived drug screening remains a key focus in anti-Toxoplasma research. Licochalcone A (Lico A), a major bioactive compound isolated from Glycyrrhiza uralensis, exhibits potent activity against Toxoplasma tachyzoites. However, systematic studies of its targets, pharmacokinetics, and efficacy are lacking, hindering its development as an anti-Toxoplasma candidate drug. In this study, we used SPR-MS to identify 33 high-affinity target proteins (affinity score > 1000). Furthermore, an AI-driven multidimensional analysis identified a cluster of five proteins (TgMORN1, D3XD37, ABCB2, MIC15, and IDH), with TgMORN1 yielding the highest composite score. RNAi experiments confirmed TgMORN1 as a key target, as its silencing attenuated the anti-proliferative effect of Lico A. Western blotting, NanoDSF, and SPR supported direct binding between Lico A and TgMORN1, suggesting that Lico A modulates TgMORN1 thermal stability through residues S168 and D203, with high species specificity. Pharmacokinetic evaluation revealed that Lico A had favorable absorption and blood–brain barrier permeability, supporting its potential utility in treating brain disease. In vitro assays showed that Lico A effectively inhibited Toxoplasma gondii brain cyst formation. Collectively, these findings support Lico A as a promising candidate for the treatment of toxoplasmosis. Full article

Depression-related mood disturbances are increasingly recognized as nutrition-sensitive conditions associated with chronic stress-induced neuroinflammation and metabolic imbalance. Polygonatum sibiricum, Poria cocos, Lilium brownii, and Radix Glycyrrhizae Preparata are edible medicinal plants commonly used in functional foods. In this study, we evaluated the antidepressant effects of a Polygonatum sibiricum-based functional formula (PSF) in a chronic restraint stress (CRS) mouse model. CRS induced prominent anhedonia and behavioral despair, accompanied by microglial overactivation, activation of the NLRP3 inflammasome, and dysregulated tryptophan metabolism. PSF supplementation significantly alleviated depressive-like behaviors and inhibited NLRP3–caspase-1–GSDMD-mediated pyroptosis, leading to reduced hippocampal IL-1β and IL-18 levels. Importantly, PSF restored tryptophan metabolism toward serotonin production, stabilized monoaminergic and glutamate/GABA neurotransmission, and protected hippocampal neurons. Moreover, PSF partially reversed stress-induced gut microbiota dysbiosis. Collectively, these results demonstrate that PSF acts as a neuroimmune–metabolic modulator that improves mood-related behaviors by regulating inflammatory signaling, tryptophan metabolism, and neurotransmitter homeostasis, supporting its potential development as a functional food intervention for stress-induced depression. Full article

Background: Xiebai San (XBS), a classical Traditional Chinese Medicine formula comprising Cortex mori, Lycii Radicis Cortex, and Glycyrrhizae Radix et Rhizoma, has long been used for pulmonary inflammatory disorders. However, its underlying mechanisms remain un-clear. This study aimed to investigate the mechanisms by which XBS alleviates allergic pulmonary inflammation. Methods: Two murine models were established, consisting of a chronic ovalbumin (OVA)-induced model simulating adaptive immune responses and an acute compound 48/80-induced model triggering non-IgE-dependent mast cell activation. Pharmacodynamic indices including serum IgE, histamine, inflammatory cytokines, leukocyte profiles, and lung histopathology were evaluated. Network pharmacology was employed to predict core pathways. Arachidonic acid metabolites (AAMs) in lung tissues were quantified by targeted UPLC-MS/MS, and p38 MAPK signaling proteins were assessed by Western blot. Results: XBS significantly alleviated lung injury in both models. In the chronic OVA-induced model, XBS significantly reduced serum immunoglobulin E levels and inflammatory cell infiltration. In the acute model, XBS suppressed histamine release and mast cell-mediated inflammatory responses. Targeted metabolomics revealed differential regulatory mechanisms: XBS reduced lipoxygenase-derived metabolites, including leukotrienes and 12-hydroxyeicosatetraenoic acid in chronic inflammation, while suppressing cyclooxygenase-related prostaglandins in acute inflammation. Network pharmacology analysis identified arachidonic acid (AA) metabolism as a potential central pathway. The p38 mitogen-activated protein kinase pathway was partially involved. Conclusions: XBS effectively alleviates both chronic and acute allergic pulmonary inflammation through differential modulation of AA metabolism, providing mechanistic insights supporting its traditional use in allergic airway diseases. Full article

This study intended to elucidate the preventive effects of Licochalcone A (Lico A, a flavonoid from Glycyrrhiza inflata) on acute alcoholic liver injury (AALI) in mice and its mechanisms. Lico A (50, 100 mg/kg) markedly decreased the serum ALT, AST, and ALP levels (p < 0.05) and elevated the ALB and TP levels in AALI mice (p < 0.05). Lico A (100 mg/kg) markedly reduced the hepatic levels of MDA, NO, TNF-α, IL-1β, and IL-6 in AALI mice (p < 0.05), while elevating SOD, GSH, ADH, and ALDH activities (p < 0.05). Furthermore, Lico A (100 mg/kg) downregulated TLR4, MyD88, IKKβ, p-IκBα/IκBα, and p-NF-κB p65/NF-κB p65 levels in the liver tissue of AALI mice (p < 0.05) and diminished the serum LPS and DAO contents (p < 0.05). Lico A (50, 100 mg/kg) upregulated the expression of the intestinal tissue ZO-1 and Occludin in AALI mice. Pathological observation also showed that Lico A significantly improved the liver tissue and intestinal mucosa tissue damage caused by alcohol. Additionally, Lico A altered gut microbiota composition, accompanied by increased concentrations of fecal short-chain fatty acids (SCFAs), which restored microbial diversity and elevated the relative abundance of Actinomycetota, Bacteroidota, Bacillota_A_368345, Limosilactobacillus, Lactobacillus, and Bifidobacterium_388775. These results indicated that Lico A had better hepatoprotective effects on AALI, and its mechanisms may involve modulation of the gut–liver axis and the TLR4/NF-κB signaling pathway. Full article

Mowing is a widely used agricultural management practice, yet its role in shaping plant–insect interactions remains largely unexplored. In this study, we investigated how mowing influences resistance of licorice (Glycyrrhiza uralensis) to the whitefly Bemisia tabaci by integrating behavioral assays with volatile analysis, transcriptomics, and metabolomics. Feeding preference assays showed that adult whiteflies strongly preferred new plants over mowed plants. Developmental assays further revealed that whiteflies exhibited a prolonged egg stage and extended egg-to-adult developmental duration on mowed plants, while adult longevity was not significantly affected. Gas chromatography–mass spectrometry analysis identified 31 volatile compounds in licorice, with alcohols dominating the volatile profile of new plants and terpenoids dominating that of mowed plants. Whitefly infestation significantly increased ester compounds in both plant types. Differential volatile analysis highlighted cis-3-hexen-1-ol and trans-3-hexen-1-ol as dominant compounds in new plants, whereas 3-carene and β-pinene were predominant in mowed plants. Transcriptomic analysis revealed that mowing primarily affected genes associated with primary metabolism and ribosome-related pathways, whereas whitefly infestation induced extensive transcriptional reprogramming, including activation of flavonoid biosynthesis, flavone and flavonol biosynthesis, MAPK signaling, and plant circadian rhythm pathways. Metabolomic profiling identified substantial accumulation of flavonoids, flavonols, and isoflavonoids following whitefly feeding. Integrated multi-omics analysis identified flavonol biosynthesis as a core pathway underlying licorice defense against B. tabaci. Overall, this study demonstrates that mowing primes G. uralensis for enhanced resistance to whitefly infestation by reshaping volatile emissions, activating secondary metabolite biosynthesis, and inducing coordinated defense signaling networks. These findings provide new insights into plant–insect interactions and highlight mowing as a potential component of sustainable pest management strategies. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology, characterized by non-specific colonic inflammation. Licorice (Glycyrrhiza uralensis Fisch.), a food–medicine dual-use botanical, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties, suggesting therapeutic potential for UC. However, the specific bioactive components of licorice and their underlying mechanisms of action require further elucidation. In this study, we investigated the efficacy and mechanisms of licorice flavonoid extract (LF) in a dextran sulfate sodium (DSS)-induced murine model of UC. The results demonstrated that oral administration of LF significantly alleviated disease pathology indices, reduced colon shortening, and improved histopathological colon damage. LF treatment suppressed the production of pro-inflammatory cytokines, likely through inhibiting the phosphorylation of MAPK and NF-κB p65, while upregulating PPARγ expression. Additionally, LF intervention restored gut microbial diversity, increasing the abundance of beneficial taxa such as Bacteroidetes and Firmicutes. The chemical characterization of LF revealed that 15 flavonoid compounds contribute to its therapeutic basis. These findings demonstrate that LF mitigates UC via integrated anti-inflammatory, immunomodulatory, and microbiota-regulating mechanisms, highlighting its potential as a natural therapeutic agent for UC management. Full article