Search Results (73)

Infectious spleen and kidney necrosis virus (ISKNV) causes systemic infections and high mortality in various freshwater and marine fish species, posing a serious threat to aquaculture and ornamental fish industries. In this study, 72 antiviral compounds were screened against five ISKNV target proteins, DNA polymerase, transcription elongation factor (TFIIS), adenosine triphosphatase (ATPase), ankyrin repeat-containing protein, and major capsid protein (MCP) using molecular docking, followed by in vitro evaluation in dwarf gourami fin (DGF) cells. Fludarabine, liquiritin, and lycorine consistently ranked among the top 20 compounds across all five targets and were selected for further evaluation. Fludarabine and lycorine strongly inhibited MCP, ATPase, and DNA polymerase expression with inhibition rates exceeding 85%. Infectious viral titers were reduced by approximately 39- and 81-fold in the fludarabine- and lycorine-treated groups, respectively, compared with those in the ISKNV-infected control group. Time-course analysis revealed that both compounds suppressed extracellular viral release and delayed the progression of cytopathic effects. These results suggest that multi-target docking combined with in vitro evaluation may be a useful strategy for prioritizing antiviral candidates against ISKNV. Full article

This study aims identify plant-derived compounds that can inhibit glutathione peroxidase 4 (GPX4) enzyme and evaluate them through molecular docking, dynamics simulations, and ADMET analyses. The 3D structure of the GPX4 protein (PDB ID: 2OBI) was obtained from the Protein Data Bank. The plant-derived ligand library was compiled from the PubChem database and screened for compliance with Lipinski’s rules using ADMETLAB 2.0. Molecular docking simulations were performed using Autodock Vina. Molecular dynamics simulations of 100 nanoseconds were performed for the selected ligand–protein complexes using AMBER Tools and OpenMM software. The ADMET properties of the ligands were evaluated using the pKCSM web server. Compared to the reference inhibitor RSL3 (−7.2 kcal/mol), five plant compounds showed stronger binding affinity: withaferin A (−8.0 kcal/mol), mahanine (−7.9 kcal/mol), pseudobufarenogin (−7.8 kcal/mol), cucurbitacin I (−7.6 kcal/mol), and liquiritin (−7.5 kcal/mol). Molecular dynamics simulations showed that the complexes of withaferin A, mahanine, and liquiritin exhibited superior structural stability. ADMET analysis revealed that the compounds generally possess acceptable pharmacokinetic profiles but require some bioavailability optimization. The identified plant-derived compounds can be considered as potential therapeutic agents in cancer treatment by inducing ferroptosis via GPX4 inhibition. These findings provide an important basis for natural product-derived drug discovery studies. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dryness and itching. Steroids are the most common therapeutic agents, may induce skin atrophy, and damage the skin barrier. Therefore, we need to find a safer alternative option. Liquiritin (LQ), a flavonoid compound extracted from licorice rhizomes, possesses anticancer, anti-inflammatory, and antioxidant effects. This study aimed to investigate the therapeutic effects of LQ on AD, focusing on its potential skin barrier-protective and anti-inflammatory mechanisms. In this research, we prepared liquiritin carbomer gel (LQ-CG) and assessed its treatment effects on mice with AD triggered by 2,4-dinitrofluorobenzene (DNFB). It effectively attenuated AD progression by ameliorating skin lesions, decreasing epidermal thickness and mast cell infiltration, downregulating inflammatory cytokine levels, and restoring the expression of claudin-1, loricrin, and occludin. It also inhibited the release of TNF-α, IL-1β, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and showed no significant toxicity to major organs in mice. In summary, our findings demonstrate that LQ-CG can effectively alleviate atopic symptoms by repairing the skin barrier and inhibiting inflammatory responses without causing significant changes in organ indices Full article

Background/Objectives: There is high demand for Anshenbunao syrup (ABS) in Chinese medicine owing to its steady therapeutic efficacy for insomnia and neurasthenia. However, it contains a substantial proportion of Polygoni Multiflori Radix Praeparata (PMRP), which is associated with reported cases of drug-induced liver injury (DILI). Here, we aim to establish an integrated approach combining PK screening with a dual-model toxicity verification system to systematically identify liver injury components (from high to low concentrations and from direct to idiosyncratic hepatotoxicity) to accurately uncover diverse potential hepatotoxicity markers. Methods: A sensitive UPLC-MS/MS method was used to accurately quantify the components in plasma at the ng/mL level and conduct a pharmacokinetic analysis. Rat models were used to evaluate exposure levels of the eight active constituents and three major metabolites after a single oral gavage dose of 10 mL/kg ABS and identify the quality markers. The early-stage and high-throughput assessment of direct and idiosyncratic hepatotoxicity was conducted in vitro utilizing HepG2 cells. After the administration of the quality markers (0.01–80 μM), CCK-8 was used to detect cell viability on both normal and susceptible cells, and the latter was induced by lipopolysaccharide. Results: As a result, seven quality markers were screened based on their contents and exposure levels in rat plasma by UPLC–MS/MS, including emodin (EM), liquiritin (LI), 2,3,5,4′–Tetrahydroxystilbene–2–O–β–D–glucoside (TSG), icariin, emodin–8–O–β–D–glucoside, baohuoside I (BA), and 18β–glycyrrhetinic acid (GTA). Moreover, the half maximal inhibitory concentration values of both normal cells and the lipopolysaccharide-induced immune stress liver injury cells were fitted within the concentration range of 0.01–80 μM, based on which, EM, BA, and GTA were identified as the principal hepatotoxic constituents in ABS at elevated concentrations. This study is the first to demonstrate that TSG, EM, LI, and GTA exhibit synergistic cytotoxicity in LPS-sensitized hepatocytes at clinically relevant concentrations, whereas EM was also a direct hepatotoxic component. Given that TSG is one of the major ingredients in ABS, the underappreciated idiosyncratic hepatotoxicity could elevate the risk of adverse clinical outcomes. Conclusions: In conclusion, this study effectively identifies hepatotoxic constituents in ABS and evaluates their hazards under immune stress and toxicity profiles in clinical concentrations, which also provides a robust foundation for the awareness of PMRP-induced DILI due to ABS. Full article

Glycyrrhiza glabra L. is an economically significant plant that naturally grows in arid regions and is widely used in the cosmetics, food, and pharmaceutical industries. Its roots are the economically important part. However, it has weak drought tolerance during the seedling stage, and water scarcity has become a major limiting factor for improving the yield and quality of cultivated licorice. Therefore, this study conducted a pot experiment in which melatonin was applied via root irrigation to examine its effects on alleviating drought stress in G. glabra seedlings and on enhancing the yield and quality of its valuable parts. The results showed that under drought conditions, applying 100 μM melatonin yielded the most significant improvements in both yield and quality. Specifically, melatonin treatment increased root biomass by 138.10% and significantly boosted the levels of key bioactive compounds, including glycyrrhizic acid, liquiritin, glabridin, liquiritigenin, and isoliquiritigenin by 60.51%, 72.08%, 182.03%, 83.86%,and 30.68%, respectively. This study uniquely combined the Mantel test and random forest modeling for a comprehensive analysis of the experimental data. The analysis indicated that these effects were attributable to exogenous melatonin, which markedly enhanced antioxidant enzyme activities in G. glabra seedlings and reduced membrane lipid peroxidation products, thereby strengthening their antioxidant defense capabilities. Additionally, melatonin promoted the accumulation of osmotic adjustment substances and effectively improved photosynthetic performance. Our research provides a scientific basis for increasing both the quality and yield of G. glabra under drought conditions. 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

Background/Objectives: Licorice (Glycyrrhiza glabra L.) is a highly important medicinal plant that is widely used in China owing to its active ingredients. Its main active components are flavonoids, including liquiritigenin, liquiritin and licochalcone A. The hairy roots (HRs) induced by Agrobacterium rhizogenes are a commonly used chassis in synthetic biology to enhance the production of active compounds in medicinal plants. Methods: A biosynthesis system to acquire the active ingredients of G. glabra was established using an HR culture system. It employed a transcriptome analysis to identify the change in gene expression following treatment with methyl jasmonate (MeJA). Results: After 28 days of suspension culture, the biomass of HRs increased by approximately 34.5-fold and reached 1.83 g/100 mL flask. Treatment with MeJA significantly increased the contents of liquiritigenin, liquiritin, and glabridin in the HRs. The transcriptome data indicated that MeJA activated the flavonoid biosynthetic pathway genes in the HRs, which was largely consistent with the qRT-PCR results. Furthermore, the overexpression of the GgCHS6 gene substantially increased the content of flavonoids in HRs. Conclusions: Collectively, this study established an HR system to biosynthesize the active ingredients of G. glabra using metabolic engineering and genetic engineering techniques and provides several valuable candidate genes for further functional study. Full article

The yield and quality have long been constraining factors for the sustainable cultivation of Glycyrrhiza uralensis. This study evaluated the effects of foliar applications of forchlorfenuron (CPPU) at different concentrations (0, 5, 10, 20, and 40 mg·L⁻¹) on plant growth and secondary metabolism through comprehensive analyses of photosynthesis, endogenous phytohormones, root biomass, and medicinal components. To ensure consumer safety, CPPU residue dynamics and associated health risks were also assessed. The 10 mg·L⁻¹ treatment yielded the most pronounced improvements, increasing root biomass by 46%, glycyrrhizic acid content by 92%, and liquiritin content by 98.7%. It also enhanced the activity of ribulose-1,5-bisphosphate carboxylase, thereby improving overall photosynthetic gas exchange capacity, and significantly stimulated the synthesis of zeatin, abscisic acid, and salicylic acid. Residue analysis showed that by the 56th day after treatment, the CPPU level in roots was merely 5.44 × 10⁻⁴ mg·kg⁻¹, with a half-life of 11.74 days. The resulting risk quotient (RQ) was below 0.01%, well under the safety threshold of 1, indicating negligible health risk to consumers. Our results demonstrate that the targeted application of CPPU offers a highly effective and safe strategy for enhancing both the productivity and commercial quality of G. uralensis. Full article

Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder that has become a prominent public health problem worldwide. As a traditional Chinese medicine formula, the ErChen decoction (ECD) possesses significant effects on metabolic syndrome. Methods: To determine whether ECD can relieve lipid accumulation and insulin resistance (IR) in liver cells, NAFLD and IR cell models were established by treating HepG2 cells with free fatty acids and an overdose of insulin, respectively. Bioinformatics and experimental evidence demonstrated that ECD could ameliorate NAFLD by modulating multiple pathways. The optimal combination of the key compounds in ECD was identified by the orthogonal experiment. Results: For lipid homeostasis, ECD suppressed de novo lipogenesis and reduced the cholesterol level by activating the AMPK signaling pathway. Concurrently, ECD enhanced hepatic β-oxidation by inducing PPARα-mediated upregulation of ACOX-1 and CPT-1α. ECD also resolved hepatic insulin resistance by activating the IRS1-Akt-FoxO1 pathway. The combined treatment with 100 μM liquiritin (LQ), 200 μM glycyrrhizic acid (GA) and 200 μM hesperidin (HEN) exhibited the best effect in reducing TG content in NAFLD model cells. Conclusions: ECD exhibited superior activities in activating the AMPK signaling pathway compared to the optimal compound combination. The comparison between the ECD and its key compounds demonstrated the superior synergistic effects of the herbs in ECD. Full article

Objective: This study systematically evaluated the nutritional compositions and bioactive compounds of six unconventional feed resources (Pepper residue (PR), Grape marc (MC), Pepper straw (PS), Lycium barbarum branches and leaves (LBBL), Licorice straw (LS), and Cyperus esculentus leaves (CES)). It also assessed the rumen degradability and rumen fermentation characteristics at different substitution levels through in vitro and in situ methods, to explore their potential application in sheep diets. Methods: Samples were analyzed considering nutrient composition, amino acids, polyunsaturated fatty acids (PUFAs), and bioactive compounds. In situ degradation was measured using rumen-fistulated sheep, and in vitro batch fermentation culture was conducted at varying substitution levels (0–100%) to measure gas production, pH, VFAs, NH₃-N, and microbial crude protein (MCP). Results: The six unconventional feed resources showed significant differences in nutrient composition, bioactive compounds, and fermentation performance. Crude protein (CP) ranged from 4.45% to 15.76%, with LS highest in total amino acids. LBBL contained 4.24 g/kg Lycium barbarum polysaccharides, LS had 9.24 g/kg liquiritin, GM was richest in proanthocyanidins, and PS had more capsaicin than PR. PR exhibited the highest DM degradation (74.77%, p < 0.001), followed by LS; CEL was lowest. PR and LS also had the highest CP degradation. In vitro fermentation revealed significant differences in fermentation characteristics among the six feeds. At 100% replacement, PR and LS exhibited high cumulative gas production, elevated MCP concentrations, and total VFAs of 54.41 and 64.02 mmol/L (p < 0.001), respectively. At 25% replacement, GM and CEL achieved high concentrations of VFAs and maintained MCP levels of 27.84 and 31.57 mg/dL (p < 0.001). PS reached its maximum total VFAs and MCP at 50% replacement, while LBBL reached 64.90 mmol/L total VFAs and 32.63 mg/dL MCP at 75% replacement. Conclusions: Nutrient composition and degradation kinetics varied significantly among substrates. PR had the highest DM degradability, while CEL had the lowest. PR and LS maintained stable fermentation at 100% substitution. GM and CEL were most effective at 25%; PS at 50%; and LBBL at 75% substitution levels. Full article

The human airway surface is covered by a mucus layer composed primarily of the mucins MUC5AC and MUC5B. Excessive mucin production and secretion by airway epithelial cells in patients with asthma result in airway obstruction and worsened asthma symptoms. This study investigated the effects of liquiritin, a widely used flavonoid, on intracellular and secreted MUC5AC and MUC5B levels in the NCI-H292 human airway epithelial cell line. Liquiritin treatment suppressed both mucin types in a dose-dependent manner, accompanied by decreased activity of extracellular signal-regulated kinase (ERK) and p38. The effect of liquiritin was further examined in cells stimulated with phorbol 12-myristate 13-acetate (PMA) to induce excessive mucin production and secretion. Liquiritin dose-dependently reduced PMA-induced increases in intracellular and secreted MUC5AC and MUC5B levels as well as PMA-induced ERK and p38 activity. Overall, these results suggest that liquiritin reduces intracellular and secreted MUC5AC and MUC5B levels by suppressing the ERK and/or p38 signaling pathway. Full article

Glycyrrhiza uralensis (G. uralensis), a leguminous plant, is an important medicinal and economic plant in saline–alkaline soils of arid regions in China. Its main bioactive components include liquiritin, glycyrrhizic acid, and flavonoids, which play significant roles in maintaining human health and preventing and adjuvantly treating related diseases. However, the cultivation of G. uralensis is easily restricted by adverse soil conditions in these regions, characterized by high salinity, high alkalinity, and nutrient deficiency. This study investigated the impacts of four multistrain microbial inoculants (Pa, Pb, Pc, Pd) on the growth performance and bioactive compound accumulation of G. uralensis in moderately saline–sodic soil. The aim was to screen the most beneficial inoculant from these strains, which were isolated from the rhizosphere of plants in moderately saline–alkaline soils of the Hexi Corridor and possess native advantages with excellent adaptability to arid environments. The results showed that inoculant Pc, comprising Pseudomonas silesiensis, Arthrobacter sp. GCG3, and Rhizobium sp. DG1, exhibited superior performance: it induced a 0.86-unit reduction in lateral root number relative to the control, while promoting significant increases in single-plant dry weight (101.70%), single-plant liquiritin (177.93%), single-plant glycyrrhizic acid (106.10%), and single-plant total flavonoids (107.64%). Application of the composite microbial inoculant Pc induced no significant changes in the pH and soluble salt content of G. uralensis rhizospheric soils. However, it promoted root utilization of soil organic matter and nitrate, while significantly increasing the contents of available potassium and available phosphorus in the rhizosphere. High-throughput sequencing revealed that Pc reorganized the rhizospheric microbial communities of G. uralensis, inducing pronounced shifts in the relative abundances of rhizospheric bacteria and fungi, leading to significant enrichment of target bacterial genera (Arthrobacter, Pseudomonas, Rhizobium), concomitant suppression of pathogenic fungi, and proliferation of beneficial fungi (Mortierella, Cladosporium). Correlation analyses showed that these microbial shifts were linked to improved plant nutrition and secondary metabolite biosynthesis. This study highlights Pc as a sustainable strategy to enhance G. uralensis yield and medicinal quality in saline–alkali ecosystems by mediating microbe–plant–nutrient interactions. Full article

Drought stress significantly hinders the cultivation of medicinal plants such as licorice (Glycyrrhiza uralensis), valued for its bioactive compounds, glycyrrhizin, and liquiritin. This study aims to investigate how co-inoculation with arbuscular mycorrhizal fungus Rhizophagus irregularis and Trichoderma harzianum can enhance licorice drought tolerance and secondary metabolite production, providing insights for sustainable agriculture in arid regions. The results demonstrate that inoculation with R. irregularis significantly improved biomass, drought stress tolerance, and increased glycyrrhizin and liquiritin concentrations by 29.9% and 3.3-fold, respectively, particularly under drought conditions. Co-inoculation with T. harzianum further boosted glycyrrhizin yield by 93.7%, indicating a synergistic relationship between the two microbes. The expression of key biosynthetic genes, including squalene synthase (SQS1) for glycyrrhizin and chalcone synthase (CHS) for liquiritin, was significantly upregulated, enhancing water use efficiency and the biosynthesis of secondary metabolites. Nutrient analysis showed improved phosphorus uptake, alongside reduced root carbon and nitrogen concentrations, leading to greater nutrient utilization efficiency. These findings suggest that co-inoculating R. irregularis and T. harzianum is a promising approach to improving licorice growth and medicinal quality under drought stress, with broad applications for sustainable crop management. Full article

Glycyrrhiza uralensis Fisch. is considered one of the most economically important medicinal plants worldwide. However, the quality of cultivated G. uralensis has not been adequate to meet the market demand. As one of the most important factors for plant growth, light influences the production and accumulation of metabolites in plants. However, the effect of light on the development and accumulation of components of G. uralensis is unclear. In this study, we found that red light and 4R1B (red/blue = 4:1) could promote the growth of licorice, such as the plant height, diameter of the reed head, and biomass accumulation, while blue light inhibited indicators of reed head diameter, biomass accumulation, etc. The impact of the light system is reflected in blue light significantly suppressing the photosynthetic rate and stomatal conductance, while red light and mixed light had the opposite effects. The red group had the lowest superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, which suggested the production and scavenging of O₂ was balanced in red light. Additionally, the red group had the highest content of soluble sugars and soluble proteins. We combined metabolomic and transcriptomic analysis and found that the gene expression in the treatment groups was up-regulated in the liquiritin synthesis pathway, and the liquiritin content of the 4R1B group and R group was significantly increased by 275% and 191% that of the CK group. Moreover, 4R1B significantly promoted the accumulation of glycyrrhizic acid (94% higher than in the CK group) and the expression of genes in the glycyrrhizic acid synthesis pathway. In addition, the light treatments affected seven phytohormone pathways (abscisic acid, brassinosteroid, salicylic acid, auxin, gibberellin, cytokinin, and jasmonic acid) in G. uralensis, which was related to cell elongation, stem elongation, stress resistance, and other aspects. In general, we analyzed the response mechanism of G. uralensis to red and blue light at the physiological, medicinal component, and molecular levels. The results will provide a new perspective for studying the regulatory effect of light quality on the growth and medicinal components of G. uralensis. Full article

Licorice roots are a rich source of bioactive compounds with multiple biological activities. The objective of this study was to evaluate the inhibitory effects of licorice root extract against a range of Listeria strains. In addition, the correlation of its phytochemical composition with antimicrobial properties was also investigated. Thus, the bacteriostatic and bactericidal effects of licorice root extract on seven Listeria monocytogenes strains, L. grayi, L. seeligeri, and L. ivanovii were determined. The minimum inhibitory and bactericidal concentrations ranged from 31.3 to 62.5 µg mL⁻¹ and from 62.5 to 250 µg mL⁻¹, respectively. The phytochemical composition of the extract was also analyzed using advanced LC-DAD- qTOF-MS; it is composed of fifty-one compounds belonging to different subgroups of flavonoids and triterpenoids. Subsequently, the anti-Listeria potency of the most abundant phytochemicals was determined using the AntiBac-Pred web tool. In silico calculation showed that liquiritin-apioside and licorice glycoside C1/C2 were strong growth inhibitors of L. monocytogenes, as their potency was comparable to well-known antibiotic substances. Overall, the present study demonstrates the potent antimicrobial effect of licorice root extract and reveals its active phytochemicals. Full article