Search Results (127)

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

This study integrated non-targeted metabolomics and transcriptomics to investigate dynamic changes in Antheraea pernyi pupae across five developmental stages. Metabolomic analysis identified 1246 metabolites, primarily organic acids, lipids, heterocyclic compounds, and oxygen-containing organics. Principal component analysis revealed stage-specific metabolic profiles: amino acid derivatives (pyruvate, proline, lysine) declined, while pyrimidines (cytidine, uridine, β-alanine) and monosaccharides (glucose, mannose) increased. 18β-glycyrrhetinic and ursolic acids accumulated significantly in the middle and late stages. Transcriptomic analysis identified 7230 differentially expressed genes (DEGs), with 366, 1705, and 5159 significantly differentially expressed genes in the T1, T3, and T5 comparison groups, respectively. KEGG enrichment highlighted ABC transporters, amino acid/pyrimidine metabolism, and tyrosine pathways as developmentally critical, with aminoacyl-tRNA biosynthesis upregulated in later phases. Integrated multi-omics analysis revealed coordinated shifts in metabolites and genes across developmental phases, reflecting dynamic nutrient remodeling during pupal maturation. This study systematically delineates the molecular transitions driving pupal development in Antheraea pernyi pupae, uncovering conserved pathway interactions and mechanistic insights into nutrient metabolism. These findings provide a scientific foundation for leveraging pupal resources in functional food innovation and bioactive compound discovery for pharmaceutical applications. Full article

Melanoma is one of the most aggressive forms of skin cancer, characterized by high metastatic potential and resistance to conventional therapies. Natural compounds, particularly terpenoids, have gained attention for their chemopreventive potential and anticancer properties. These plant-derived compounds exhibit diverse biological activities, e.g., cell viability and proliferation inhibition, apoptosis induction, cell cycle regulation, and immune system modulation. The review evaluates the current state of the art on the chemopreventive and anticancer activity of lupane- (betulinic acid), oleanane- (oleanolic acid, β-amyrin, escin, hederagenin, glycyrrhetinic acid), and ursane-type (ursolic acid, asiatic acid, madecassic acid, α-amyrin) triterpenoids in melanoma, highlighting their mechanisms of action, therapeutic potential, and challenges in clinical application. Full article

Background: Bai Hu Tang (BHT) is a classic antipyretic in traditional Chinese medicine, however, there is little scientific evidence on the mechanism and material basis of its antipyretic effect. Methods: In LPS-induced febrile rats, after administration of BHT at 42 g/kg for half an hour, body temperature was measured at hourly intervals for 9 consecutive hours. Then, serum levels of TNF-α, IL-1β, and IL-6, and serum and cerebrospinal fluid (CSF) levels of AVP, cAMP, PGE2, Ca and CRH, and the remaining sera were used for metabolomics. These were then combined with network pharmacology methodology to further analyse the antipyretic effect of BHT and then dock key targets with differential components. Results: Administration of BHT to LPS-induced febrile rats significantly reduced elevated body temperature, TNF-α, IL-1β and IL-6 levels, but serum and CSF levels of AVP, cAMP, PGE2, Ca²⁺ and CRH were significantly elevated compared to the control group. Network pharmacological analyses indicated that the putative functional targets of BHT were regulation of immune responses, associated protein binding and inflammatory responses, and fine-tuning of phosphatase binding and activation of signalling pathways such as MAPK, PI3K, AKT, NF-kB, cAMP and inflammatory pathways. Metabolomic analysis showed that the antipyretic effect of BHT and its mechanism are likely to be involved in fatty acid metabolism, bile acid metabolism and amino acid metabolism in the organism, with L-arginine, glycyrrhetinic acid and N-acetylpentraxine as the main differential metabolites that play a significant role in heat recovery. The results also showed better docking of glycyrrhetinic acid with TNF-α, IL-6R, PTGS2. Conclusions: BHT provides a valuable adjunct to traditional clinical antipyretics by improving body temperature and metabolism and reducing inflammation. Full article

Background: Oral administration remains the most common route for drug absorption. Emerging evidence highlights the important role of gut microbiome in the pharmacokinetics of oral medications. Glycyrrhizic acid (GL), a widely used hepatoprotective drug, is orally administrated and subsequently biotransformed by the gut microbiota into its active metabolite, glycyrrhetinic acid (GA), which exerts a therapeutic effect. However, it remains unclear whether the disturbance of the gut microbiome directly impacts the metabolism of GL. Methods: Antibiotic cocktail and probiotic Lacticaseibacillus rhamnosus R0011 were applied as two interventions targeting the gut microbiome. Pharmacokinetic parameters were evaluated by LC-MS, and 16S rRNA sequencing was applied to analyze the gut microbiome composition. The transcriptome analysis of Caco-2 cells was used to elucidate the regulation mechanism of polar metabolites resulting from gut microbiome perturbation. Results: R0011 supplementation could significantly increase the Area Under Curve (AUC) value of GA, which was positively correlated with the change in gut microbiome composition. In contrast, the plasma levels of GA were nearly undetectable following antibiotic intervention. Furthermore, the relative expressions of transporter multidrug resistance gene 1 (MDR1) in the ileum were site specifically downregulated under the probiotic intervention. The polar gut microbial metabolites may play a crucial role in differentiated regulating MDR1 expression, likely through the modulation of transcription factors FoxO1 and TP53. Conclusions: Our research provides new insights into the regulatory mechanism by which the gut microbiome affects the bioabsorption of orally administrated drugs, potentially offering strategies to optimize drug bioavailability and improve clinical efficacy. Full article

Background: Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods: A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w/w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results: The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug (p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls (p < 0.001), leading to 58.7% tumor volume reduction (p < 0.001). Conclusions: The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy. Full article

Background: Photodynamic therapy (PDT) has evolved as a reliable therapeutic modality for cancer. However, the broad application of the technique is still limited because of poor bioavailability and the non-selective distribution of photosensitizers within host tissues. Herein, zein, a natural corn protein, was functionalized with glycyrrhetinic acid (GA) and polyethylene glycol (Z-PEG-GA) as a targeting platform for liver cancer cells. Parietin, as novel photosensitizer, was successfully encapsulated into zein via nanoprecipitation and used for the therapy of hepatocellular carcinoma. Methods: The in vitro phototoxicity of Z-PEG-GA nanoparticles and their non-functionalized control (Z-PEG) were assessed against hepatocellular carcinoma (HepG2 cells) and the In vivo biodistribution was determined in an adult male CD-1 Swiss albino mice model. Results: The formulated Z-PEG and Z-PEG-GA showed spherical shapes with average sizes of 82.8 and 94.7 nm for unloaded nanoparticles, respectively, and 109.7 and 111.5 nm for loaded nanoparticles carrying more than 70% of parietin, and Quantum yield measurements show that parietin’s photodynamic potential is conserved. Moreover, parietin-loaded Z-PEG-GA exhibited three-fold higher toxicity against liver cancer cells than its non-functionalized control and attained more than an eleven-fold enhancement in the generated intracellular reactive oxygen species (ROS) at a 9 J/cm² radiant exposure. The generated intracellular ROS led to mitochondrial disruption and the release of cytochrome c. In vivo biodistribution studies revealed that fluorescence signals of Z-PEG-GA can persist in the excised animal liver for up to 24 h post-administration. Conclusions: Consequently, tailored zein can hold great potential for delivering several hydrophobic photosensitizers in anticancer PDT. Full article

Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis canadensis, Lobelia inflata, Scutellaria baicalensis, and Zingiber officinale. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from Echinacea, Glycyrrhiza, and Codonopsis, identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements. Full article

Biomimetic nanoassemblies derived from natural products are considered promising nanomaterials due to their self-assembling ability and their favorable interactions with biological molecules leading to their numerous applications as therapeutic agents or as molecular probes. In this work, we have created peptide nanoconjugates of two natural products, β-Boswellic acid (BA) and β-glycyrrhetinic acid (GH). Both BA and GH are known for their medicinal value, including their role as strong antioxidants, anti-inflammatory, neuroprotective and as anti-tumor agents. To enhance the bioavailability of these molecules, they were functionalized with three short peptides (YYIVS, MPDAHL and GSGGL) to create six conjugates with amphiphilic structures capable of facile self-assembly. The peptides were also derived from natural sources and have been known to display antioxidant activity. Depending upon the conjugate, nanofibers, nanovesicles or a mixture of both were formed upon self-assembly. The binding interactions of the nanoconjugates with α-Synuclein, a protein implicated in Parkinson’s disease (PD) was examined through in silico studies and FTIR, circular dichroism and imaging studies. Our results indicated that the nanoassemblies interacted with alpha-synuclein fibrils efficaciously. Furthermore, the nanoassemblies were found to demonstrate high viability in the presence of microglial cells, and were found to enhance the uptake and interactions of α-Synuclein with microglial cells. The nanoconjugates designed in this work may be potentially utilized as vectors for peptide-based drug delivery or for other therapeutic applications. Full article

Background/Objectives: Following tooth extraction, resveratrol (RSV) can support healing by reducing inflammation and microbial risks, though its poor solubility limits its effectiveness. This study aims to develop a solid nanocomposite by embedding RSV in lipid nanoparticles (mLNP) within a hydrophilic matrix, to the scope of improving local delivery and enhancing healing. Hydroxyapatite (HXA), often used as a bone substitute, was added to prevent post-extraction alveolus volume reduction. Methods: The mLNP-RSV dispersion was mixed with seven different polymers in various mLNP/polymer ratios. Following freeze-drying, the powders were redispersed, and the resulting dispersions were tested by DLS experiments. Then, the best two nanocomposites underwent extensive characterization by SEM, XRD, FTIR, Raman spectroscopy, and thermal analysis as well as in vitro partitioning studies aimed at verifying their ability to yield the mLNP-RSV from the hydrophilic matrix to a lipophilic tissue. The characterizations led to identify the best nanocomposite, which was further combined with HXA to obtain hybrid nanocomposites, further evaluated as pharmaceutical powders or in form of mini-tablets. Results: PEG-based nanocomposites emerged as optimal and, following HXA insertion, the resulting powders revealed adequate bulk properties, making them useful as a pharmaceutical intermediate to produce ≈59 mm³ mini-tablets, compliant with the post-extraction socket. Moreover, they were proven ex vivo to be able to promote RSV and GA accumulation into the buccal tissue over time. Conclusions: The here-proposed mini-tablet offers an innovative therapeutic approach for alveolar wound healing promotion as they led to a standardized dose administration, while being handy and stable in terms of physical solid identity as long as it takes to suture the wound. Full article

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action. Full article

Objective: To investigate the effects of licorice functional ingredient intake on blood pressure, explore its potential mechanisms of action, and provide safety information for personalized nutritional interventions in special populations and for the application of licorice-derived functional foods. Methods: PubMed, Cochrane Library, Medline, Embase, EBSCO, ScienceDirect, and Web of Science databases were searched from inception to 31 August 2024. Randomized controlled trials (RCTs) investigating the intake of licorice or its functional components were included. The range of continuous variables was assessed using the weighted mean difference (WMD) with 95% confidence intervals. Genes associated with hypertension were screened using an online database. Machine learning, receiver operating characteristic(ROC) curve analysis, molecular docking, and gene set enrichment analysis (GSEA) were employed to explore the potential mechanisms underlying licorice-induced blood pressure fluctuations. Results: Eight RCTs (541 participants) were included in the meta-analysis, which indicated interventions containing glycyrrhizic acid (GA) as the main component increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: WMD [95% CI] = 3.48 [2.74, 4.21], p < 0.001; DBP: WMD [95% CI] = 1.27 [0.76, 1.78], p < 0.001). However, interventions dominated by licorice flavonoids(LF) had no significant effect on SBP or DBP (SBP: WMD [95% CI] = 0.58 [−1.15, 2.31], p = 0.511; DBP: WMD [95% CI] = 0.17 [−1.53, 1.88], p = 0.843). Three machine learning algorithms identified five biomarkers associated with hypertension: calmodulin 3 (CALM3), cluster of differentiation 9 (CD9), growth factor independence 1B transcriptional repressor (GFI1B), myosin light chain kinase (MYLK), and Ras suppressor-1 (RSU1). After removing biomarkers with lower validity and reliability, GFI1B, MYLK, and RSU1 were selected for subsequent analysis. The network toxicology results suggested that GA and its metabolite glycyrrhetinic acid may act on GFI1B, MYLK, and RSU1, influencing blood pressure fluctuations by modulating nitrogen metabolism signaling pathways. Conclusions: There were distinct differences in the effects of licorice functional components on blood pressure. Functional constituents dominated by GA were shown to increase both SBP and DBP, whereas those dominated by LF did not exhibit significant effects on blood pressure. The hypertensive mechanism of GA may involve the modulation of GFI1B, MYLK, and RSU1 to regulate nitrogen metabolic pathways. Full article

Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the potential anti-proliferative effects of licorice and GA on PTC cell cultures. Licorice extract (LE) was produced from the root and tested on BCPAP and K1 cell lines, as well as GA and aldosterone. We used the MTT test to investigate the anti-proliferative activity, the wound healing test for the migratory activity, and finally, we analyzed cell cycle distribution, apoptosis, and oxidative stress after LE, GA, or aldosterone incubation. Both LE and GA reduced cell viability at 48 h and cell migration at 24 h in both PTC cultures. Aldosterone reduced cell migration only in K1 cells. LE and GA induced cell cycle arrest in the G0/G1 phase in the BCPAP cell line, while LE and aldosterone induced it in the K1 culture. GA but not LE increased the apoptosis rate in both cell lines, whereas LE but not GA increased oxidative stress in both cultures. This study presents the first evidence of the in vitro anti-proliferative and anti-migratory activity of LE and GA on PTC. Full article

The search for novel plant-based antioxidant and antibacterial medication has garnered a lot of attention lately. Glycyrrhiza glabra, known as licorice, is one of the most important medicinal plants. The primary component of Glycyrrhiza glabra is glycyrrhizin, which is biotransformed into 18α- and 18β-glycyrrhetinic acid for a variety of medicinal purposes. The goal of this study was to improve the bioavailability of glycyrrhizin by its biotransformation into glycyrrhetinic acid by Aspergillus niger. The biotransformation process was optimized using response surface methodology. A two-level Plackett–Burman design was employed to identify the factors that had a significant impact on the process of biotransformation. The three main variables were pH, glycerrhizin concentration, and incubation time. These three medium components were further optimized using a 3-level Box–Behnken design, and their optimum levels were pH of 8, an incubation period of 6 days, and a glycyrrhizin concentration of 1%. Using these optimum conditions, the maximum level obtained was 159% greater than in the screening experiment. Regarding the antimicrobial activity of glycyrrhizin extract, Bacillus subtilis emerged as the most sensitive organism with the lowest MIC (60 µg/mL) and the highest zone of inhibition (17 mm). The most resistant organism was Pseudomonas aeruginosa, which had the highest MIC (400 µg/mL) and the smallest zone of inhibition (10 mm). In the case of glycyrrhetinic acid, Bacillus subtilis was the most sensitive organism with the highest zone of inhibition (32 mm) and the lowest MIC (20 µg/mL). Pseudomonas aeruginosa was the most resistant organism, with the lowest zone of inhibition (18 mm), and the highest MIC (140 µg/mL). The antioxidant activity of glycyrrhizin extract increased from 12.81% at a concentration of 63 µg/100 µL to 41.41% at a concentration of 1000 µg/100 µL, while that of glycyrrhetinic acid extract increased from 35.5% at a concentration of 63 µg/100 µL to 76.85% at a concentration of 1000 µg/100 µL. The present study concluded that biotransformation of glycyrrhizin into glycyrrhetinic acid increased its bioavailability and antioxidant and antimicrobial activities. Glycyrrhizin and glycyrrhetinic acid might be used as a natural antimicrobial and antioxidant in pharmaceutical industries Full article

The seeds of Glycyrrhiza uralensis Fisch. used for cultivating are primarily sourced from wild populations. However, the types of habitats where wild G. uralensis grow are diverse. We studied the effects of salinity on the growth, antioxidant capacity, and photosynthetic physiology of two-month-old licorice seedlings from different habitats to evaluate their salt tolerance. With the increasing NaCl concentration, compared with non-salinized habitats, seedlings originating from seeds collected from salinized habitats showed milder inhibition in root biomass and root volume. Also, the crown diameter increased more significantly. Activities of superoxide dismutase, catalase, and peroxidase are higher. Correspondingly, the electrolyte leakage rate of the leaves is low. Their leaves had a higher photoprotection capacity and potential maximum photochemical efficiency of PSII. Net photosynthetic rate, transpiration rate, and stomatal conductance showed less inhibition under 4 and 6 g/kg NaCl treatment. The content of glycyrrhizic acid and glycyrrhetinic acid in their roots was significantly increased under 2 g/kg NaCl treatment and was significantly higher than that of seedlings from non-salinized habitats under the same NaCl treatment. In conclusion, seeds from salinized habitats show improved tolerance to salt stress at the seedling stage, which is attributed to their superior phenotypic adaptability, strong antioxidant, and especially high light protection ability. Full article