Search Results (54)

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

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

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

Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4′-O-glucoside (1), 3′,4′,7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3’[O], 4’-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4′-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4′-dihydroxy-2′-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18β-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra. Full article

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure–activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,β-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins. Full article

Glycyrrhetinic acid (GA) is a saponin compound, isolated from licorice (Glycyrrhiza glabra), which has been wildly explored for its intriguing pharmacological and medicinal effects. GA is a triterpenoid glycoside displaying an array of pharmacological and biological activities, including anti-inflammatory, anti-bacterial, antiviral and antioxidative properties. In this study, we investigated the underlying mechanisms of GA on acne vulgaris through network pharmacology and proteomics. After the intersection of the 154 drug targets and 581 disease targets, 37 therapeutic targets for GA against acne were obtained. A protein–protein interaction (PPI) network analysis highlighted TNF, IL1B, IL6, ESR1, PPARG, NFKB1, STAT3 and TLR4 as key targets of GA against acne, which is further verified by molecular docking. The experimental results showed that GA inhibited lipid synthesis in vitro and in vivo, improved the histopathological damage of skin, prevented mast cell infiltration and decreased the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6. This study indicates that GA may regulate multiple pathways to improve acne symptoms, and the beneficial effects of GA against acne vulgaris might be through the regulation of sebogenesis and inflammatory responses. Full article

Hybrid systems with antioxidant properties have been developed by integrating bioactive compounds derived from plant resources with layered double hydroxides (LDHs). Anion exchange has been used to substitute intercalated nitrate anions in Mg-Al LDH with carboxylate anions derived from trans-ferulic acid, rosmarinic acid, and 18β-glycyrrhetinic acid. These organic compounds are known for their powerful antioxidant, anti-inflammatory and antimicrobial properties and are highly suitable for cosmetics, biomedicine, and food packaging. To enhance sustainability, a multistage procedure has been developed with the aim of recovering unexchanged carboxylate anions from residual reaction water, ensuring an environmentally friendly and easily scalable preparation process. The process, adapted for each of the three molecules, allows the production of a consistently high-quality hybrid product containing an organic fraction ranging from 10 to 48% by weight, depending on the specific molecule used. The immobilization of organic compounds has occurred either within the layers of LDH through intercalation or on the external surface through adsorption. Good antioxidant capacity has been exhibited by these powdered hybrid systems, as assessed through both the DPPH and linoleic acid/β-carotene tests. Sustainable production practices are enabled by this innovative approach, which also opens avenues for the development of advanced materials for diverse applications across various industries. Full article

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using ¹H NMR, ¹³C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC₅₀ value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC₅₀ value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC₅₀ value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics. Full article

The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% w/w gellan gum and 0.5% w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC₅₀) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC₅₀ = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC₅₀ = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication. Full article

Klippel–Trenanauy syndrome (KTS) is a rare genetic disease determined by overexpression of the phosphatidylinositol-4-5-bisphosphate 3 kinase catalytic subunit (PIK3CA) gene. The clinical presentation is characterized by venous and capillary malformations and lymphatic malformation. To date, no definitive treatment has been suggested in order to improve the clinical symptoms related to the developments of a skin wound. In this case, we describe a young man with KTS that developed a severe skin wound in the lower right limb unresponsive to the common treatment but responsive to a treatment with oxygen-ozone therapy, pulsed magnetic fields (diamagnetic treatment), and topical fixed association of cocum caprylate, oleic acid, quercetin, and 18-β glycyrrhetinic acid. This is the first case that supports a multistep approach to treat a rare and severe disease, and we hope that other studies can support our data. Full article

Periprosthetic osteolysis (PPO) induced by wear particles is the most severe complication of total joint replacement; however, the mechanism behind PPO remains elusive. Previous studies have shown that osteocytes play important roles in wear-particle-induced osteolysis. In this study, we investigated the effects of connexin 43 (Cx43) on the regulation of osteocyte-to-osteoblast differentiation. We established an in vivo murine model of calvarial osteolysis induced by titanium (Ti) particles. The osteolysis characteristic and osteogenesis markers in the osteocyte-selective Cx43 (CKO)-deficient and wild-type (WT) mice were observed. The calvarial osteolysis induced by Ti particles was partially attenuated in CKO mice. The expression of β-catenin and osteogenesis markers increased significantly in CKO mice. In vitro, the osteocytic cell line MLO-Y4 was treated with Ti particles. The co-culturing of MLO-Y4 cells with MC3T3-E1 osteoblastic cells was used to observe the effects of Ti-treated osteocytes on osteoblast differentiation. When Cx43 of MLO-Y4 cells was silenced or overexpressed, β-catenin was detected. Additionally, co-immunoprecipitation detection of Cx43 and β-catenin binding in MLO-Y4 cells and MC3T3-E1 cells was performed. Finally, β-catenin expression in MC3T3-E1 cells and osteoblast differentiation were evaluated after 18α-glycyrrhetinic acid (18α-GA) was used to block the intercellular communication of Cx43 between MLO-Y4 and MC3T3-E1 cells. Ti particles increased Cx43 expression and decreased β-catenin expression in MLO-Y4 cells. The silencing of Cx43 increased the β-catenin expression, and the over-expression of Cx43 decreased the β-catenin expression. In the co-culture model, Ti treatment of MLO-Y4 cells inhibited the osteoblastic differentiation of MC3T3-E1 cells and Cx43 silencing in MLO-Y4 cells attenuated the inhibitory effects on osteoblastic differentiation. With Cx43 silencing in the MLO-Y4 cells, the MC3T3-E1 cells, co-cultured alongside MLO-Y4, displayed decreased Cx43 expression, increased β-catenin expression, activation of Runx2, and promotion of osteoblastic differentiation in vitro co-culture. Finally, Cx43 expression was found to be negatively correlated to the activity of the Wnt signaling pathway, mostly through the Cx43 binding of β-catenin from its translocation to the nucleus. The results of our study suggest that Ti particles increased Cx43 expression in osteocytes and that osteocytes may participate in the regulation of osteoblast function via the Cx43 during PPO. Full article