Ursolic Acid Research Articles

Gastric cancer (GC) is a common type of cancer known for its challenges in early detection and unfavorable prognosis. The pathway involving Wnt/β-catenin and the improper regulation of microRNAs (miRNAs), especially miR-27a-3p, are crucial in the advancement of GC. Ursolic acid (UA), which is a naturally occurring anticancer agent, shows promise in the inhibition of GC. Although UA’s anticancer effects have been recognized, the underlying molecular mechanisms in GC remain incompletely defined. Our findings indicate that UA strongly restricts the expansion, motility, and invasive behavior of GC cells by dampening activity within the Wnt/β-catenin cascade. Treatment with UA lowered miR-27a-3p expression, and blocking this miRNA further curtailed tumor cell aggressiveness by restoring DKK2, which functions as a suppressor of Wnt-driven signaling. The protein under investigation showed lower expression in advanced tumors. Its expression in these advanced tumors correlated with better pathologic outcomes and survival prognosis. Thus, we can categorize this protein as a novel tumor suppressor in GC. Consistent with these in vitro results, in vivo assays demonstrated that UA effectively curtailed tumor development. Taken together, these findings indicate that UA restricts GC progression via modulation of the miR-27a-3p/DKK2/Wnt/β-catenin axis, providing mechanistic insights for potential therapeutic strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03283-y.

Bladder and ovarian cancers impose a significant burden on healthcare systems due to their high incidence, mortality rates, and the challenges associated with early diagnosis. Current chemotherapy regimens, which typically involve combinations of drugs, often cause severe side effects that negatively impact patient adherence and treatment efficacy. Recently, studies have explored the use of herbal medicines to mitigate the adverse effects of chemotherapy. One such herbal compound is ursolic acid (UA), a triterpene known for its anti-inflammatory, antioxidant, and antitumor properties. This study aimed to evaluate the effects of UA on bladder and ovarian cancer cells harboring TP53 mutations through various assays, including cytotoxicity, clonogenic survival, cell migration, morphological changes, apoptosis, cell cycle analysis, JHDM1D expression and selectivity using MRC-5 cells, along with in silico evaluation. The treatment demonstrated selectivity for tumoral cells and significant antiproliferative effects in both cell types, leading to decreased cell viability, reduced colony-forming ability, inhibited cell migration, morphological changes characteristic of cell death, and increased expression of JHDM1D. In conclusion, UA exhibited antiproliferative activity against bladder and ovarian cancer cell lines with different TP53 mutation sites, suggesting its potential as a promising therapeutic alternative. Moreover, our study demonstrated for the first time the presence of UA in the species F. formosa.

Oxidosqualene cyclases and cytochrome P450s involved in the biosynthesis of diverse triterpenes in Centipeda minima.

SARS-CoV-2 remains a critical global health concern due to its high transmissibility, evolving variants, and the absence of a universally effective treatment. Phytocompounds, known for their antiviral, anti-inflammatory, and immunomodulatory properties, continue to be explored as potential therapeutic agents. This study evaluated 20 phytocompounds and four approved antiviral drugs, Remdesivir, Favipiravir, Hydroxychloroquine, and Ivermectin, against nine SARS-CoV-2 spike glycoprotein structures, including five wild-type and four variants (Alpha, Beta, Delta, and Omicron). Molecular docking using two software platforms identified ursolic acid, betulinic acid, β-sitosterol, and ivermectin as top candidates, with binding affinities ranging from − 6.7 to − 9.6 kcal/mol. These compounds also displayed favorable pharmacokinetic properties and druggability. 100 ns molecular dynamics simulations were performed on the highest-affinity complexes to assess stability. Betulinic acid and β-sitosterol demonstrated stable binding interactions, with low RMSD values (~ 0.2–0.3 nm) and consistent hydrogen bonding (1–3 bonds), suggesting structural stability. In contrast, ursolic acid and ivermectin showed unstable binding and higher structural fluctuations during simulation. Overall, the study highlights betulinic acid and β-sitosterol as presumptive SARS-CoV-2 inhibitors, warranting further experimental validation through in vitro and in vivo studies to confirm their therapeutic potential.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-25242-7.

Vector-borne diseases cause 700,000 deaths annually. Aedes aegypti (Stegomyia) is a transmitter of infections such as dengue, which results in 96 million symptomatic cases and 40 000 deaths per year. According to the INS, in March 2025 a total of 47 559 dengue cases were reported. This issue carries both health and economic implications due to this vector; therefore, plant extracts offer potential as pesticides and repellents. Accordingly, this study aimed to evaluate the structure–activity relationship of compounds present in Alstonia scholaris (Ditta) leaves with larvicidal activity. Ditta leaves were processed following the guidelines of Quality Control Methods for Medicinal Plant Materials. Chemical groups were identified through qualitative and quantitative tests using UHPLC-ESI+-OrbitrapHRMS. Subsequently, computational predictions and bioassays were performed on Ae. aegypti larvae and Artemia salina nauplii exposed to different concentrations and controls, where mortality and LC50 were evaluated. A molecular docking analysis was carried out between the identified phenolic compounds and biological targets related to the vector’s life cycle; binding energies and interactions were recorded in each simulation. The leaves of A. scholaris met the established criteria for the species. The extract revealed the presence of alkaloids, tannins, saponins, flavonoids, phenols, leucoanthocyanidins, sterols, and terpenes, consistent with the literature reports. The polyphenolic compounds identified were ursolic acid (71.3 mg/kg) and rosmarinic acid (5.7 mg/kg), both possessing pharmacokinetic properties that would allow them to exert biological effects. They are non-toxic to humans, although rosmarinic acid is more toxic in other species. Molecular docking showed binding energies from –5.50 kcal/mol to –6.08 kcal/mol for rosmarinic acid and from –8.01 kcal/mol to –11.64 kcal/mol for ursolic acid, indicating favorable ligand–target interactions. In vivo assays yielded LD50 values of 733.612 mg/L for Aedes aegypti and 403.82 µg/L for Artemia salina, consistent with predictive models. Alstonia scholaris demonstrated activity against Ae. aegypti (Stegomyia); however, its toxic potential should continue to be explored through the combination of in silico and in vivo approaches. Furthermore, this study highlights the importance of pharmacognostic research to ensure quality, identity, and purity of plant species.

Background Chronic bronchitis (CB) is a common yet heterogeneous condition characterized by persistent inflammation, oxidative stress, airway hyperresponsiveness, and mucus hypersecretion. As an early stage of various severe pulmonary diseases, current therapeutic strategies remain unsatisfactory. Substantial evidence indicates that medicinal plants and compounds hold potential for treating inflammatory lung disorders. This study aims to consolidate recent and reliable evidence concerning the multi-targeted roles and underlying molecular mechanisms of these natural products in the treatment of CB. Methods This systematic review followed a prospectively registered protocol (PROSPERO ID: CRD42024588912). A comprehensive literature search encompassed multiple electronic databases, including PubMed, Scopus, Embase, Web of Science, VIP, Wan-fang, SinoMed, and the China National Knowledge Infrastructure Study selection strictly adhered to the PICOS principles to systematically identify medicinal plants and compounds with therapeutic potential against Chronic bronchitis. Results The results identified 13 medicinal plants and 19 compounds that exhibited anti-inflammatory activity. Additionally, 8 plants and 12 compounds demonstrated further therapeutic effects, including antioxidant, anti-mucus, and potential bronchodilatory activities. The underlying mechanisms primarily involved the NF-κB, PI3K/AKT/mTOR, TLR4, MAPK, and Nrf2 pathways. Ursolic acid emerged as the most promising clinical candidate. Conclusion This review represents the first comprehensive synthesis of experimentally verified efficacy and mechanisms associated with medicinal plants and compounds in CB treatment. Preclinical animal studies have confirmed the therapeutic benefits of these natural agents in alleviating CB symptoms, establishing a solid foundation for novel drug development and underscoring their considerable translational potential.

Alpine rhododendron has high ornamental value because of its vibrant color. However, growing them in urban landscapes is challenging, as high temperatures can slow the growth of Rhododendron roots and cause leaf burning. At present, the metabolic pathways involved in the response of Rhododendron to heat stress are still poorly understood. Rhododendron moulmainense has all the characteristics of alpine Rhododendron; however, its heat tolerance is relatively strong. Here, we report the systematic response of R. moulmainense to high-temperature stress. Combined analysis of the transcriptome and metabolome revealed that under high-temperature stress, the tryptophan and terpenoid metabolic pathways were significantly activated in the leaves and roots of R. moulmainense. Additionally, the levels of the triterpenoid compound oleanolic acid and its isomer ursolic acid, which have antioxidant effects, were significantly increased under high-temperature stress conditions. Moreover, the levels of these compounds were significantly increased in the roots of R. moulmainense with good growth. Furthermore, exogenous oleanolic acid application experiments verified that oleanolic acid can significantly increase the heat tolerance of R. moulmainense. In addition, a combination of trend analysis and cis-acting element analysis revealed that MYB transcription factors may be key regulatory factors involved in regulating the synthesis of oleanolic acid and the response to high-temperature stress. Integrated transcriptomic and metabolomic analyses revealed that high-temperature stress activates tryptophan and terpenoid metabolism in R. moulmainense. Notably, oleanolic acid plays an important role in regulating environmental adaptability, and MYB might a key regulator of oleanolic acid biosynthesis under heat stress. These findings provide valuable insights into the molecular basis of thermotolerance in alpine rhododendrons and offer potential targets for domestication and breeding of heat-resilient cultivars.

This study aimed to evaluate the skin-beneficial properties of the ethanol extract from S. medusula, a tree native to Central America. The leaves of this species were collected in the Colombian Chocó region, where the plant is traditionally used to treat intestinal disorders. The extract was characterized using phytochemical screening and UV-Visible spectrophotometry, followed by precise identification and quantification of 22 phytocompounds through UHPLC-ESI ± Orbitrap-HRMS analysis. Notably, high concentrations of Catechin (3,127.8 mg/Kg), Quercetin (57.4 mg/Kg), Ursolic acid (31.4 mg/Kg), and p-Coumaric acid (23.0 mg/Kg) were identified, compounds well-known for their antioxidant properties and anti-aging. The FRAP, H-ORAC, and DPPH assays demonstrated a strong reducing power and effective free radical scavenging capacity of the extract, demonstrating protective effects against oxidative stress. Enzymatic inhibition assays evaluated at 0.250 mg/mL demonstrated significant elastase inhibition (98.86%) and moderate tyrosinase inhibition (80.79%), indicating potential anti-aging and skin-lightening effects. Cytotoxicity assessment on HaCaT cells revealed no toxic effects at high concentrations of the extract, while low doses (2.9 µg/mL) promoted cell proliferation, suggesting potential regenerative properties. These findings highlight S. medusula extract as a promising candidate for natural cosmeceutical applications aimed at cellular protection, skin regeneration, and mitigation of aging and hyperpigmentation.

In China, Pyracantha fortuneana has been consumed as a nutritious plant to improve indigestion. In the current study, the main chemical composition of P. fortuneana fruits was extracted and analysed for composition. Free fatty acids (FFA)-induced normal human hepatic L02 cells were used to construct a high-fat cell model, and lipid deposition in Caenorhabditis elegans was induced by a high concentration of glucose to study the anti-hyperlipidemic effects of the main components. The results showed that the flavonoid content of PFF (P. fortuneana Flavonoid Fractions) was 80.28%, and it contained various flavonoids such as epicatechin, isoquercetin, rutin, quercetin, and myricitrin, while the saponin content of PFS (P. fortuneana Saponin Fractions) was 74.4%, and it contained saponins such as shionone, crategolic acid, and ursolic acid. PFF and PFS significantly reduced the content of lipid droplets in high-fat L02 cells, inhibited mitochondrial membrane potential decline, regulated the fat accumulation by up-regulating the relative mRNA expression levels in the Nrf2/ARE signaling pathway, as well as the CPT-1 and SIRT1 genes in lipid metabolism. Meanwhile, both PFF and PFS significantly reduced lipid deposition, reactive oxygen species (ROS) levels, malondialdehyde (MDA) content, and catalase activity in C. elegans. In summary, our results indicated that the flavonoids and saponins of P. fortuneana are potential natural products in antihyperlipidemic effect.

According to the World Health Organization, cancer is still the leading cause of death for humans worldwide. Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these drugs. The use of complementary and alternative medicinal products from plants has continued to increase in past decades, due to fewer side effects of bioactive compounds from medicinal plants of which pentacyclic triterpenoids have been identified as one class of secondary metabolites that could play an important role in the treatment and management of a number of non-communicable diseases. The main aim of this study is to extract, isolate, identify, and elucidate pentacyclic triterpenoid (ursolic acid, UA (1), and oleanolic acid, OA (2)) from Mimusops caffra. Semi-synthesis of UA was carried out to obtain some triterpenoid derivatives (3-O-acetyl ursolic acid, AUA (3), ursolic-28-methylate, UM (4), and 3-acetylursolic-methylate, AUM (5)), and we evaluated these compounds as anti-cancer therapeutic agents. Isolation of ursolic acid (UA) (1) from M. caffra is always accompanied by its isomer oleanolic acid (OA) (2) due to their similar retention factors (Rf) values. Acetylation and deacetylation techniques were used to isolate compounds 1 and 2. In vitro cytotoxicity activities of UA, AUA UM, and AUM were evaluated against various cancer cell lines, such as human breast adenocarcinoma cancer cell lines (MDA), human liver cancer cell lines (HepG2), human prostate cancer cell lines (PC3) and non-cancerous human fibroblast cell lines (KMST-6) using MTT assays. The UM exhibited remarkable cytotoxic activities against cancer cells, while little or no activities were observed on non-cancerous cell lines, which indicates that the addition of methyl at C-28 of UA is essential to enhance its activity as a therapeutic agent for cancer. The AUA showed moderate or no cytotoxicity against the different cancer cell lines, which is less than that of the UA parent compound. Moreover, these results suggest that ursolic acid and UA derivatives are potential therapeutic drugs for human breast, liver, and prostate cancers.

Abstract In this work, all extracts of Euphorbia tithymaloides growing in Vietnam, including petroleum ether (PE), ethyl acetate (EA), methanol (Me), and aqueous (W), were evaluated for their intracellular ROS scavenging capacity. The W extract was revealed to be the most effective in ROS scavenging (S = 54.99 ± 1.66% at 200 µg mL−1). The extracts were also analyzed for their volatile and non‐thermostable contents via gas chromatography‐mass spectrometry with a headspace (H‐GC‐MS) method, the results of which were characteristic properties in their composition. From the PE extract, three compounds were isolated (methyl gallate (1), 3,3′,4′‐tri‐O‐methylellagic acid (2), and α‐tocopheryl acetate (3)), while fifteen compounds were obtained from the EA one, including p‐anisidine (4), vanillin (5), gallic acid (6), resveratrol (7), rhapontigenin (8), scopoletin (9), scoparone (10), novobiocin (11), epigallocatechin‐3‐O‐gallate (12), ursolic acid (13), oleanolic acid (14), 18β‐glycyrrhetic acid (15), β‐sitosterol (16), diosgenin (17), and pennogenin (18). Their structure was elucidated using nuclear magnetic resonance spectroscopy and high‐resolution electrospray ionization mass spectrometry. The isolation of novobiocin enriches the coumarin profile of E. tithymaloides. Some isolated compounds were taken to the cytotoxicity against normal and cancer cells, α‐glucosidase inhibitory activity, and intracellular ROS scavenging capacity. With such achievements, the phytochemical profile of E. tithymaloides has been widened significantly, and its medicinal potential has been evidently reinforced.

Osteoarthritis (OA) is increasingly recognized as a degenerative joint disease that leads to a serious problem of public health, yet the underlying molecular mechanisms remain incompletely understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets from the Gene Expression Omnibus (GEO) to systematically investigate oxidative stress–related genes and pathways in OA. Gene set enrichment analysis (GSEA) revealed significant activation of oxidative stress signaling in OA cartilage tissues, with 58 differentially expressed oxidative stress-related genes identified. Subsequent LASSO regression analysis highlighted seven diagnostic genes (STC2, LSP1, COL6A1, FOS, SELENON, TP53, and HSPA8), which demonstrated robust diagnostic performance in both training and validation cohorts. Single-cell analysis further revealed cell-type-specific differences in oxidative stress activity, with homeostatic chondrocytes (HomCs) exhibiting the highest pathway scores. Among the identified genes, FOS emerged as a hub regulator, showing elevated expression in HomCs from OA samples and strong associations with immune infiltration and proinflammatory pathways. Functional assays demonstrated that FOS knockdown significantly attenuated IL-1β-induced oxidative stress, apoptosis, and inflammatory cytokine (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) release in chondrocytes. Furthermore, molecular docking and dynamics simulations identified ursolic acid (UA) as a stable small-molecule FOS binder, and in vitro experiments confirmed its inhibitory effects on oxidative stress and inflammation, comparable to FOS silencing or pharmacological inhibition. Collectively, our findings suggest that oxidative stress–related genes, particularly FOS, play a central role in OA pathogenesis by linking redox imbalance to immune dysregulation and chondrocyte injury, and highlight UA as a potential therapeutic candidate for OA management.

Targeting norovirus RdRp: A computational study on the inhibitory potential of ursolic acid and apigenin-7-O-glucoside

Phytochemicals are plant-derived compounds extensively studied for the discovery and development of new drugs. Ursolic acid (UA), a pentacyclic triterpenoid phytochemical extracted from the bark and leaves of plants in the Lamiaceae family, has been the focus of research due to its antiproliferative potential, which has not yet been evaluated in tumor spheroids. This study aimed to analyze the antiproliferative effects and mechanisms of action of UA in 3D cultures (spheroids) of HepG2/C3A cells (human hepatocarcinoma). The analyses in 3D culture included average spheroid volume, genotoxicity using the comet assay, and the influence on mRNA expression, based on the cytotoxicity of UA assessed by the resazurin assay in 2D culture. The data showed that after 24 h of treatment, UA exhibited cytotoxicity at concentrations of 100 and 150 μM, reduced spheroid growth, demonstrated genotoxicity, and induced an increase in MTOR gene expression (2.38×). At 72 h, there was an upregulation of GADD45A (8.8×) and a downregulation of CDKN1A (2×). It is concluded that UA exhibits antiproliferative actions, promoting changes in the expression of genes associated with cell cycle control and DNA damage. This study has contributed to understanding the mechanism of action of this phytochemical for its therapeutic potential.

Background: Liver regeneration is a complex process involving multiple signaling pathways that coordinate hepatocyte proliferation, survival, and tissue repair. Natural compounds like silymarin, ursolic acid, quercetin, and resveratrol have shown regenerative potential, though their precise molecular mechanisms remain unclear. 6-O-trans-feruloyl catalpol (6FC), a major bioactive compound from Catalpa ovata, exhibits anti-inflammatory and potential antioxidant effects via regulation of NF-κB signaling and redox-sensitive pathways such as Akt and MAPK, which are critical for cell survival and proliferation. Moreover, 6FC exhibits peroxynitrite-scavenging activity, suggesting its potential antioxidant properties that may protect hepatocytes from oxidative damage during regeneration. However, the role of 6FC in liver regeneration has not been elucidated, positioning it as a promising natural therapeutic candidate for hepatic repair. Purpose: This study aimed to determine whether 6FC promotes hepatocyte proliferation and liver regeneration in vivo using a 2/3 PHx mouse model, and to validate its proliferative effects in vitro with HGF-stimulated Hep3B cells. Methods: A 2/3 PHx liver regeneration model was used to evaluate 6FC-mediated liver regeneration. Histological and molecular analyses assessed hepatocyte proliferation and signaling activation. HGF-stimulated Hep3B cells were also used to examine 6FC proliferative effects in vitro. Results: 6FC significantly promoted liver regeneration by restoring the liver-to-body weight ratio and reducing serum ALT and AST levels without inducing excessive immune responses. Mechanistic studies revealed that 6FC activates Akt and MAPK pathways, increases the expression of critical growth factors, and upregulates cell cycle regulators. These effects were also observed in HGF-stimulated Hep3B cells, suggesting that 6FC may enhance hepatocyte proliferation without triggering excessive immune responses. Conclusions: 6FC accelerates hepatocyte proliferation and promotes liver regeneration by activating key redox-sensitive signaling pathways, highlighting its potential as a natural antioxidant-based therapeutic agent.

Background/Objectives: The prevalence of obesity globally has increased steadily in the past decades. Obesity, sarcopenic obesity (SO) and nonalcoholic fatty liver disease (NAFLD) commonly coexist. Ursolic acid (UA), a natural pentacyclic triterpenoid, has demonstrated potential anti-obesity properties. This study was designed to evaluate the anti-obesity efficacy of UA in a mouse model of high-fat diet (HFD)-induced obesity, with a particular focus on its impact on muscle function and NAFLD. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to three groups (n = 20 per group): a control group (CON) fed a normal chow diet, a high-fat diet group (HFD), and a UA treatment group (UA). The HFD and UA groups received a high-fat diet for 10 weeks to induce obesity. Thereafter, mice in the UA group were administered UA orally once daily for 6 weeks. Results: In HFD-induced obese mice, UA administration significantly reduced body weight (BW), abdominal fat weight and liver weight; improved grip strength and muscle weight; and enhanced lipid profiles, including triglycerides, total cholesterol, low-density lipoprotein cholesterol and free fatty acid levels in serum. UA also improved histological changes in the liver and abdominal adipose tissues, regulated serum GH, IGF-1, T3, T4 and leptin levels and downregulated the inflammation-associated gene expression of TNF-α and IL-1β in abdominal adipose tissue. Conclusions: UA could enhance muscle strength, improve lipid metabolism and hepatic steatosis and might be considered a potential therapeutic agent for managing obesity and related metabolic diseases.

A computational study of bioactive compounds from Vitex negundo showed significant binding interactions with crucial protein targets involved in rheumatoid arthritis (RA) pathogenesis. Molecular docking studies using PyRx and Biovia Discovery Studio evaluated the binding affinities of vitexin, ursolic acid, oleanolic acid, and tris(2,4-di-tert-butyl) phosphate against NF-κB, TLR4, JNK, and sPLA2. The docking analysis demonstrated notable binding energies, with vitexin exhibiting the strongest affinity (-8.7 kcal/mol) toward NF-κB, followed by ursolic acid-TLR4 complex (-8.5 kcal/mol). Detailed interaction analysis showed stable conformations supported by hydrogen bonding, hydrophobic interactions, and metal coordination, particularly in the vitexin-NF-κB complex involving LEU19, CYS5, and zinc ion coordination. SwissADME evaluation confirmed favorable drug-likeness properties and ADME characteristics of the compounds. The molecular-level interactions and pharmacokinetic predictions indicate the therapeutic potential of Vitex negundo phytoconstituents as multi-target agents for RA treatment.

Background/Objectives: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development of drug formulations. This study investigates the preparation of a nano-UA suspension by wet grinding, researches the influence of process parameters on particle size, and explores the rules of particle breakage and agglomeration by combining model fitting. Methods: Wet grinding experiments were conducted using a laboratory-scale grinding machine. The particle size distributions (PSDs) of UA suspensions under different grinding conditions were measured using a laser particle size analyzer. A single-factor experimental design was employed to optimize operational conditions. Model parameters for a population balance model considering both breakage and agglomeration were determined by an evolutionary algorithm optimization method. By measuring the degree to which UA inhibits the colorimetric reaction between salicylic acid and hydroxyl radicals, its antioxidant capacity in scavenging hydroxyl radicals was indirectly evaluated. Results: Wet grinding process conditions for nano-UA particles were established, yielding a UA suspension with a D50 particle size of 122 nm. The scavenging rate of the final grinding product was improved to three times higher than that of the UA raw material (D50 = 14.2 μm). Conclusions: Preparing nano-UA suspensions via wet grinding technology can significantly enhance their antioxidant properties. Model regression analysis of PSD data reveals that increasing the grinding mill’s stirring speed leads to more uniform particle size distribution, indicating that grinding speed (power) is a critical factor in producing nanosuspensions.

Dipsacus azureus (family Dipsacaceae) is used as a traditional medicinal plant for the treatment of rheumatism, skin ulcers, and stomach cancer. Experiments have shown that it has analgesic and stimulating effects on the cardiovascular system. A study was conducted on the carbohydrates, lipids, and other low-molecular-weight metabolites of the aerial parts of D. azureus, collected during the flowering period in the Tashkent region. The alcohol-soluble sugars are represented by fructose, sucrose, and glucose. The yield of water-soluble polysaccharides extracted with cold water (WSPC-c) was 0.38%, and those extracted at 70°C (WSPC-h) were 1.92%. The monosaccharide composition of WSPC-c and WSPC-h includes acidic and neutral monosaccharides: galacturonic and glucuronic acids, galactose, glucose, and arabinose, with rhamnose detected in smaller quantities. The monosaccharide composition of pectic substances includes uronic acid, galactose, glucose, and arabinose, with xylene and rhamnose present in trace amounts. The monosaccharide composition of hemicellulose consists of acidic and neutral monosaccharides: uronic acid, galactose, glucose, arabinose, xylene, and rhamnose. The air-dried crushed aboveground rt of Dipsacus azureus contains 1.71% neutral lipids (NL) and 2.57% polar lipids (PL) consisting of NL residues, glycolipids (GL) and phospholipids (PL). Thus, the aboveground rt of the plant contain 4.28% total lipids. Hence contain 18 (NL) and 17 (PL) LCs with predominance from saturated fatty acids 16:0 (22.56-27.44%) and from unsaturated 18:2-ω6-linolenic acid (15.13-18.80%) and much higher content of 18:3-α-linolenic acid (24.51-31.45%). The sum of polyunsaturated fatty acids (18:2; 18:3; 20:4) is 47.17% in NL and 44.13% in PL (18:2; 18:3; 20:2). It should be noted that the peculiarity of the LC set of the aboveground rt of D. azureus is the presence of high-molecular acids with chain lengths from 22 to 24 C atoms in the acids of NL and PL. Individual compounds 1-6 were isolated from an 80% ethanol extract of the plant, which were identified ased on the study of spectral data 1D (1H, 13C) and 2D (HSQC, HMBC, COSY) NMR spectroscopy, as well as comparison with information published in the literature and authentic samples identified by ursolic acid, methyl glycoside, hederogenin, oleanolic acid, as well as the iridoid glycosides loganin and sveroside.

Abstract BACKGROUND Glioblastoma (GBM) is among the most aggressive adult brain tumors, with poor prognosis and high recurrence. Despite surgery and chemoradiotherapy, treatment remains ineffective due to the invasive nature of glioma cells and the lack of targeted postoperative options. Residual cancer cells often persist post-resection, underscoring the need for strategies that can specifically eliminate them. MATERIAL AND METHODS We developed a zeolitic imidazolate framework (ZIF-8) nanoparticle system, UFZ-HM, loaded with ursolic acid (UA) and Fe₃O₄, and coated with a neutrophil-glioma hybrid membrane. UA induces apoptosis, while Fe₃O₄ triggers ferroptosis via the Fenton reaction. The system leverages the dual targeting properties of neutrophil and glioma membranes. In vitro, we assessed cytotoxicity, ROS generation, mitochondrial disruption, and BBB penetration using CCK-8, live/dead staining, and a Transwell BBB model. In vivo, an orthotopic glioma model in mice was used to evaluate tumor targeting, therapeutic efficacy, and biosafety. RESULTS UFZ-HM showed strong glioma cell inhibition, effective BBB penetration, and significant induction of ferroptosis. In vivo, it markedly reduced tumor growth, prolonged survival, and exhibited high biosafety. CONCLUSION UFZ-HM demonstrates biosafety and dual-targeting capacity via inflammatory and homologous recognition. Its pH-responsive release enables precise drug delivery, effectively suppressing glioma growth and improving survival. UFZ-HM offers a promising nanoplatform for enhancing GBM therapy.