Oleanolic Acid Research Articles

Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity

BackgroundObesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied.MethodNetwork pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets.ResultsThe network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation’s Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity.ConclusionOverall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.

Expansion of the antifungal activities through in silico docking study of compounds from Albizia lebbeck fruits

The development of new computational and experimental techniques that are efficient, fast, and accurate has become a priority for researchers in all domains around the world. The present manuscript deals with the computational investigation of quercitrin (1), lebbeckisoetin A (2), quercetin-3-O-_β_-D-glucopyranoside (3), (_E_)-_p_-coumaric acid (4), eugenol (5), eugenol, 1-acetate (6), chiakine (7), hexancosan-1',26'-dioate of bis[(2_S_), 2,3-dihydroxypropyl] (8), oleanolic acid (9), betulin (10), hopan-29-ol (11), hopan-30-ol (12), 22-hydroxyhopan-3-ol (13), and lupeol (14). These compounds were all isolated from the fruit of _Albizia lebbeck_. Only lebbeckisoetin A (2) and chiakine (7) were previously evaluated for their experimental antimicrobial activities, which both revealed potent antifungal activities. This theoretical study was undertaken in the framework of better understanding the experimental results at the atomic level and to expand the antimicrobial assays of the other non-tested compounds. The virtual screening of the antimicrobial activity was performed on Maestro Schrӧdinger 4.2.1 software using the crystal structures of sterol 14-alpha demethylase (CYP51) from _Candida albicans_ in complex with the tetrazole-based antifungal drug candidate VT1161 (VT1) (PDB Id: 5TZ1) and the crystal structure of sterol 14-alpha demethylase (CYP51) from the pathogenic yeast _Candida albicans_ in complex with the antifungal drug posaconazole (PDB Id: 5FSA). This is the first docking study of natural compounds using these 5TZ1 and 5FSA as proteins. Compounds (1-10) reveal interesting binding strength with both 5TZ1 and 5FSA proteins, with a docking score ranging from -7.892 to -5.256, supporting the experimental results. In addition, compounds (1-9) were mostly active due to the formation of π-π interactions, H-bonds, and hydrophobic interactions, as well as π-cation and salt bridge interactions, with both 5TZ1 and 5FSA.

Eremane, viscidane and isozizaene diterpenoids from the leaves of Eremophila rigida and their absolute configurations

Previously undescribed eremane, viscidane, and isozizaene diterpenoids, eremorigidanes A-F, along with six known O-methylated flavonoids and three known triterpenoids were isolated and identified from the leaves of Eremophila rigida Chinnock by combined use of high-resolution PTP1B inhibition profiling, semipreparative- and analytical-scale HPLC separations, HPLC-PDA-HRMS analysis, and NMR spectroscopy. The absolute configuration of the unreported diterpenoids were determined by comparison of their experimental and calculated ECD spectra as well as by biosynthetic arguments. All isolates were evaluated for their PTP1B inhibitory activities, which revealed the flavonoid penduletin (3) to show inhibition with an IC50 value of 18.3 μM, and the triterpenoids 3,4-seco-olean-12-ene-3,28-dioic acid (15), oleanolic acid (16), and 3-oxo-oleanolic acid (17) to show inhibition with IC50 values of 55.7, 9.9, and 6.3 μM, respectively. The preliminary structure-activity relationship (SAR) of isolated flavonoids and triterpenoids is discussed. Plausible biosynthetic steps involved in eremane and isozizaene metabolism are presented and discussed.

Cuticular wax biosynthesis in blueberries (Vaccinium corymbosum L.): Transcript and metabolite changes during ripening and storage affect key fruit quality traits.

In fruits, cuticular waxes affect fruit quality traits such as surface color at harvest and water loss during postharvest storage. This study investigated the transcriptional regulation of cuticular wax deposition in northern highbush blueberries (Vaccinium corymbosum L.) in relation to fruit water loss and surface color during ripening and postharvest storage, as well as the effects of abscisic acid (ABA)-mediated changes in cuticular wax deposition on these fruit quality traits. Total cuticular wax content (μg∙cm-2) decreased during fruit ripening and increased during postharvest storage. Transcriptome analysis revealed a transcript network for cuticular wax deposition in blueberries. Particularly, five OSC-Likes were identified as putative genes for triterpene alcohol production, with OSC-Like1 and OSC-Like2 encoding mixed amyrin synthases, OSC-Like3 encoding a lupeol synthase, and OSC-Like4 and OSC-Like5 encoding cycloartenol synthases. The expression of three CYP716A-like genes correlated to the accumulation of two triterpene acids oleanolic acid and ursolic acid, the major wax compounds in blueberries. Exogenous ABA application induced the expression of triterpenoid biosynthetic genes and the accumulation of β-amyrin and oleanolic acid, as well as increased the ratio of oleanolic acid to ursolic acid. These changes were associated with reduced fruit water loss. The content of β-diketones was also increased by ABA application, and this increase was associated with increased fruit lightness (measured as L* using CIELAB Color Space by a colorimeter). This study provided key insights on the molecular basis of cuticular wax deposition and its implications on fruit quality traits in blueberries.

Acylation of Oleanolic Acid Oximes Effectively Improves Cytotoxic Activity in In Vitro Studies.

(1) Background: The aim of the presented work was to obtain a set of oleanolic acid derivatives with a high level of anticancer activity and a low level of toxicity by applying an economic method. Three types of oleanolic acid derivatives were obtained: (i) derivatives of methyl oleanonate oxime, (ii) derivatives of methyl oleanonate oxime with an additional 11-oxo function, and (iii) derivatives of morpholide of oleanonic acid oxime. (2) Methods: The above oximes were acylated with aliphatic or aromatic carboxylic acid. The newly obtained compounds were subjected to ADMETox analysis and were also tested for cytotoxicity activity on the HeLa, KB, MCF-7, A-549, and HDF cell lines with the MTT assay. (3) Results: Among the tested acylated oximes of oleanolic acid, some derivatives, particularly those with two nitro groups attached to the aromatic ring, proved to be the most potent cytotoxic agents. These triterpene derivatives significantly inhibited the growth of the HeLa, KB, MCF-7, and A-549 cancer cell lines in micromolar concentrations. (4) Conclusions: The introduction of different moieties, particularly the 3,5-dinitro group, resulted in the synthesis of highly potent cytotoxic agents with favorable SI and ADMETox parameters.

Mechanism study of oleanolic acid derivative, K73-03, inducing cell apoptosis in hepatocellular carcinoma

Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a kind of pentacyclic triterpene, which widely distributes in nature. OA possesses a powerful anti-cancer effect; however, its low solubility limits its bioavailability and application. In this study, a new OA derivative, K73-03, was used to determine its effect on liver cancer cells and detailed molecular mechanisms. Here, we show that K73-03 may lead to the disorder of mitochondria in HepG2 cells, leading to excessive ROS production and apoptosis in cells. Meanwhile, K73-03 could induce cell apoptosis by inhibiting JAK2/STAT3 pathway and NF-κB/P65 pathway. Collectively, this study may provide a preliminary basis for further cancer treatment of hepatocellular carcinoma.

An Inducible CRISPR-dCas9-Based Transcriptional Repression System for Cancer Therapy.

Gene therapy has been adapted for improving malignant tumor treatment. However, pharmacotherapies targeting cancer remain limited and are generally inapplicable for rare disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment for many disorders. Here, the congruent pharmacological activities of OA and CRISPR-dCas9 in targeting AURKA or KDM1A and improving disease-specific prognosis and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs are utilized. In particular, the OA-triggered CRISPR-dCas9 transcriptional repression system rapidly and simultaneously attenuated lung and thyroid cancer. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficiencies of single therapeutics.

(5Z,9Z)-14-[(3,28-Dioxoolean-12-en-28-yl)oxy]tetradeca-5,9-dienoic Acid with Cytotoxic Activity

For the first time, a synthetic analogue of natural (5Z,9Z)-dienoic acid has been synthesized in the form of a hybrid molecule containing a fragment of oleanolic acid and (5Z,9Z)-tetradeca-5.9-dienedicarboxylic acid, synthesized using a new reaction of Ti-catalyzed homo-cyclomagnesiation 1,2-dienes. The high cytotoxic activity of (5Z,9Z)-14-[(3,28-dioxoolean-12-en-28-yl)oxy]tetradeca-5,9-dienoic acid against tumor cells Jurkat, K562, U937 and HL60 was established. This compound is also an inducer of apoptosis, affects the cell cycle and inhibits human topoisomerase I.

Chromatographical fingerprint analysis, in silico investigation, and identification of hepatoprotective active compounds from Capparis decidua Edgwe (Forssk.)

Liver disorders are globally distributed with a high burden of disease costs. The methanolic extract of Capparis decidua stem part and its dichloromethane (DCM) and ethylacetate fractions showed significant hepatoprotective activity, so this study aimed to develop gas chromatography/mass spectrometry (GC/MS), high-performance thin layer chromatography (HPTLC) fingerprint profile and in silico docking of identified compounds from both fractions responsible for hepatoprotective activity. Hexadecanoic acid, 9-octadecenoic acid, 9,12,15-octadecatrienoic acid, and dihydrolinalool are known hepatoprotective and antioxidant agents that were identified from both fractions by GC/MS, they have various degrees of hepatoprotective and antioxidant properties, this is the first time to identify hexadecanoic acid in C. decidua stem. Both fractions were chromatogramed with known hepatoprotective standard compounds, they were rutin, quercetin, kaempferol, ferulic acid, oleanolic acid, and β-sitosterol; β-sitosterol and oleanolic were isolated and identified in the DCM fraction by HPTLC, but nothing of these standard compounds were identified in the ethylacetate fraction. According to International Council for Harmonization guidelines, the HPTLC fingerprint profile method was validated to confirm our isolation and identification process of β-sitosterol and oleanolic acid in the DCM fraction, also their contents were quantified and they were 9.21 and 7.73 μg/mg, respectively, in the total dry fraction weight, this was the first time to isolate and identify oleanolic acid from C. decidua stem part. In silico docking was carried and was found that hexadecanoic acid showed significant predicted binding properties on Nrf2, p38 mitogen-activated protein kinase, and IL-1 receptor proteins. 9-octadecenoic acid (elaidic acid) showed significant predicted interactions with IL-1 receptor, Nrf2, and peroxisome proliferator-activated receptor-α (PPAR-α) proteins. Oleanolic acid showed significant predicted bindings with p65, JNK, and NF-kb. β-sitosterol showed significant predicted interaction with IL-6α protein, while 9,12,15-octadecatrienoic acid revealed significant binding with PPAR-α protein. Therefore, we recommend considering our active compounds in the field of drug development (structure-activity relationship) and the possibility of the presence of synergism if they are combined and administered together. Moreover, we recommend liquid chromatography-mass spectrometry and nuclear magnetic resonance on both fractions to search for the possibility of the presence of other hepatoprotective compounds.

In Vitro Evaluation of the Effect of Oleanolic Acid as a Potential Root Canal Medicament on Viability and Proliferation of Dental Pulp Stem Cells

Abstract Objective In light of the potential drawbacks associated with certain intracanal medicaments, such as triple antibiotic paste (TAP) and calcium hydroxide (Ca(OH2)), the introduction of herbal agents has ushered in a new era in the field of dentistry. Consequently, this study aimed to explore the impact of oleanolic acid (OA) on the viability and proliferation of dental pulp stem cells (DPSCs), comparing its effects to those of conventional intracanal medicaments, TAP and Ca(OH2). Materials and Methods DPSCs were derived from the third molars of an adult donor. Flow cytometry was utilized to do a phenotypic study on DPSCs. The methyl-thiazol tetrazolium (MTT) test was used to evaluate cellular viability. The cells were subjected to various concentrations of TAP and Ca(OH)2 (5, 2.5, 1, 0.5, and 0.25 mg/mL), in addition to OA (40, 20, 10, 5, and 2.5 µM). A cell proliferation experiment assessed the cell growth precisely at 3, 5, and 7 days. Results DPSCs were characterized by flow cytometry. The mesenchymal markers (CD73, CD90, and CD105) had a positive expression. However, the hematological markers (CD14, CD34, and CD45) showed negligible expression. A notable reduction in cellular viability was seen in cells subjected to concentrations exceeding 0.5 mg/mL of TAP and Ca(OH)2 compared to the cells that were not treated (p < 0.05). The cells treated with different concentrations of OA 2.5, 5, 10, and 20 µM did not exhibit any significant variance in cell viability compared to untreated cells (p > 0.05). Moreover, the concentrations of OA (20, 10, and 5 µM) showed high proliferation level compared to TAP and Ca(OH2) especially 5µM of OA after 7 days (p < 0.05). Conclusion Our results revealed that OA exerted significant effect on the viability and proliferation of DPSCs compared to TAP and Ca(OH2).

RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines

Chronic inflammation is crucial in developing insulin resistance and type 2 diabetes. Previous studies have shown that a leaf extract of Eucalyptus tereticornis, with ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL) as the main molecules (78 %) mixed with unknown minor metabolites (22 %), provided superior anti-inflammatory, hypoglycemic, and hypolipidemic effects than reconstituted triterpenoid mixtures in macrophage cell lines and a pre-diabetic mouse model. Further identification of the molecular mechanisms of action of this mixture of triterpenes is required. This study aims to analyse the RNA expression profiles of mouse and human macrophage cell lines treated with the natural extract and its components. Activated macrophage cell lines were treated with the natural extract, UA, OA, UAL or a triterpene mixture (M1). RNA was extracted and sequenced using the DNBseq platform and the EnrichR software to perform gene enrichment analysis using the Gene Ontology database, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To conduct clustering analysis, we standardised the normalised counts of each gene and applied k-means clustering. The combination of molecules in the natural extract has an additive or synergic effect that affects the expression of up-regulated genes by macrophage activation. Triterpenes (M1) regulated 76 % of human and 68 % of mouse genes, while uncharacterised minority molecules could regulate 24 % of human and 32 % of mouse genes. The extract inhibited the expression of many cytokines (IL6, IL1, OSM), chemokines (CXCL3), inflammatory mediators (MMP8 and MMP13) and the JAK-STAT signalling pathway in both models. The natural extract has a more powerful immunomodulatory effect than the triterpene mixture, increasing the number of genes regulated in mouse and human models. Our study shows that Eucalyptus tereticornis extract is a promising option for breaking the link between inflammation and insulin resistance.

Oleanolic acid alleviate intestinal inflammation by inhibiting Takeda G-coupled protein receptor (TGR) 5 mediated cell apoptosis.

Oleanolic acid (OA) is a bioactive compound present in plant-based foods known for its beneficial impact on gastrointestinal health, specifically in alleviating diarrhea. Nonetheless, the underlying mechanisms by which OA mitigates gut epithelial damage have yet to be elucidated. In this study, OA significantly markedly ameliorated adverse effects induced by Dextran Sulfate Sodium (DSS), including weight loss and epithelial morphological damage in a murine model. Remarkably, compared to normal mice, standalone administration of OA had no discernible impact on the animals. Concurrently, we identified a significant up-regulation in the expression levels of TGR5 and BAX in the intestines of DSS-exposed mice, coupled with a decline in Bcl2 expression. Correlation analyses revealed a robust association between TGR5 and BAX expression. Oral administration of OA efficaciously counteracted these alterations. To probe the role of TGR5 in cellular apoptosis, further, a lentivirus transfection approach was utilized to induce TGR5 overexpression in intestinal epithelial cells (IPEC-J2). RNA sequencing indicated that TGR5 overexpression significantly influenced biological processes, particularly in modulating cellular activation and intercellular adhesion, in contrast to the control group cells. Functional assays substantiated that TGR5 overexpression compromised cell viability and accelerated apoptosis. Notably, OA treatment in TGR5-overexpressed cells restored cell viability, suppressed TGR5 and BAX expression, and augmented Bcl2 expression. In sum, our data suggest that OA mitigates intestinal epithelial apoptosis and bolsters cellular proliferation by downregulating TGR5. This research provides valuable insights into the prospective utility of OA as a functional food supplement or adjunctive therapeutic agent for enhancing gastrointestinal health.

A Comprehensive Review of the Phytochemical Constituents and Bioactivities of Ocimum tenuiflorum.

Ocimum tenuiflorum, commonly known as Tulsi, is revered in Ayurveda for its extensive medicinal properties. However, there is a need to consolidate current knowledge on its phytochemical constituents and their pharmacological activities to identify potential areas for further research and drug development. This review aims to bridge this gap by providing a comprehensive analysis of the bioactive secondary metabolites found in O. tenuiflorum, such as rosmarinic acid, oleanolic acid, luteolin, ursolic acid, and limonene, and their associated therapeutic effects. The review will highlight the pharmacological importance of these metabolites, which exhibit antioxidant, neuroprotective, anticancer, and anti-inflammatory properties. Additionally, this study will explore the plant's wide range of beneficial qualities, including anti-inflammatory, antioxidant, anticholinergic, pain-relieving, antimicrobial, stress-reducing, antidiabetic, anticancer, liver-protective, ulcer-inhibiting, antifungal, and wound-healing attributes. Furthermore, this review focuses on the plant's potential in treating conditions such as asthma, persistent fever, tuberculosis, malaria, skin discoloration, itching, digestive issues, hemorrhoids, bone fractures, gout, urinary tract infection, and diabetes. By reviewing the current literature, the aim is to identify the gaps in the existing research and propose directions for future studies. This comprehensive review will serve as a valuable resource for researchers in the development and investigation of novel drugs derived from O. tenuiflorum.

Screening of potential antioxidant bioactive Q-markers of paeoniae radix rubra based on an integrated multimodal strategy.

Paeoniae Radix Rubra (PRR) has been used widely to promote blood circulation and eliminate blood stasis in China clinical practice owing to its extensive pharmacological effects. However, the "quality markers" (Q-markers) of the antioxidant effects remains unknown. To explore the Q-markers of antioxidant activity based on multiple strategies, which would provide reference for the quality evaluation of PRR based on specific pharmacodynamic-oriented. Firstly, the "fingerprint" profiles of 15 batches of PRR were acquired and identified by ultrahigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF MS/MS) and the common peaks extracted. Meanwhile, the MTT assay was used to evaluate the effect of 15 batches of PRR on H2O2-induced oxidative stress in HT-22 cells. The antioxidant activity of PRR was investigated simultaneously by superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) commercial kits. The relationship between common peaks and antioxidant indexes were constructed by grey relational analysis (GRA) and partial least squares-discriminant analysis (PLS-DA) for the identification of preselected Q-markers. Secondly, experimental verification was conducted to investigate the protective effect of the preliminary components on HT-22 cells undergoing oxidative stress. Finally, for the further validation of effectiveness of antioxidant Q-markers, network pharmacology was applied to explore potential targets, and the molecular docking technology was used to value the binding ability of the potential active components of PRR to the antioxidant targets. Thirty-seven common peaks from 15 batches of PRR were identified qualitatively by UHPLC-Q-TOF MS/MS. The MTT assay showed that PRR could reduce the oxidative damage induced by H2O2 upon HT-22 cells according to the index of MDA, SOD and GSH. Eight potential antioxidant components were screened by spectrum-effect correlation analysis: paeoniflorin, galloylpaeoniflorin, albiflorin, 1,2,3,4,6-o-pentagalloylglucose, benzoylpaeoniflorin, pinocembrin, oleanic acid, and isorhamnetin-3-o-nehesperidine. Each of these preliminary components showed significant protections on cellular oxidative stress (P < 0.05). Interleukin-6 (IL-6), protein kinase B (AKT1), and tumor necrosis factor (TNF) were predicted to be the major potential targets of PRR, and the good binding ability were presented between the potential active components of PRR and each target as a whole. Eight components were identified as the antioxidant Q-markers of PRR based on an integrated multimodal strategy.

The natural sources, extraction, and nephroprotective function of oleanolic acid and ursolic acid: a review

The natural sources, extraction, and nephroprotective function of oleanolic acid and ursolic acid: a review

Efficient and selective extraction of oleanolic acid from grape pomace with dimethyl carbonate

A selective and environmentally friendly method for the extraction of oleanolic acid from grape pomace using bio-based and non-toxic dimethyl carbonate.

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Synthesis and Antichlamydial Activity of Oleanolic Acid Aza-Derivatives

Synthesis and Antichlamydial Activity of Oleanolic Acid Aza-Derivatives

Comparative Analysis of Agronomic Traits, Yield, and Effective Components of Main Cultivated Ganoderma Mushrooms (Agaricomycetes) in China.

To assess the strain resources and address production challenges in Ganoderma cultivation. 150 Ganoderma strains were collected from 13 provinces in China. A comparative analysis of agronomic traits and effective components was conducted. Among the 150 strains, key agronomic traits measured were: average stipe diameter (15.92 mm), average stipe length (37.46 mm), average cap horizontal diameter (94.97 mm), average cap vertical diameter (64.21 mm), average cap thickness (15.22 mm), and average fruiting body weight (14.30 g). Based on these agronomic traits, four promising strains, namely, L08, L12, Z21, and Z39, were recommended for further cultivation and breeding. The average crude polysaccharide content ranged from 0.048% to 0.977%, and triterpenoids ranged from 0.804% to 2.010%. In addition, 73 triterpenoid compounds were identified, constituting 47.1% of the total compounds. Using a distance discrimination method, the types, and relative contents of triterpenoid compounds in 150 Ganoderma strains were classified, achieving 98% accuracy in G. lingzhi identification. The 16 triterpenoid components used for G. lingzhi identification included oleanolic acid, ursolic acid, 3β-acetoxyergosta-7,22-dien-5α-ol, ganoderic acid DM, ganoderiol B, ganorderol A, ganoderic acid GS-1, tsugaric acid A, ganoderic acid GS-2, ganoderenic acid D, ganoderic acid Mf, ganoderic acid A, ganoderic acid K, ganoderic acid V, ganoderic acid G, and leucocontextin J. This study provides valuable insights for exploring and utilizing Ganoderma resources and for the development of new varieties.

인간 기도 상피세포에서 IKK/IκBα/NF-κB p65 신호전달 경로를 경유한 호흡기 MUC5AC 뮤신 유전자의 발현에 미치는 올레아놀산의 영향

In the present study, we investigated whether oleanolic acid, an anti-inflammatory natural product, significantly affects the phorbol 12-myristate 13-acetate (PMA)-induced gene expression of airway MUC5AC mucin. Confluent NCIH292 cells were pretreated with oleanolic acid for 30 min and then stimulated with PMA for 24 h or the indicated periods. The MUC5AC mucin mRNA expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. To elucidate the action mechanism of oleanolic acid, effect of oleanolic acid on PMA-induced NF-B signaling pathway was investigated by western blot analysis. The results were as follows: (1) Oleanolic acid significantly inhibited the production of MUC5AC mucin protein and down-regulated the expression of MUC5AC mucin mRNA; (2) Oleanolic acid inhibited PMA-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa Ba (IB); (3) Oleanolic acid inhibited PMA-induced nuclear translocation of nuclear factor kappa B (NF-B) p65, led to the down-regulation of MUC5AC mucin gene expression in NCI-H292 cells. These results suggest that oleanolic acid can regulate the gene expression of mucin by acting on airway epithelial cells through regulation of NF-B signaling pathway.