Corosolic Acid Research Articles

Ethyl acetate fraction of Osmanthus fragrans var. aurantiacus and its triterpenoids suppress proliferation and survival of colorectal cancer cells by inhibiting NF-κB and COX2

Ethnopharmacological relevanceColorectal cancer (CRC) remains a significant global health concern, and targeting inflammation has emerged as a promising approach for its prevention and treatment. Medicinal plants and phytochemicals have garnered attention for their potential efficacy against inflammation with minimal toxicity. Osmanthus fragrans var. aurantiacus Makino (O. fragrans) has a history of traditional use in Korea and China in treating various inflammation-related conditions, but its potential use for CRC has not been uncovered. Aim of the studyThis study aims to explore the potential anti-proliferative and pro-apoptotic properties of O. fragrans, focusing on its impact on CRC treatment. By investigating O. fragrans, we aim to uncover its anti-proliferative and apoptotic effects in human CRC cells, potentially paving the way for effective and well-tolerated therapeutic strategies for CRC patients. Materials and methodsEthanol (EtOH) extracts of O. fragrans leaf and flower, along with specific fractions (n-hexane, ethyl acetate (EtOAc), n-butanol, and the aqueous residue) were evaluated for their anti-proliferative effects in human CRC cells using MTT assays, and compared to normal colon cells. Mechanistic insights and chemical profiling were obtained through flow cytometry, colorimetric assays, western blotting, and molecular docking, and high-performance liquid chromatography (HPLC) system. ResultsBoth flower and leaf EtOH extracts of O. fragrans exhibited significant anti-proliferative effects in human CRC cells, with the leaf extract demonstrating higher potency. The EtOAc fraction from the leaf extract displayed the strongest anti-CRC cell proliferative effects while no cytotoxic effects in normal colon cells. Chemical profiling of these fractions identified triterpenoids as significant components in the EtOAc fractions. The leaf EtOAc fraction caused cell cycle arrest and apoptosis, accompanied by elevating intracellular reactive oxygen species and mitochondrial dysfunction in CRC cells. Additionally, it inhibited NF-κB and ERK1/2 signaling, leading to reduced COX2 expression. Notably, two triterpenoids isolated from the leaf EtOAc fraction, maslinic acid and corosolic acid, displayed potent anti-cancer activity in CRC cells without affecting normal colon cells. Corosolic acid exhibited a strong binding affinity to COX2 and reduced its expression, supporting its role in the anti-inflammatory and anti-cancer effects. ConclusionsOur findings suggest that O. fragrans, particularly its triterpenoid-rich EtOAc fraction, holds promise as a novel therapeutic agent for CRC prevention and therapy. These results provide valuable insights into the potential application of O. fragrans and its bioactive compounds in combating CRC.

Medicinal plant Miconia albicans synergizes with ampicillin and ciprofloxacin against multi-drug resistant Acinetobacter baumannii and Staphylococcus aureus

BackgroundGiven the rising occurrence of antibiotic resistance due to the existence and ongoing development of resistant bacteria and phenotypes, the identification of new treatments and sources of antimicrobial agents is of utmost urgency. An important strategy for tackling bacterial resistance involves the utilization of drug combinations, and natural products derived from plants hold significant potential as a rich source of bioactive compounds that can act as effective adjuvants. This study, therefore, aimed to assess the antibacterial potential and the chemical composition of Miconia albicans, a Brazilian medicinal plant used to treat various diseases.MethodsEthanolic extracts from leaves and stems of M. albicans were obtained and subsequently partitioned to give the corresponding hexane, chloroform, ethyl acetate, and hydromethanolic phases. All extracts and phases had their chemical constitution investigated by HPLC–DAD-MS/MS and GC–MS and were assessed for their antibiofilm and antimicrobial efficacy against Staphylococcus aureus. Furthermore, their individual effects and synergistic potential in combination with antibiotics were examined against clinical strains of both S. aureus and Acinetobacter baumannii. In addition, 10 isolated compounds were obtained from the leaves phases and used for confirmation of the chemical profiles and for antibacterial assays.ResultsBased on the chemical profile analysis, 32 compounds were successfully or tentatively identified, including gallic and ellagic acid derivatives, flavonol glycosides, triterpenes and pheophorbides. Extracts and phases obtained from the medicinal plant M. albicans demonstrated synergistic effects when combined with the commercial antibiotics ampicillin and ciprofloxacin, against multi-drug resistant bacteria S. aureus and A. baumannii, restoring their antibacterial efficacy. Extracts and phases also exhibited antibiofilm property against S. aureus. Three key compounds commonly found in the samples, namely gallic acid, quercitrin, and corosolic acid, did not exhibit significant antibacterial activity when assessed individually or in combination with antibiotics against clinical bacterial strains.ConclusionsOur findings reveal that M. albicans exhibits remarkable adjuvant potential for enhancing the effectiveness of antimicrobial drugs against resistant bacteria.

Corosolic acid inhibits metastatic response of human renal cell carcinoma cells by modulating ERK/MMP2 signaling.

Corosolic acid (CA), a plant-derived pentacyclic triterpenoid, has potent anti-inflammatory, anti-metabolic, and anti-neoplastic actions against a variety of human cancers. However, the specific mechanism by which CA inhibits the progression of renal cell carcinoma (RCC) is yet unclear. We found that CA (≤8 μM) had no influence on either the growth or viability of RCC cell lines (786-O, ACHN, and Caki-1) or normal HK2 cells. However, in a dose-dependent manner, CA prevented the invasion and migration of RCC cells. Human protease array analysis showed that CA reduced MMP2 expression. At increasing concentrations of CA, the expression of MMP2 was dose-dependently reduced, as shown by western blot and RT-PCR analyses as well as immunofluorescence staining. CA also stimulated ERK1/2 phosphorylation in 786-O and Caki-1 cells. Transfection of CA-treated RCC cells with siRNA-ERK restored MMP2 protein expression and the motility and invasion capabilities of RCC cells. Molecular docking study results showed that CA and MMP2 interact strongly. These findings elucidate the mechanism by which CA prevents RCC cells from migrating and invading, and these findings indicate that CA may be a potential anti-metastatic therapy for RCC.

Extraction of triterpene acids from loquat leaves via a novel hydrophobic deep eutectic solvent screened by COSMO-SAC model

Triterpene acids (TTAs) have promising applications in functional food, medicine and other fields. Here, ultrasonic-assisted hydrophobic deep eutectic solvent (HDES) extraction was employed to gain TTAs from loquat leaves. Combining COSMO-SAC model prediction with experimental verification，the HDES, composed of thymol and benzyl alcohol (molar ratio 2:1), was proved to have the highest extraction ability for TTAs. The preliminarily optimized extraction conditions were solid to solvent ratio 1:10 (g/g), temperature 60 °C and extraction time 60 min. Under these conditions, the extraction yield of ursolic acid (the main component of loquat leaf TTAs) was 17.769 ± 0.799 mg/g dry loquat leaf. HDES and TTAs were recovered from HDES extracting solution via gradient elution (60% and 80% ethanol aqueous solution, respectively) based on C18 reverse-phase silica gel column chromatography under low pressure (0.5 MPa). Recovered HDES could be reused for extracting TTAs from loquat leaves directly and had a similar extraction performance compared to fresh HDES. The purity of the obtained crude TTAs sample was 81.18% based on the total contents of maslinic acid (MA), corosolic acid (CA), oleanolic acid (OA) and ursolic acid (UA), with a mass ratio of 11:26:10:53. Crude TTAs sample was further separated by C18 reverse-phase silica gel column chromatography using 80% ethanol aqueous solution as mobile phase under high pressure (15 Mpa). By this mean, CA sample with 69.30% purity (MA to CA mass ratio 7:18) and UA sample with 93.94% purity (OA to UA mass ratio 4:21) were obtained. The in vitro antioxidant ability order of the attained TTAs samples was CA sample > crude TTAs sample > UA sample. This study laid a good scientific basis for applying HDES and C18 reverse-phase silica gel column chromatography in the bioactive component extraction and separation fields. It also provided theoretical basis and technical support for obtainment and utilization of high-purity loquat leaf TTAs in the fields of medicine, functional food, cosmetics and so on.

Enzyme immobilized on magnetic fluorescent bifunctional nanoparticles for α-glucosidase inhibitors virtual screening from Agrimonia pilosa Ledeb extracts accompanied with molecular modeling

Agrimonia pilosa Ledeb (APL) is a significant source of inhibitors for α-glucosidase, which is an essential target enzyme for the treatment of type 2 diabetes, cancer and acquired immune deficiency syndrome. Ligand fishing is a suitable approach for the highly selective screening of bioactive substances in complex mixtures. Yet it is unable to conduct biomedical imaging screening, which is crucial for real-time identification. In this case, a bioanalytical platform combining magnetic fluorescent ligand fishing and in-situ imaging technique was established for the screening and identification of α-glucosidase inhibitors (AGIs) from APL crude extract, utilizing α-glucosidase coated CuInS2/ZnS-Fe3O4@SiO2 (AG-CIZSFS) nanocomposites as extracting material and fluorescent tracer. The AG-CIZSFS nanocomposites prepared through solvothermal and crosslinking methods displayed fast magnetic separation, excellent fluorescence performance and high enzyme activity. The tolerance of immobilized enzyme to temperature and pH was stronger than that of free enzyme. Prior to proof-of-concept with APL crude extract, a number essential parameters (glutaraldehyde concentration, immobilized time, enzyme amount, reaction solution pH, incubation temperature, incubation time, percentage of methanol in eluen, elution times and eluent volume) were optimized using an artificial test mixture. The fished ligands were identified by UPLC-MS/MS and their biological activities were preliminarily evaluated by real-time cellular morphological imaging of human colon carcinoma (HCT-116) cells based on confocal laser scanning microscope (CLSM). Their α-glucosidase inhibitory activities were further verified and studied by classical pNPG method and molecular docking. The isolated compounds exhibited significant α-glucosidase inhibitory activities with a IC50 value of 11.57 µg·mL−1. Six potential AGIs including tribuloside, ivorengenin A, tormentic acid, 1β, 2β, 3β, 19α-Tetra hydroxyurs-12-en-28-oic acid, corosolic acid and pomolic acid were ultimately screened out and identified from APL crude extracts. The proposed approach, which combined highly specific screening with in-situ visual imaging, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicine (TCM).

Antioxidant and hypercholesterolemia effects of Lagerstroemia speciosa ethanolic green and red leaf extracts against Lauric acid and ketogenic diets in female albino rats

The study investigates the therapeutic value of Lagerstroemia speciosa ethanolic green and red leaf extracts against Lauric acid (LA) and a Ketogenic diet (KGD) in Albino rats. Lauric acid is an important constituent in breast milk, forming nutritional factors and having various medicinal values. It is present in 6.2% of human breast milk, 3.1% of goat milk, and 2.9% in cow milk. It is also found in plant sources like coconut, cohune, and palm kernel oil. The Ketogenic diet uses fat, protein, and low carbohydrate for energy. The experimental groups were fed a Ketogenic diet for 21 days, with the treated groups showing a significant increase in blood cell count and Hg levels. The phytochemical profile reveals abundant phytoconstituents, including corosolic acid, lagerstroemin, and anthocyanin, at high levels. The study compared experimental groups fed with LELE Low Dose and High Dose (250 and 500 mg/kg body weight) and standard groups treated with KGD and Lauric acid. The treated groups showed significant elevations in biochemical parameters and increased blood cells and Hg levels. LELE's anti-hypercholesterolemia activity in KGD significantly reduced body weight, total lipid profile, and blood glucose in a dose-dependent manner. The study found that LELE is safe and non-toxic, with the treated group demonstrating dose dependence and decreased obesity.

Anti-Dyslipidemic and Anti-Diabetic Properties of Corosolic Acid: A Narrative Review

Corosolic acid (CA), a natural compound derived from the Banaba tree (Lagerstroemia speciosa), has attracted attention for its potential therapeutic properties in the management of metabolic diseases. This narrative review aims to summarize the current evidence on the anti-dyslipidemic, anti-diabetic, and anti-inflammatory effects of CA and to understand the pharmacokinetics and molecular mechanisms through the analysis of preclinical and clinical studies.

Functional network analysis identifies multiple virulence and antibiotic resistance targets in Stenotrophomonas maltophilia

Stenotrophomonas maltophilia, an emerging multidrug-resistant opportunistic bacterium in humans is of major concern for immunocompromised individuals for causing pneumonia and bloodborne infections. This bacterial pathogen is associated with a considerable fatality/case ratio, with up to 100%, when presented as hemorrhagic fever. It is resistant to commonly used drugs as well as to antibiotic combinations. In-silico based functional network analysis is a key approach to get novel insights into virulence and resistance in pathogenic organisms. This study included the protein-protein interaction (PPI) network analysis of 150 specific genes identified for antibiotic resistance mechanism and virulence pathways. Eight proteins, namely, PilL, FliA, Smlt2260, Smlt2267, CheW, Smlt2318, CheZ, and FliM were identified as hub proteins. Further docking studies of 58 selected phytochemicals were performed against the identified hub proteins. Deoxytubulosine and corosolic acid were found to be potent inhibitors of hub proteins of pathogenic S. maltophilia based on protein-ligand interactive study. Further pharmacophore studies are warranted with these molecules to develop them as novel antibiotics against S. maltophilia.

Pharmacoinformatics-based identification of phytochemicals from Solanum torvum Swartz. fruits as potential inhibitors for MAPK14 protein

Plants and phytocompounds gained more attention because of their unrivalled variety of chemical diversity. In this view, the present study was executed to predict the anticancer potential of Solanum torvum Swartz. fruits derived phytocompounds against one of the breast cancer target proteins (MAPK14, PDB ID: 5ETA, resolution: 2.80 Å) through pharmacoinformatics-based screening and molecular dynamics simulation tools. Initially, a graph theoretical network approach was used to visualize the genes, enzymes, and proteins involved in the signalling pathway of breast cancer and identify the significant target protein (MAPK14). A total of thirty-three active compounds were selected from S. torvum sw. through the IMPPAT database, and their structures were drawn by Chemsketch software. The drug-like behaviours of the compounds were assessed through pharmacokinetics and physicochemical characterization studies. Five compounds, namely chlorogenin (−10.90 kcal × mol−1), corosolic acid (−10.80 kcal × mol−1), solaspigenin (−10.80 kcal × mol−1), paniculogenin (−10.70 kcal × mol−1), spirostane-3,6-dione (−10.70 kcal × mol−1) exhibited top binding score against MAPK14, these are higher than that of the standard drug (Doxorubicin) (−8.60 kcal × mol−1). Additionally, the five top-binding compounds revealed better drug-likeness traits and the lowest toxicity profiles. MD simulation studies confirmed the stability of the top five scored compounds with the MAPK14 binding pockets. According to these findings, the selected five compounds might be used as significant MAPK14 inhibitors and can be used as new medicines for the treatment of breast cancer. Communicated by Ramaswamy H. Sarma

Antibacterial activity of Lagerstreomia speciosa and its active compound, corosolic acid, enhances cefotaxime inhibitory activity against Staphylococcus aureus.

Various epidemiology studies have reported the emergence of Staphylococcus aureus and its methicillin resistance strain causing global health concerns, especially during and post-COVID-19 pandemic. This pathogen presents as a co-infection in patients with COVID-19. In addition, certain virulence factors and resistance to β-lactam antibiotics, including cefotaxime, have been identified. We aimed to investigate the antibacterial activity of Lagerstreomia speciosa, a medicinal plant with antidiabetic activity, against S. aureus, including the strain resistant to methicillin. Furthermore, we examined whether the extract and one of its bioactive compounds, corosolic acid, can enhance the therapeutic effect of cefotaxime on antibiotic-resistant S. aureus. The minimum inhibitory concentration of each substance was determined using the standard broth microdilution test following the checkerboard dilution. The type of interactions, synergistic, additivity, indifference, or antagonism, were determined using isobolograms analysis and the dose reduction index (DRI). The evaluation of synergy and bactericidal activity of the natural products in combination with cefotaxime was performed using the time-kill kinetic assay. Corosolic acid, L. speciosa leaves extract, and bark extract alone showed antibacterial activity against all tested S. aureus ATCC 33591, S. aureus ATCC 29213, S. aureus ATCC 25923, and clinical isolated S. aureus. Corosolic acid enhanced the antibacterial activity of cefotaxime, showing a synergistic effect and greater DRI of cefotaxime against all tested S. aureus strains. Time-kill kinetic assay showed that corosolic acid has a more profound effect than L. speciosa extracts to potentiate the bactericidal activity of cefotaxime. Whereas L. speciosa leaves and bark extract showed some inhibitory effect on the growth of S. aureus after a single administration. Lagerstreomia speciosa leaves and bark extract and its active compound, corosolic acid, could be used as a potential anti-Staphylococcus aureus treatment to enhance the therapeutic use of cefotaxime.

Utilization and evaluation of catalytic activity of hydroxyapatite on the synthesis of some corosolic acid amide

Hydroxyapatite was employed as a catalyst for the synthesis of 17C-corosolic amide by the condensation of 17C-corosolic acid chloride and phenyl hydrazide under solvent-free microwave irradiation technique. In this condensation the obtained yield is more than 87%. Within this condensation the catalytic activity and reusability of this hydroxy apatite was investigated on the basis of percentage of yield. The prepared amide was characterized by their analytical and spectroscopic data.

Dietary Polyphenols Remodel DNA Methylation Patterns of NRF2 in Chronic Disease.

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in regulating cellular homeostasis and apoptosis. The NRF2 gene has been implicated in various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. NRF2 can be regulated genetically and epigenetically at the transcriptional, post-transcriptional, and translational levels. Although DNA methylation is one of the critical biological processes vital for gene expression, sometimes, anomalous methylation patterns result in the dysregulation of genes and consequent diseases and disorders. Several studies have reported promoter hypermethylation downregulated NRF2 expression and its downstream targets. In contrast to the unalterable nature of genetic patterns, epigenetic changes can be reversed, opening up new possibilities in developing therapies for various metabolic disorders and diseases. This review discusses the current state of the NRF2-mediated antioxidative and chemopreventive activities of several natural phytochemicals, including sulforaphane, resveratrol, curcumin, luteolin, corosolic acid, apigenin, and most other compounds that have been found to activate NRF2. This epigenetic reversal of hypermethylated NRF2 states provides new opportunities for research into dietary phytochemistry that affects the human epigenome and the possibility for cutting-edge approaches to target NRF2-mediated signaling to prevent chronic disorders.

Integrating network pharmacology and experimental models to examine the mechanisms of corosolic acid in preventing hepatocellular carcinoma progression through activation PERK-eIF2a-ATF4 signaling.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with a high recurrence rate and heterogeneity. We aimed to examine the effect of corosolic acid (CRA) on HCC. We employed transcriptomics to validate the target molecules in CRA-treated HCC cells and conducted enrichment analyses that revealed their involvement in the regulation of endoplasmic reticulum (ER) stress and apoptosis. Our experimental data indicated that CRA markedly induced apoptosis in human HCC cell lines through the mitochondrial apoptosis pathway. We also revealed that the pro-apoptotic effects of CRA depended on ER stress, as pretreatment with selective ERS inhibitor salubrinal effectively reversed CRA-induced cell apoptosis. Furthermore, the knockdown of the unfolded protein response (UPR) protein CHOP remarkably abrogated CRA-induced expression of ER stress-associated proteins. Collectively, our results suggest that CRA triggers ER stress-mediated apoptosis in HCC cells via activation of the PERK-eIF2a-ATF4 pathway. Our findings provide novel insights into the potential therapeutic strategies for HCC.

Modulation of Kv7 Channel Currents by Echinocystic Acid.

Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-7.5). Pentacyclic triterpenes display extensive pharmacological activities including anti-tumor, anti-inflammatory, and anti-depression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and ⍺-boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC50) of 2.5 µM. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid non-selectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. Significance Statement Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and anti-depression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a non-selective manner.

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

BackgroundCorosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization.MethodsDifferentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting.ResultsA total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels.ConclusionOur results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.

Bioassay-guided isolation of BACE1 inhibitors from Crataegus pinnatifida

BackgroundCrataegus pinnatifida, functional food has been used in traditional Chinese medicine due to its significant pharmacological effects on various metabolic disorders, neurodegenerative diseases, as well as anti-cancer and anti-viral properties. Despite numerous studies reporting its anti-Alzheimer's disease (AD) activity, there is currently no research on the potential of its extract or constituents to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE1). MethodsThe study aimed to evaluate the inhibitory effects of the methanolic extract of C. pinnatifida and its solvent-soluble fractions on cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Following a bioassay-guided isolation, we identified several compounds, including two triterpenoids [corosolic acid (1), euscaphic acid (2)], β-sitosterol glucoside (3), three flavonoids [astragalin (4), hyperoside (5), isovitexin (6)], and four phenolic acid derivatives [gentisic acid (7), protocatechuic acid (8), p-hydroxybenzoic acid (9), p-coumaric acid (10)] from EtOAc fraction. Additionally, two triterpenoids (3-epicorosolic acid (11) and ursolic acid (12)) and β-sitosterol (13) were isolated from the CH2Cl2 fraction, while isoorientin (14) and hymenoside X (15) were isolated from n-BuOH fraction. Notably, compounds 2, 7, 10, and 14 were reported for the first time from the fruit of C. pinnatifida. ResultsWe observed that 3-epicorosolic acid (11) exhibited promising inhibitory activity against BACE1 with IC50 values of 40.12 ± 1.72 µM. Hyperoside (5) showed moderate activity with IC50 values of 98.50 ± 4.20 µM, while corosolic acid (1) and astragalin (4) displayed mild BACE1 inhibitory activity, with IC50 values of 179.55 ± 1.57 and 192.30 ± 5.14 µM, respectively. We also investigated the structure activity relationship of ursane-type triterpenoids based on in vitro and in silico results, which revealed that the hydroxyl groups position of the triterpenes have a significant impact on their potency. Our findings suggest that α‑hydroxyl group at the C-2 and C-3 positions and the absence of α‑hydroxyl group at the C-19 position are essential for BACE1 inhibitory activity. ConclusionsThis study highlights the significance of the configuration and position of hydroxyl groups and their impact on BACE1 inhibitory activity. The findings of this study could be leveraged to develop novel therapeutic approaches for Alzheimer's disease.

Corosolic acid-modified lipid nanoparticles as delivery carriers for DNA vaccines against avian influenza

Cholesterol (CHOL) is essential for developing lipid nanoparticles (LNPs) for gene delivery because it enhances membrane fusion and improves the delivery efficiency of gene cargos. An attractive pDNA carrier, corosolic acid (CA)-modified lipid nanoparticles (CLNPs), was developed by replacing CHOL in LNPs to deliver pDNA at various ratios of nitrogen groups to phosphate groups (N/P). The resultant CLNPs with a higher CHOL/CA ratio exhibited similar mean particle size, zeta potential, and encapsulation efficiency to those of LNPs. In comparison with LNPs, CLNPs (CHOL:CA ratio = 2:1) achieved increased cellular uptake and enhanced transfection efficacy while maintaining low cytotoxicity. In vivo results from chicken experiments demonstrated that CLNPs encapsulating DNA vaccines against avian influenza at a N/P ratio of 3 could elicit similar-level humoral and cellular immune responses compared with those of LNPs at a higher N/P ratio, thereby suggesting the induction of desirable immune effects using less ionizable lipids. Our study provides a reference for further research on the application of CA in LNPs for gene delivery, and the development of novel delivery systems for DNA vaccines against avian influenza.

An in vitro investigation of the apoptosis-inducing activity of corosolic acid in breast cancer cells.

Breast cancer is the most prevalent cancer among females with different molecular subtypes. Corosolic acid is a pentacyclic triterpenoid with anti-cancer properties. The MTT assay was used to assess the cytotoxic activity of corosolic acid on MDA-MB-231 and MCF7 cell lines. To determine the apoptotic cells, the flow cytometry technique was utilized. The expression levels of apoptosis-related genes and proteins were quantified using quantitative real time-PCR (qRT-PCR) and Western blotting methods. The activity of caspase enzymes was measured by spectrophotometry. Corosolic acid significantly inhibited the proliferation of both cell lines compared with controls. This agent markedly induced apoptosis in MDA-MB-231 cells but did not affect MCF7 cells compared with controls. Treating the MADA-MB-231 and MCF7 cell lines with corosolic acid showed an inducing effect on apoptosis-associated caspases, including Caspase-8, 9, and -3, in MADA-MB-231 cells with no effect on apoptotic markers in MCF7 cells. Further experiments uncovered corosolic acid-induced apoptosis in MADA-MB-231 cells by decreasing the expression of the phosphorylated form of JAK2 and STAT3 proteins. The present data suggested that corosolic acid is an apoptosis-inducing phytochemical in triple-negative breast cancer MADA-MB-231 cells. Also, corosolic acid triggered apoptosis in these cells by stimulating both pathways of apoptosis and inhibiting the JAK/STAT signaling. Furthermore, corosolic acid was found to inhibit MCF7 cell proliferation by a non-apoptotic mechanism.

Phytochemistry, Pharmacological Properties and Medicinal Uses of Apium leptophyllum: A Review

Apium leptophyllum seeds are used as an important drug in Ayurveda from ancient times. The main constituents of the seed are fats, fibre, carbohydrates and essential oils, about 50% of which consists of Thymol. Chromatographic analysis of the seed showed various essential compounds viz. Pentacosanol, β-Sitosterol, 1-nonadecanol, 8-hydroxy cuminic acid, Corosolic acid and Stigmasterol. The seeds have shown strong antioxidant properties along with various other pharmacological properties like anti-microbial, anti-fungal, anti-diabetic, anti-inflammatory, anti-diarrheal, antiasthmatic and anti-cancer properties. This review aims to provide a comprehensive overview of scientific research literature on the chemical composition and pharmacological activities of Apium leptophyllum. We are the first to report vast and updated review of this plant, as much of the work has not been done on this plant. So this review may be helpful for the researchers to explore the pharmacological properties of this plant which may lead to new discoveries in drug development.

The Cardioprotective Effect of Corosolic Acid in the Diabetic Rats: A Possible Mechanism of the PPAR-γ Pathway.

The study was conducted to determine whether corosolic acid could protect the myocardium of diabetic rats from damage caused by isoproterenol (ISO) and, if so, how peroxisome proliferator-activated receptor gamma (PPAR-γ) activation might contribute into this protection. Diabetes in the rats was induced by streptozotocin (STZ), and it was divided into four groups: the diabetic control group, diabetic rats treated with corosolic acid, diabetic rats treated with GW9662, and diabetic rats treated with corosolic acid plus GW9662. The study was carried out for 28 days. The diabetic control and ISO control groups showed a decrease in mean arterial pressure (MAP) and diastolic arterial pressure (DAP) and an increase in systolic arterial pressure (SAP). The rat myocardium was activated by corosolic acid treatment, which elevated PPAR-γ expression. A histopathological analysis showed a significant reduction in myocardial damage by reducing myonecrosis and edema. It was found that myocardial levels of CK-MB and LDH levels were significantly increased after treatment with corosolic acid. By decreasing lipid peroxidation and increasing endogenous antioxidant levels, corosolic acid therapy showed a significant improvement over the ISO diabetic group. In conclusion, our results prove that corosolic acid can ameliorate ISO-induced acute myocardial injury in rats. Based on these results, corosolic acid seems to be a viable new target for the treatment of cardiovascular diseases and other diseases of a similar nature.