Pentacyclic Triterpenoid Acids Research Articles

The inhibitory mechanism of pentacyclic triterpenoid acids on pancreatic lipase and cholesterol esterase

Inhibiting pancreatic Lipase (PL) and cholesterol esterase (CEase) can effectively control blood triglycerides and cholesterol levels. The interaction characteristics of pentacyclic triterpenoid acids (oleanolic acid [OA], ursolic acid [UA], and corosolic acid [CA]) with PL and CEase were studied by inhibition kinetics, multispectroscopy, and molecular docking methods. Enzyme inhibition and inhibition kinetics showed that pentacyclic triterpenoid acids effectively inhibited PL and CEase in a competitive manner with IC50 values ranging from 0.077 mg/mL to 0.446 mg/mL. UV–Vis, fourier transform infrared, fluorescence quenching, and circular dichroism analysis demonstrated that OA, UA, and CA disrupted the conformation of PL and CEase through hydrogen bonding and hydrophobic forces, resulting in loose protein structures. Molecular docking analysis revealed that pentacyclic triterpenoid acids could stably bind at key residues in the active site of PL and CEase. Molecular dynamics (MD) simulation further confirmed the stable binding of pentacyclic triterpene acids to PL and CEase. This study suggested that OA, UA, and CA could have an essential value as digestive enzyme inhibitors.

The Chinese herb Styrax triggers pharmacokinetic herb-drug interactions via inhibiting intestinal CYP3A.

Human cytochrome P450 3A4 (hCYP3A4) is a predominant enzyme to trigger clinically relevant drug/herb-drug interactions (DDIs or HDIs). Although a number of herbal medicines have been found with strong anti-hCYP3A4 effects in vitro, the in vivo modulatory effects of herbal medicines on hCYP3A4 and their potential risks to trigger HDIs are rarely investigated. Herein, we demonstrate a case study to efficiently find the herbal medicine(s) with potent hCYP3A4 inhibition in vitro and to accurately assess the potential HDIs risk in vivo. Following screening over 100 herbal medicines, the Chinese herb Styrax was found with the most potent hCYP3A4 inhibition in HLMs. In vitro assays demonstrated that Styrax could potently inhibit mammalian CYP3A in liver and intestinal microsomes from both humans and rats. In vivo pharmacokinetic assays showed that Styrax (i.g., 100 mg/kg) significantly elevated the plasma exposure of two CYP3A-substrate drugs (midazolam and felodipine) when midazolam or felodipine was administered orally. By contrast, the plasma exposure of either midazolam or felodipine was hardly affected by Styrax (i.g.) when the victim drug was administered intravenously. Further investigations demonstrated that seven pentacyclic triterpenoid acids (PTAs) in Styrax were key substances responsible for CYP3A inhibition, while these PTAs could be exposed to intestinal tract at relatively high exposure levels but their exposure levels in rat plasma and liver were extremely low. These findings well explained why Styrax (i.g.) could elevate the plasma exposure of victim drugs only when these agents were orally administrated. Collectively, our findings demonstrate that Styrax can modulate the pharmacokinetic behavior of CYP3A-substrate drugs via inhibiting intestinal CYP3A, which is very helpful for the clinical pharmacologists to better assess the HDIs triggered by Styrax or Styrax-related herbal products.

Protective effects of maslinic acid on high fat diet-induced liver injury in mice

AimsDue to the prevalence of high-fat diets and lack of exercise, diseases related to nutrient metabolism such as nonalcoholic fatty liver disease (NAFLD) have become one of the reasons causes endangering human liver health. Maslinic acid (MA) is a pentacyclic triterpenoid acid that is abundant in fruits such as hawthorn and jujube. In this study, we investigated the effect of MA on NAFLD to inform the development of dietary supplements for the treatment and prevention of NAFLD. Materials and methodsThe NAFLD model was established by feeding mice a high-fat diet (HFD). HEPG2 cells were treated with oleic acid and used as a cell culture model. Testing kits, haematoxylin and eosin staining, oil red O staining, western blotting, and immunofluorescence were performed with in vivo and in vitro experiments. Key findingsThe current study revealed that MA significantly reduced liver weight, body weight and serum lipid levels, and protected against liver steatosis and injury induced by a HFD. MA increased the expression of Beclin1, ATG1, and Bcl-2 mRNA and protein while decreasing the expression of TNF-α and IL-1β, caspase-3 and Bax mRNA and protein. Beclin1, and ATG1 were obviously increased, and the mRNA and protein expression of TNF-α and IL-1β were obviously reduced, the mRNA and protein expression of Caspase-3 and Bax were obviously reduced, and the mRNA and protein expression of Bax were obviously increased by MA. SignificanceMA reduces the content of fat in the liver cells of NAFLD mice through lipophagy activitiy and reduces inflammation and apoptosis injury.

Role of Pentacyclic Triterpenoid Acids in the Treatment of Bladder Cancer

Abstract: Bladder cancer carries a poor prognosis and has proven resistance to chemotherapy. Pentacyclic Triterpenoid Acids (PTAs) are natural bioactive compounds that have a well-known impact on cancer research because of their cytotoxic and chemopreventive activities. This review focuses on bladder cancer which can no longer be successfully treated by DNA damaging drugs. Unlike most of the existing drugs against bladder cancer, PTAs are non-toxic to normal cells. Collecting findings from both in vitro and in vivo studies, it has been concluded that PTAs may serve as promising agents in future bladder cancer therapy. In this review, the roles of various PTAs in bladder cancer have been explored, and their mechanisms of action in the treatment of bladder cancer have been described. Specific PTAs have been shortlisted from each of the chief skeletons of pentacyclic triterpenoids, which could be effective against bladder cancer because of their mode of action. This review thereby throws light on the multi targets and mechanisms of PTAs, which are responsible for their selective anticancer effects and provides guidelines for further research and development of new natural antitumor compounds.

A simplified HPLC-UV method for the analysis of triterpenoid acids from heritage apples (Malus domestica) from western North Carolina, USA

Background: Pentacyclic triterpenoid acids are common in a number of food and spice plant species. Apples (Malus domestica) are the most common human food source for these potentially beneficial phytochemicals. Pre-20th century heritage apples have long been grown in mountainous western North Carolina and may be a wide-ranging source of these phytochemicals. Objectives: Existing extraction and analytical methods were improved and used to assess the content of three triterpenoid acids in heritage apple cultivars grown in western North Carolina, USA.Methods: Apples from a local farmers market were collected during the fall apple season. Apple peels were freeze dried, ground, and extracted with ethanol thrice. Extracts were analyzed by HPLC against external standards for betulinic, oleanolic, and ursolic acids.Results: The improved method was used to extract and to analyze the triterpenoid acid levels in 16 heritage apple cultivars grown in the Appalachian region of western North Carolina. Total triterpenoid acids ranged from 2 to 29 mg/g dry weight of peels. Content did not vary by apple color or time of harvest. Russeted varieties contained noticeably less triterpenoids.Conclusions: An improved and simplified method was used for the analysis of heritage apple varieties in western North Carolinas. A wide range of values was found for these compounds of increasing interest in the human diet and in human health.Keywords:apples, phytochemicals, triterpenoids, ursolic acid, Appalachia

Isolation of Bioactive Pentacyclic Triterpenoid Acids from Olive Tree Leaves with Flash Chromatography

The present study reports on the use of the flash chromatography for the isolation and purification of oleanolic and maslinic acids from olive leaf extracts. Although the separation and identification of these acids is considered challenging due to the similarity in their structure, oleanolic and maslinic acids were detected, identified, and separated. Solubility prediction was used to help to match compatibility of extraction solvent with targeted triterpenoid acids. Aqueous washing was used, to first selectively remove unwanted interferents from the extraction solvent. The extracts obtained with different solvents and solvent mixtures were fractionated using flash chromatography and then analyzed. HPTLC chromatography was used to assess collected fractions as either semi-pure or pure, and to identify the fractions containing oleanolic and maslinic acids. The yields of oleanolic and maslinic acids reported here are significantly higher than yields obtained in previously reported isolations. The presence and purity of oleanolic and maslinic acid in collected fractions was confirmed by ATR-FTIR and NMR spectrometry.

Potential Mechanism of Maslinic Acid against Hypolipidemia Based on Network Pharmacology and Molecular Docking Integration Strategy

Maslinic acid is a pentacyclic triterpenoid acid. Recent research has shown that it has various biological activities such as anti-tumor, hypoglycaemic and hypolipidemic. Among them, the hypolipidemic effect is prominent and this study aims to further explore its mechanism of action in the treatment of hyperlipidemia. The chemical structure of maslinic acid was obtained from PubChem. Based on its chemical structure, the bioavailability and drug-like properties of maslinic acid were analyzed using Swiss absorption, distribution, metabolism and excretion and its potential targets were obtained from SwissTargetPrediction and PharmMapper. Then, the differentially expressed genes between hyperlipidemia patients and the health group were analyzed through the gene expression omnibus data set, and the related targets of hyperlipidemia were complemented using DrugBank, online Mendelian inheritance in man, GeneCards, DisGeNET and therapeutic target databases. Then, the protein-protein interaction network was constructed, the CytoNCA plugin and VarElect were used to screen core targets and metascape was used to systematically analyze the core targets and explore the mechanism. Finally, molecular docking showcased the interaction model. A total of 288 maslinic acid targets and 289 hyperlipidemia-related targets were collected and 18 potential therapeutic targets were found. The enrichment analysis results further systematically explained the effect of maslinic acid on hyperlipidemia. Maslinic acid can treat hyperlipidemia through complex interactions in which the regulation of core genes including albumin, peroxisome proliferator activated receptor alpha and apolipoprotein, and the regulation of peroxisome proliferator activated receptor signaling pathway play a major role.

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.

Liver-targeted delivery of asiatic acid nanostructured lipid carrier for the treatment of liver fibrosis

Liver fibrosis is a major global health concern. Management of chronic liver disease is severely restricted in clinics due to ineffective treatment approaches. However, a lack of targeted therapy may aggravate this condition. Asiatic acid (AA), a pentacyclic triterpenoid acid, can effectively protect the liver from hepatic disorders. However, the pharmaceutical application of AA is limited by low oral bioavailability and poor targeting efficiency. This study synthesized a novel liver-targeting material from PEG-SA, chemically linked to ursodeoxycholic acid (UA), and utilized it to modify AA nanostructured lipid carriers (UP-AA-NLC) with enhanced targeting and improved efficacy. The formulation of UP-AA-NLC was optimized via the Box–Behnken Experimental Design (BBD) and characterized by size, zeta potential, TEM, DSC, and XRD. Furthermore, in vitro antifibrotic activity and proliferation of AA and NLCs were assessed in LX-2 cells. The addition of UP-AA-NLC significantly stimulated the TGF-beta1-induced expression of α-SMA, FN1, and Col I α1. In vivo near-infrared fluorescence imaging and distribution trials in rats demonstrated that UP-AA-NLC could significantly improve oral absorption and liver-targeting efficiency. Oral UP-AA-NLC greatly alleviated carbon tetrachloride-induced liver injury and fibrosis in rats in a dosage-dependent manner, as reflected by serum biochemical parameters (AST, ALT, and ALB), histopathological features (H&E and Masson staining), and antioxidant activity parameters (SOD and MDA). Also, treatment with UP-AA-NLC lowered liver hydroxyproline levels, demonstrating a reduction of collagen accumulation in the fibrotic liver. Collectively, optimized UP-AA-NLC has potential application prospects in liver-targeted therapy and holds great promise as a drug delivery system for treating liver diseases.

Discovery and characterization of pentacyclic triterpenoid acids in Styrax as potent and reversible pancreatic lipase inhibitors

• Styrax extract was found with strong pancreatic lipase (PL) inhibition activity. • Bioactivity and LC-MS guided fractionation strategy was used to identify naturally occurring PL inhibitors in Styrax. • Oleanonic acid (ONA) and betulonic acid (BNA) potently inhibit PL, with IC 50 values less than 1.5 μM. • Inhibitory mechanisms of ONA and BNA against PL were investigated by inhibition kinetic analyses and in silico analysis. Pancreatic lipase (PL) inhibitor therapy is one of the most effective ways to treat obesity and obesity-associated metabolic disorders. Herein, bioactivity and liquid chromatograph-mass spectrometer (LC-MS) guided fractionation strategy was used to identify the naturally occurring PL inhibitors in Styrax, a popular folk medicine in Asia and Turkey. The results clearly showed that five pentacyclic triterpenoid acids in Styrax displayed strong inhibition on PL, with IC 50 values ranging from 0.49 µM to 6.35 µM. Further investigations demonstrated that oleanonic acid and betulonic acid (the most two potent PL inhibitors in Styrax) potently inhibited PL in a reversible and mixed inhibition manner, while molecular dynamics simulations showed that these two agents could stably bind at the entrance to the active site of PL. Collectively, our findings revealed the molecular basis for the anti-obesity effects of Styrax, while the newly identified PL inhibitors in this herb could be used for development of novel anti-obesity agents.

Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism

BackgroundStyrax, one of the most famous folk medicines, has been frequently used for the treatment of cardiovascular diseases and skin problems in Asia and Africa. It is unclear whether Styrax or Styrax-related herbal medicines may trigger clinically relevant herb-drug interactions. PurposeThis study was carried out to investigate the inhibitory effects of Styrax on human cytochrome P450 enzymes (CYPs) and to clarify whether this herb may modulate the pharmacokinetic behavior of the CYP-substrate drug warfarin when co-administered. Study DesignThe inhibitory effects of Styrax on CYPs were assayed in human liver microsomes (HLM), while the pharmacokinetic interactions between Styrax and warfarin were investigated in rats. The bioactive constituents in Styrax with strong CYP3A inhibitory activity were identified and their inhibitory mechanisms were carefully investigated. MethodsThe inhibitory effects of Styrax on human CYPs were assayed in vitro, while the pharmacokinetic interactions between Styrax and warfarin were studied in rats. Fingerprinting analysis of Styrax coupled with LC-TOF-MS/MS profiling and CYP inhibition assays were used to identify the constituents with strong CYP3A inhibitory activity. The inhibitory mechanism of oleanonic acid (the most potent CYP3A inhibitor occurring in Styrax) against CYP3A4 was investigated by a panel of inhibition kinetics analyses and in silico analysis. ResultsIn vitro assays demonstrated that Styrax extract strongly inhibited human CYP3A and moderately inhibited six other tested human CYPs, as well as potently inhibited warfarin 10-hydroxylation in liver microsomes from both humans and rats. In vivo assays demonstrated that compared with warfarin given individually in rats, Styrax (100 mg/kg) significantly prolonged the plasma half-life of warfarin by 2.3-fold and increased the AUC(0-inf) of warfarin by 2.7-fold when this herb was co-administrated with warfarin (2 mg/kg) in rats. Two LC fractions were found with strong CYP3A inhibitory activity and the major constituents in these fractions were characterized by LC-TOF-MS/MS. Five pentacyclic triterpenoid acids (including epibetulinic acid, betulinic acid, betulonic acid, oleanonic acid and maslinic acid) present in Styrax were potent CYP3A inhibitors, and oleanonic acid was a competitive inhibitor against CYP3A-mediated testosterone 6β-hydroxylation. ConclusionStyrax and the pentacyclic triterpenoid acids occurring in this herb strongly modulate the pharmacokinetic behavior of warfarin via inhibition of CYP3A.

Pentacyclic triterpenoid acids in Styrax as potent and highly specific inhibitors against human carboxylesterase 1A.

Human carboxylesterase 1A1 (hCES1A) is a promising target for the treatment of hyperlipidemia and obesity-associated metabolic diseases. To date, the highly specific and efficacious hCES1A inhibitors are rarely reported. This study aims to find potent and highly specific hCES1A inhibitors from herbs, and to investigate their inhibitory mechanisms. Following large-scale screening of herbal products, Styrax was found to have the most potent hCES1A inhibition activity. After that, a practical bioactivity-guided fractionation coupling with a chemical profiling strategy was used to identify the fractions from Styrax with strong hCES1A inhibition activity and the major constituents in these bioactive fractions were characterized by LC-TOF-MS/MS. The results demonstrated that seven pentacyclic triterpenoid acids (PTAs) in two bioactive fractions from Styrax potently inhibit hCES1A, with IC50 values ranging from 41 nM to 478 nM. Among all the identified PTAs, epibetulinic acid showed the most potent inhibition activity and excellent specificity towards hCES1A. Both inhibition kinetic analyses and in silico analysis suggested that epibetulinic acid potently inhibited hCES1A in a mixed inhibition manner. Collectively, our findings demonstrate that some PTAs in Styrax are potent and highly specific inhibitors of hCES1A and these constituents can be used as promising lead compounds for the development of more efficacious hCES1A inhibitors.

Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors.

Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular end-points with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-κB, STAT3, Nrf2, TGR5) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (5b) was selected for further studies, and evaluation of its effect on HIF-1α expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.

Bioactive triterpenoids from the caffeine-rich plants guayusa and maté

Unlike all other caffeinated plants, guayusa (Ilex guayusa Loes.) and maté (Ilex paraguariensis A. St. Hill) contain high amounts of pentacyclic triterpenoid acids and alcohols. A phytochemical investigation on these plants revealed a similar triterpenoid profile and a content of ursolic acid (0.7–1%) and amyrin esters (up to 0.5%), quite unusual for dietary plants. The major constituent of the amyrin complex from both plants is α-amyrin palmitate (2a), accompanied by lower amounts of its corresponding palmitoleate (2b) and by the corresponding constitutional isomers from the β-series (3a and 3b, respectively). Ursolic acid (1) was identified as the responsible for the activity of maté and guayusa extracts in the activation of TGR5, a nuclear receptor of relevance for the prevention and management of diabetes and metabolic syndrome because of its involvement in the regulation of energy expenditure and insulin sensitivity.

Solid inclusion complexes of oleanolic acid with amino-appended β-cyclodextrins (ACDs): Preparation, characterization, water solubility and anticancer activity

Oleanolic acid (OA) is a pentacyclic triterpenoid acid of natural abundance in plants which possesses important biological activities. However, its medicinal applications were severely impeded by the poor water solubility and resultant low bioavailability and potency. In this work, studies on solid inclusion complexes of OA with a series of amino-appended β-cyclodextrins (ACDs) were conducted in order to address this issue. These complexes were prepared by suspension method and were well characterized by NMR, SEM, XRD, TG, DSC and Zeta potential measurement. The 2:1 inclusion mode of ACDs/OA complexes was elucidated by elaborate 2D NMR (ROESY). Besides, water solubility of OA was dramatically promoted by inclusion complexation with ACDs. Moreover, in vitro anticancer activities of OA against human cancer cell lines HepG2, HT29 and HCT116 were significantly enhanced after formation of inclusion complexes, while the apoptotic response results indicated their induction of apoptosis of cancer cells. This could provide a novel approach to development of novel pharmaceutical formulations of OA.

Plastotoma rotundifolium aerial tissue extract has antibacterial activities

Despite efforts in recent years, infectious diseases remain a worldwide major public health problem. Several infectious agents have become resistant to conventional antibiotics and there is thus urgent need to discover new antimicrobial drugs to overcome resistances. Platostoma rotundifolium (Briq.) A. J. Paton, an African plant, is mainly used to treat microbial infections in traditional Burundian medicine. From the ethyl acetate extract of the aerial parts, five pentacyclic triterpenoid acids were isolated and characterized. Based on spectral analysis, these compounds were elucidated to be 2α, 3α, 19β-trihydroxyurs-12-en-28-oic acid (that was named jeremic acid) (1), 3β-hydroxyurs-12-en-28-oic acid (ursolic acid) (2), 2α, 3β-dihydroxyurs-12-en-28-oic acid (corosolic acid) (3), 2α, 3β, 19α-trihydroxyurs-2-en-28-oic acid (tormentic acid) (4) and 19-hydroxy-2-hydroxymethyl norursa-2, 12-dien-28-oic acid (hyptadienic acid) (5). Ursolic (MIC=17.5–68μM) and corosolic (MIC=17–68μM) acids showed significant antibacterial activities against both the Gram-positive Staphylococcus aureus (methicillin-susceptible and -resistant strains) and the Gram-negative Escherichia coli, which may substantiate the use of P. rotundifolium in traditional Burundian medicine. Such hydroxylated pentacyclic triterpenoid acids could point to new antimicrobial strategies that may help overcoming the antimicrobial resistances actually observed throughout the world.

Optimization of Betulinic Acid Extraction from Tecomella undulata Bark Using a Box-Behnken Design and Its Densitometric Validation.

Betulinic acid (BA) is a pentacyclic triterpenoid acid obtained from the stem bark of Tecomella undulata Seem. (Bignoniaceae). Development of an efficient extraction method for the isolation of BA is important as it has a wide range of pharmacological activity. A Box-Behnken design (BBD) was used to investigate the effect of extraction variables such as temperature (30–60 °C), time (4–8 h) and solvent to drug ratio (300–500 mL/100 g) on the maximization of BA yield and its quantification using validated densitometric high performance thin layer chromatography coupled with ultraviolet detection (HPTLC-VIS). A quadratic polynomial model was found to best fit the model with R2 = 0.99. The optimized Soxhlet extraction yielded 2.449% w/w of BA at a temperature 53.86 °C, time 6.38 h and solvent to drug ratio 371 mL/100 g. BA in Tecomella undulata bark was detected at Rf value of 0.65 at 510 nm using the solvent system toluene–ethyl acetate–glacial acetic acid (8.5:1.5:0.02 v/v/v). The analytical method was validated and the linear regression analysis reflects good linear relationship (R2 = 0.9902). Lower %RSD and SEM suggested that the developed HPTLC-VIS method was precise, accurate and robust. Therefore, these economical techniques are very efficient and promising for the extraction and quantification of pharmaceutically important BA.

Triterpenoids from the seedpods of Holarrhena curtisii King and Gamble

Two new hydroperoxy pentacyclic triterpenoids, 3β-hydroxy-11α-hydroperoxyolean-12-en-28-oic acid (1) and 3β-hydroxy-11α-hydroperoxyursan-12-en-28-oic acid (2), together with nine known triterpenoids, squalene (3), β-amyrin acetate (4), α-amyrin acetate (5), lupeol acetate (6), lupeol (7), lanosta-7,24-dien-3β-ol (8), cycloeucalenol (9), oleanolic acid (11) and ursolic acid (12), a known phytosterol, 24-methylenepollinastanol (10), and two known flavanols, (–)-catechin (13) and (–)-gallocatechin (14), were isolated from the methanolic extract of the fresh seedpods of Holarrhena curtisii. Their structures were determined by spectroscopic analysis (one and two dimensional nuclear magnetic resonance, high resolution electrospray ionization mass spectrometry and attenuated total reflectance-Fourier transform infrared spectroscopy). All compounds (except squalene) were evaluated for their in vitro α-glucosidase inhibitory activity. Compounds 1, 2, 11 and 12, which had a pentacyclic triterpenoid acid skeleton, showed a strong in vitro α-glucosidase inhibitory activity compared to that of the standard control, acarbose.

Recent Advances in Enone and NO-Releasing Derivatives of Oleanolic Acid with Anti-cancer Activity

Oleanolic acid (OA) is a natural pentacyclic triterpenoid acid with diverse biological activities including antiinflammation, suppression of tumor promotion, protection of the liver against toxic injury, and induction of differentiation. However, the potency of OA as an anti-cancer agent is relatively weak. Therefore, remarkable progress has been made in the modification of OA to improve its anti-cancer activity over the past few years. This paper reviews the progress mainly on anti-cancer activity of enone derivatives and nitric oxide (NO)-releasing derivatives of OA over the last decade. Keywords: Anti-cancer, CDDO, enone derivative, nitric oxide (NO), NO-releasing derivative, oleanolic acid (OA).

Ursolic acid inhibits nuclear factor-κB signaling in intestinal epithelial cells and macrophages, and attenuates experimental colitis in mice

AimsUrsolic acid (UA), a natural pentacyclic triterpenoid acid, has been reported to show immunomodulatory activity. This study investigated the effects of UA on nuclear factor-kappa B (NF-κB) signaling in cells and experimental murine colitis. Main methodsHuman intestinal epithelial cells (IECs) COLO 205 and peritoneal macrophages from IL-10-deficient (IL-10−/−) mice were pretreated with UA and then stimulated with tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS), respectively. The expression of pro-inflammatory cytokines was determined by real-time RT-PCR and ELISA. The effect of UA on NF-κB signaling was examined by immunoblot analysis to detect IκBα phosphorylation/degradation and electrophoretic mobility shift assay to assess the DNA binding activity of NF-κB. For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10−/− mice were treated with or without UA. Colitis was quantified by histopathologic evaluation. Immunohistochemical staining for phosphorylated IκBα was performed in the colonic tissue. Key findingsUA significantly inhibited the production of pro-inflammatory cytokines, IκBα phosphorylation/degradation and NF-κB DNA binding activity in both IEC and IL-10−/− peritoneal macrophages stimulated with TNF-α and LPS, respectively. UA significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histopathology. UA also significantly ameliorated the severity of colitis in IL-10−/− mice. Furthermore, UA suppressed IκBα phosphorylation in the colonic tissue. SignificanceUA inhibits NF-κB activation in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that UA is a potential therapeutic agent for inflammatory bowel disease.