2α-hydroxyursolic Acid Research Articles

Protective Effects of Dipterocarpus tuberculatus in Blue Light-Induced Macular Degeneration in A2E-Laden ARPE19 Cells and Retina of Balb/c Mice.

Natural products with significant antioxidant activity have been receiving attention as one of the treatment strategies to prevent age-related macular degeneration (AMD). Reactive oxygen intermediates (ROI) including oxo-N-retinylidene-N-retinylethanolamine (oxo-A2E) and singlet oxygen-induced damage, are believed to be one of the major causes of the development of AMD. To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against blue light (BL)-caused macular degeneration, alterations in the antioxidant activity, apoptosis pathway, neovascularization, inflammatory response, and retinal degeneration were analyzed in A2E-laden ARPE19 cells and Balb/c mice after exposure of BL. Seven bioactive components, including 2α-hydroxyursolic acid, ε-viniferin, asiatic acid, bergenin, ellagic acid, gallic acid and oleanolic acid, were detected in MED. MED exhibited high DPPH and ABTS free radical scavenging activity. BL-induced increases in intracellular reactive oxygen species (ROS) production and nitric oxide (NO) concentration were suppressed by MED treatment. A significant recovery of antioxidant capacity by an increase in superoxide dismutase enzyme (SOD) activity, SOD expression levels, and nuclear factor erythroid 2-related factor 2 (NRF2) expression were detected as results of MED treatment effects. The activation of the apoptosis pathway, the expression of neovascular proteins, cyclooxygenase-2 (COX-2)-induced inducible nitric oxide synthase (iNOS) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was remarkably inhibited in the MED treated group compared to the Vehicle-treated group in the AMD cell model. Furthermore, MED displayed protective effects in BL-induced retinal degeneration through improvement in the thickness of the whole retina, outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) in Balb/c mice. Taken together, these results indicate that MED exhibits protective effects in BL-induced retinal degeneration and has the potential in the future to be developed as a treatment option for dry AMD with atrophy of retinal pigment epithelial (RPE) cells.

Analysis of the pharmacodynamic difference between Xiaojin Pills taken with Chinese Baijiu and water based on serum pharmacochemistry and pharmacokinetics

Ethnopharmacological relevanceXiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs “taken orally after soaked with Chinese Baijiu” in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. Aim of the studyTo analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs “taken orally after soaked with Chinese Baijiu”. Materials and methodsUltra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. ResultsThe identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-β-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-β-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-β-boswellic acid in XJP&B were relatively longer. ConclusionThis research proved that “taking XJPs orally after being soaked with Chinese Baijiu” can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs “taken orally after soaked with Chinese Baijiu”, which can provide a theoretical basis for the optimization of XJPs’ clinical administration method.

Modulating the ERK1/2-MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells.

Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA’s antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan–Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells’ progression through inhibition of the ERK1/2–MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC.

Therapeutic Effects of Dipterocarpus tuberculatus with High Antioxidative Activity Against UV-Induced Photoaging of NHDF Cells and Nude Mice.

To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against UV-induced photoaging, we assessed for alterations in the antioxidant activity, anti-apoptotic effects, ECM modulation, skin appearances, and anti-inflammatory response in normal human dermal fibroblast (NHDF) cells and nude mice orally treated with MED. High levels of tannin content and high free radical scavenging activity to DPPH were determined in MED, while seven active components, namely, gallic acid, bergenin, ellagic acid, ε-viniferin, asiatic acid, oleanolic acid, and 2α-hydroxyursolic acid, were identified using LC–MS analyses. UV-induced alterations in the NO concentration, SOD activity, and Nrf2 expression were remarkably recovered in MED-treated NHDF cells. Moreover, the decreased number of apoptotic cells and G2/M phase arrest were observed in the UV + MED-treated groups. Similar recoveries were detected for β-galactosidase, MMP-2/9 expression, and intracellular elastase activity. Furthermore, MED treatment induced suppression of the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation in UV-radiated NHDF cells. The anti-photoaging effects observed in NHDF cells were subsequently evaluated and validated in UV + MED-treated nude mice through skin phenotypes and histopathological structure analyses. Taken together, these results indicate that MED exerts therapeutic effects against UV-induced photoaging and has the potential for future development as a treatment for photoaging.

A Computational Approach to Investigate the HDAC6 and HDAC10 Binding Propensity of Psidium guajava-derived Compounds as Potential Anticancer Agents

Different parts of Psidium guajava are consumed as food and used for medicinal purposes around the world. Although studies have reported their antiproliferative effects via different biochemical mechanisms, their modulatory effects on epigenetic modification of DNA molecules via histone deacetylases (HDACs) are largely unknown. This study was carried out to investigate the histone deacetylase 6 (HDAC6) and histone deacetylase 10 (HDAC10) binding propensity of guava-derived compounds, using in silico methods, in other to identify compounds with HDAC inhibitory potentials. Fifty-nine guava-derived compounds and apicidin, a standard HDAC inhibitor, were docked with HDAC6 and HDAC10 using AutodockVina after modeling (SWISS-MODEL server) and validating (ERRAT and VERIFY-3D) the structure of HDAC10. Molecular interactions between the ligands and the HDACs were viewed with Discovery Studio Visualizer. Prediction of binding sites, surface structural pockets, active sites, area, shape and volume of every pocket and internal cavities of proteins was done using Computed Atlas of Surface Topography of proteins (CASTp) server, while absorption, distribution, metabolism, and excretion (ADME) study of notable compounds was done using Swiss online ADME web tool. 2α-hydroxyursolic acid, asiatic acid, betulinic acid, crategolic acid, guajadial A and B, guavacoumaric acid, guavanoic acid, ilelatifol D, isoneriucoumaric acid, jacoumaric acid, oleanolic acid, psiguadial A, B, and C demonstrated maximum interaction with the selected HDACs. ADME studies revealed that although isoneriucoumaric and jacoumaric acid ranked very high as HDAC inhibitors, they both violated the Lipinski's rule of 5. This study identified 13 drugable guava-derived compounds that can be enlisted for further studies as potential HDAC6 and HDAC10 inhibitors.

IRIDOIDES, TRITERPENOS E OUTROS CONSTITUINTES DAS CASCAS DO CAULE E FLORES DE Tabebuia caraiba BIGNONIACEAE

The trunk bark of Tabebuia caraiba Bignoniaceae was found to contain four novel iridoids, 6-O-E-p-coumaroyljioglutin D (2), 6-O-E-p-coumaroyl-3-demethyl-3-O-ethyljioglutin D (3), 6-O-E-p-coumaroyl-1-demethyl-1-O-ethyljioglutin D (4), 7-O-E-p-coumaroyljiofuranaldehyde (5), three known iridoids, including one iridoid glucoside, jioglutin D (1), rehmaglutin D (6), 6-O-E-p-coumaroylcatalpol (7). From the flowers were obtained six triterpenes, betulinic acid (8), olean-12-en-3-one (9), β-amyrin (10), oleanolic acid (11), ursolic acid (12), 3-O-E-p-coumaroylursolic acid (13), 2α-hydroxyursolic acid (14), 6β,19α-dihydroxyursolic acid (15), and one phenylethanoid, tyrosol (16), in addition to β-sitosterol, β-sitosterol-3-O-β-D-glucopyranoside and β-sitosterol-3-O-β-D-(6´-O-acyl)-glucopyranoside and E-p-coumaric acid. The structures of the isolated compounds were established on the basis of 1D and 2D NMR spectroscopic techniques. The chemical profile of the trunk bark of the plant was determined by HPLC/DAD/HRESIMS and did not present a good correlation with the phytochemical study. It did not detect most of the isolated substances and allowed to propose the presence of some non-isolated compounds.

Two new polyhydroxylated pentacyclic triterpenes with cytotoxic activities from Manilkara pellegriniana (Sapotaceae)

Two new polyhydroxylated urs-12(13)-ene pentacyclic triterpenes namely 2α, 3α, 19α, 20β, 23-pentahydroxyurs-12-en-28-oic acid (1) and 1β, 2α, 3α, 5, 19α, 24-hexahydroxyurs-11(12), 20(30)-dien-28-oic acid (2) were isolated from the stem bark of Manilkara pellegriniana together with seven known compounds: ursolic acid 3, 1β-hydroxyeucaphic acid 4, β-Amyrin acetate 5, taraxerol 6, taraxerol acetate 7, 3α-spinasterol 8, and spinasterone 9. In addition, the chemical investigation of another specie of the same genus, M. argentea afforded six known compounds: 3β,6α,19α,23-tetrahydroxyurs-12-en-28-oic acid 10, 2α-hydroxyursolic acid 11, garbanzol 12, 3α-spinasterol glucoside 13, 3,5,7,4′,5′-pentahydroxyflavan 14, and (+)-proto-quercitol 15. Their structures were established from spectral data, mainly HRESIMS, 1D NMR and 2D NMR and by comparison with literature data. The cytotoxicity activities of compounds 1 and 2 as well as doxorubicin were evaluated on four cancer cell lines. Compound 1 had significant cytotoxic effect towards SPC212 lung cancer cells with IC50 value of 0.52 μM.

Guava fruit extract and its triterpene constituents have osteoanabolic effect: Stimulation of osteoblast differentiation by activation of mitochondrial respiration via the Wnt/β-catenin signaling

The aim of this study was to evaluate the skeletal effect of guava triterpene-enriched extract (GE) in rats and identify osteogenic compounds thereof, and determine their modes of action. In growing female rats, GE at 250 mg/kg dose increased parameters of peak bone mass including femur length, bone mineral density (BMD) and biomechanical strength, suggesting that GE promoted modeling-directed bone growth. GE also stimulated bone regeneration at the site of bone injury. In adult osteopenic rats (osteopenia induced by ovariectomy, OVX) GE completely restored the lost bones at both axial and appendicular sites, suggesting a strong osteoanabolic effect. Serum metabolomics studies showed changes in several metabolites (some of which are related to bone metabolism) in OVX compared with ovary-intact control and GE treatment to OVX rats reversed those. Out of six abundantly present triterpenes in GE, ursolic acid (UA) and 2α-hydroxy ursolic acid (2α-UA) induced osteogenic differentiation in vitro as did GE by activating Wnt/β-catenin pathway assessed by phosphorylation of GSK-3β. Over-expressing of constitutively active GSK-3β (caGSK-3β) in osteoblasts abolished the differentiation-promoting effect of GE, UA and 2α-UA. All three increased both glycolysis and mitochondrial respiration but only rotenone (inhibitor of mitochondrial electron transfer) and not 2-deoxyglucose (to block glycolysis) inhibited osteoblast differentiation. In addition, caGSK-3β over-expression attenuated the enhanced mitochondrial respiration caused by GE, UA and 2α-UA. We conclude that GE has osteoanabolic effect which is contributed by UA and 2α-UA, and involve activation of canonical Wnt signaling which in turn modulates cellular energy metabolism leading to osteoblast differentiation.

2α-Hydroxyursolic Acid Inhibited Cell Proliferation and Induced Apoptosis in MDA-MB-231 Human Breast Cancer Cells through the p38/MAPK Signal Transduction Pathway.

The mechanisms of action of 2α-hydroxyursolic acid in inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 human breast cancer cells were investigated. The antiproliferative activity and cytotoxicity were determined by the methylene blue assay. The expression of proteins was determined using Western blot. 2α-Hydroxyursolic acid significantly inhibited MDA-MB-231 cell proliferation, and no cytotoxicity was observed at concentrations below 30 μM. 2α-Hydroxyursolic acid significantly down-regulated expressions of TRAF2, PCNA, cyclin D1, and CDK4 and up-regulated the expressions of p-ASK1, p-p38, p-p53, and p-21. 2α-Hydroxyursolic acid induced apoptosis in MDA-MB-231 cells by significantly increasing the Bax/Bcl-2 ratio and inducing the cleaved caspase-3. Additionally, treatment of SB203580, a p38 MAPK specific inhibitor, reversed the inhibition of PCNA, cyclin D1, and Bcl-2 expression induced by 2α-hydroxyursolic acid in MDA-MB-231 cells. These results suggested that 2α-hydroxyursolic acid exhibited anticancer activity through the inhibition of cell proliferation and the induction of apoptosis by regulating the p38/MAPK signal transduction pathway.

Chemical Constituents of Gold‐red Apple and Their α‐Glucosidase Inhibitory Activities

Ten compounds were isolated and purified from the peels of gold-red apple (Malus domestica) for the 1st time. The identified compounds are 3β, 20β-dihydroxyursan-28-oic acid (1), 2α-hydroxyoleanolic acid (2), euscaphic acid (3), 3-O-p-coumaroyl tormentic acid (4), ursolic acid (5), 2α-hydroxyursolic acid (6), oleanolic acid (7), betulinic acid (8), linolic acid (9), and α-linolenic acid (10). Their structures were determined by interpreting their nuclear magnetic resonance and mass spectrometry (MS) spectra, and by comparison with literature data. Compound 1 is new, and compound 2 is herein reported for the 1st time for the genus Malus. α-Glucosidase inhibition assay revealed 6 of the triterpenoid isolates as remarkable α-glucosidase inhibitors, with betulinic acid showing the strongest inhibition (IC50 = 15.19 μM). Ultra-performance liquid chromatography-electrospray ionization MS analysis of the fruit peels, pomace, flesh, and juice revealed that the peels and pomace contained high levels of triterpenes, suggesting that wastes from the fruit juice industry could serve as rich sources of bioactive triterpenes.

Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APC-mutated colon cancer cells through promotion of β-catenin degradation

Ursolic acid (UA) and corosolic acid (CA), naturally occurring pentacyclic triterpene acids, exhibit antiproliferative activities against various cancer cells, but a clear chemopreventive mechanism of these triterpenoids in colon cancer cells remains to be answered. Here we used a cell-based reporter system for detection of β-catenin response transcription (CRT) to identify UA as an antagonist of the Wnt/β-catenin pathway. UA promoted the degradation of intracellular β-catenin that was accompanied by its N-terminal phosphorylation at Ser33/37/Thr41 residues, marking it for proteasomal degradation. Consistently, UA down-regulated the intracellular β-catenin level in colon cancer cells with inactivating mutations of adenomatous polyposis coli (APC). In addition, UA repressed the expression of β-catenin/T-cell factor (TCF)-dependent genes, thereby inhibiting cell proliferation in colon cancer cells. The functional group analysis revealed that the major structural requirements for UA-mediated β-catenin degradation are a carboxyl group at position 17 and a methyl group at position 19. Notably, CA (2α-hydroxyursolic acid) was also found to decrease the level of intracellular β-catenin and to suppress the growth of APC-mutated colon cancer cells. Our findings suggest that UA and CA exert their anticancer activities against colon cancer cells by promoting the N-terminal phosphorylation and subsequent proteasomal degradation of β-catenin.

Triterpenes from Isodon xerophilus

AimTo investigate the chemical constituents of Isodon xerophilus. MethodsThe constituents were isolated by various chromatographic methods, and the chemical structures were elucidated on the basis of spectral analyses. Their cytotoxicity was evaluated by the MTT method in 96-well microplates. ResultsTen triterpenes were isolated and identified as oleanolic acid (1), ursolic acid (2), maslinic acid (3), 2α-hydroxyursolic acid (4), hederagenin (5), 3β, 23-dihydroxy-urs-12-en-28-oic acid (6), arjunolic acid (7), asiatic acid (8), 2α, 3α, 24-trihydroxyolean-12-en-28-oic acid (9), and 2α, 3α, 24-trihydroxyurs-12-en-28-oic acid (10). All compounds were tested against three human tumor cell lines, K562, MKN45, and HepG2. ConclusionAll of the compounds were isolated from this plant for the first time. The proposed biosynthetic pathway of these triterpenes was discussed. All of the triterpenes showed noncytotoxic activity against the above-mentioned three human tumor cell lines.

Chemical constituents of flowers and fruits of Rabdosia excisa

Aim To study the chemical constituents in the flowers and fruits of Rabdosia excisa. Methods The compounds were isolated and purified by silica gel column chromatography and their structures were identified by spectroscopic methods. Results Sixteen compounds isolated from the flowers and fruits of this plant were identified as: stigm asterol (I), α-amyrin palmitate (II), ursolic acid (III), 2α, 3α, 19-trihydroxy-urs-12-en-28-oic acid (IV), 2α-hydroxyursolic acid (V), maslinic acid (VI), isodonal (VII), maoyecrystal E (VIII), kamebakaurin (XI), macrocalyxin G (X), epinodosinol (XI), rabdosichuanin C (XII), kamebacetal A (XIII), oridonin (XIV), enmenol-glucoside (XV), and lasiononin (XVI). Conclusion All the constituents were found in Rabdosia excisa for the first time, except constituents III, IX, XII and XIV.

Chemical constituents and antibacterial activity of Melastoma malabathricum L.

The aqueous methanolic extracts of Melastoma malabathricum L. exhibited antibacterial activity when assayed against seven microorganisms by the agar diffusion method. Solvent fractionation afforded active chloroform and ethyl acetate fractions from the leaves and the flowers, respectively. A phytochemical study resulted in the identification of ursolic acid (1), 2α-hydroxyursolic acid (2), asiatic acid (3), β-sitosterol 3-O-β-D-glucopyranoside (4) and the glycolipid glycerol 1,2-dilinolenyl-3-O-β-D-galactopyanoside (5) from the chloroform fraction. Kaempferol (6), kaempferol 3-O-α-L-rhamnopyranoside (7), kaempferol 3-O-β-D-glucopyranoside (8), kaempferol 3-O-β-D-galactopyranoside (9), kaempferol 3-O-(2″,6″-di-O-E-p-coumaryl)-β-D-galactopyranoside (10), quercetin (11) and ellagic acid (12) were found in the ethyl acetate fraction. The structures of these compounds were determined by chemical and spectral analyses. Compounds 1–4, the flavonols (6 and 11) and ellagic acid (12) were found to be active against some of the tested microorganisms, while the kaempferol 3-O-glycosides (7–9) did not show any activity, indicating the role of the free 3-OH for antibacterial activity. Addition of p-coumaryl groups results in mild activity for 10 against Staphylococcus aureus and Bacillus cereus. Compounds 2–5, 7 and 9–12 are reported for the first time from M. malabathricum. Compound 10 is rare, being reported only once before from a plant, without assignment of the double bond geometry in the p-coumaryl moiety.

Anti-metastatic properties of the leaves of Eriobotrya japonica

The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including gastroenteric disorders, diabetes mellitus, chronic bronchitis and asthma. In the present study, the anti-metastatic action of the EtOAc fraction of the leaves of E. japonica (LEJ) was investigated. LEJ showed potent inhibitory effects on MMP-2 and MMP-9 activities and expressions via down-regulation of NF-κB translocation to the nucleus in B16F10 cells. In addition, the cell migration and invasion were down-regulated by LEJ. LEJ also significantly suppressed lung metastasis in vivo. Moreover, we isolated the compounds ursolic acid and 2α-hydroxyursolic acid from LEJ and both compounds also significantly suppressed MMP-2 and MMP-9 activities, indicating that they are the active components of LEJ. The present results demonstrate that LEJ may be used as valuable antimetastatic agent for the treatment of cancer metastasis.

Constituintes químicos de Hyptidendron canum (Pohl ex Benth.) R. Harley (Lamiaceae)

Chemical investigation of Hyptidendron canum stems resulted in the isolation of betulinic, ursolic and euscaphic acids. From the leaves were isolated 3β-O-β-galactopiranosilsitosterol, ursolic aldehyde, and mixtures of maslinic acid and 2α-hydroxyursolic acid, α and β-amyrin, uvaol and erythrodiol, sitosterol and stigmasterol, spathulenol and globulol. Hexane and chloroform leave fractions as well as ursolic and betulinic acids showed antifungal activities against the yeast form of Paracoccidioides brasiliensis.

Corosolic acid stimulates osteoblast differentiation by activating transcription factors and MAP kinases

Recently, the use of anabolic agents to enhance bone mass has been a source of interest. Previous work by us suggested that corosolic acid (2alpha-hydroxyursolic acid), an active component of banaba leaves (Lagerstroemia speciosa L.), potentially stimulates the differentiation of mouse osteoblasts. Therefore, the present study investigated whether corosolic acid stimulates osteoblast differentiation, and its possible mechanisms of action. At low concentrations (up to 5 microm), corosolic acid significantly stimulated osteoblast differentiation and mineralization without cytotoxicity. Corosolic acid induced NF-kappaB and MAP kinase activity at an early stage of osteoblast differentiation and increased the activity of the transcription factor AP-1 during late-stage osteoblast differentiation. These results suggest that the anabolic effects of corosolic acid upon osteoblast differentiation could result from its activation of transcription factors and MAP kinases.

Effect of 2α-Hydroxyursolic Acid on NF-κB Activation Induced by TNF-α in Human Breast Cancer MCF-7 Cells

Apples are one of the largest contributors of fruit phenolics of all fruits consumed by Americans and contain a variety of bioactive compounds, which have health benefits. Consumption of apples has been linked to reduced risk of chronic diseases such as cancer and cardiovascular disease. Apple extracts have been shown to have the capabilities of inhibiting NF-kappaB activation in human breast cancer MCF-7 cells. 2Alpha-hydroxyursolic acid is one of the major triterpenoids isolated from apple peels, and its effects on cell proliferation and TNF-alpha-induced NF-kappaB activation in MCF-7 cells were examined. 2Alpha-hydroxyursolic acid significantly inhibited MCF-7 cell proliferation at doses of 20 microM (p < 0.05). Preincubation with 2alpha-hydroxyursolic acid suppressed TNF-alpha-induced NF-kappaB activation in a dose-dependent manner and significantly inhibited the activation at a dose of 20 microM of 2alpha-hydroxyursolic acid (p < 0.05). 2Alpha-hydroxyursolic acid treatment did not affect the phosphorylation level of NF-kappaB inhibitor (IkappaB-alpha), but proteasome activity in MCF-7 cells was inhibited significantly at doses of 10 and 20 microM ( p < 0.05). These results suggest that 2alpha-hydroxyursolic acid has antiproliferative activities against MCF-7 cells and capabilities inhibiting NF-kappaB activation induced by TNF-alpha partially by suppressing proteasome activities.

Characterization of antioxidant compounds in Eriobotrya fragrans Champ leaf

Both loquat ( Eriobotrya fragrans Champ) fruits and leaves are often used as important ingredients in Chinese herbal formulations for medicinal treatments against cough and asthma, but little information is available about the inherent bioactive chemicals. In this study, 11 major compounds were identified from the acetic ether extract of leaves of the fragrance flower loquat. These chemicals are (1) 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid, (2) 2α-hydroxyursolic acid, (3) ursolic acid, (4) 2α-hydroxyoleanolic acid, (5) tormentic acid, (6) β-daucosterol, (7) epicatechin, (8) cinchonain Ia (9), cinchonain Ib, (10) quercetin-3- O-α- l-rhamnoside and (11) arbutin. Meanwhile, the antioxidant activities of these compounds were evaluated by the DPPH and FRAP assays. Cinchonain Ib exhibited the highest antioxidant activity, followed by cinchonain Ia, epicatechin, quercetin-3- O-α- l-rhamnoside and arbutin.

Four pentacyclic triterpenoids with antifungal and antibacterial activity from Curtisia dentata (Burm.f) C.A. Sm. leaves

Ethnopharmacological relevance Curtisia dentata is used in southern Africa to treat various diseases of bacterial and fungal origin in humans and animals to such a degree that the species is vulnerable and declining [Dold, A.R., Cocks, M.L., 2001. Traditional veterinary medicine in the Alice district of the Eastern Cape Province, South Africa. South African Journal of Science 97, 375–379]. Preliminary studies indicated good activity against Candida albicans. Aim of the study The phytochemistry and antimicrobial activity of this plant species has not been extensively investigated, and a closer examination of the compounds responsible for antimicrobial activity was warranted. Materials and methods Broth microdilution assay and bioautography were used to evaluate antibacterial and antifungal activity in Curtisia dentata leaf extracts and fractions. Bioassay-directed fractionation using column chromatography yielded four compounds characterised by spectroscopic methods. Results Lupeol ( 1), betulinic acid ( 2), ursolic acid ( 3) and 2α-hydroxyursolic acid ( 4) were isolated from Curtisia dentata leaves. Betulinic acid, ursolic acid and 2α-hydroxyursolic acid appreciably inhibited fungal growth with MIC values ranging from 8 to 63 μg/mL. Conclusions The isolation of four antibacterial and antifungal triterpenoids is reported for the first time from Curtisia dentata. This study provides information on the antimicrobial compounds of this species, as well as a preliminary rationale for the use in traditional South African medicine.