Corosolic Acid Research Articles

Chemical constituents from Barringtonia racemosa

To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3β-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3β, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3β-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3β, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC₅₀>50 mg•L⁻¹).

바나나 잎 추출물의 주름개선 효과

To examine the possibility of using Musa sapientum L. (Banana) leaf extract as a cosmetic raw material, banana leaves grown in Jeju Island were extracted with 70% ethanol. Polysaccharides present in banana leaf extract were discarded by precipitation with cold ethanol. Polysaccharidediscarded banana leaf extract promoted procollagen and COL1A1 gene expression, but inhibited matrix metalloproteinase (MMP)-1 and MMP-2 gene expression in human skin fibroblasts when examined by real-time reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The active compound in banana leaves was identified by fractionation with various solvents. The chloroform fraction showed the highest anti-wrinkle efficacy and the active compound of chloroform fraction was identified as corosolic acid by NMR, FT-IR, EA, and HPLCMS. In addition, banana leaf extract showed anti-oxidative efficacy with an IC50 value of 67.91 ppm, as determined by DPPH free radical scavenging assay. Finally, the anti-wrinkle efficacy of banana leaf extract-containing cream was confirmed by clinical tests. Based on these results, banana leaves could have an application as a cosmetic raw material with anti-wrinkle efficacy.

Triterpenoids from the fruits ofPrunus davidiana

The fruits of Prunus davidiana were extracted with 80 % aqueous methanol at room temperature. The concentrated extract was partitioned as ethyl acetate (EtOAc), n-butyl alcohol, and water fractions. From the EtOAc fraction, three triterpenoids were isolated through the repeated silica gel (SiO2) and octadecyl SiO2 column chromatographies. Based on physico-chemical and spectroscopic data including nuclear magnetic resonance, mass spectrometry, and infrared, the compounds were identified to be ursolic acid (1), corosolic acid (2), and α-amyrin (3).

Chemical Fingerprint and Determination of Triterpenoids in Cultured Cyclocarya paliurus Cells by High-Performance Liquid Chromatography

ABSTRACTCyclocarya paliurus is a medicinal plant containing various bioactive components with significant health benefits. Cell cultures of C. paliurus have been used to produce these bioactive metabolites. A chemical fingerprint was obtained by high-performance liquid chromatography (HPLC) to monitor the synthesis of major triterpenoids in cultured C. paliurus cells and provide a reliable quality assessment for the cell strain screening. The determination of five triterpenoids, namely, maslinic acid, corosolic acid, betulinic acid, oleanic acid, and ursolic acid, was also performed. The HPLC method for the determination of triterpenoids in the cultured cells was accurate, stable, and reliable, and therefore suitable for chemical fingerprint analysis. Sixteen C. paliurus cell strains varied dramatically in their triterpenoid accumulations. The concentrations of the triterpenoids were 0.45–2.19 (maslinic acid), 0.92–5.34 (corosolic acid), 2.58–4.70 (betulinic acid), 4.07–12.47 (oleanic acid), and 12.64–40.98 (ursolic acid) mg/g. A high yield cell strain had a total triterpenoid concentration of 66.34 mg/g. Ten peaks in the HPLC chromatogram with reasonable height and high resolution were assigned as characteristic for fingerprint and analysis. A reference fingerprint was also obtained for cell strain assessment.

Microbial transformation of the anti-diabetic agent corosolic acid by Cunninghamella echinulata

The pentacyclic triterpenoid corosolic acid was metabolized by Cunninghamella echinulata CGMCC 3.2000 to its C-24 aldehyde group metabolite and five other hydroxylated metabolites: madasiatic acid (2), 2α, 3β, 7β-trihydroxyurs-12-en-28-oic acid (3), 2α, 3β, 15α-trihydroxyurs-12-en-28-oic acid (4), 2α, 3β, 6β, 7β-tetrahydroxyurs-12-en-28-oic acid (5), 2α, 3β, 7β, 15α-tetrahydroxyurs-12-en-28-oic acid (6), and 2α, 3β,7β-trihydroxy-24-al-urs-12-en-28-oic acid (7); compounds 3, 5, and 7 were new compounds. The α-glucosidase inhibitory effects of the metabolites were also evaluated.

Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage.

Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms. In CA-treated diabetic animals, diabetes-induced albuminuria, increased serum creatinine and blood urea nitrogen were significantly attenuated, and glomerular hypertrophy, mesangial expansion and fibrosis were ameliorated. Furthermore, CA significantly inhibited proliferation of GMCs and phosphorylation of ERK1/2 and p38 MAPK in both diabetic animals and high glucose (HG)-induced GMCs. CA also normalized Δψm and inhibited HG-induced NADPH oxidase activity, ROS generation and NOX4, NOX2, p22phox and p47phox expression. More importantly, CA inhibited GMC proliferation mediated by NADPH/ERK1/2 and p38 MAPK signaling pathways. These findings suggest that CA exert the protective effect on DN by anti-proliferation resulted from inhibition of p38 MAPK- and NADPH-mediated inactivation of ERK1/2.

Bioactive constituents from roots of Salvia syriaca L.: Acetylcholinesterase inhibitory activity and molecular docking studies

Several Salvia species have been used to enhance memory in European traditional medicine. Accordingly, we aimed to evaluate the acetone extract of the roots of Salvia syriaca for anti-Alzheimer constituents. Structures of purified compounds were determined as ursolic acid, corosolic acid, β-sitosterol, urs-12-en-2α,3β-diol and daucosterol (1–5). β-sitosterol and daucosterol exhibited high acetylcholinesterase inhibitory activities (24.1 and 34.3μg/mL, respectively). The experimental results were also confirmed by docking analysis.

Characteristics of Subcritical Water Extraction and Kinetics of Pentacyclic Triterpenoids from Dry Loquat (Eriobotrya japonica) Leaves

Abstract In this study, pentacyclic triterpenoids (PTTs) were extracted from loquat leaves by subcritical water extraction (SWE) technique in a dynamic mode. The results revealed that PTTs yield increased up to 5.38±0.12 mg/g with the increasing temperature at 180 °C for corosolic acid (CA) and up to 7.20±0.11 mg/g at 200 °C for ursolic acid (UA) within experimental times. The optimum flow rates to obtain concentrated CA and UA extracts were found to be 33.33 and 41.67 mL/min, respectively. Furthermore, extraction temperatures strongly influenced the extraction rate as demonstrated by the rate constant of each temperature tested. Moreover, the kinetic rate constant decreased as the function of temperature indicating the yield of both CA and UA were significantly influenced by subcritical temperatures and extraction times.

Corosolic acid induces potent anti-cancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway

<p class="Abstract">The main objective of the present study was to investigate the anti-tumor activity of corosolic acid in CaSki human cervical cancer cells. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Results revealed that corosolic acid exerted potent, dose- and time-dependent growth inhibitory effects in CaSki cell proliferation. Cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM concentrations of corosolic acid, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Corosolic acid also induced G2/M cell cycle arrest in a dose-dependent manner. Increasing doses of corosolic acid treatment to these cells resulted in significant and dose-dependent down-regulation of PI3K and Akt protein expressions.</p><p><strong>Video Clip</strong></p><p><a href="https://youtube.com/v/N4EivZECRZE">Western blot assay</a>: 2 min 1 sec </p>

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.

Inhibition of Mitochondrial Fission and NOX2 Expression Prevent NLRP3 Inflammasome Activation in the Endothelium: The Role of Corosolic Acid Action in the Amelioration of Endothelial Dysfunction.

Corosolic acid (CRA) is a natural triterpenoid with antioxidative activity. This study was designed to elucidate the mechanism through which CRA protected vessel endothelial homeostasis by combating oxidative stress. In endothelial cells, CRA induced dynamin-related protein 1 (Drp1) phosphorylation at Ser637 and thus inhibited mitochondrial fission in response to oxidative stress. It promoted AMP-activated protein kinase (AMPK) activity in an LKB1-dependent manner, and silencing AMPK abrogated its inhibitory effect on Drp1 activation and mitochondrial fission. CRA inhibited the translocation of p47(phox) and p67(phox) and the overexpression of gp91(phox) induced by palmitate (PA), demonstrating its action in suppression of NOX2 activation. Drp1 knockdown reduced PA-induced gp91(phox) expression, while Drp1 induction was also diminished by gp91(phox) knockdown, suggesting the reciprocal relationship between NOX2 and Drp1. Knockdown Drp1 or gp91(phox) attenuated PA-induced NLRP3 induction and enhanced inhibitory effects of CRA. Oral administration of CRA in high-fat diet mice reproduced similar regulation in the aorta endothelium, further confirming its protection on endothelial homeostasis in vivo. This study demonstrated that the defect in mitochondrial morphology is associated with the oxidative stress and NLRP3 inflammasome activation in the endothelium. Drp1 and NOX2 regulated each other and worked together to induce NLRP3 inflammasome activation, suggesting that modulation of Drp1 phosphorylation (Ser637) might be a potential therapeutic target for combating oxidative stress in vessel diseases. CRA prevented mitochondrial fission by regulation of Drp1 phosphorylation (Ser637) in an AMPK-dependent manner, and this action contributed to blocking NOX2 oxidase signaling and suppressing NLRP3 inflammasome activation in the endothelium. Antioxid. Redox Signal. 24, 893-908.

Synthesis of water soluble glycosides of pentacyclic dihydroxytriterpene carboxylic acids as inhibitors of α-glucosidase

A series of compounds were synthesized by glycosylation of maslinic acid (MA) and corosolic acid (CA) with monosaccharides and disaccharides, and the structures of the derivatives were elucidated by standard spectroscopic methods including 1H NMR, 13C NMR and HRMS. The α-glucosidase inhibitory activities of all the novel compounds were evaluated in vitro. The solubility and inhibitory activity of α-glucosidase assays showed that the bis-disaccharide glycosides of triterpene acids possessed higher water solubility and α-glucosidase inhibitory activities than the bis-monosaccharide glycosides. Among these compounds, maslinic acid bis-lactoside (8e, IC50 = 684 µM) and corosolic acid bis-lactoside (9e, IC50 = 428 µM) had the best water solubility, and 9e exhibited a better inhibitory activity than acarbose (IC50 = 478 µM). However, most of glycosylated derivatives possessed lower inhibitory activities than the parent compounds, although their water solubility was enhanced obviously. Moreover, the kinetic inhibition studies indicated that 9e was a non-competitive inhibitor, and structure–activity relationships of the derivatives are also discussed.

Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro

abstractContext 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine.Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines.Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4′-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays.Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 μg/mL, respectively. TEO (40 μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio.Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.

Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice

BackgroundAdipose tissue inflammation is tightly associated with the development of insulin resistance. Corosolic acid (CRA), a natural triterpenoid, is well known as “phyto-insulin” due to its insulin-like activities. However, its underlying mechanism remains unknown. PurposeIn this study, we investigated the mechanisms of CRA on improving insulin resistance both in vivo and in vitro. MethodsC57BL/6 mice were fed with normal diet, high-fat diet (HFD) or HFD with CRA, respectively. General biochemical parameters in blood and glucose intolerance in mice were assayed. Meanwhile, proinflammatory cytokines and macrophage infiltrations in adipose tissues were analyzed by real-time PCR and immunohistochemical staining. The effects of CRA on insulin signaling transduction and AMPK activity in adipose tissues were investigated by western blot. Furthermore, the effects of CRA on AMPK were confirmed on 3T3-L1 cells by using both AMPK inhibitor and AMPKα1/2-specific siRNA ResultsCRA attenuated hyperlipidemia, improved insulin sensitivity and glucose intolerance in mice. Meanwhile, it alleviated inflammation in adipose tissues, demonstrated by the suppression of IKKβ phosphorylation and down-regulation of gene expressions of proinflammatory cytokines. Histological analysis revealed that CRA attenuated macrophage infiltrations into adipose tissue. It also improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt, thereby improved insulin sensitivity in HFD-fed mice. Furthermore, CRA regulated AMPK activation in a LKB1-dependent manner. AMPKα knockdown in adipocytes abolished the inhibitory effects of CRA on IKKβ and IRS-1 serine phosphorylation, indicating that CRA inhibited inflammation and ameliorated insulin resistance via AMPK activation. ConclusionsCRA inhibited inflammation with improvement in adipose tissue dysfunction and ameliorated insulin resistance in an AMPK–dependent manner.

Triterpenes suppress octanoylated ghrelin production in ghrelin-expressing human gastric carcinoma cells.

Ghrelin is an appetite-stimulating peptide hormone with an octanoyl modification at serine 3 that is essential for its orexigenic effect. Ghrelin O-acyltransferase (GOAT) is the enzyme that catalyzes ghrelin acylation using fatty acyl-coenzyme A as a substrate. We previously developed an assay system based on the AGS-GHRL8 cell line that produces octanoylated ghrelin in the presence of octanoic acid, and demonstrated that some fatty acids suppressed octanoylated ghrelin production. Recent studies have reported that triterpenes have anti-obesity effect. Since such triterpenes, like fatty acids, have a carboxyl group, we speculated that they can suppress octanoylated ghrelin production. To test this hypothesis, we investigated the effect of triterpenes on octanoylated ghrelin production. Asiatic acid, corosolic acid, glycyrrhetinic acid, oleanolic acid and ursolic acid suppressed octanoylated ghrelin levels in AGS-GHRL8 cells without decreasing transcript expression of GOAT or furin, a protease required for ghrelin maturation. β-amyrin had no effect on octanoylated ghrelin level, which was only slightly inhibited by uvaol; the fact that both these triterpenes lack a carboxyl group indicates that this group is important for suppressing octanoylated ghrelin production. These results suggest that triterpenes may have the potential as obesity-preventing agents with suppressive effect on octanoylated ghrelin production.

Kayeassamin A Isolated from the Flower of Mammea siamensis Triggers Apoptosis by Activating Caspase-3/-8 in HL-60 Human Leukemia Cells.

Background:Mammea siamensis (Miq.) T. Anders. is used as a medicinal plant in Thailand and has several traditional therapeutic properties. In a previous study, we isolated eight compounds from the flower of M. siamensis and demonstrated that kayeassamin A (KA) exhibited potent antiproliferative activity against human leukemia and stomach cancer cell lines.Objective:In this study, we investigated the effect of KA on cell viability and apoptotic mechanisms in HL-60 human leukemia cells.Materials and Methods:Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nuclear morphology and DNA fragmentation were observed using Hoechst 33258 staining and agarose gel electrophoresis, respectively. The sub-G1 phase of cells was analyzed by flow cytometry after the cellular DNA had been stained with propidium iodide. The protein levels of poly (ADP-ribose) polymerase (PARP) and caspases were determined by Western blotting.Results:KA exhibited a significant cytotoxic effect in a dose- and time-dependent manner, and induced chromatin condensation, DNA fragmentation, and sub-G1 phase DNA content, known as molecular events associated with the induction of apoptosis. In addition, KA strongly induced the activation of PARP and caspase-3 and -8, with weak caspase-9 activation. Furthermore, KA-induced DNA fragmentation was abolished by pretreatment with z-VAD-FMK (a broad caspase inhibitor), z-DEVD-FMK (a caspase-3 inhibitor), and z-IETD-FMK (a caspase-8 inhibitor), but not by z-LEHD-FMK (a caspase-9 inhibitor) pretreatment.Conclusion:These results indicate that KA triggers apoptotic cell death by activation of caspase-3 and -8 in HL-60 cells.SUMMARY Kayeassamin A (KA) isolated from the flower of Mammea siamensis exhibited a significant cytotoxic effect in HL-60 human leukemia cells. KA triggers apoptotic cell death by activating caspase-3/-8. Abbreviations Used: KA: Kayeassamin A; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PARP: Poly (ADP-ribose) polymerase; PI: Propidium iodide; CA: Corosolic acid

Biocatalytic Synthesis of a Novel Corosolic Acid Derivative

Biocatalytic Synthesis of a Novel Corosolic Acid Derivative

Role of phytochemicals in the management of metabolic syndrome

BackgroundThe World Health Organization (WHO) for some years has been focusing on what is now commonly referred to as an "epidemic of obesity and diabetes" ("diabesity"): behind this outbreak, there are several risk factors grouped in what is called "metabolic syndrome" (MetS). The basis of this "epidemic" is either a diet too often characterized by excessive consumption of saturated and trans-esterified fatty acids, simple sugars and salt, either a sedentary lifestyle. PurposeThe aim of this review is to focus on the phytochemicals that have a more positive effect on the treatment and/or prevention of MetS. ChaptersTreatment strategies for MetS include pharmacologic and non-pharmacologic options, with varying degrees of success rate. The first is indicated for patients with high cardiovascular risk, while the second one is the most cost-effective preventive approach for subjects with borderline parameters and for patients intolerant to pharmacological therapy. MetS non-pharmacological treatments could involve the use of nutraceuticals, most of which has plant origins (phytochemicals), associated with lifestyle improvement. The chapter will discuss the available evidence on soluble fibres from psyllium and other sources, cinnamaldehyde, cinnamic acid and other cinnamon phytochemicals, berberine, corosolic acid from banaba, charantin from bitter gourd, catechins and flavonols from green tea and cocoa. Vegetable omega-3 polyunsaturated fatty acids, alliin from garlic, soy peptides, and curcumin from curcuma longa. ConclusionSome nutraceuticals, when adequately dosed, should improve a number of the MetS components.

Simultaneous determination of five triterpenic acids in four Corydalis herb medicines by reversed-phase high performance liquid chromatography–fluorescence-mass spectrometer (RP-HPLC–FLD-MS) based on pre-column derivatization

ABSTRACTA rapid and sensitive reversed-phase high performance liquid chromatography– fluorescence-mass spectrometer (RP-HPLC–FLD-MS) method based on pre-column derivatization using 2-(5-benzoacridine)ethyl-p-toluenesulfonate (BAETS) as labelling reagent has been developed for simultaneous determination of five triterpenic acids (asiatic acid (AA), maslinic acid (MA), corosolic acid (CA), oleanolic acid (OA), and betulinic acid (BA). The presented method was validated for linearity (correlation coefficient R2 > 0.9994), precision (RSD 2.1%–3.9%) and reproducibility (RSD 0.01%–2.1%). The limits of detection (LODs) and the limits of quantitation LOQs were within the range of 0.71–1.02 ng mL−1 and 2.28–3.24 ng mL−1, respectively. The proposed method was successfully applied to simultaneously determine five triterpenic acids of four Corydalis plants and showed satisfactory reproducibility and credibility. Moreover, several main parameters affecting extraction procedure and derivatization efficiency were investigated by response surface methodology (RSM), respectively. Triterpenic acid content in four Corydalis plants was measured according to the established method and the results indicated that triterpenic acid contents were various in different organs and herbs.

Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.

A series of pentacyclic tritperpenes found in Perilla frutescens (P. frutescens), including ursolic acid (UA), oleanolic acid (OA), corosolic acid (CA), 3-epi-corosolic acid (3-epiCA), maslinic acid (MA), and 3-epi-maslinic acid (3-epiMA) were evaluated for their effects on epidermal cell signaling, proliferation, and skin inflammation in relation to their ability to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) and compared to UA as the prototype compound. All compounds were given topically 30 min prior to each TPA application and significantly inhibited skin tumor promotion. 3-epiCA and MA were significantly more effective than UA at inhibiting tumor development. All of these compounds significantly inhibited epidermal proliferation induced by TPA, however, CA, 3-epiCA and MA were more effective than UA. All compounds also reduced skin inflammation (assessed by infiltration of mast cells and T-cells) and inflammatory gene expression induced by TPA, however, 3-epiCA and MA were again more effective than UA. The greater ability of 3-epiCA and MA to inhibit skin tumor promotion was associated with greater reduction of Cox-2 and Twist1 proteins and inhibition of activation (i.e., phosphorylation) of IGF-1R, STAT3 and Src. Further study of these compounds, especially 3-epiCA and MA, for chemopreventive activity in other cancer model systems is warranted.