Research Update of Ursolic acid.

  seminal trace...Ursolic acid.C30H48O3.CAS No.77-52-1.malol;prunol;Ursolic acid;urson,micromerol,Loquat Leaf extract.Glossy privet leaf Extract.Ursolic acid.25%50%95%HPLC.Pentacyclic Triterpenes....

 


   Phytochemical info of Ursolic acid:

 Product Name:
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 Definition: Loquat Leaf extract are majorly composed of
 Chemical information disclosed as following table:


   Research update of Loquat Leaf extract and Ursolic acid and Pentacyclic Triterpenes related.

   Ursolic acid: a potent Inhibitor of superoxides produced in the cellular system.:Phytother Res. 2007 Feb 13;Ali MS, Ibrahim SA, Jalil S, Choudhary MI.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.[PMID: 17295383]

 Triterpenoids of ursane class: ursolic acid, ilelatifol D, corosolic acid and euscaphic acid were isolated for the first time from Leonurus cardiaca, a member of the family Lamiaceae. The isolated compounds were tested for their cell-based antiinflammatory potential by suppressing respiratory burst activity and superoxide scavenging property by using xanthine/xanthine oxidase system to produce superoxides in the cell-free system. Ursolic acid was found to be an excellent inhibitor for the superoxides produced in the cellular system, while the same was inactive in the superoxide scavenging activity in cell-free system.

   Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis.:Z Naturforsch [C]. 2006 Nov-Dec;61(11-12):777-82.Jedinak A, Muckova M, Kost'alova D, Maliar T, Masterova I.Institute of Molecular Physiology and Genetics, Vlarska 5, Bratislava 83334, Slovakia. andrejjedinak@orangemail.sk[PMID: 17294686]

 Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for beta-ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. beta-Ursolic acid showed the strongest inhibition activity to urokinase (IC50 = 12 microM) and cathepsin B (IC50 = 10 microM) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of beta-ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of beta16 mouse melanoma cells in vivo. We found, that beta-ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p < 0.05).

   Characterization of Topical Antiinflammatory Compounds in Rosmarinus officinalis L.:J Agric Food Chem. 2007 Mar 7;55(5):1718-23. Epub 2007 Feb 9.Altinier G, Sosa S, Aquino RP, Mencherini T, Loggia RD, Tubaro A. D.M.R.N., University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy, and Department of Pharmaceutical Sciences, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy.[PMID: 17288440]

 The topical antiinflammatory activity of three extracts at increasing polarity (n-exane, chloroform, and methanol) from the leaves of Rosmarinus officinalis L. (Labiatae) has been tested using the croton oil ear test in mice. Both the n-hexane and the chloroform (CE-1) extracts from the leaves showed a dose-dependent activity, the last one possessing an antiinflammatory potency similar to that of indomethacin, the nonsteroidal antiinflammatory drug used as a reference drug (ID50 = 83 and 93 mug/cm2, respectively). The bioassay-oriented fractionation of CE-1 led to the identification of tritepenes, ursolic acid, oleanolic acid, and micromeric acid as the main antiinflammatory principles. Furthermore, the CE-1 extract obtained from the residue of the steam distillation of the leaves (extract A) showed the same antiinflammatory potency of CE-1, suggesting this waste product as a source of antiinflammatory products. Keywords: Rosemary; Rosmarinus officinalis L; topical antiinflammatory activity; ursolic acid; oleanolic acid; micromeric acid.

   Triterpenes from herb of Potentilla chinesis.:Zhongguo Zhong Yao Za Zhi. 2006 Nov;31(22):1875-9.Liu P, Duan HQ, Pan Q, Zhang YW, Yao Z.College of Pharmaceuticals and Biotechnology, Tianjin University, Tianjin 300072, China.[PMID: 17285988]

 OBJECTIVE: To study the chemical constituents of Potentilla chinesis and their anticancer activities. METHOD: Chemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis. The isolated compounds were screened with two anticancer models. RESULT: Fifteen triterpenes, alpha-amyrin (1) , beta-amyrin (2) , ursolic acid (3) , corosolic acid (4), euscaphic acid (5) , pomolic acid (6) , tormentic acid (7), 2alpha, 3alpha-dihydroxyurs-12-en-28-oic acid (8), 2beta, 3beta, 19alpha-trihydroxyurs-12-en-28-oic acid (9), asiatic acid (10) , 24-hydroxy tormentic acid (11) , myrianthic acid (12), oleanolic acid (13), maslinic acid (14) and 2alpha, 3alpha-dihydroxyolean-12-en-28-oic acid (15) , were isolated from P. chinesis. CONCLUSION: Compounds 1, 2, 4 -15 were isolated from the plant for the first time. Compounds 4, 8 - 10, 12, 14 and 15 show anticancer activities. Compounds 4, 9 show strong activities.

   Studies of selected plant raw materials as alternative sources of triterpenes of oleanolic and ursolic acid types.:J Agric Food Chem. 2007 Feb 7;55(3):656-62.Kowalski R.Department of Analysis and Evaluation of Food Quality, Central Apparatus Laboratory, University of Agriculture, 13 Akademicka Street, 20-950 Lublin, Poland. radoslaw.kowalski@ar.lublin.pl[PMID: 17263457]

 The qualitative and quantitative evaluation of triterpene aglycones of saponin fractions isolated from vegetative and generative organs of three Silphium species, Silphium perfoliatum, Silphium trifoliatum, and Silphium integrifolium, as compared to materials used in the herbal industry such as Panax quinquefolium root and Calendula officinalis flower, was performed. The analyses revealed that triterpene aglycones of saponins isolated from tested Silphium and Calendula species were oleanolic acid and ursolic acid. It was found that Panax roots contained only the aglycone of oleanolic acid within the triterpene saponin group. The leaves of Silphium harvested in May were characterized by the highest content of oleanolic acid-They contained 17.03 mg/g dry weight of the triterpenic acid, on average. The seasons before flowering and at the beginning of that stage appeared to be the most efficient periods for leaf collection in reference to triterpene aglycone contents in plant yield. Moreover, it was found that inflorescences of S. trifoliatum and S. integrifolium contained oleanolic acid in amounts of 22.05 and 17.95 mg/g dry weight respectively, whereas Calendula flowers contained 20.53 mg/g dry weight. The oleanolic acid content in Panax roots was 3.15 mg/g dry weight. Ursolic acid most abundantly occurred in S. integrifolium and S. trifoliatum at concentrations of about 14.98 mg/g dry weight in leaves harvested before flowering (June) and to 15.50 mg/g dry weight in leaves collected during flowering.


   Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells.:Phytother Res. 2007 Jan 30;Heo HJ, Kim C, Lee HJ, Kim YS, Kang SS, Seo UK, Kim YH, Park YC, Seok JH, Lee CJ.Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Korea.[PMID: 17262888]

 This study investigated whether carbenoxolone, oleanolic acid and ursolic acid affect ATP-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using (3)H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on (3)H-mucin secretion. The possible cytotoxicity of each agent was investigated with a lactate dehydrogenase assay. The results were as follows: (1) carbenoxolone, oleanolic acid and ursolic acid significantly inhibited the secretion of airway mucin induced by ATP; (2) none of the compounds showed significant cytotoxicity at any concentration. This result suggests that carbenoxolone, oleanolic acid and ursolic acid can regulate 'mucin secretion induced by ATP' - a phenomenon simulating mucus overproduction from inflamed airway epithelial cells - by directly acting on airway mucin-secreting cells.

   Ursolic acid plays a role in Nepeta sibthorpii Bentham CNS depressing effects.:Phytother Res. 2007 Jan 18;Taviano MF, Miceli N, Monforte MT, Tzakou O, Galati EM.Pharmaco-Biological Department, School of Pharmacy, University of Messina, Vill. SS. Annunziata, 98168 Messina, Italy.[PMID: 17236171]

 The sedative, anticonvulsant and analgesic activity of ursolic acid, a terpenoid bioassay-isolated from Nepeta sibthorpii Bentham, was evaluated in mice. The oral administration of ursolic acid (2.3 mg/kg) produced a significant depressant effect on CNS by reducing spontaneous motor activity and the number and lethality of pentylenetetrazol (PTZ)-induced seizures. Two models of nociception, the writhing test and the hot plate test, were also used to examine the analgesic effect of ursolic acid. At a dose of 2.3 mg/kg, ursolic acid caused an inhibition of acetic acid-induced abdominal constriction, but was inactive in the hot plate test. Treatment at a higher dose (20 mg/kg) significantly increased the reaction time in the hot plate test. This effect, reversed by naloxone, evidently involves opioid receptors, but the analgesic activity of ursolic acid may be related also to the antiinflammatory and antioxidant properties of this compound.

   Study on the chemical constituents of the leaves from Crataegus pinnatifida Bge. var. major N. E. Br.:Zhong Yao Cai. 2006 Nov;29(11):1169-73.Liu RH, Yu BY.Jiangxi College of Traditional Chinese Medicine, Nanchang 330006, China. rhliu@163.com[PMID: 17228656]

 OBJECTIVE: to study the chemical components of the leaves from Crataegus pinnatifida Bge. var major N. E. Br. METHODS: Constituents were isolated by using silica gel, porous resin, Sephadex LH-20 chromatographic technique, etc. Their structures were elucidated by chemical and spectroscopic methods. RESULTS: Fourteen compounds were identified as quercetin (1), hyperoside (2), quercetin 3-O-beta-D-glucoside (3), rutin (4), quercetin 3-O-[alpha-L-rhamnopyranosyl(1-4)-alpha-L-rhamnopyranosyl-(1-6)-beta-glucopyranoside] (5), vitexin (6), 6"-O-acetyl-vitexin (7), vitexin 2"-O-rhamnoside (8), vitexin 4"-O-glucoside (9), chlorogenic acid (10), ursolic acid (11), beta-sitosterol (12), beta-daucosterol (13), n-triacontanol (14). CONCLUSION: Compound 5 and 14 were isolated from Crataegus L. for the first time.

   Quantification of eugenol, luteolin, ursolic acid, and oleanolic acid in black (Krishna Tulasi) and green (Sri Tulasi) varieties of Ocimum sanctum Linn. using high-performance thin-layer chromatography.:J AOAC Int. 2006 Nov-Dec;89(6):1467-74.Anandjiwala S, Kalola J, Rajani M. B.V. Patel Pharmaceutical Education and Research Development Centre, Pharmacognosy and Phytochemistry Department, Thaltej, Ahmedabad-380 054, Gujarat, India.[PMID: 17225591]

 Ocimum sanctum (family Lamiaceae) is a reputed drug of Ayurveda, commonly known as Tulasi. In the present work, we quantified 4 marker compounds, viz., eugenol, luteolin, ursolic acid, and oleanolic acid, from the leaf of green and black varieties of O. sanctum using high-performance thin-layer chromatography (HPTLC) with densitometry. The methods were found to be precise, with relative standard deviation (RSD) values for intraday analyses in the range of 0.52 to 0.91%, 0.77 to 1.29%, 0.11 to 0.16%, and 0.34 to 0.42% and for interday analyses in the range of 0.73 to 0.96%, 1.02 to 2.08%, 0.11 to 0.12%, and 0.39 to 0.64% for different concentrations of eugenol, luteolin, ursolic acid, and oleanolic acid, respectively. Instrumental RSD values were 0.24, 0.39, 0.21, and 0.18% for eugenol, luteolin, ursolic acid, and oleanolic acid, respectively. Accuracy of the methods was checked by conducting a recovery study at 3 different levels for the 4 compounds, and the average recoveries were found to be 99.73, 99.3, 100.58, and 100.57%, respectively. Eugenol content ranged from 0.175 to 0.362% (w/w) and luteolin from 0.019 to 0.046% (w/w) in the samples analyzed. Green variety was found to contain higher amounts of ursolic acid [0.478 and 0.348% (w/w), from Sources 1 and 2, respectively] than the black variety [0.252 and 0.264% (w/w) from Sources 1 and 2, respectively]. Black variety had 0.174 and 0.218% (w/w) of oleanolic acid from Sources 1 and 2, respectively, while it was not detected in the green variety. Ursolic acid and oleanolic acid ran at the same Rf value and could not be resolved in several solvent systems tried. However, we observed that only ursolic acid gave yellow fluorescence under 366 nm ultraviolet light after derivatization with anisaldehyde-sulfuric acid reagent. The HPTLC-densitometry methods for the quantification of the 4 markers in O. sanctum leaf will have the applicability in quality control.

   Insulin-mimetic and insulin-sensitizing activities of a pentacyclic triterpenoid insulin receptor activator.:Biochem J. 2007 Jan 4;Jung SH, Ha YJ, Shim EK, Choi SY, Jin JL, Yun-Choi HS, Lee JR. [PMID: 17201692]

 Five pentacyclic triterpenoids isolated from Campsis grandiflora were tested for insulin-mimetic and insulin-sensitizing activity. The compounds enhanced the activity of insulin on tyrosine phosphorylation of the insulin receptor (IR) beta-subunit in Chinese-hamster ovary cells expressing human IR. Among the compounds tested, ursolic acid (CG7) gave the greatest enhancement, and myrianthic acid (CG11) the least. We further characterized the effect of CG7, and showed that it acted as an effective insulin-mimetic agent at doses above 50microgram/ml and as an insulin-sensitizer at doses as low as 1microgram-ml. Additional experiments showed that CG7 increased the number of IR that were activated by insulin. This indicates that a major mechanism by which CG7 enhances total IR auto-phosphorylation is by promoting the tyrosine phosphorylation of additional IR. CG7 not only potentiated insulin-mediated signaling (tyrosine phosphorylation of the IR beta-subunit, phosphorylation of Akt and glycogen synthase kinase-3beta) but also enhanced the effect of insulin on translocation of glucose transporter 4 in a classical insulin-sensitive cell type, 3T3-L1 adipocytes. The results of the present study demonstrate that a specific pentacyclic triterpenoid, CG7, exerts an insulin-sensitizing effect as an IR activator in CHO/IR cells and adipocytes. The enhancement of insulin activity by CG7 may be useful for developing a new class of specific IR activators for treatment of type 1 and type 2 diabetes.


   Radical-scavenging activities of new hydroxylated ursane triterpenes from cv. Annurca apples.:Chem Biodivers. 2005 Jul;2(7):953-8.D'Abrosca B, Fiorentino A, Monaco P, Pacifico S. Dipartimento di Scienze della Vita, Seconda Universita degli Studi di Napoli, via Vivaldi 43, I-81100 Caserta.[PMID: 17193186]

 Two new ursolic acid triterpene derivatives, compounds 2 and 3, have been isolated from cv. Annurca apple fruit, a high-quality apple variety widely cultivated in southern Italy, together with the known 2-oxopomolic acid (1). The new compounds were identified by means of different spectroscopic techniques as 3-epi-2-oxopomolic acid (= (3alpha)-3,19-dihydroxy-2-oxours-12-en-28-oic acid; 2) and (1alpha)-1-hydroxy-3-oxours-12-en-28-oic acid (3). Compounds 1-3 were tested for their radical-scavenging activities with the aid of a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (Fig. 2). All three constituents showed activities similar to that of the reference antioxidant alpha-tocopherol (vitamin E).

   Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines.:Int J Gynecol Cancer. 2006 Nov-Dec;16(6):2023-31.Yim EK, Lee MJ, Lee KH, Um SJ, Park JS. Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, The Catholic University of Korea, Seoul, Republic of Korea.[PMID: 17177841]

 The chemical structure of ursolic acid is very similar to that of dexamethasone, a synthetic glucocorticoid. Herein, we investigated the antiproliferative and antiviral effects of ursolic acid and dexamethasone in human papillomavirus (HPV)-associated cervical cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide assay to measure antiproliferative activity, and also characterized apoptosis by DNA fragmentation, 4'-6-diamidino-2-phenylindole (DAPI) staining, and flow cytometry (FACS) analysis. We investigated apoptosis-related proteins using western blots. After in vitro treatment, we used reverse transcription-polymerase chain reaction for the expression of the HPV E6/E7 gene to observe the antiviral effects. Ursolic acid suppressed the growth of HPV-positive cervical carcinoma cells (HeLa, CaSki, and SiHa) in a dose- and time-dependent manner, but not the HPV-negative cervical cancer cell line (C33A). Ursolic acid-treated HeLa cells showed typical apoptosis characteristics in DNA fragmentation, DAPI staining, and FACS analysis. The expression of Fas protein was induced, and caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP) proteins were cleaved after ursolic acid treatment. HPV-18 E6/E7 gene expression decreased after ursolic acid treatment in HeLa cells, but the levels of p53 and Rb proteins did not change. In contrast, dexamethasone, which has a similar structure, did not inhibit proliferation. Our findings may offer new insight into the mechanism of antiproliferative and antiviral effect of ursolic acid. Also, these results suggest that ursolic acid might be a useful anticancer drug in treatment of HPV-associated cervical neoplasia.

   Reduction of DNA-damaging effects of anti-HIV drug 3'-azido-3'-dideoxythymidine on human cells by ursolic acid and lignin biopolymer.:Neoplasma. 2006;53(6):485-91.Slamenova D, Horvathova E, Bartkova M, Krajcovicova Z, Labaj J, Kosikova B, Masterova I. Laboratory of Mutagenesis and Carcinogenesis, Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. darina.slamenova@savba.sk[PMID: 17167716.]

 In this study we verified our assumption that the genotoxicity of the effective anti-HIV drug 3'-azido-3'-dideoxythymidine (AZT) on human cells could be reduced by non-toxic concentrations of two antioxidants that occur frequently in nature (ursolic acid and lignin biopolymer). Cytotoxicity of these natural compounds, well-known by their antimutagenic effects, was evaluated by the trypan blue exclusion technique. Genotoxic activity of AZT was measured on the basis of AZT-induced single and double strand breaks to DNA in two histopathologically different types of human cells, hepatoma cells HepG2 and colonic cells Caco-2. Induction of DNA strand breaks was measured by the comet assay processed in parallel at pH > or = 13.0 (standard alkaline technique which enables to recognize single strand DNA breaks of different origin) and at pH = 9.0 (neutral technique which enables to recognize double strand DNA breaks). As the level of AZT-induced double strand DNA breaks was rather low, protective effects of the antioxidants tested were evaluated only against AZT-induced single strand DNA breaks by the standard alkaline comet assay. Our findings showed that 1 h pre-incubation of cells with ursolic acid or lignin preceding to 3 h treatment of cells with AZT (3 mg/ml) significantly decreased in both cell types the level of AZT-induced single strand DNA breaks. Pre-incubation of HepG2 or Caco-2 cells with a mixture of both natural antioxidants did not increase the effects of individual treatments. This study confirms that AZT is genotoxic toward both used cell types of human origin and that ursolic acid and biopolymer lignin can protect the cells studied against genotoxic effect of AZT.

   The cosmetic treatment of wrinkles.:J Cosmet Dermatol. 2004 Jan;3(1):26-34.Rona C, Vailati F, Berardesca E.Department of Dermatology University of Pavia, Pavia, Italy.[PMID: 17163944]

 Wrinkles now have a greater social impact because people live longer. Science and hedonism overlap in the search for causes, treatments and prevention of wrinkles. The cosmetic approach to wrinkles includes: i Cleansing ii Photoprotection iii Active ingredients Active ingredients go well beyond simple moisturisers and exert a more complex activity in protecting skin from external injuries, nourishing it and removing its superficial layers. Transport systems and excipients are increasingly effective. Functional agents currently include alpha hydroxy acids (AHAs), poly-AHAs, complex poly-AHAs, retinoids, fish polysaccharides, anti-enzymatic agents, antioxidants (including ascorbic acid, pycnogenol, ursolic acid, vegetable isoflavones, vitamin E, coenzyme Q10, lipoic acid, resveratorol, l-carnosine and taurine) as well as agaricic acid and various plant extracts. All are reviewed in this text. Most are topical, some can be given by mouth, even as food supplements. Cosmetics are becoming closer to drugs in preventing and treating wrinkles. Included amongst the cosmeceuticals are the anti-wrinkle agents described herein.

   Studies on chemical constituents of Paederia scandense.:Zhongguo Zhong Yao Za Zhi. 2006 Sep;31(17):1436-41.[PMID: 17087085]

 OBJECTIVE: To study the chemical constituents of Paederia scandense. METHOD: The constituents were isolated and purified by silica gel and Sephadex LH - 20 column chromatography. Their structures were elucidated by physicochemical properties and spectral analysis. RESULT: 20 compounds were obtained and identified as rubiadin-1-methylether (1), diadzein (2), cleomiscosin B (3), cleomiscosin D (4), isolariciresinol (5), linarin (6), isoscopoletin (7), caffic acid (8), coumarinic acid (9), p-hydroxyl-benzoic acid (10), oleanolic acid (11), ursolic acid (12), beta-sitosterol (13), daucosterol (14), paederoside (15), paederosidic acid (16), paederosidic acid methyl ester (17), saprosmoside E (18), paederoscandoside (19), caffeic acid 4-O-beta-D-glucopyranoside (20). CONCLUSION: Compounds 1-10, and 20 were isolated from this plant for the first time.


   Studies on triterpenoids from Potentilla chinensis.:Zhongguo Zhong Yao Za Zhi. 2006 Sep;31(17):1434-6.Wang QH, Li ZY, Shen Y, Lin HW, Shu W, Zhou JB.College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200246, China.[PMID: 17087084]

 OBJECTIVE: To investigate the chemical constituents of Potentilla chinensis. METHOD: Silica gel column chromatography and Sephadex LH - 20 gel column chromatography were employed for the isolation and purfication. The structures were identified on the basis of spectral data and chemical evidence. RESULT: Six compounds were isolated and identified as follows: 3-hydroxy-11-ursen-28, 13-olide, 11, 12-dehydroursolic acid lactone (1), 3-O-acetyl pomolic acid (2), betulinic acid (3), 3-oxo-12-ursen-28-oic acid (4), ursolic acid (5), oleanic acid (6). CONCLOUSION: All these compounds were isolated from P. chinensis for the first time, compound 1, 2, 4 were isolated from this genus for the first time.

   Trypanocidal activity of triterpenes from Arrabidaea triplinervia and derivatives.:Biol Pharm Bull. 2006 Nov;29(11):2307-9.Leite JP, Oliveira AB, Lombardi JA, Filho JD, Chiari E. Departamento de Produtos Farmaceuticos, Faculdade de Farmacia, UFMG, Brazil.[PMID: 17077535]

 Ethanol extract from Arrabidaea triplinervia leaves showed in vitro activity (ED100 5.0 mg/ml) against trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas; disease. Bioactivity-directed fractionation of this extract led to the isolation of ursolic and oleanolic acids as trypanocidal compounds besides pomolic acid (not tested) and alpinetine (inactive). A series of natural and synthetic derivatives of ursolic and oleanolic acids was simultaneously assayed for structure activity relationships (SAR) studies. Ursolic acid (ED100 0.4 mg/ml) was four times more active than oleanolic acid (ED100 1.6 mg/ml). The presence of free hydroxy and/or carboxy groups is necessary for the trypanocidal activity as could be deduced from the effect of the acetates, methyl ester, and aldehyde derivatives.

   Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats.:Int J Cardiol. 2006 Oct 17;Senthil S, Chandramohan G, Pugalendi KV.Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.[PMID: 17052790]

 The efficiency and safety of oleanolic acid (OA) and its isomer, ursolic acid (UA) in myocardial ischemia are poorly documented. This study appraised the efficacy of OA and UA in protecting the heart against oxidative damage induced by isoproterenol, since oxidative injury has been investigated as a potential initiator of myocardial necrosis. The level of TBARS increased whereas the antioxidants decreased significantly in the myocardium of ischemic animals. The levels were brought back to near normalcy in OA and UA pre-treated rats by scavenging the free radicals and blocking the induction of lipid peroxidation. These findings provide evidence that OA and UA protect rat myocardium against ischemic insult and the protective effect could be attributed to its antioxidant property and/or to a strengthening of myocardial membrane by its membrane stabilizing action. Among the two isomeric compounds, UA showed higher activity than OA.

   Studies on chemical constituents in spikes of Schizonepeta tenuifolia.:Zhongguo Zhong Yao Za Zhi. 2006 Aug;31(15):1247-9.Zhang YH, Zhou L, Shi RB, Guo YJ, Dong Y.Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang. zhangyuanhu@263.net.[PMID: 17048568]

 OBJECTIVE: To study the chemical constituents in the spikes of Schizonepeta tenuifolia. METHOD: Compounds were isolated and purified with silica gel, ODS and Sephadex LH-20 gel column chromatography, and their structures were determined by using spectroscopic analysis including MS and NMR. RESULT: Nine compounds were isolated and identified as 5, 7-dihydroxy-6, 4'-dimethoxyflavone (1), 5, 7-dihydroxy-6, 3', 4'-trimethoxyflavone (2), ursolic acid (3), 3-hydroxy-4(8)-ene-p-menthane-3(9)-lactone (4), 5, 7, 4'-trihydroxyflavone (5), 5, 4'-dihydroxy-7-methoxyflavone (6), hesperidin (7), luteolin (8) and daucesterol (9). CONCLUSION: Compounds 1, 2, 6 were first obtained from the spikes of S. tenuifolia.

   Protective effects of ursolic acid and oleanolic acid in leukemic cells.:Mutat Res. 2006 Aug 30;600(1-2):131-7. Epub 2006 Jul 10.Ovesna Z, Kozics K, Slamenova D. Department of Mutagenesis and Carcinogenesis, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic. zdenka.ovesna@savba.sk[PMID: 16831451]

 Ursolic acid (UA) and oleanolic acid (OA) have similar chemical structures but differ in the position of one methyl group on the ring E. We investigated protective effects of these two triterpenoic acids against H(2)O(2)-induced DNA damage in leukemic L1210, K562 and HL-60 cells using single-cell gel electrophoresis (SCGE). We compared their protective effects (antioxidant activities) with respect to the different position of the methyl group in their chemical structures. After 24h pre-treatment of cells both compounds investigated inhibited significantly the incidence of DNA single strand breaks induced by H(2)O(2). The concentration range of UA and OA was in all experiments 2.5-10 micromol/l. The antioxidant activity of OA determined by SCGE was significantly higher compared to UA in L1210 ((+)P<0.05) and K562 cells ((+++)P<0.001). Significant difference of the antioxidant activities of the two compounds was evidently connected with the different position of the methyl group. The protective effect of OA was in HL-60 cells slightly lower compared to the activity of UA, but the difference between the protective effects of UA and OA was not significant. In conclusion we can say that both natural pentacyclic triterpenoic acids investigated, UA and OA, manifested potent antioxidant effects. The different position of one methyl group in their chemical structures caused moderately different biological activities of these compounds on three leukemic cell lines. To explore their mechanisms of action further investigation seems to be therefore worthwhile.


   Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake.:Biochim Biophys Acta. 2006 Oct;1760(10):1505-12. Epub 2006 Jun 7.Zhang W, Hong D, Zhou Y, Zhang Y, Shen Q, Li JY, Hu LH, Li J. National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.[PMID: 16828971]

 Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

   Quantification of the polyphenols and triterpene acids in chinese hawthorn fruit by high-performance liquid chromatography.:J Agric Food Chem. 2006 Jun 28;54(13):4574-81.Cui T, Li JZ, Kayahara H, Ma L, Wu LX, Nakamura K.College of Food Science and Technology, Agricultural University of Hebei, Hebei 071001, China.[PMID: 16787000]

 The levels of seven polyphenols (epicatechin, procyanidin B2, procyanidin B5, procyanidin C1, hyperoside, isoquercitrin, and chlorogenic acid) and two triterpene acids (oleanolic acid and ursolic acid) in the matured fruits of Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.) were determined by high-performance liquid chromatography methods. The average contents of those constituents in 37 representative cultivars were 1405, 1505, 339, 684, 56, 41, 234, 952, and 147 microg/g fresh weight (FW), respectively. A significant inverse correlation between the procyanidin contents and the latitude of the geographical origin of the cultivars was observed (r = 0.3851, P < 0.02). Correlation analysis of the levels of the nine compounds in the 37 cultivars yielded a strong correlation (P < 0.001) between the individual levels of the four procyanidins and the sum of the procyanidins level (r = 0.7413-0.9898) and between the flavonoids and the chlorogenic acid (r = 0.5383-0.9212). The changes in level of the nine compounds in the hawthorn fruit were evaluated during maturation using the Hebei Dajinxing cultivar. Sixty-one days after blossom, the polyphenol level reached the highest point and the sum of the contents was 1.36 g/100 g FW.

   Ursolic acid induces apoptosis in colon cancer HT-29 cells.:Zhonghua Zhong Liu Za Zhi. 2006 Feb;28(2):99-102.Tan J, Shen ZX, Geng W.Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China.[PMID: 16750011]

 OBJECTIVE: To study the antitumor effects of ursolic acid and mechanisms of its action. METHODS: The cells of human colorectal carcinoma cell line HT-29 were treated with ursolic acid at different concentration. The proliferation inhibition was examined by MTT assay. Morphological examination, TUNEL method and flow cytometry were used to detect apoptosis. Immunohistochemical method was used to detect the expression of apoptosis related genes caspase-9 and bcl-2. The semi-quantification of protein expression was analyzed by pathological image-analysis. RESULTS: UA inhibited the proliferation of HT-29 cells moderately. Apoptosis of HT-29 cells was induced by ursolic acid treatment. The morphology of HT-29 showed changes such as nuclear chromatin condensation and fragmentation. Sub-G(1) peak was found by flow cytometry. The maximal apoptosis rate was 11.63%. The expression of caspase-9 gene was enhanced. The expression of bcl-2 gene was decreased. All these effects were in a dose-dependent and time-depend manner. CONCLUSION: Apoptosis in colon cancer HT-29 cells is one of the key mechanisms of ursolic acid action and its antitumor activity may be applicable for the treatment of cancers.

   Antimutagenicity of ursolic acid and oleanolic acid against doxorubicin-induced clastogenesis in Balb/c mice.:Life Sci. 2006 Aug 22;79(13):1268-73. Epub 2006 Apr 7.Aparecida Resende F, de Andrade Barcala CA, da Silva Faria MC, Kato FH, Cunha WR, Tavares DC.Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201-Parque Universitario, 14404-600, Franca, Sao Paulo, Brazil.[PMID: 16647723]

 Ursolic acid (UA) and oleanolic acid (OA) are triterpenoid compounds found in food, medicinal herbs and various other plants in free form or bound to glycosides. Both substances are known for their antimicrobial, hepatoprotective, anti-inflammatory, antiallergic, antiviral and cytotoxic activities. In the present study, we evaluated the antimutagenic potential of UA and OA using the micronucleus test in peripheral blood and bone marrow of Balb/c mice. The animals were divided into 10 treatment groups: mice treated with UA (80 mg/kg b.w.); OA (80 mg/kg b.w.); a mixture of UA and OA (80 mg/kg b.w.); the antineoplastic agent doxorubicin (DXR, 90 mg/kg b.w.); DMSO and DXR; UA and DXR; OA and DXR; UA, OA and DXR, and negative and solvent controls. UA, OA and a mixture of UA and OA were administered to the animals by gavage, followed by the intraperitoneal injection of DXR. The results showed a significant reduction in micronucleus frequency in the groups concomitantly treated with the triterpenoid compounds and DXR compared to that treated with DXR alone. The present results demonstrate the antimutagenic activity of UA and OA under the experimental conditions used in this study.

   Ursolic acid enhances cyclooxygenases and tumor necrosis factor-alpha expression in mouse skin.:Biosci Biotechnol Biochem. 2006 Apr;70(4):1033-7.[PMID: 16636478]

 An anti-inflammatory triterpenoid, ursolic acid (UA), has recently been found unexpectedly to induce the release of a pro-inflammatory mediator in resting macrophages. In this study, we found that topical applications of UA to mouse skin twice a week for 2 weeks significantly enhanced mRNA expression of cyclooxygenase (COX)-1, COX-2, and tumor necrosis factor-alpha, whereas its effect on tumor promotion was unclear.


   Dereplication of pentacyclic triterpenoids in plants by GC-EI/MS.:Phytochem Anal. 2006 Mar;17(2):102-6.Gu JQ, Wang Y, Franzblau SG, Montenegro G, Timmermann BN. Department of Pharmacology and Toxicology, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.[PMID: 16634286]

 Three common plant-derived pentacyclic triterpenoids, oleanolic acid (1), betulinic acid (2) and ursolic acid (3), have been found to exhibit moderate anti-tubercular activity in a microplate alamar blue assay. In order to facilitate the discovery of novel anti-tubercular leads with diverse chemical structures, a new and rapid GC-EI/MS method was developed simultaneously and unambiguously to dereplicate 1-3 as their methyl esters with limits of detection of 25.6, 26.9 and 26.8 ng, respectively.

   A study of the trypanocidal activity of triterpene acids isolated from Miconia species.:Phytother Res. 2006 Jun;20(6):474-8.Cunha WR, Crevelin EJ, Arantes GM, Crotti AE, Andrade e Silva ML, Furtado NA, Albuquerque S, Ferreira Dda S.Nucleo de Pesquisas em Ciencias Exatas e Tecnologicas da Universidade de Franca, Franca, SP, Brasil. wrcunha@unifran.br[PMID: 16619351]

 Triterpene acids, including ursolic acid (1), urjinolic acid (4) and oleanoic acid (5) along with a mixture of 2alpha-hydroxyursolic acid (2) and maslic acid (3) were isolated from methylene chloride extracts of the Miconia sellowiana and M. ligustroides species and their activities against the trypomastigote blood forms of Trypanosoma cruzi were evaluated. The potassium salt derivative of ursolic acid (1a) was also tested. The in vitro assays showed that compounds 1, 5 and 1a were the most active (IC(50) 17.1 microm, 12.8 microm and 8.9 microm, respectively). In contrast, a mixture of 2 plus 3, that exhibit a hydroxyl at C-2 and C-3, is much less potent than a mixture of 1 and 5 (IC(50) 48.5 microm and 11.8 microm, respectively). In the same manner, compound 4, that differs from 5 by two additional hydroxyl groups (at C-2 and C-23) displayed weak trypanocidal activity (IC(50) 76.3 microm) when compared with the other triterpenes. These results suggest that the free hydroxyl at C-3 and the polarity of C-28 are the most influential structural features for determining the in vitro trypanocidal activity of triterpenes. In vivo assays were also undertaken for the most active compounds 1, 1a and the mixture of 1 plus 5. The most significant reduction in parasite number in the parasitemic peak were obtained for compound 1 and its salt derivative 1a (75.7% and 70.4%, respectively). Moreover, the survival time was increased for all the treated animals.

   Mechanisms of inhibiting proliferation and inducing apoptosis of human gastric cancer cell line SGC7901 by ursolic acid.:Ai Zheng. 2006 Apr;25(4):432-7.Zhang YY, Deng T, Hu ZF, Zhang QP, Zhang J, Jiang H.Department of Gastroenterology, People's Hospital, Wuhan University, Wuhan, Hubei 430060, P. R. China.[PMID: 16613675]

 BACKGROUND & OBJECTIVE: Some studies have showed that ursolic acid (UA) can inhibit proliferation and induce apoptosis of many tumor cell lines, however its effect on gastric cancer cells has rarely been reported. Cyclooxygenase-2 (COX-2) is highly expressed in various precursor lesions and cancerous tissues. This study was to investigate the effect of UA on COX-2, Bcl-2 and Bax expression in human gastric cancer cell line SGC7901, and explore its potential mechanisms of inhibiting proliferation and inducing apoptosis. METHODS: MTT assay was used to observe the effect of UA (0, 10, 20, 30, 40 micromol/L) on proliferation of SGC7901 cells. Cell apoptosis was observed by fluorescence microscopy when treated with UA for 24 h. Cell cycle and apoptosis were analyzed by flow cytometry (FCM). The expression of COX-2, Bcl-2 and Bax was detected by Western blot. The level of prostaglandin E2 (PGE2) was measured by radioimmunoassay (RIA). RESULTS: UA (20-40 micromol/L) significantly inhibited the proliferation of SGC7901 cells in dose-and time-dependent manners, the IC50 value of UA at 12 h, 24 h, 36 h, 48 h were (57.50+/-1.18) micromol/L, (34.28+/-2.05) micromol/L, (27.54+/-1.11) micromol/L, and (24.83+/-1.02) micromol/L, respectively. When treated with 20-40 micromol/L UA for 24 h, SGC7901 cells were arrested at G0/G1 phase, and the apoptosis rates were (9.10+/-2.39)%, (26.30+/-1.25)%, and (35.20+/-2.26)%, respectively; meanwhile, COX-2 expression and its catalysate PGE2 were decreased, Bcl-2 expression was also decreased, whereas Bax expression was unchanged. CONCLUSION: UA could inhibit proliferation and induce apoptosis of SGC7901 cells through arresting cell cycle, inhibiting COX-2 expression to reduce PGE2 production and down-regulate Bcl-2 expression.

   Simultaneous quantification of three major bioactive triterpene acids in the leaves of Diospyros kaki by high-performance liquid chromatography method.:J Pharm Biomed Anal. 2006 Jun 7;41(3):950-6. Epub 2006 Mar 9.Fan JP, He CH.Department of Chemical Engineering, Zhejiang University, Hangzhou 310027, PR China.[PMID: 16527439]

 The leaf of Diospyros kaki, which is a traditional Chinese medicine, has been used for the treatment of various diseases. In order to improve the quality assurance of the leaves of D. kaki, derived extracts and phytomedicines, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed to simultaneously assess the three bioactive triterpene acids: barbinervic acid (BA) and its epimer, rotungenic acid (RA), along with 24-hydroxy ursolic acid (HA). This HPLC assay was performed on a reversed-phase C18 column with methanol and aqueous H3PO4 as the mobile phase and using a monitoring wavelength at 210 nm. This method was successfully applied to quantify these three bioactive triterpene acids in five different solvent extracts of the leaves of D. kaki and in the leaves from six different locations in China. The results demonstrated the total content and quantity of each of the main bioactive compounds were strongly dependent on the extraction solvents and locations, indicating that the quality control of the bioactive ingredients in the leaves of D. kaki, derived extracts and phytomedicines is critical to ensure its clinical benefits. The content of the total triterpenoids was also determined by the less selective colorimetric method, and the comparison with the HPLC method was given.

   Dual activity of triterpenoids: apoptotic versus antidifferentiation effects.:Arch Toxicol. 2006 Jul;80(7):429-35. Epub 2006 Feb 16.Cipak L, Grausova L, Miadokova E, Novotny L, Rauko P.Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833-91 Bratislava, Slovakia. exoncip@savba.sk[PMID: 16496127]

 Triterpenoids are natural, biologically active compounds extracted from many plants. They possess antiinflammatory, anticancer, and antioxidant properties. In the report presented, antiproliferative effects and leukemia cell growth and apoptosis modulating activities of ursolic acid (UA) and oleanolic acid (OA) were investigated. Both triterpenoids are inhibitors of leukemia cell growth and inductors of apoptosis. However, when applied in combination with anthracycline antitumor antibiotic doxorubicin (Dox), UA and OA diversely modulate therapeutic efficacy of Dox, due to different antioxidant activities. Compare to OA showing synergism/additive effect with Dox, UA (stronger antioxidant) acts antagonistically and reduces leukemia cell growth inhibiting and differentiation effects induced by Dox. In conclusion, these findings suggest that although triterpenoids UA and OA can induce apoptosis, their antioxidant activities can interfere with the therapeutic effect of antitumor antibiotic Dox which mechanism of action is attributed to the production of reactive oxygen species.


   Human ACAT-1 and ACAT-2 inhibitory activities of pentacyclic triterpenes from the leaves of Lycopus lucidus TURCZ.:Biol Pharm Bull. 2006 Feb;29(2):382-4.Lee WS, Im KR, Park YD, Sung ND, Jeong TS.National Research Laboratory of Lipid Metabolism & Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.[PMID: 16462051]

 Acyl-CoA: cholesterol acyltransferase (ACAT) catalyzes the acylation of cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition is a useful strategy for treating hypercholesterolemia or atherosclerosis. Pentacyclic triterpenes, ursolic acid (1), oleanolic acid (2), and betulinic acid (3) were isolated from the methanol extracts of the leaves of Lycopus lucidus TURCZ. by bioassay-guided fractionation. The structures of compounds 1-3 were elucidated by their spectroscopic data analysis. Among them, betulinic acid (3) exhibited more potent human ACAT-1 and ACAT-2 inhibitory activities with IC(50) values of 16.2+/-0.6 and 28.8+/-1.3 microM, respectively.

   Phytocomponents of triterpenoids, oleanolic acid and ursolic acid, regulated differently the processing of epidermal keratinocytes via PPAR-alpha pathway.:Exp Dermatol. 2006 Jan;15(1):66-73.Lee HK, Nam GW, Kim SH, Lee SH.BK21 Project for Medical Science, Yonsei University, Seoul, Korea.[PMID: 16364033]

 Naturally occurring triterpenoids such as oleanolic acid (OA) and ursolic acid (UA) are known to have anti-inflammatory and anticarcinogenic activities in some types of cells. Although it has been reported that UA increases the amount of ceramide in keratinocytes, there is little study on the mechanism of triterpenoids involved in the differentiation of keratinocytes as well as their effects on epidermal permeability barrier. A study was therefore conducted to determine whether OA and UA could stimulate the differentiation of epidermal keratinocytes through peroxisome proliferator-activated receptor (PPAR)-alpha activation. This work was then extended to investigate the rate of formation of cornified envelope as a marker in the terminal differentiation of keratinocytes and the amount of transglutaminase in human keratinocytes treated with OA and UA. It was shown that OA induced the differentiation of keratinocytes, whereas UA had little effect. In addition, reporter gene assay using PPAR response element activity demonstrated that OA might be related to the increase of PPAR-alpha activity in CV-1 cells. Moreover, it enhanced the recovery of epidermal permeability barrier function as well as increased ceramides in epidermis after topical application. We therefore propose that the effect of OA on the stimulation of differentiation in epidermal keratinocytes seems to be highly related to activation of PPAR-alpha.

   Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages.:Biochem Pharmacol. 2005 Nov 15;70(10):1497-505. Epub 2005 Sep 26.[PMID: 16188240]

 Macrophage migration inhibitory factor (MIF) plays some pivotal roles in innate immunity and inflammation. Ursolic acid (UA), an anti-inflammatory triterpene carboxylic acid, was recently reported to induce the release of pro-inflammatory mediators in resting macrophages (Mvarphi). We investigated the effects of UA on MIF protein release in resting RAW264.7 mouse Mvarphi, and found that it decreased intracellular MIF protein levels and promoted the release of MIF into the culture media in dose- and time-dependent manners, without affecting mRNA levels. Further, the triterpene strikingly induced activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) within 30min, whereas no phosphorylation of p38 MAPK or JNK protein was observed. In addition, UA-promoted MIF release was significantly inhibited by PD98059, a MEK1/2 inhibitor, while siRNA for ERK2, but not ERK1, significantly decreased the amount of MIF protein released. These results suggest that UA triggers the release of intracellular MIF protein through the ERK2 activation.

   Antiviral activities of extracts and selected pure constituents of Ocimum basilicum.:Clin Exp Pharmacol Physiol. 2005 Oct;32(10):811-6.Chiang LC, Ng LT, Cheng PW, Chiang W, Lin CC.Department of Microbiology, Kaohsiung Medical University, Kaohsiung, Taiwan.[PMID: 16173941]

 1. Ocimum basilicum (OB), also known as sweet basil, is a well known medicinal herb in traditional Chinese medicine preparations. In the present study, extracts and purified components of OB were used to identify possible antiviral activities against DNA viruses (herpes viruses (HSV), adenoviruses (ADV) and hepatitis B virus) and RNA viruses (coxsackievirus B1 (CVB1) and enterovirus 71 (EV71)). 2. The results show that crude aqueous and ethanolic extracts of OB and selected purified components, namely apigenin, linalool and ursolic acid, exhibit a broad spectrum of antiviral activity. Of these compounds, ursolic acid showed the strongest activity against HSV-1 (EC50 = 6.6 mg/L; selectivity index (SI) = 15.2), ADV-8 (EC50 = 4.2 mg/L; SI = 23.8), CVB1 (EC50 = 0.4 mg/L; SI = 251.3) and EV71 (EC50 = 0.5 mg/L; SI = 201), whereas apigenin showed the highest activity against HSV-2 (EC50 = 9.7 mg/L; SI = 6.2), ADV-3 (EC50 = 11.1 mg/L; SI = 5.4), hepatitis B surface antigen (EC50 = 7.1 mg/L; SI = 2.3) and hepatitis B e antigen (EC50 = 12.8 mg/L; SI = 1.3) and linalool showed strongest activity against AVD-II (EC50 = 16.9 mg/L; SI = 10.5). 3. No activity was noted for carvone, cineole, beta-caryophyllene, farnesol, fenchone, geraniol, beta-myrcene and alpha-thujone. 4. The action of ursolic acid against CVB1 and EV71 was found to occur during the infection process and the replication phase. 5. With SI values greater than 200, the potential use of ursolic acid for treating infection with CVB1 and EV71 merits further investigation.

   Studies on the chemical constituents in herb of Mentha haplocalyx.:Zhongguo Zhong Yao Za Zhi. 2005 Jul;30(14):1086-8.Liu Y, Zhang YH, Shi RB.School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China.[PMID: 16161444]

 OBJECTIVE: To study the chemical constituents of Mentha haplocalyx. METHOD: The chemical constituents were isolated and purified with column chromatography and the structures were elucidated by spectral analysis. RESULT: Nine compounds were obtained and identified as emodin (I), chrysophanol (II), physcione (II), benzoic acid (IV), trans-cinnamic acid (V), beta-sitosterol (VI), aloe-emodin (VII), ursolic acid (VIII) and daucosterol (IX). CONCLUSION: Compounds I, II, III, V, VII were first isolated from M. haplocalyx.


   Study on the extracting of ursolic acid by uniform design].:Zhong Yao Cai. 2005 May;28(5):425-7.Liu Z, Ma R, Wang Y.College of Life Science & Technology, Beijing University of Chemical Technology, Beijing.[PMID: 16131040]

 Uniform design method was adopted to research the extraction of ursolic acid. The ethanol concentration, the extraction time, the liquid to solid ratio and the extraction times were researched by U7 (7(4)). The optimal conditions were achieved by optimization treatment and confirmed by experiment:the ethanol concentration being 75%, liquid to solid ratio being 7, extraction time 60 minutes, extracted two times.

   Oleanolic acid and ursolic acid: research perspectives.:J Ethnopharmacol. 2005 Aug 22;100(1-2):92-4.Liu J.Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, NCI at NIEHS, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Liu6@niehs.nih.gov[PMID: 15994040]

 Oleanolic acid and ursolic acid are ubiquitous triterpenoids in plant kingdom, medicinal herbs, and are integral part of the human diet. During the last decade over 700 research articles have been published on their research, reflecting tremendous interest and progress in our understanding of these triterpenoids. This included the isolation and purification of these tritepernoids from various plants and herbs, the chemical modifications to make more effective and water soluble derivatives, the pharmacological research on their beneficial effects, the toxicity studies, and the clinical use of these triterpenoids in various diseases including anticancer chemotherapies. A briefly commentary is attempted here for their research perspectives.

   Effects of ursolic acid, betulin and sulfur-containing compounds on mucin release from airway goblet cells.:Planta Med. 2004 Dec;70(12):1119-22.Lee CJ, Seok JH, Hur GM, Lee JH, Park JS, Seol IC, Kim YH.Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Korea. LCJ123@cnu.ac.kr[PMID: 15643543]

 In this study, we investigated whether ursolic acid, betulin and 2 kinds of sulfur-containing compounds--NAC and MESNA--affect mucin release from airway goblet cells and compared the possible activities of these agents with the inhibitory action on mucin release by PLL and the stimulatory action by ATP. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on 3H-mucin release. The results were as follows: ursolic acid, betulin, MESNA and NAC increased mucin release (40-50 % above control) at the highest concentrations (10(-5) M-10(-3) M). We conclude that ursolic acid and betulin can stimulate mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further investigated for the possible use as mucoregulators in the treatment of chronic airway diseases.

   Effects of ursolic acid on different steps of the angiogenic process.:Biochem Biophys Res Commun. 2004 Jul 23;320(2):402-8.Cardenas C, Quesada AR, Medina MA.Central Culture Cell Service, University of Malaga, Spain.[PMID: 15219842]

 Ursolic acid is a triterpenoid with pleiotropic biological effects. In this report, we study the effects of ursolic acid on different key steps of angiogenesis. Our results show that ursolic acid is able to inhibit key steps of angiogenesis in vitro, including endothelial cell proliferation, migration, and differentiation. At the same time, it seems to stimulate other key steps of angiogenesis, such as extracellular matrix degradation by MMP-2 and urokinase. Although ursolic acid can inhibit in vivo angiogenesis in the CAM assay, the different signs of the effects it causes on different steps of angiogenesis force one to be cautious concerning its anti-angiogenic potential.

   Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes.:Life Sci. 2004 Apr 16;74(22):2769-79.Kim KA, Lee JS, Park HJ, Kim JW, Kim CJ, Shim IS, Kim NJ, Han SM, Lim S.Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, 1 Hoegidong, Dongdaemoongu, Seoul, 130-701, South Korea.[PMID: 15043991]

 Oleanolic acid (OA) and ursolic acid (UA), triterpene acids having numerous pharmacological activities including anti-inflammatory, anti-cancer, and hepato-protective effects, were tested for their ability to modulate the activities of several cytochrome P450 (CYP) enzymes using human liver microsomes. OA competitively inhibited CYP1A2-catalyzed phenacetin O-deethylation and CYP3A4-catalyzed midazolam 1-hydroxylation, the major human drug metabolizing CYPs, with IC50 (Ki) values of 143.5 (74.2) microM and 78.9 (41.0) microM, respectively. UA competitively inhibited CYP2C19-catalyzed S-mephenytoin 4'-hydroxylation with an IC50 (Ki) value of 119.7 (80.3) microM. However, other CYPs tested showed no or weak inhibition by both OA and UA. The present study demonstrates that OA and UA have inhibitory effects on CYP isoforms using human liver microsomes. It is thus likely that consumption of herbal medicines containing OA or UA, or administration of OA or UA, can cause drug interactions in humans when used concomitantly with drugs that are metabolized primarily by CYP isoforms. In addition, it appears that the inhibitory effect of OA on CYP1A2 is, in part, related to its anti-inflammatory and anticancer activities.


   A new pentacyclic triterpenoid glucoside from Prunus serrulata var. spontanea.:Chem Pharm Bull. 2004 Jan;52(1):157-9.Jung HA, Chung HY, Jung JH, Choi JS. Faculty of Food Science and Biotechnology, Pukyong National University, Busan 608-737, Korea.[PMID: 14709888]

 A new triterpenoid, 2alpha,3alpha,24-trihydroxyurs-12-en-28-oic acid-28-O-beta-D-glucopyranosyl ester (4) along with four known triterpenoids, ursolic acid (1), 2alpha-hydroxyursolic acid (2), 2alpha,3alpha,24-trihydroxyurs-12-en-28-oic acid (3), and 2alpha,3alpha,19alpha,24-tetrahydroxyurs-12-en-28-oic acid-28-O-beta-D-glucopyranosyl ester (5), were isolated from the leaves of Prunus serrulata var. spontanea (Rosaceae). Compounds 3-5 showed ONOO(-) scavenging activity, whereas compounds 1 and 2 were virtually inactive.

   Effects of ursolic acid on liver-protection and bile secretion.:Zhong Yao Cai. 2003 Aug;26(8):578-81.Xiong X, Chen W, Cui J, Yi S, Zhang Z, Li K.Yichun College, Yichun, Jiangxi 336000.[PMID: 14649204]

 OBJECTIVE: To study the liver-protection and promoting bile secretion of ursolic acid. METHODS: Ursolic acid was administrated to the mice with liver injury induced by CCl4 or APIT. ALT, AST levels in serum were examined. The bile flow rate and the concentration of the main components in the bile of rats administrated with ursolic acid were estimated. RESULTS: Ursolic acid could decrease the serum ALT, AST, SB levels in the mice treated with CCl4 or APIT, promote the secretion of bile and increase the concentration of bilirubin in the bile. CONCLUSION: Ursolic acid exhibited significant liver protection and promoting blie secretion.

   Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system.:Phytomedicine. 2003;10(6-7):483-9.Raphael TJ, Kuttan G. Amala Cancer Research Centre, Amalanagar, Thrissur, Kerala, India. amalaresearch@rediffmail.com[PMID: 13678231]

 The effect of naturally occurring triterpenoid compounds such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin on the immune system was studied using Balb/c mice. Intraperitoneal treatments with 5 doses of these terpenoid compounds were found to enhance the total white blood cells (WBC) count. In ursolic acid, oleanolic acid and nomilin treated animals the maximum total WBC count was observed on the 6th day, while in glycyrrhizic acid treated animals it was observed only on the 9th day after the drug treatment. In ursolic acid, oleanolic acid and nomilin treated animals the percentage of increase in the total WBC count was to 91.48 +/- 4.6%, 135.75 +/- 6.4% and 117.33 +/- 17.9% respectively. In the glycyrrhizic acid treated animals the total WBC count was increased to 114.9 +/- 18%. Bone marrow cellularity and alpha-esterase positive cells were also enhanced by the treatment with these terpenoids. Treatment with various triterpenoids along with antigen produced an enhancement in the specific antibody titre and the number of plaque forming cells (PFC) in the spleen. Triterpenoids remarkably inhibited delayed type hypersensitivity reaction (DTH). These results indicate the immunomodulatory activity of naturally occurring triterpenoids such as glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin.

   High-performance liquid chromatographic analysis of bioactive triterpenes in Perilla frutescens.:J Pharm Biomed Anal. 2003 Aug 21;32(6):1175-9.Chen JH, Xia ZH, Tan RX. State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing 210093, China.[PMID: 12907261]

 Perilla frutescens (L.) Britt. (Lamiaceae), a famous traditional Chinese medicine, has been used for the treatment of various diseases. To evaluate the quality of P. frutescens, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed for the assessment of three bioactive triterpene acids: tormentic acid (TA), oleanolic acid (OA) and ursolic acid (UA). The HPLC system used an Spherisob octadecylsilyl silica (ODS) column with acetonitrile and aqueous H(3)PO(4) as the mobile phase and detection at 206 nm. The method was precise with relative standard deviations for these three constituents that ranged between 0.6-1.5% (intraday) and 0.7-2.6% (interday). The content of these three phytochemicals in the leaves of P. frutescens growing at eight different locations of China was determined to establish the effectiveness of the method.

   Determination of ursolic acid in herba of Verbena officinalis by HPLC.:Zhongguo Zhong Yao Za Zhi. 2002 Dec;27(12):916-8.Liu CH, Liu Y. Institute for Drug and Instrument Control of PLA, Beijing 100071, China. liuchenghong@chinaren.net[PMID: 12776531]

 OBJECTIVE: To establish a HPLC method for determination of ursolic acid in dried aerial part of Verbena officinalis. METHOD: The column used was a Kromasil C18 (4.6 mm x 250 mm) packed with a 5 microns stationary phase. The mobile phase consisted of methanol-sodium phosphate buffer [monobasic sodium phosphate (MW = 119.98) 1.7997 g and phosphoric acid (85%) 1.02 mL, combined and brought the total volume of 1,000 mL with water] (89:11); the mobile phase was maintained at a flow-rate of 0.8 mL per minute; the column was maintained at 40 degrees C; the DAD detector was set at 210 nm. RESULTS: The liner range was 0.251-10.04 micrograms (r = 1.0000). An average recovery of 98.1% (n = 6) was obtained with a RSD of 1.0%. CONCLUSION: The method is simple, accurate and suitable for the qualify control.


   Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension.:Phytomedicine. 2003 Mar;10(2-3):115-21.Somova LO, Nadar A, Rammanan P, Shode FO.Department of Human Physiology, University of Durban-Westville, Durban, South Africa. somova@pixie.udw.ac.za[PMID: 12725563]

 Cardiovascular (systolic and diastolic blood pressure, heart rate), antihyperlipidemic (tryglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase--GPx, and superoxide dismutase--SOD), diuretic/saluretic and hypoglycemic activity of 98% pure oleanolic (OA) and ursolic (UA) acid were studied in Dahl salt-sensitive (DSS), insulin resistant rat model of genetic hypertension. Both OA and UA displayed low toxicity, with LC50 0.10 and 0.95 mg/ml, respectively. Although both triterpenoids did not have direct hypotensive effect, after 6-week application in a daily dose 60 mg/kg b.w., i.p., they prevented the development of severe hypertension. The antihypertensive effect was attributed to their potent diuretic-natriuretic-saluretic activity; direct cardiac effect (heart rate decrease by 34% and 32%, respectively); antihyperlipidemic (more than two times decrease of LDL and triglycerides); antioxidant (GPx increase by 12% and 10%, respectively; SOD increase by 12% and 22%, respectively), and hypoglycemic (blood glucose decrease by 20% and 50%, respectively) effects on the DSS rats. Except for the antihyperlipidemic effects, the other described above in vivo antihypertensive effects of OA and UA are reported for the first time and the underlying mechanisms are currently under investigation.

   Antifeedant activity of some pentacyclic triterpene acids and their fatty acid ester analogues.:J Agric Food Chem. 2003 Mar 26;51(7):1952-5.Mallavadhani UV, Mahapatra A, Raja SS, Manjula C.Forest and Marine Products Department, Natural Resources Division, Regional Research Laboratory (CSIR), Bhubaneswar-751 013, Orissa, India. uvmavadani@yahoo.com[PMID: 12643657]

 The 3-O-fatty acid ester derivatives (C(12)-C(18)) of two pentacyclic triterpenic acids, ursolic acid and oleanolic acid, were synthesized under mild esterification conditions in excellent yields (80-85%) and screened for their antifeedant activity, together with the parent acids, against the agricultural pest tobacco caterpillar larvae (Spodoptera litura F) in a no-choice laboratory study. The Urs-12-ene-28-carboxy-3beta-octadecanoate and olean-12-ene-28-carboxy-3beta-hexadecanoate were found to exhibit exceptionally potent antifeedant activities at 50 microg/cm(2) concentration, even after 48 h.

   Determination of oleanolic acid and ursolic acid in spica Prunellae by derivative GC method.:Zhongguo Zhong Yao Za Zhi. 1999 Dec;24(12):744-5, 764.Yan H, Zhao L, Zhu D, Ding L. Baoji Municipal Institute for Drug Control, Baoji 721001.[PMID: 12205984]

 OBJECTIVE: To develop a GC method to determine the oleanolic acid and ursolic acid in Spica Prunellae. METHOD: Before GC analysis, the sample was derivatized with CH2N2 solution. The GC conditions were as follows: comumn-10% SE-30(2m x 3mm) and column temperature -270 degrees C. RESULT: The two constituents were well separated and had good linearity in the range of 0.0025-0.4000 mg/ml. The average recoveries and RSD of oleanolic acid were 93.53% and 3.5%, 94.18% and 3.0% respectively. CONCLUSION: The method is good for determining oleanolic acid and ursolic acid in Chinese medicines.

   Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris.:Planta Med. 2000 May;66(4):358-60.Ryu SY, Oak MH, Yoon SK, Cho DI, Yoo GS, Kim TS, Kim KM. [PMID: 10865455]

 The activity-guided fractionation of the extract of the herb of Prunella vulgaris (Labiatae) led to the isolation of four triterpenes, i.e., betulinic acid, ursolic acid, 2 alpha,3 alpha-dihydroxyurs-12-en-28-oic acid, and 2 alpha-hydroxyursolic acid. One of these compounds, 2 alpha,3 alpha-dihydroxyursolic acid, demonstrated significant inhibition on the release of beta-hexosaminidase from the cultured RBL-2H3 cells in a dose-dependent manner; the IC50 value was calculated to be 57 microM. When the isolated compounds were tested for their effects on the production of nitric oxide from cultured murine macrophages, RAW 264.7 cells, ursolic acid and 2 alpha-hydroxyursolic acid exhibited strong inhibitory activities (IC50 values, 17 and 27 microM, respectively).

   Study on the use of ultrasound technique in extraction of polysaccharides from Loquat leaf.:Zhong Yao Cai. 2006 Nov;29(11):1230-3.Wang MY, Xu RB, He JX. Department of Chemical Engineering, Huaihai Institute of Technology, Lianyungang 222005, China. wmingyanzhao@hotmail.com[PMID: 17228666]

 In order to gain the optimal extract condition of extraction polysaccharides in Loquate leaf by ultrasound technique, the single factor and the orthogonal experiments were carried. The results showed that the optimal condition turned out to be ultrasound extraction time 35 min, ultrasound power 120W, extraction temperature 60 degrees C and the liquid-to-solid ratio 12: 1. In contrast to conventional extraction method, the ultrasound technique could be a better method for extracting the polysaccharides from Loquat leaf with a higher yield and shorter time.


  Scientific References:

  1.Ursolic acid:Actions,Commonly Known Benefit and Research.
  2.Research Update of Ursolic acid.