77-52-1 Usage
Uses
Used in Cosmetics Industry:
Ursolic acid is used as an active ingredient in cosmetics for its skin rejuvenation and anti-aging properties. It promotes collagen synthesis and enhances skin elasticity, contributing to a youthful and healthy appearance.
Used in Pharmaceutical Industry:
Ursolic acid is used as a therapeutic agent for its STAT3 pathway inhibiting properties. It has been shown to inhibit endothelial cell proliferation and migration, as well as angiogenesis, making it a potential candidate for the treatment of various cancers.
Additionally, ursolic acid promotes skeletal muscle rejuvenation through enhanced SIRT1 expression, which can help protect against muscle atrophy and boost muscle growth. It also induces apoptosis in malignant mesothelioma cells, further highlighting its potential as an anticancer agent.
Origins
Ursolic acid can be isolated from various medicinal plants, Lamiaceae family being one of the most known sources of triterpenes, with contents up to 2.95% d.w[8]. In Rosmarinus officinalis leaves, one of the traditional commercial sources[9]. UA has also been identified in a variety of sources, particularly in leaves and flowers[10]. The triterpenic acids oleanolic and ursolic were recently detected for the first time in wild edible mushrooms[11] and in some commercial dried fruits[12].
UA content in the samples from different sources were significantly different, and the geographic variation was also observed in Paulownia fortune, Ocimum species, Argania spinosa[13]. The outer barks of Eucalyptus trees from temperate and Mediterranean zones are richer in triterpenic acids than the species from sub-tropical and tropical regions[14].
Properties and biological effects
Ursolic acid displayed lower toxicity than OA, 0.95 up from 0.10 mg/mL, respectively[15], but the data ranged depending on the raw material source, the extraction solvent, the type of activity, the disease, the clinical, cosmetically or pharmacological study, the study in animal or human, etc. Bioavailability studies confirmed a low plasma concentrations of UA in plasma of mice orally administered with high dose of UA, suggested either high binding activity in organs or low bioavailability or metabolism by the gut wall of the intestine and liver[16]. Despite many aspects of the biological activities of UA are not completely understood, the pharmacological effects could be attributed, in part, to their action against free radicals. Cardiovascular protection and anti-hyperlipidemic effect Cardiovascular protection, antihyperlipidemic (triglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase and superoxide dismutase activities), hypoglycemic effects and prevention of hypertension were observed in rats, displaying UA a low toxicity (LC50 0.95 mg/mL). Ursolic acid fed to rabbits and rats prevented the experimental atherosclerosis and lowered blood cholesterol[17]. A strong synergistic effect derived from the combination of ursolic acid and artesunate can reduce both triglyceride and cholesterol, showing more potent effects than either agent alone. Ethanolic extract from the stems and roots of Celastrus orbiculatus Thunb decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed a high-fat diet, and increases high-density lipoprotein; likewise, it reduce lipid accumulation and promote reverse cholesterol transport in vivo and in vitro[18].
Antitumor effect
Beneficial action of ursolic acid and its derivatives was reported based on their anti-tumor, including inhibition of angiogenesis, invasion of tumor cells and metastasis, induction of apoptosis in tumor cells and prevention of malignant transformation of normal cells, and it also interferes with numerous enzymes[19]. Clinical tests suggesting the possibility of practical use of UA have already been conducted[20]. Ursolic acid was identified as active components of different plants for inhibiting mutagenicity and tumor-promotion. Ursolic acid exert anticancer effects in various cancer cell systems[20], it may have a potential application as a chemopreventive agent in gastric cancer, colorectal carcinogenesis and tumors of the colon, lung cancer, prostate cancer, UA pretreatment potentiated cell cycle arrest and UV radiation-induced apoptosis selectively in skin melanoma cells[21].
Antimicrobial
Ursolic acid and its derivatives have shown growth inhibition of gram-positive and gram-negative bacteria and fungi, and UA showed ability to control bacterial growth, biofilm formation, and elastase activity[22]. Synergistic effect of UA and two semi-synthetic derivatives and the aminoglycosides antibiotics neomycin, amikacin, kanamycin and gentamicin towards twelve bacterial pathogens strains was observed. Ursolic acid is the active components in natural extracts to inhibit the growth of some food-associated bacteria and yeast, protozoa (Trypanosoma cruzi), promoting an anti-inflammatory response during Leishmania infection[23].
Anti-diabetes, anti-inflammatory and anti-aging effect
Ursolic acid exhibits potential anti-diabetic and immunomodulatory properties by increasing insulin levels with preservation of pancreatic beta-cells and modulating blood glucose levels, T-cell proliferation and cytokines production by lymphocytes in type 1 diabetic mice fed a high-fat diet, compared to the diabetic group[24]. Type-2 diabetes is associated with obesity and ursolic acid may prevent or treat this disorder and its related comorbidities by acting as hypoglycemic and anti-obesity agent with five effects: reduction of the absorption of glucose, decrease the endogenous glucose production and increase the glycogen synthesis, increase the insulin sensitivity, improvement of lipid homeostasis, and promotion of the body weight regulation[9].
UA was twice as potent as indomethacin, and has been proposed for the treatment of rheumatism, fever and arthritis. The mechanisms of the anti-inflammatory action of ursolic acid and novel derivatives may be ascribed to inhibition of histamine release from mast cells, lipoxygenases, cyclooxygenases activity, inducible nitric oxide synthase and elastase, suppress the inflammatory cytokine-induced expression of E-selectin (an early response adhesion molecule expressed on the surface of endothelial cells during inflammation) in endothelial cells via inhibition of NF-kappa B activation[25] and suppressed the production of intracellular reactive oxygen species[26].
The epidermal permeability barrier plays a crucial role in human physical, chemical and biological cutaneous functions. Sensitive skin, associated with increased transepidermal water loss, penetrability and susceptibility to irritants, is related with impaired barrier function and reduction in ceramides. The atopic dermatitis displays impaired epidermal permeability barrier function, diminished water-holding properties and decreased ceramide levels. UA are great moisturizing candidates that do not create any cutaneous irritations[27]. Induction of ceramide synthesis is usually associated with keratinocyte differentiation. The ursolic acid increases the expression of genes required for terminal keratinocyte differentiation (involucrin, loricrin and filaggrin), improving the recovery of skin barrier function.
References
Lim, S. W et al (2007). Journal of Dermatology, 34(9), 625–634.
Kashyap, D., Tuli, H. S., & Sharma, A. K. (2016). Life Sciences,146, 201–213.
Wo?niak, L., Sk?pska, S., & Marsza?ek, K. (2015). Molecules, 20(11), 20,614–20,641.
Kunkel, S. D. et al (2012). PLoS ONE, 7(6)?
Deane, C. S., et al (2017). American Journal of Physiology Endocrinology and Metabolism, 321(4), E282–E299.
De Almeida et al (2014). Journal of Thermal Analysis and Calorimetry, 115(3), 2401–2406.
Navina, R., Lee, Y. G., & Kim, S. M. (2017). Molecular biological roles of ursolic acid in he treatment of human diseases. Current Bioactive Compounds, 13(3), 177–185.
Razborsek, M. I., Voncina, D. B., Dolecek, V., & Voncina, E. (2008). Determination of oleanolic, betulinic and ursolic acid in Lamiaceae and mass spectral fragmentation of their trimethylsilylated derivatives. Chromatographia, 67(5–6), 433–440
Silva, F. S. G., Oliveira, P. J., & Duarte, M. F. (2016). Oleanolic, ursolic, and betulinic acids as food supplements or pharmaceutical agents for type 2 diabetes: Promise or Illusion? Journal of Agricultural and Food Chemistry, 64, 2991–3008.
Han, S. K., et al (2014). Oleanolic acid from Fragaria ananassa calyx leads to inhibition of alpha-MSH-induced melanogenesis in B16-F10 melanoma cells. Journal of the Korean Society for Applied Biological Chemistry, 57(6), 735–742
Kalogeropoulos, N., Yanni, A. E., Koutrotsios, G., & Aloupi, M. (2013). Toxicology, 55, 378–385.
Zhang, F., Daimaru, E., Ohnishi, M., Kinoshita, M., & Tokuji, Y. (2013). Food Science and Technology Research, 19(1), 113–116.
Guinda, á., Rada, M., Delgado, T., & Castellano, J. M. (2011). Pentacyclic triterpenic acids from Argania spinosa. European Journal of Lipid Science and Technology, 113(2), 231–237.
Domingues, R. M. A., et al (2011). Cellulose Chemistry and Technology, 45(7–8), 475–481
Somova, L. I., Shode, F. O., & Mipando, M. (2004). Phytomedicine, 11, 121–129.
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Liu, J. (1995). Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology, 49, 57–68.
Zhang, Y., Si, Y., et al (2016). Lipids, 51, 677–692.
Dong, H., et al (2015). Biochemical Pharmacology, 93(2), 151–162.
Wo?niak, L., Sk?pska, S., & Marsza?ek, K. (2015). Molecules, 20(11), 20,614–20,641
Lee, Y. H., Wang, E. X., Kumar, N., & Glickman, R. D. (2014). Ursolic acid differentially modulates apoptosis in skin melanoma and retinal pigment epithelial cells exposed to UV–VIS broadband radiation. Apoptosis, 19(5), 816–828.
Gilabert, M., Marcinkevicius, K., Andújar, S., Schiavone, M., Arena, M. E., & Bardón, A. (2015). Sesquiand triterpenoids from the liverwort Lepidozia chordulifera inhibitors of bacterial biofilm and elastase activity of human pathogenic bacteria. Phytomedicine, 22(1), 77–85.
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Biochem/physiol Actions
Triterpenoid found in a variety of fruits, including apples. Cardioprotective and anti-tumor agent. Under study as a potential Alzheimer′s disease therapeutic due to its inhibitory effect on the interactions between amyloid-β and the CD36 receptor.
Anticancer Research
It is a triterpenoid, derived from basil, and suppresses the activation of NF-κB byinhibiting a kinase that activates NF-κB(IKK) (Aggarwal and Shishodia 2004). It suppresses tumorigenesis, tumor promotion, and angiogenesis by downregulationof the expression of lipoxygenases (LOX), MMP-9, and COX-2. It is reported toinduce apoptosis in breast cancer, melanoma, hepatoma, prostate cancer, andacute myelogenous leukemia by preventing replication of DNA, inhibition of proteintyrosine kinases, activation of caspases, induction of calcium release, anddownregulating apoptosis gene cellular inhibitor. Ursolic acid inhibits IκBαkinase activity, degradation of IκBα, phosphorylation, NF-κB-dependent reportergene expression, p65 nuclear translocation, and p65 phosphorylation. Inhibitionof NF-κB leads to the reduction of cyclin D1, COX-2, and MMP9 expression.This downregulates STAT-3 activation and its regulated gene products such ascyclin D1, Mcl-1, Bcl-xL, survivin, Bcl-2, and VEGF. It also induces the expressionof tyrosine phosphatase SHP-1 protein and of mRNA (Aggarwal et al. 2008;Hsu et al. 2004).
Cytotoxicity
IC50 (μg/mL): 6.7 (518A2), 5.3 (A2780), 7(A549), 6.4 (FaDu), 4.8 (HT29), 5.8(MCF-7), 8.5 (NIH3T3) (Wiemann et al.2016) IC50 (μg/mL): 12.38 (MGC-803),17.12(HCT-116), 13.39 (T24), 13.81(HepG2), 16.36 (A549), >45.7 (HL-7702)(Hua et al. 2015).
Check Digit Verification of cas no
The CAS Registry Mumber 77-52-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 7 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 77-52:
(4*7)+(3*7)+(2*5)+(1*2)=61
61 % 10 = 1
So 77-52-1 is a valid CAS Registry Number.
InChI:InChI=1/C30H48O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18-19,21-24,31H,9-17H2,1-7H3,(H,32,33)/p-1/t18-,19+,21+,22-,23+,24+,27+,28-,29-,30+/m1/s1
77-52-1Relevant articles and documents
Identification and characterization of human UDP-glucuronosyltransferases responsible for the in?vitro glucuronidation of ursolic acid
Gao, Rui,Liu, Mingyi,Chen, Yu,Xia, Chunhua,Zhang, Hong,Xiong, Yuqing,Huang, Shibo
, p. 261 - 268 (2016)
This study aims to characterize the glucuronidation kinetics of ursolic acid (UA) in human liver microsomes (HLMs) and intestinal microsomes (HIMs) and identify the main UDP-glucuronosyltransferases (UGTs) involved. In our present study, only one type of UA glucuronide was observed after incubation with HLMs and HIMs respectively and was identified as a UA hydroxyl O-glucuronide. The glucuronidation of UA can be shown in HLMs and HIMs with Km values of 3.29?±?0.16 and 3.74?±?0.22?μM and Vmax values of 0.33?±?0.03 and 0.42?±?0.03?nmol/min/(mg protein). Among the 12 recombinant UGT enzymes investigated, UGT1A3 and UGT1A4 were identified as the major enzymes catalyzing the glucuronidation of UA [Km values of 2.58?±?0.12 and 4.66?±?0.60?μM, Vmax values of 0.72?±?0.01 and 1.00?±?0.06?nmol/min/(mg protein)]. The chemical inhibition study showed that the IC50 for hecogenin inhibition of UA glucuronidation was 51.79?±?4.32?μM in HLMs. And chenodeoxycholic acid inhibited UA glucuronidation in HLMs with an IC50 of 28.26?±?2.91?μM. In addition, UA glucuronidation in a panel of eight HLM was significantly correlated with telmisartan glucuronidation (r2?=?0.7660, p?2?=?0.5866, p??0.01) respectively. These findings collectively indicate that UGT1A3 and UGT1A4 were the main enzymes responsible for the glucuronidation of UA in human.
One new flavonoid xyloside and one new natural triterpene rhamnoside from the leaves of Syzygium grande
Samy, Mamdouh N.,Sugimoto, Sachiko,Matsunami, Katsuyoshi,Otsuka, Hideaki,Kamel, Mohamed S.
, p. 86 - 90 (2014/12/10)
One new flavonoid glycoside, myricetin 4′-methyl ether 3-O-β-d-xylopyranoside (1) and one new natural triterpene glycoside, grandoside (2) were isolated from a MeOH extract of the leaves of Syzygium grande, together with thirteen known compounds (3-15). The structures of the new compounds were determined through a combination of spectroscopic and chemical analyses. All of the isolated compounds were evaluated for their antifungal, antibacterial, anti-leishmania, DPPH radical-scavenging and cytotoxic activities by means of MTT assay.
Highly efficient and selective deprotection method for prenyl, geranyl, and phytyl ethers and esters using borontrifluoride-etherate
Narender,Venkateswarlu,Madhur,Reddy, K. Papi
, p. 26 - 33 (2012/10/30)
An efficient, simple, and practical method has been developed for the deprotection of prenyl, geranyl, and phytyl ethers and esters of aromatic and aliphatic compounds using borontrifluoride-etherate (BF3· OEt2) at room temperature in good to excellent yields for the first time. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
An efficient and recyclable catalyst for the cleavage of tert-butyldiphenylsilyl ethers
Yan, Shiqiang,Ding, Ning,Zhang, Wei,Wang, Peng,Li, Yingxia,Li, Ming
experimental part, p. 6 - 20 (2012/07/13)
An efficient, chemoselective, and environment-friendly method for the deprotection of tert-butyldiphenylsilyl ethers mediated by triflic acid supported on silica gel is reported. A wide range of tert-butyldiphenylsilyl ethers derived from carbohydrate and saponin residues can be smoothly cleaved in the presence of various types of other protecting groups in good to excellent yields in acetonitrile. This heterogeneous reaction does not require aqueous workup, and the supported catalyst can be readily recycled.
Chemical constituents, antischistosomal and antioxidant activities of the methanolic extract of Azadirachta indica
El-Sayed,Mahmoud,El-Nahas, Hanan A.,El-Toumy,El-Wakil, Eman A.,Ghareeb
, p. 99 - 113 (2013/05/22)
THE PRESENT study was performed to evaluate the in vitro schistosomicidal effect of 70% methanolic extract of the leaves of Azadirachta indica and its derived ethyl acetate and n-butanol fractions against adult Schistosoma mansoni worms. Also, antioxidant properties of these extracts were determined. Owing to the high antischistosomal and antioxidant activities of EtOAc and n-BuOH fractions, they were subjected to chromatographic isolation using different chromatographic techniques. Two flavonoid compounds; (1,2) were isolated from EtOAc fraction whereas one flavonoid; (3) quercetin-3-O-a-L-rhamnopyranoside and two bidesmosidic saponins; (4,5) were isolated from the butanolic fraction. Their structures were established using spectroscopic methods. Compounds 1-3 showed high antioxidant activity whereas compounds 4 and 5 were inactive. It is the first time that antischistosomal activity of A.indica and isolation of compounds 2-5 from this plant were carried out.
Use of tall oil pitch extract and compositions which contain it
-
, (2011/08/03)
Use of the unsaponificable fraction of tall oil pitch in the preparation of a food, cosmetic and/or pharmaceutical composition for the treatment, care and/or prevention of a disease, disorder and/or condition associated with the 5-α-reductase activity.
Process for preparing high purity corosolic acid and high purity ursolic acid
-
Page/Page column 5-6, (2008/12/04)
According to the present invention, there is provided a process for preparing corosolic acid comprising the steps of (1) dissolving crude extract of Japanese loquat leaves in alkali and aqueous alcohol and (2) applying the solution to a nonpolar adsorption resin to obtain corosolic acid.
Submicron-liposome containing triterpenoid and a method for preparing the same
-
, (2008/06/13)
Disclosed herein is submicron-liposome containing highly concentrated triterpenoid prepared by using nontoxic solvent without intense mechanical treatment and a method for preparing the same.
Submicron-liposome containing triterpenoid and a method for preparing the same
-
, (2008/06/13)
Disclosed herein is submicron-liposome containing highly concentrated triterpenoid prepared by using non-toxic solvent without intense mechanical treatment and a method for preparing the same.
Retrovirus protease inhibitors
-
, (2008/06/13)
A compound composition and method of treating a retrovirus infection are disclosed. In particular, isolated triterpenes have been shown to have significant inhibitory activity against HIV-1.
