Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities
Abstract
:1. Introduction
2. Natural Occurrence and Biosynthesis of Ursolic Acid
3. Ursolic Acid as a Tool in Cancer Prevention and Therapy
3.1. General Review of Literature Data on Ursolic Acid Anti-Cancer Activities
3.2. Cellular Signaling Pathways and Enzyme Inhibition—The Key to the Ursolic Acid Activity against Cancer
Carcinoma Type | Model Used | Mechanism of Action |
---|---|---|
bladder cancer | cell lines (NTUB1 and T24) | |
breast cancer | rodent model (mice) |
|
cell lines (MCF-7, MCF-7/ADR and MDA-MB-231) | ||
cervical cancer | cell lines (HeLa and SiHa) | |
colorectal cancer | cell lines (Caco-2, CO115, CT26, DLD1, HCT15, HCT116, HT29, SW480 and SW620) | |
fibrosarcoma | cell lines (HT1080) |
|
gastric cancer | cell lines (AGS, BGC823, SGC7901 and SNU-484) |
|
glioma | rodent model (rats) |
|
cell lines (1321N1, U87 and U251) | ||
hepatic cancer | rodent model (mice) | |
cell lines (H22, Hep3B, HepG2 and Huh7) | ||
melanoma | rodent model (mice) |
|
cell lines (A375, B16F10 and M4Beu) | ||
leukemia | cell lines (Jurkat, HL60, HL60/ADR, K562, K562/ADR, THP1 and U937) | |
lung cancer | cell lines (A549, ASTC-a-1, Calu-6, H640 and H3255) | |
lymphoma | cell lines (Daudi) |
|
multiple myeloma | cell lines (U266, RPMI and 8226.MM1.S) |
|
neuroblastoma | cell lines (IMR32 and SH-SY5Y) | |
ovarian cancer | cell lines (CAOV and SK-OV-3) |
|
pancreatic cancer | cell lines (AsPC-1, Capan-1, MIA, Paca-1 and PANC-2) | |
prostate cancer | rodent model (mice) | |
cell lines (DU145, LNCaP and PC3) |
| |
thyroid cancer | cell lines (ARO) |
|
Preventive Effect | Model Used | Mechanism of Action |
---|---|---|
anti-inflammatory | mouse primary splenocytes | inhibition of Th2 cytokines production [76] |
activated T cells, B cells and macrophages; mice | suppression of NF-κB, AP-1 and NF-AT activity [77] | |
rat edema tests | unclear, probably connected with glucocorticoids [78] | |
mice | reductions of Th2 cytokines and ovalbumin-specific IgE production, and eosinophil infiltration via the Th2-GATA-3, STAT6, and IL-17-NF-κB pathways [79] | |
human intestinal epithelial cells and peritoneal macrophages from mice | inhibition of production of pro-inflammatory cytokines, IκBα phosphorylation/degradation and NF-κB DNA binding activity [80] | |
rat mast cells | inhibition of histamine release [81] | |
murine peritoneal macrophages | suppression of NO production and iNOS expression via downregulation of NF-κB activation; attenuation of expression of COX-2 and the secretion of proinflammatory cytokines like TNF-α and IL-6 [82] | |
PC12 cells | attenuation of H2O2 and MPP-induced release of IL-6 and TNF-α [83] | |
oedema in mice | attenuation of inflammation [84] | |
pleurisy in mice | reduction of leukocytes, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels [85] | |
phagocyte cells | inhibition of histamine release; inhibition of prostaglandins and leukotrienes production [86] | |
arthritis-induced mice | alteration of Th1/Th2 cytokine production [87] | |
Th17 cells | suppression of interleukin-17 production by antagonizing function of RORγt protein [88] | |
biochemical assays | inhibition of cyclooxygenase-2 catalyzed prostaglandin biosynthesis [89] | |
anti-oxidative | PC12 cells | attenuation of H2O2 and MPP-induced impairment in catalase and superoxide dismutase activity [83] |
rat liver microsomes | protection against lipid peroxidation [90] | |
RAW247 cells | inhibition of NO production [91] | |
isolated rat heart mitochondria | decrease in H2O2 production in the mitochondria [92] | |
human blood lymphocytes | normalization of antioxidant levels; reduction of lipid peroxidation [93] | |
Caco-2 cells | protection of DNA against oxidative damage [94] | |
chemical-induced cancer | mouse skin | inhibition of binding benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene to DNA [95] |
rats | suppression of preneoplastic lesions formation by 1,2-dimethylhydrazine [96] | |
rats | inhibition of formation of aberrant crypt foci by azoxymethane [97] | |
human bronchial epithelial cells and mice | inhibition of tobacco smoke extract-induced cell injury [98] | |
radiation-induced cancer | mice | enhancement of hematopoietic system recovery [99] |
ROS-induced cancer | murine T cells | inhibition of cell activation through modulation of NF-κB signaling [100] |
rats | attenuation of hepatocellular carcinoma induction by diethylnitrosamine-induced reactive oxygen species [101] | |
keranocite cell line and mice | skin cancer prevention; protection against hydrogen peroxide induced DNA damage [102] | |
viral-induced cancer | Raji cell line and mice | inhibition of Epstein-Barr virus activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) [103,104,105] |
3.2.1. Signaling Pathways
3.2.2. FOXM1 Transcription Factor
3.2.3. Apoptosis Regulating Proteins
3.2.4. Endogenous Reverse Transcriptase
3.2.5. Factors Involved in Metastasis and Angiogenesis
3.2.6. Cyclooxygenase-2 (COX-2)
3.3. Protection against Tumor-Inducing Agents
3.4. Ursolic Acid as a Drug—Clinical Trials
4. Impact of Ursolic Acid on Condition and Functioning of Body Organs
4.1. The Liver
4.2. The Heart
4.3. The Brain
4.4. Skeletal Muscles
4.5. Bones
4.6. Other Organs
5. Anti-Microbial Properties of Ursolic Acid
5.1. Anti-Bacterial Activity
Species | References |
---|---|
Bacteria | |
Aeromonas caveae | [171] |
Bacillus cereus | [171,172] |
Bacillus sphaericus | [173] |
Bacillus subtilis | [173,176] |
Enterococcus faecalis | [177] |
Escherichia coli | [171,176,177] |
Klebisiella pneumoniae | [171] |
Listeria monocytogenes | [171,175,178] |
Mycobacterium tuberculosis | [179,180,181] |
Pseudomonas aeruginosa | [171,177] |
Pseudomonas syrinagae | [173] |
Ralstonia solanacearum | [175] |
Shigella flexneri | [171] |
Staphylococcus aureus | [171,176,177,182,183,184] |
Staphylococcus epidermis | [175] |
Streptococcus mutans | [185,186,187] |
Streptococcus pneumoniae | [178,183] |
Streptococcus sobrinus | [186] |
Streptomyces scabies | [176] |
Vibrio cholerae | [171] |
Viruses | |
Human immunodefiency virus | [188,189,190,191,192] |
Hepatitis C virus | [189,193,194] |
Herpes simplex virus | [195] |
Protozoa | |
Leishmania amazonensis | [196] |
Plasmodium falciparum | [197,198,199,200] |
Trypanosoma brucei rhodesiense | [197] |
Trypanosoma cruzi | [201] |
Fungi | |
11 species | [202] |
Nematodes (Roundworms) | |
Brugia malayi | [203] |
Wuchereria bancrofti | [203] |
5.2. Anti-Viral Properties
5.3. Activity against other Microbes and Parasites
6. Conclusions
Conflicts of Interest
References
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Woźniak, Ł.; Skąpska, S.; Marszałek, K. Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities. Molecules 2015, 20, 20614-20641. https://doi.org/10.3390/molecules201119721
Woźniak Ł, Skąpska S, Marszałek K. Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities. Molecules. 2015; 20(11):20614-20641. https://doi.org/10.3390/molecules201119721
Chicago/Turabian StyleWoźniak, Łukasz, Sylwia Skąpska, and Krystian Marszałek. 2015. "Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities" Molecules 20, no. 11: 20614-20641. https://doi.org/10.3390/molecules201119721