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Ursolic Acid is a Triterpene acid used in cosmetics, that also has STAT3 pathway inhibiting properties. It inhibits endothelial cell proliferation and migration (IC50=5 μM) and angiogenesis. Promotes skeletal muscle rejuvenation via enhanced SIRT1 expression. Induces apoptosis in malignant mesothelioma cells. Ursolic acid protects against muscle atrophy and boosts muscle growth (see also tomatidine T538500).

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ursolic acid helps maintain the look and feel of the skin, acts as a perfume and helps mask odor. Therapeutic benefits in skin care include anti-inflammatory activity. ursolic acid has demonstrated anti-microbial, anti-bacterial, and anti-fungal action as well.

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ChEBI: Ursolic acid is a pentacyclic triterpenoid that is urs-12-en-28-oic acid substituted by a beta-hydroxy group at position 3. It has a role as a plant metabolite and a geroprotector. It is a pentacyclic triterpenoid and a hydroxy monocarboxylic acid. It derives from a hydride of an ursane.

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Ursolic acid (UA) is a hydroxyl pentacyclic triterpenoic acid (HPTA), which exhibits anti-bacterial, anti-cancer, anti-oxidative and anti-inflammatory effects. It can also promote neuroregeneration after peripheral nerve injury. UA can enhance sleep duration by activating the GABAergic neurotransmitter system. [GABA= γ-aminobutyric acid]

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).

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Adverse effects of Ursolic acid include reduction of sperm viability and inhibition of spermatogenesis, leading to infertility. Ursolic acid is capable of inducing endothelial cell death at concentrations above 12.5uM, and the mechanism of death is related to apoptosis. In addition, it also appears to cause DNA strand breaks.

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).

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