Oleanolic acid

About: Oleanolic acid is a research topic. Over the lifetime, 2964 publications have been published within this topic receiving 59576 citations. The topic is also known as: Giganteumgenin C & Virgaureagenin B.

Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress

Abstract: A series of synthetic triterpenoid (TP) analogues of oleanolic acid are powerful inhibitors of cellular inflammatory processes such as the induction by IFN-γ of inducible nitric oxide synthase (iNOS) and of cyclooxygenase 2 in mouse macrophages. Here, we show that these analogues are also extremely potent inducers of the phase 2 response [e.g., elevation of NAD(P)H-quinone oxidoreductase and heme oxygenase 1], which is a major protector of cells against oxidative and electrophile stress. Moreover, like previously identified phase 2 inducers, the TP analogues use the antioxidant response element–Nrf2–Keap1 signaling pathway. Thus, induction of the phase 2 response and suppression of the iNOS induction was abrogated in nrf2–/– and keap1–/– mouse embryonic fibroblasts. The high potency of TP analogues in inducing the phase 2 response and blocking inflammation depends on the presence of activated Michael reaction (enone) functions at critical positions in rings A and C. The most potent TP doubles NAD(P)H–quinone oxidoreductase in murine hepatoma cells at 0.28 nM and has an IC50 for suppression of iNOS induction in primary mouse macrophages of 0.0035 nM. The direct interaction of this TP with thiol groups of the Keap1 sensor for inducers is demonstrated spectroscopically. The antiinflammatory and phase 2 inducer potencies of 18 TP are closely linearly correlated (r2 = 0.91) over 6 orders of magnitude of concentration. Thus, in addition to blocking inflammation and promoting differentiation, these TP exhibit another very important protective property: the induction of the phase 2 response.

Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts.

Abstract: Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of new multi-targeting bioactive agents. Screening of 39 plant materials identified triterpene rich (> 0.1% dry matter) plant parts. Plant materials with high triterpene concentrations were then used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50 - 90%. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations.