| In vitro: |
| PLoS One. 2012;7(7):e41545. | | DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.[Pubmed: 22844495] | The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied.
METHODS AND RESULTS:
The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals.
CONCLUSIONS:
Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ. |
|
| In vivo: |
| Phytomedicine. 2004 Feb;11(2-3):121-9. | | Cardiotonic and antidysrhythmic effects of oleanolic and ursolic acids, methyl maslinate and uvaol.[Pubmed: 15070161] | The cardiotonic and antidysrhythmic effects of four triterpenoid derivatives, namely oleanolic acid (OA), ursolic acid (UA), and uvaol (UV), isolated from the leaves of African wild olive (Olea europaea, subsp. africana) as well as methyl maslinate (MM) isolated from the leaves of Olea europaea (Cape cultivar) were examined.
METHODS AND RESULTS:
The derivatives showed low toxicity on brine shrimp test. They displayed significant, dose-response vasodepressor effect and sinus bradicardia, most prominent for OA and MM. The derivatives acted as beta-adrenergic antagonists, blocking the effect of adrenaline and isoprenaline. The established positive inotropic and dromotropic effects were most distinctive for OA and MM. The antidysrhythmic effects were evaluated on CaCl2- and adrenaline-induced chemical arrhythmias, and on ischemia-reperfusion arrhythmia. OA and UA displayed antidysrhythmic effects on both types of chemical arrhythmia; OA and UV in dose 40 mg/kg conferred significant antidysrhythmic activity on ischemia and reperfusion arrhythmias. The effect was comparable to that of propranolol and suggestive of beta-adrenergic antagonistic activity.
CONCLUSIONS:
On the basis of the vasodepressor, cardiotonic and antidysrhythmic effects of these compounds, it was concluded that OA and UV isolated from wild African olive leaves, or crude extract containing all components, can provide a cheap and accessible source of additive to conventional treatment of hypertension, complicated by stenocardia and cardiac failure. | | Eur J Pharmacol . 2016 Jun 5;780:232-42. | | Uvaol attenuates pleuritis and eosinophilic inflammation in ovalbumin-induced allergy in mice[Pubmed: 27038519] | | Abstract
Uvaol, a triterpene present in olives and virgin olive oil, has been shown to possess anti-inflammatory properties and antioxidant effects. However, until now, no studies have demonstrated its potential effects on allergic inflammation. The aim of this study was to evaluate the anti-inflammatory effects of uvaol in a mouse model of allergy characterized by eosinophil-dominant inflammation in actively sensitized mice. The anti-inflammatory effect of uvaol was analyzed in two murine models of allergic inflammation (pleurisy and asthma). In these models, Swiss mice were sensitized and challenged with ovalbumin (OVA). In the pleurisy model, the pleural eosinophilic inflammation and IL-5 concentrations were examined 24h after the OVA challenge, while in the asthma model were examined the airway inflammation via bronchoalveolar lavage (BAL) fluid cytology and lung histopathology analyses. Our results showed that uvaol decreased the accumulation of eosinophils and the concentration of IL-5 in pleural effluent. Uvaol also demonstrated important anti-inflammatory activity by inhibiting production of IL-5 and influx of leukocytes, mainly of eosinophils, in BAL fluid, but without interfering with levels of reactive oxygen species in leukocytes. Moreover, the eosinophil infiltration, mucus production, number of alveoli that collapsed, and IL-5 levels in the lung were clearly decreased by uvaol treatment. These findings indicate that uvaol can be a good candidate for the treatment of allergic inflammation by inhibiting eosinophil influx and IL-5 production in ovalbumin-induced allergy.
Keywords: Eosinophil; IL-5; Inflammation; Triterpene; Uvaol; Uvaol (PubChem CID: 92802). |
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Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
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