Antiprotease and Antimetastatic Activity of Ursolic Acid Isolated from Salvia officinalis

Abstract

Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for -ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. -Ursolic acid showed the strongest inhibition activity to urokinase (IC 50 = 12 μm) and cathepsin B (IC 50 = 10 μm) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of -ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of B16 mouse melanoma cells in vivo. We found, that -ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p Ͻ 0.05).

Anti-metastatic properties of the leaves of Eriobotrya japonica

“…Thus, in this study, we have shown that LEJ most likely exerts its anti-metastatic effects via ursolic acid and 2α-hydroxyursolic acid. Many reports have noted that ursolic acid has potent antimetastatic activity (Jedinák et al, 2006;Raphael and Kuttan, 2008). However, as far as we know, the MMP-2 and MMP-9 inhibitory activity of 2α-hydroxyursolic acid has not yet been reported.…”

Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells through ß-catenin signaling

“…Therefore, new therapeutic drugs with reduced side-effects and better bioavailability are needed. Triterpenoids are structurally diverse organic compounds with promising anticancer and antimetastatic activity (25,26). The medicinal mushroom G. lucidum is a rich source of triterpenes with anticancer activity.…”

Therapeutic Interventions Using Ursolic Acid for Cancer Treatment

“…Additionally, immunohistochemistry revealed that UA also regulates the metastatic biomarker ICAM-1 [37]. Tumor invasion linked to proteases, such as urokinase and cathepsin B, is also suppressed by UA [38]. A study of C6 glioma cells found that UA inhibits the expression of matrix metalloproteases (MMPs) by regulating NF-κB via the up-regulation of IκB inhibitors [39].…”