Alphitolic acid

Food Res. Int., 2015, 77(2):109-17.

Quali-quantitative determination of triterpenic acids of Ziziphus jujuba fruits and evaluation of their capability to interfere in macrophages activation inhibiting NO release and iNOS expression.[Reference: WebLink]

Ziziphus jujuba Mill fruits are recognized as an outstanding source of biologically active compounds including triterpenic acids. In order to evaluate the triterpenic profile of these edible and little commercial fruits and to contribute to the improvement of their potential value as food, a quali-quantitative study along with biological assays were carried out.
METHODS AND RESULTS:
The phytochemical investigation of the triterpenic fraction yielded nine triterpenic acids, ceanothic acid (1), Alphitolic acid (2), maslinic acid (3), 3- O-cis-coumaroyl Alphitolic acid (4), 3- O-trans-coumaroyl Alphitolic acid (5), 3- O-trans-coumaroyl maslinic acid (6), 3- O-cis-coumaroyl maslinic acid (7), betulinic acid (8), and oleanolic acid (9). In order to perform the quantitative determination of compounds 1- 9 in Z. jujuba fruits, an analytical method based on liquid chromatography coupled to mass spectrometry with ESI source and triple quadrupole analyzer (LC-ESI(QqQ)MS), using the very sensitive and selective mass tandem experiment called Multiple Reaction Monitoring (MRM), was developed and validated.Furthermore, the antiproliferative activity of compounds 1- 9 was determined on three different cultured cell lines, namely J774A.1, MCF7 and A459 cells.
CONCLUSIONS:
For compounds 1, 2, 5 and 9, exhibiting no significant antiproliferative activity, the effects on nitrite production by LPS-stimulated J774.A1 cultured macrophages were evaluated (10-100. μM), showing the ability of Alphitolic acid (2), and 3- O-trans-coumaroyl Alphitolic acid (5) to reduce significantly (P. <. 0.001) and in a concentration related manner NO production. The capability of compounds 2 and 5 to influence the expression of the inducible nitric oxide synthase (iNOS) was also investigated, showing that both compounds reduced iNOS expression in a concentration related manner.

Planta Med. 2000 Dec;66(8):768-9.

Antimicrobial triterpenoids from Licania heteromorpha.[Pubmed: 11199141 ]

METHODS AND RESULTS:
Six triterpenoids having a lupane and oleane skeleton were isolated from the leaves and young branches of Licania heteromorpha Bentham var. heteromorpha and were identified as: betulinic acid 1, Alphitolic acid 2, 3 beta-O-trans-p-coumaroyl Alphitolic acid 3, 3 beta-O-cis-p-coumaroyl Alphitolic acid 4, 3 beta-O-trans-p-coumaroyl maslinic acid 5, 3 beta-O-cis-p-coumaroyl maslinic acid 6. The antimicrobial activity of these compounds was evaluated in vitro on clinically isolated microorganisms employing a microdilution method.
CONCLUSIONS:
Compounds 2, 3, 5, and 6 showed antimicrobial activity on Gram-positive bacteria and yeasts, whereas none of the six triterpenoids were active against Gram-negative organisms.

J. Funct. Foods, 2015,18:368-78.

Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway.[Reference: WebLink]

The antitumour mechanism of Alphitolic acid (ALA), an anti-inflammatory triterpene, in oral squamous cell carcinoma (OSCC) cells was investigated.
METHODS AND RESULTS:
ALA suppressed the proliferation of SCC4 and SCC2095 OSCC cells with IC50values of 12 and 156508M, respectively, via apoptotic induction. Mechanistically, this drug effect on apoptosis was, in part, associated with its ability to block Akt–NF-κB signalling. Moreover, ALA induced autophagy, as evidenced by increased expression of the autophagy biomarkers Beclin 1, Atg7, and LC3B-II, and autophagosome formation. This autophagy induction played a protective role as autophagy inhibitors enhanced cellular susceptibility to ALA-induced apoptosis. Also noteworthy is the involvement of p53 in ALA-mediated cytotoxicity. ALA increased p53 phosphorylation/expression, accompanied by parallel decreases in the expression of the oncogenic E3 ligase MDM2, and shRNA-mediated knockdown of p53 partially rescued ALA-mediated cytotoxicity.
CONCLUSIONS:
Together, these findings suggest the translational value of ALA as an ingredient in functional food/dietary supplement for OSCC prevention.

Bioorg. Med. Chem.,2008 ,16(21):9420-4.

Hedgehog/GLI-mediated transcriptional inhibitors from Zizyphus cambodiana.[Pubmed: 18842418 ]

The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. By screening tropical plant extracts by using our screening system, Zizyphus cambodiana was found to include Hh/GLI signaling inhibitors.
METHODS AND RESULTS:
Bioassay-guided fractionation of this plant extract led to the isolation of three active pentacyclic triterpenes, colubrinic acid (1), betulinic acid (2) and Alphitolic acid (3), as potent inhibitors. The inhibition of GLI-related protein expression with 1 or 2 was observed in HaCaT cells with exogenous GLI1, or human pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited by 1 or 2. We also examined the cytotoxicity of these active compounds against PANC1, human prostate cancer cells (DU145) and mouse embryo fibroblast cells (C3H10T1/2). The cytotoxicity against cancer cells (PANC1 and DU145) by 1 or 2 would be caused by inhibition of the expression of the anti-apoptosis protein BCL2.
CONCLUSIONS:
These pentacyclic triterpene inhibitors showed an important relationship between Hh/GLI signaling inhibition, the decrease of BCL2, and cytotoxicity against cancer cells.