Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives.

Syzygium is a large genus of flowering plants, with several species, including the clove tree, used as important resources in the food and pharmaceutical industries. In our continuing search for anticancer agents from higher plants, a chloroform extract of the leaves and twigs of Syzygium corticosum collected in Vietnam was found to be active toward the HT-29 human colon cancer cell line. Separation of this extract guided by HT-29 cells and nuclear factor-kappa B (NF-κB) inhibition yielded 19 known natural products, including seven triterpenoids, three ellagic acid derivatives, two methylated flavonoids, a cyclohexanone, four megastigmanes, a small lactone, and an aromatic aldehyde. The full stereochemistry of (+)-fouquierol (2) was defined for the first time. Biological investigations showed that (+)-ursolic acid (1) is the major cytotoxic component of S. corticosum, which exhibited also potent activities in the NF-κB and mitochondrial transmembrane potential (MTP) inhibition assays conducted, with IC50 values of 31 nM and 3.5 µM, respectively. Several analogues of (+)-ursolic acid (1) were synthesized, and a preliminary structure-activity relationship (SAR) study indicated that the C-3 hydroxy and C-28 carboxylic acid groups and 19,20-dimethyl substitution are all essential in the mediation of the bioactivities observed for this triterpenoid.

Ren Y ，Anaya-Eugenio GD ，Czarnecki AA ，Ninh TN ，Yuan C ，Chai HB ，Soejarto DD ，Burdette JE ，de Blanco EJC ，Kinghorn AD ... -  《-》

The chemical and biological potential of C ring modified triterpenoids.

A convenient and elegant route has been developed to separate the natural regioisomers triterpenoids ursolic acid (UA) and oleanolic acid (OA) as well as derivatives thereof. Eleven unknown derivatives of OA were designed, synthesized, and their cytotoxicity was investigated. Further sixteen compounds were prepared to correlate all compounds in a SAR study. It could be shown that C-ring modifications of OA and UA have only a moderate influence onto the cytotoxic activity of the compounds but a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780).

Siewert B ，Wiemann J ，Köwitsch A ，Csuk R ... -  《-》

[Synthesis and anti-tumor activity of ursolic acid derivatives].

Meng YQ ，Liu D ，Bai ZW ，Cai LL ，Ai HR ... -  《-》

Betulinic acid, isolated from the leaves of Syzygium cumini (L.) Skeels, ameliorates the proteinuria in experimental membranous nephropathy through regulating Nrf2/NF-κB pathways.

Membranous nephropathy (MN) is associated with increased oxidative stress and inflammatory markers in the kidney. Betulinic acid (BA) is a potent antioxidant and anti-inflammatory compound isolated from the leaves of Syzygium cumini (L.) Skeels. In the present study, we investigated the effects of BA on experimental MN in rats and explored the mechanisms by which it enhances antioxidant activities and resolves inflammatory condition in experimental MN. Passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats by a single tail vein injection of anti- Fx1A antiserum. The rats were orally administered BA (25 and 50 mg kg -1 d -1) or dexamethasone (DEX; 0.07 mg kg-1, reference compound) for 4 weeks after the induction of PHN. Blood, urine, and kidney tissue were collected for analysis at the end of the study. Treatment of PHN rats with BA or DEX significantly attenuated renal dysfunction, histopathological alterations and reduced immune complex deposition in the kidneys. Furthermore, BA ameliorated mRNA and protein expression of NF-κB, iNOS, TNF-α, Nrf2, HO-1 and NQO1 in the kidney. BA also restored malondialdehyde level and antioxidant enzyme activities in the kidney. In a nutshell, the protective effect of BA can be explained by its anti-inflammatory and anti-oxidant activities, which in turn is due to downregulation of NF-κB pathway and activation of Nrf2. The results indicated that BA can effectively suppress experimental PHN in rats by regulating Nrf2/NF-κB pathways.

Sutariya B ，Taneja N ，Saraf M 《-》

New phenylpropanoid-conjugated pentacyclic triterpenoids from the whole plants of Leptopus lolonum with their antiproliferative activities on cancer cells.

Most of Euphorbiaceae plants are considered as folk medicinal plants because of their various pharmacological effects. However, there are eight Leptopus genus plants which belong to Euphorbiaceae have never be investigated. Thus, four Leptopus genus plants were collected to study their chemical constituents and pharmacological activities. In the present work, the cytotoxicities of the extracts of four Leptopus genus plants were evaluated before phytochemical experiments. And nine new phenylpropanoid-conjugated pentacyclic triterpenoids, along with twenty-two known compounds were isolated from the whole plants of Leptopus lolonum. The structures of these new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. All triterpenoids were screened for their cytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Among these isolates, the triterpenoid with a phenylpropanoid unit showed increasing cytotoxicity on cancer cells, which suggested the importance of the phenylpropanoid moiety.

Qi SZ ，Liu T ，Wang M ，Zhang XX ，Yang YR ，Jing WH ，Long LP ，Song KR ，Jin Y ，Gao HY ... -  《-》