Isolation, chemotaxonomic significance and cytotoxic effects of quassinoids from Brucea javanica

Ye, Qingmei; Bai, Liangliang; Hu, Shuzhi; Tian, Hai‐Yan; Ruan, Li-Jun; Tan, Yisheng; Hu, Liping; Ye, Wen‐Cai; Zhang, Dongmei; Jiang, Ren‐Wang

doi:10.1016/j.fitote.2015.06.004

Cited by 33 publications

(22 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brusatol was therefore provided to C57BL/6J mice in their drinking water at 1 mg/kg per day to determine whether HFD-induced glucose intolerance was affected. The dose given in the drinking water is lower than doses given by tail injection in previous studies (13) because we wanted to avoid the toxicity associated with high doses of brusatol (28). Brusatol is rapidly cleared from the blood (t 1/2 = 5.9 min in mice) and is instead taken up in different tissues, particularly in the lung, where it remains with a much longer half-life (29).…”

Section: Effects Of Brusatol On Hfd-induced Glucose Intolerance and Imentioning

confidence: 99%

The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination

et al. 2018

View full text Add to dashboard Cite

The naturally occurring quassinoid compound brusatol improves the survival of insulin‐producing cells when exposed to the proinflammatory cytokines IL‐1β and IFN‐γ in vitro. The aim of the present study was to investigate whether brusatol also promotes beneficial effects in mice fed a high‐fat diet (HFD), and if so, to study the mechanisms by which brusatol acts. In vivo, we observed that the impaired glucose tolerance of HFD‐fed male C57BL/6 mice was counteracted by a 2 wk treatment with brusatol. Brusatol treatment improved both β‐cell function and peripheral insulin sensitivity of HFD‐fed mice. In vitro, brusatol inhibited β‐cell total protein and proinsulin biosynthesis, with an ED50 of ∼40 nM. In line with this, brusatol blocked cytokine‐induced iNOS protein expression via inhibition of iNOS mRNA translation. Brusatol may have affected protein synthesis, at least in part, via inhibition of eukaryotic initiation factor 5A (eIF5A) hypusination, as eIF5A spermidine association and hypusination in RIN‐5AH cells was reduced in a dose‐ and time‐dependent manner. The eIF5A hypusination inhibitor GC7 promoted a similar effect. Both brusatol and GC7 protected rat RIN‐5AH cells against cytokine‐induced cell death. Brusatol reduced eIF5A hypusination and cytokine‐induced cell death in EndoC‐βHl cells as well. Finally, hypusinated eIF5A was reduced in vivo by brusatol in islet endocrine and endothelial islet cells of mice fed an HFD. The results of the present study suggest that brusatol improves glucose intolerance in mice fed an HFD, possibly by inhibiting protein biosynthesis and eIF5A hypusination.—Turpaev, K., Krizhanovskii, C., Wang, X., Sargsyan, E., Bergsten, P., Welsh, N. The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB J. 33, 3510–3522 (2019). http://www.fasebj.org

show abstract

Section: Effects Of Brusatol On Hfd-induced Glucose Intolerance and Imentioning

confidence: 99%

The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination

et al. 2018

View full text Add to dashboard Cite

show abstract

“…BOL possesses antitrypanosomal, antibabesial, and anti-tumor effects [6][7][8][9]. Additionally, its analogs, including bruceantin, bruatol, bruceine A, and bruceine D, have exhibited different biological effects, including antitrypanosomal, anthelmintic, antibabesial, hypoglycemic, and cytotoxic activities [10][11][12][13][14].…”

Section: A Rapid and Sensitive Uplc-ms/ms Methods For Quantification Omentioning

confidence: 99%

A Rapid and Sensitive UPLC-MS/MS Method for Quantification of Bruceantinol in Rat Plasma and Its Application to a Pharmacokinetic Study

Zheng

Zhen

et al. 2017

Planta Med

View full text Add to dashboard Cite

Bruceantinol (BOL), a quassinoid compound isolated from the fruits of , has been reported to have cytotoxic and antibacterial effects. In this study, a rapid, sensitive, and specific ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitative determination of BOL in rat plasma. The samples were treated by simple liquid-liquid extraction with ethyl acetate and separated on an UPLC BEH C18 column (2.1 mm × 50 mm) using a 3-min gradient elution scheme, which consists of water (0.1% v/v, formic acid) and methanol (0.1%, v/v, formic acid) to achieve the separation of BOL and sinomenine (IS) with high selectivity. The electrospray ionization source was used in positive ion mode; the multiple reaction monitoring quantified the target fragment ions 629.6 → 569.5 for BOL and 330.5 → 207.3 for IS. This work was evaluated with regards to the specificity, extraction recovery, matrix effect, linearity, accuracy, precision, stability, and dilution integrity. This approach was used to examine the pharmacokinetics of BOL in rats after oral (0.3 mg/kg) and intravenous (0.15 mg/kg) administration. BOL presented fast excretion and very low oral bioavailability.

show abstract

“…Previously it was demonstrated that the quassinoid 2′‐( R )‐ O ‐acetylglaucarubinone, derived from the Odyendyea gabonensis (Pierre) Engler plant, demonstrated potent cytotoxicity against a number of cancer cell lines including breast cancer cells (Usami et al ., ). More recently, quassinoids from the fruits of Brucea javanica were found to exhibit potent inhibitory activity in breast cancer cells (Ye et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Glaucarubulone glucoside from Castela macrophylla suppresses MCF‐7 breast cancer cell growth and attenuates benzo[a]pyrene‐mediated CYP1A gene induction

Badal

Valenzuela

Zylstra

et al. 2017

J of Applied Toxicology

View full text Add to dashboard Cite

Quassinoids often exhibit anti-oxidant and anti-proliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons (PAHs) into carcinogenic metabolites. Gg reduced the viability of MCF-7 breast adenocarcinoma cells (IC50 = 121 nM) to a greater extent than standard of care anticancer agents 5-fluorouracil, tamoxifen (IC50 > 10 μM) and the tamoxifen metabolite 4-hydroxytamoxifen (IC50 = 2.6 μM), yet was not cytotoxic to non-tumourigenic MCF-10A breast epithelial cells. Additionally, Gg induced MCF-7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF-10A cells mediated by PAH benzo[a]pyrene (B[a]P) metabolite benzo[a]pyrene 1,6 quinone, yet down-regulated the expression of genes that promote antioxidant activity in MCF-7 cells. This implies that Gg exhibits anti-oxidant and cytoprotective actions in non-tumourigenic breast epithelial cells and pro-oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non-competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF-7 cells. These data indicate that Gg selectively suppresses MCF-7 breast cancer cell growth without impacting non-tumourigenic breast epithelial cells and blocks B[a]P-mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer.

show abstract

Isolation, chemotaxonomic significance and cytotoxic effects of quassinoids from Brucea javanica

Cited by 33 publications

References 28 publications

The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination

The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination

A Rapid and Sensitive UPLC-MS/MS Method for Quantification of Bruceantinol in Rat Plasma and Its Application to a Pharmacokinetic Study

Glaucarubulone glucoside from Castela macrophylla suppresses MCF‐7 breast cancer cell growth and attenuates benzo[a]pyrene‐mediated CYP1A gene induction

Contact Info

Product

Resources

About