The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway.

The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC 7221 cells.

Brucine, an alkaloid from seeds of Strychnos nux-vomica Linn., represses hepatocellular carcinoma cell migration and metastasis: The role of hypoxia inducible factor 1 pathway

In an attempt to dissect the mechanism of Strychnos nuxvomica, a commonly used Chinese folk medicine in the therapy of liver cancer, the cytotoxic effects of four alkaloids in Strychnos nux-vomica, brucine, brucine N-oxide, strychnine, and isostrychnine, on human hepatoma cells (HepG2) were screened by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay. Brucine, among the four alkaloids, exhibited the strongest toxic effect, the mechanism of which was found to cause HepG2 cell apoptosis, since brucine caused HepG2 cell shrinkage, the formation of apoptotic bodies, DNA fragmentation, cell cycle arrest, as well as phosphatidylserine externalization, all of which are typical characteristics of apoptotic programmed cell death. Brucine-induced HepG2 cell apoptosis was caspase dependent, with caspase-3 activated by caspase-9. Brucine also caused the proteolytic processing of caspase-9. In addition, brucine caused depolarization of the mitochondrial membrane of HepG2 cells, the inhibition of which by cyclosporine A completely abrogated the activation of casapses and release of cytochrome c in brucinetreated HepG2 cells. These findings suggested a pivotal role of mitochondrial membrane depolarization in HepG2 cell apoptosis elicited by brucine. Furthermore, brucine induced a rapid and sustained elevation of intracellular [Ca 2+ ], which compromised the mitochondrial membrane potential and triggered the process of HepG2 cell apoptosis. Finally, Bcl-2 was found to predominately control the whole event of cell apoptosis induced by brucine. The elevation of [Ca 2+ ]i caused by brucine was also suppressed by overexpression of Bcl-2 protein in HepG2 cells. From the facts given above, Ca 2+ and Bcl-2 mediated mitochondrial pathway

The Apoptotic Effect of Brucine from the Seed of Strychnos nux-vomica on Human Hepatoma Cells is Mediated via Bcl-2 and Ca 2+ Involved Mitochondrial Pathway

The purpose of this review is to provide comprehensive and relevant information on the utilization and pharmacological activities of Strychnos nux-vomica Linn. (Loganiaceae), used for the treatment of various diseases. Strychnos nux-vomica is an evergreen tree native to Southeast Asia and its dried seeds are used for the treatment of neurodisorders, arthritis and vomiting. The different use of this plant as herbal remedy in Chinese medicine is also reported in the literature. Strychnine and brucine are major pharmacologically active phytoconstituents of Strychnos nux-vomica, which are central nervous stimulant, but also found to be poisonous at high dosage. Owing to its diversity of phytoconstituents, it is used for treatment of various disorders. Pharmacologically it has been validated for its effect on inflammation, microbial infections, gastrointestinal problem, nervous system, bones cells, cardiovascular systems, cancer and blood glucose level. It also has antioxidant activity and antifeedant activity. Informations about Strychnos nux-vomica, compiled in the present review article could be useful to the researchers for the scientific validation of its traditional claim in the future.

A review on medicinal uses, analytical techniques and pharmacological activities of Strychnos nux-vomica Linn.: A concise report.

AIM To study the pharmacokinetic process about the concentration in rat plasma of the alkaloids from processed seeds of Strychnos nux-vomica with RP-HPLC method. METHODS Hypersil BDS C18 column was used and the mobile phase consisted of acetonitrile-water at the flow rate of 0.8 mL.min-1. The UV detection wave length was 254 nm. RESULTS The concentration-time data of strychnine, brucine, strychnine N-oxide and brucine N-oxide were all in accordance with an open two-compartment model after i.v. alkaloids. Their parameters were as follows: T1/2 alpha were (8 +/- 5), (4 +/- 3), (6.2 +/- 1.7) and (3.0 +/- 0.8) min, T1/2 beta were (262 +/- 125), (416 +/- 131), (285 +/- 50) and (342 +/- 141) min, CL were (17 +/- 4), (21 +/- 12), (1.9 +/- 1.8) and (2.8 +/- 1.1) mL.min-1, Vc were (1.4 +/- 0.5), (1.7 +/- 1.1), (0.24 +/- 0.16) and (0.23 +/- 0.06) L.kg-1, Vd were (6.0 +/- 1.2), (12 +/- 7), (0.8 +/- 0.6) and (1.5 +/- 0.6) L.kg-1, AUC were (57,578 +/- 25,578), (35,240 +/- 15,616), (93,088 +/- 22,375) and (177,712 +/- 120,110) h.microgram.L-1, respectively. CONCLUSION The method is a good reference for pharmacokinetics in human bodies.

Yang Pan

Papers

[Pharmacokinetics of the alkaloids from the processed seeds of Strychnos nux-vomica in rats].