铁锈色藤檀叶不同提取物对大鼠肝脏线粒体膜通透性转换孔开放的调节作用。D.C.

Modulation of opening of rat liver mitochondrial membrane permeability transition pore by different fractions of the leaves of Cnestis ferruginea. D.C.

作者信息

Adisa R A, Alabi T D, Olorunsogo O O

机构信息

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

出版信息

Afr J Med Med Sci. 2012 Dec;41 Suppl:157-69.

PMID:23678652

Abstract

BACKGROUND

Increased attention is now directed towards the search for novel naturally occurring anticancer agents that can induce mitochondrial membrane permeability transition (MMPT) pore opening and cell death as a chemotherapeutic mechanism to combat cancer incidence.

AIM

The inductive effects of partially purified fractions of leaves of Cnestis ferruginea- on rat liver MMPT pore opening was investigated.

METHOD

De-fatted methanol extract of leaves of Cnestis ferruginea was partitioned between water, chloroform, ethylacetate, or butanol separately in succession. The extract solutions were concentrated at 40 degrees C to obtain water (WF), chloroform (CF), ethylacetate (EF) and butanol (BF) fractions. The effects of these fractions (0.2- 1.4 mg/ml) on MMPT pore opening or mitochondrial swelling in the presence and absence of calcium were evaluated The effects of these fractions on the rat liver mitochondrial F0F1-ATPase activity were also assessed.

RESULTS

Ca(2+)-induced MMPT pore opening was inhibited by 1 mg/ml each of MECF, CF, BF, WF and EF by 75.0%, 83.0%, 88.0%, 68.0%, and 71.0%, respectively and compared with the effect of spermine, a standard inhibitor. However, in the absence of Ca2+, the fractions significantly induced MMPT pore opening in intact mitochondria by 7.0, 5.7, 0.7, 4.8, 10.9 folds, respectively. In normal rat liver mitochondria, F1F0-ATPase activity was stimulated maximally by MECF, CF, EF, BF and WF by 4.7, 12.7, 1.6, 3.6 and 1.5 folds, respectively, thus indicating that the chloroform fraction is the most potent and therefore contains the active principle in the plant.

CONCLUSION

The present study revealed that the leaves of Cnestis ferruginea contain bioactive substances that induced mitochondrial membrane permeability transition and activated the specific activity of F0F1 ATPase. Thus, suggesting strongly that these bioactive agents may serve as a useful chemotherapeutic strategy in cancer therapy.

摘要

背景

目前人们越来越关注寻找新型天然抗癌剂，这些抗癌剂可诱导线粒体膜通透性转换（MMPT）孔开放和细胞死亡，作为对抗癌症发生的一种化疗机制。

目的

研究铁锈叶下珠叶部分纯化组分对大鼠肝脏MMPT孔开放的诱导作用。

方法

依次将铁锈叶下珠叶的脱脂甲醇提取物分别用水、氯仿、乙酸乙酯或正丁醇进行分配。提取物溶液在40℃浓缩，得到水相（WF）、氯仿相（CF）、乙酸乙酯相（EF）和正丁醇相（BF）组分。评估这些组分（0.2 - 1.4mg/ml）在有钙和无钙情况下对MMPT孔开放或线粒体肿胀的影响。还评估了这些组分对大鼠肝脏线粒体F0F1 - ATP酶活性的影响。

结果

1mg/ml的MECF、CF、BF、WF和EF分别使Ca(2+)诱导的MMPT孔开放抑制75.0%、83.0%、88.0%、68.0%和71.0%，并与标准抑制剂精胺的作用进行比较。然而，在无Ca2+时，这些组分分别使完整线粒体中的MMPT孔开放显著增加7.0、5.7、0.7、4.8、10.9倍。在正常大鼠肝脏线粒体中，MECF、CF、EF、BF和WF分别使F1F0 - ATP酶活性最大程度地提高4.7、12.7、1.6、3.6和1.5倍，因此表明氯仿相最具活性，因此含有该植物中的活性成分。