Isolation, characterization and modulatory potentials of β-stigmasterol, ergosterol and xylopic acid from Anchomanes difformis on mitochondrial permeability transition pore in vitro

IF 4.7 4区医学 Q1 CHEMISTRY, MEDICINAL Chinese Herbal Medicines Pub Date : 2023-10-01 DOI:10.1016/j.chmed.2023.01.006

Kehinde Oluseun Sodeinde , Akinwunmi Oluwaseun Adeoye , Adedeji Adesipo , Adebayo A. Adeniyi , John Adeolu Falode , Tajudeen Olabisi Obafemi , Samuel Olalekan Olusanya , Linette Twigge , Jeanet Conradie , Timothy O. Mosaku

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Abstract

Objective

Secondary metabolites and polyphenolic compounds from medicinal plants have been demonstrated to have multiple biological functions with promising research and development prospects. This study examined the effect of β-stigmasterol (with ergosterol) and xylopic acid isolated from Anchomanes difformis on liver mitochondrial permeability transition pore (mPTP).

Methods

The compounds were isolated by vacuum liquid chromatography. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions.

Results

¹H and ¹³C NMR spectroscopic elucidation of the isolates affirmed the presence of β-stigmasterol with ergosterol (1:0.3) and xylopic acid. The isolates reversed the increase in lipid peroxidation and inhibited the opening of mitochondrial permeability transition pores caused by calcium and glucose. Pharmacological inhibition of mPTP offers a promising therapeutic target for the treatment of mitochondrial-associated disorders.

Conclusion

Reduction in the activity of calcium ATPase and the expression of Caspase-3 and −9 were observed, suggesting that they could play a role in protecting physicochemical properties of membrane bilayers from free radical-induced severe cellular damage and be useful in the management of diseases where much apoptosis occurs.

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异角鳗β-豆甾醇(含麦角甾醇)和木酸对线粒体通透性转移孔的分离、表征及调控作用

目的药用植物次生代谢产物和多酚类化合物具有多种生物学功能，具有广阔的研究开发前景。本研究考察了从异角螯虾中分离的β-豆甾醇(含麦角甾醇)和木酸对肝脏线粒体通透性过渡孔(mPTP)的影响。方法采用真空液相色谱法分离化合物。线粒体肿胀通过琥珀酸激活条件下吸光度的变化来评估。结果经1h和13C核磁共振鉴定，证实该分离物中含有β-豆甾醇、麦角甾醇(1:0.3)和木酸。分离物逆转了脂质过氧化的增加，抑制了钙和葡萄糖引起的线粒体通透性过渡孔的开放。药理抑制mPTP为线粒体相关疾病的治疗提供了一个有希望的治疗靶点。结论钙atp酶活性降低，Caspase-3和- 9表达降低，提示它们可能在保护膜双分子层的物理化学性质免受自由基诱导的严重细胞损伤中发挥作用，并在细胞凋亡较多的疾病的治疗中发挥作用。

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