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Archive > Volume 16 Issue 1 > 2024,16(1):113-120. DOI:https://doi.org/10.1016/j.chmed.2023.06.002 Prev Next

Jatonik多草藥混合物誘導(dǎo)正常Wistar大鼠肝臟MMPT開孔的體外和體內(nèi)研究

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Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies

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    摘要:
    目的:研究Jatonik多草藥混合物甲醇和乙酸乙酯提取物(JME和JEE)的急性毒性、體外和體內(nèi)對(duì)線粒體相關(guān)參數(shù)的影響及其對(duì)肝臟酶活性的影響。 方法:采用洛克法測(cè)定JME和JEE的急性毒性。用分光光度法測(cè)定線粒體膜通透性過渡孔(MMPT孔)的開度。體外和體內(nèi)研究了以丙二醛(MDA)產(chǎn)量為指標(biāo)的脂質(zhì)過氧化和線粒體ATP酶活性，并研究了JME和JEE對(duì)肝臟酶如堿性磷酸酶(ALP)、天冬氨酸和丙氨酸轉(zhuǎn)氨酶(AST和ALT)和γ -氨酰轉(zhuǎn)移酶(GGT)活性的影響。 結(jié)果:JME對(duì)大鼠的LD50為3808 mg/kg bw, JEE對(duì)大鼠的LD50大于5000 mg/kg bw。在給大鼠喂食這兩種提取物后，肝臟組織的顯微照片顯示沒有明顯的毒性癥狀。從體外和體內(nèi)研究來(lái)看，這兩種提取物都促使完整的線粒體打開其MMPT孔。與對(duì)照組相比，脂質(zhì)過氧化產(chǎn)物釋放量和ATP酶活性顯著增加(P < 0.05)。50 mg/kg JME處理后，谷丙轉(zhuǎn)氨酶、谷丙轉(zhuǎn)氨酶和谷丙轉(zhuǎn)氨酶活性均降低，而JEE處理后谷丙轉(zhuǎn)氨酶活性顯著提高(P < 0.05)。結(jié)果表明，JME和JEE均具有較低的毒性、較強(qiáng)的MMPTpore誘導(dǎo)作用、較強(qiáng)的ATP酶活性和較強(qiáng)的MDA產(chǎn)量。 結(jié)論:Jatonik提取物可能是細(xì)胞凋亡失調(diào)疾病的一個(gè)有希望的藥物開發(fā)靶點(diǎn)，但需要進(jìn)一步的研究來(lái)更好地闡明這些現(xiàn)象的分子機(jī)制。

    Abstract:
    Objective: To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes. Methods: Acute toxicity of JME and JEE was determined using Lorke’s method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gammaglutamyl transferase (GGT)was also investigated. Results: JME had an LD50 of 3808 mg/kg b.w whereas JEE had an LD50 greater than 5000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production. Conclusion: Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.

    關(guān)鍵詞:
    急性毒性;藿香薊;細(xì)胞凋亡;傘形仔欖樹;印加蘿卜;線粒體ATP酶;線粒體脂質(zhì)過氧化;線粒體膜通透性過渡孔;多草藥混合物;埃塞木瓣樹

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