五味子提取物可降低大鼠体内氯乙醛的生成，并减轻环磷酰胺对肝脏、肾脏和大脑的毒性。
Schisandra chinensis extract decreases chloroacetaldehyde production in rats and attenuates cyclophosphamide toxicity in liver, kidney and brain.
机构信息
School of Traditional Chinese Material, Shenyang Pharmaceutical University, Shenyang, China; Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
出版信息
J Ethnopharmacol. 2018 Jan 10;210:223-231. doi: 10.1016/j.jep.2017.08.020. Epub 2017 Aug 15.
ETHNOPHARMACOLOGICAL RELEVANCE
Schisandra chinensis (Turcz.) Baill (S. chinensis) has been used for thousands years in China, and is usually applied in treatment of urinary tract disorders and liver injury. S. chinensis extract (SCE) has board protective effects on liver, kidney and nervous system. Schisandra lignans are generally considered as the bioactive components of SCE.
AIM OF THE STUDY
To investigate the pharmacokinetic herb-drug interactions (HDIs) between SCE and cyclophosphamide (CTX). To evaluate the protective effects of SCE against CTX induced damage in rat liver, kidney and brain.
MATERIALS AND METHODS
The pharmacokinetic HDIs between SCE and CTX were investigated by determining plasma concentrations of CTX and three metabolites, namely 4-ketocyclophosphamide (4-Keto), 2-dechloroethylcyclophosphamide (DCCTX) and carboxyphosphamide (CPM) using a previously developed UPLC-MS/MS method. To evaluate the protective effects of SCE pretreatment, toxicity and oxidation stress assessments along with histology investigations were carried out in rat liver, kidney and brain.
RESULTS
The equimolar produced metabolite DCCTX was chosen to reflect chloroacetaldehyde (CAA, a toxic metabolite of CTX) production in rats. Single-dose pretreatment of SCE significantly reduced CAA production and decreased the C and AUC of DCCTX by 69% and 49% respectively (P < 0.05). After pretreated with SCE for 7 consecutive days, the C and AUC of DCCTX were still decreased (-25% and -37%, P < 0.05) when compared with CTX alone group. Parallel toxicity and oxidation stress investigations showed that single-dose SCE pretreatment significantly decreased plasma BUN and Cr levels (-12% and -46%, respectively) and reduced liver AST activity (-32%). Moreover, SCE pretreatment potently increased the brain GSH content by 7.8-fold, and reduced MDA levels in rat liver, kidney and brain by 39%, 28% and 31%, respectively (compared with CTX alone group). The protective effects of SCE were also supported by histological observations.
CONCLUSION
Our experiment results suggest that S. chinensis may find use as a complementary medicine in CTX treatment.
民族药理学相关性
五味子（Turcz.）Baill（五味子）在中国已使用了数千年，通常用于治疗尿路疾病和肝损伤。五味子提取物（SCE）对肝、肾和神经系统有广泛的保护作用。五味子木脂素通常被认为是 SCE 的生物活性成分。
研究目的
研究 SCE 与环磷酰胺（CTX）之间的药代动力学草药-药物相互作用（HDIs）。评估 SCE 对 CTX 诱导的大鼠肝、肾和脑损伤的保护作用。
材料和方法
采用已建立的 UPLC-MS/MS 方法，测定血浆中环磷酰胺和三种代谢物，即 4-酮环磷酰胺（4-Keto）、2-去氯乙基环磷酰胺（DCCTX）和羧基磷酰胺（CPM）的浓度，研究 SCE 与 CTX 之间的药代动力学 HDIs。为了评估 SCE 预处理的保护作用，在大鼠肝、肾和脑中进行了毒性和氧化应激评估以及组织学研究。
结果
选择等摩尔产生的代谢物 DCCTX 来反映氯乙醛（CTX 的一种毒性代谢物）在大鼠体内的产生。SCE 单次预处理显著降低了 CAA 的产生，并使 DCCTX 的 C 和 AUC 分别降低了 69%和 49%（P < 0.05）。连续 7 天预处理 SCE 后，与 CTX 单独组相比，DCCTX 的 C 和 AUC 仍分别降低了（-25%和-37%）（P < 0.05）。平行的毒性和氧化应激研究表明，SCE 单次预处理显著降低了血浆 BUN 和 Cr 水平（-12%和-46%），并降低了肝 AST 活性（-32%）。此外，SCE 预处理可使脑 GSH 含量增加 7.8 倍，并降低大鼠肝、肾和脑的 MDA 水平，分别降低 39%、28%和 31%（与 CTX 单独组相比）。SCE 的保护作用也得到了组织学观察的支持。
结论
我们的实验结果表明，五味子可能在 CTX 治疗中作为一种辅助药物使用。
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