Eissa Manar A, Farag Mohamed A, Saleh Dalia O, Shabana Marwa E, Abou El-Ezz Rania F, El-Kersh Dina M
Pharmacology and Toxicology Department, Faculty of Pharmacy, Merit University, New Sohag, 82755, Egypt.
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118904. doi: 10.1016/j.jep.2024.118904. Epub 2024 Oct 5.
Tongkat Ali (Eurycoma longifolia Jack) is a chief herbal medicine that is well recognized for its aphrodisiac properties, available in various commercial products worldwide.
The aim of this work is to identify the different classes of secondary metabolites present in Tongkat Ali commercial products versus authenticated root, and to assess its root extract mitigative effect against 5-flurouracil (5FU)-induced testicular toxicity.
High-resolution UHPLC-QTOF-MS/MS metabolites analysis was utilized on the ethanolic Tongkat Ali extract (TAE) parallel to three Mlayasian commercial products, followed by a multivariate data analysis to understand the variability among UHPLC-MS metabolites datasets. Adult male rats were treated with 5-Fluorouracil (5FU) ± Tongkat Ali extract. Semen parameters, serum testosterone, LH, and FSH, and testicular oxidative stress biomarkers like malondialdehyde (MDA) levels, Nuclear factor kappa B (NF-κB) and erythroid 2-related factor 2 (Nrf2) were analyzed.
The main categories of secondary metabolites identified through UHPLC-MS/MS profiling were quassinoids, alkaloids, fatty acids, lignans and coumarins. Long Jack Plus® ELP-2 clustered alongside authentic roots ELR on the negative side, while Naturelle® ELP-1 and Nu-Prep-LEAKI® ELP-3 were positioned on the opposite side. The OPLS-DA model was used to identify markers for preparations from authentic roots, with commercial products enriching in ailanthone epoxide. In vivo results showed that 5FU reduced sperm parameters by 42%, while TAE improved sperm quality by 35-43% and 58-74% at dose of 400 and 800 mg/kg, respectively. Testosterone, reduced by 74% with 5FU, increased 2.3- to 3.2-fold with TAE. TAE also reduced MDA by 31-62%, NF-κB by 32-55% and increased Nrf2 by 1-2 folds.
The manuscript presents a comparative metabolomics study and in vivo investigation into the potential of Tongkat Ali root to improve testicular function in male rats intoxicated with 5FU, an area not previously explored. Further research is required to understand the mechanisms.
东革阿里（Eurycoma longifolia Jack）是一种主要的草药，因其壮阳特性而广为人知，在全球各种商业产品中都有销售。
本研究的目的是确定东革阿里商业产品与经鉴定的根部中存在的不同类别的次生代谢产物，并评估其根提取物对5-氟尿嘧啶（5FU）诱导的睾丸毒性的缓解作用。
对东革阿里乙醇提取物（TAE）以及三种马来西亚商业产品进行了高分辨率超高效液相色谱-四极杆飞行时间串联质谱（UHPLC-QTOF-MS/MS）代谢物分析，随后进行多变量数据分析，以了解UHPLC-MS代谢物数据集之间的变异性。成年雄性大鼠用5-氟尿嘧啶（5FU）±东革阿里提取物进行处理。分析了精液参数、血清睾酮、促黄体生成素（LH）和促卵泡生成素（FSH），以及睾丸氧化应激生物标志物，如丙二醛（MDA）水平、核因子κB（NF-κB）和红细胞2相关因子2（Nrf2）。
通过UHPLC-MS/MS分析确定的次生代谢物的主要类别为苦木素类、生物碱、脂肪酸、木脂素和香豆素。Long Jack Plus® ELP-2在负极与正宗根ELR聚集在一起，而Naturelle® ELP-1和Nu-Prep-LEAKI® ELP-3则位于相反一侧。OPLS-DA模型用于识别正宗根制剂的标志物，商业产品中富含臭椿环氧酮。体内结果表明，5FU使精子参数降低了42%，而TAE在400和800 mg/kg剂量下分别使精子质量提高了35-43%和58-74%。睾酮水平在5FU作用下降低了74%，在TAE作用下增加了2.3至3.2倍。TAE还使MDA降低了31-62%，NF-κB降低了32-55%，并使Nrf2增加了1-2倍。
本手稿展示了一项比较代谢组学研究以及对东革阿里根改善5FU中毒雄性大鼠睾丸功能潜力的体内研究，这是一个此前未探索的领域。需要进一步研究以了解其机制。
