Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.
Biomed Pharmacother. 2023 Nov;167:115596. doi: 10.1016/j.biopha.2023.115596. Epub 2023 Oct 3.
Cyclophosphamide (CPA) is a chemotherapeutic drug used for various types of cancers. However, patients receiving CPA for long periods suffer cognitive impairment associated with difficulties in learning, decreased concentration, and impaired memory. Chemotherapy-induced cognitive impairment, known as chemobrain, has been attributed to enhanced oxidative stress and inflammatory response. The current study aimed to identify the phytoconstituents of Callistemon subulatus extract (CSE) using HPLC-ESI/MS-MS analysis and evaluate its neuroprotective activity against CPA-induced chemobrain in rats. Fourteen compounds were identified following HPLC analysis including, five phlorglucinols, four flavonol glycosides, a triterpene, and a phenolic acid. Forty rats were divided into five groups treated for ten days as follows; group I (control group), group II received CPA (200 mg/kg, i.p.) on the 7th day, groups III and IV received CSE (200 and 400 mg/kg respectively, orally) for ten days and CPA (200 mg/kg, i.p.) on the 7th day, and group V received only CSE (400 mg/kg, orally) for ten days. The administration of CSE effectively ameliorated the deleterious effects of CPA on spatial and short-term memories, as evidenced by behavioral tests, Y-maze and passive avoidance. Such findings were further confirmed by histological examination. In addition, CSE counteracted the effect of CPA on hippocampal acetylcholinesterase (AChE) activity enhancing the level of acetylcholine. Owing to the CSE antioxidant properties, it hindered the CPA-induced redox imbalance, which is represented by decreased catalase and reduced glutathione levels, as well as enhanced lipid peroxidation. Therefore, CSE may be a promising natural candidate for protection against CPA-induced chemobrain in cancer patients.
环磷酰胺（CPA）是一种用于各种类型癌症的化疗药物。然而，长期接受 CPA 治疗的患者会出现认知障碍，表现为学习困难、注意力下降和记忆力受损。化疗引起的认知障碍，即所谓的化疗脑，归因于氧化应激和炎症反应的增强。本研究旨在使用 HPLC-ESI/MS-MS 分析鉴定桃金娘科植物细叶澳洲茶提取物（CSE）的植物成分，并评估其对大鼠 CPA 诱导的化疗脑的神经保护活性。通过 HPLC 分析鉴定出 14 种化合物，包括 5 种 phlorglucinol、4 种黄酮醇糖苷、1 种三萜和 1 种酚酸。将 40 只大鼠分为 5 组，连续 10 天给药，如下所示：第 1 组（对照组）、第 2 组在第 7 天给予 CPA（200mg/kg，ip）、第 3 组和第 4 组分别给予 CSE（200 和 400mg/kg，口服）10 天和第 7 天给予 CPA（200mg/kg，ip）、第 5 组仅给予 CSE（400mg/kg，口服）10 天。CSE 的给药有效改善了 CPA 对空间和短期记忆的有害影响，这可以通过行为测试、Y 迷宫和被动回避来证明。组织学检查进一步证实了这一发现。此外，CSE 拮抗 CPA 对海马乙酰胆碱酯酶（AChE）活性的影响，增加乙酰胆碱水平。由于 CSE 的抗氧化特性，它阻止了 CPA 诱导的氧化还原失衡，表现为过氧化氢酶和还原型谷胱甘肽水平降低以及脂质过氧化增强。因此，CSE 可能是一种有前途的天然候选物，可用于保护癌症患者免受 CPA 诱导的化疗脑。
