Univ Rouen Normandie, Normandie Univ, NorDiC UMR 1239, 76000, Inserm, Rouen, France.
Laboratory of Physiology/Pharmacology, Physiopathology Bioactive Substances and Innocuity Research Unit (PBSI), Faculty of Sciences, of Lomé, Lomé, Togo, 01BP 1515.
J Mol Neurosci. 2024 Apr 17;74(2):44. doi: 10.1007/s12031-024-02222-6.
Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (HO) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against HO and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.
植物是药理学研究和新药发现的宝贵信息来源。本研究旨在评估药用植物滇枣叶的神经保护潜力。在体外,使用荧光二乙酸酯(FDA)作为存活探针、乳酸脱氢酶(LDH)活性测定、针对间隙连接蛋白 43 的免疫细胞化学染色以及参与凋亡、坏死或氧化应激的基因表达的定量分析,测试滇枣叶干水醇提取物(SSE)对暴露于过氧化氢(HO)或 6-羟多巴胺(6-OHDA)的培养小脑颗粒神经元(CGN)存活的影响。在体内,通过测量小脑匀浆中 caspase-3 活性、组织提取物中某些基因的表达、小脑皮质层厚度和运动协调来评估 SSE 对 8 天大 Wistar 大鼠发育中大脑的腹腔(ip)注射的影响,这些大鼠因乙醇神经毒性而暴露。在体外,SSE 在 10 µg/mL 剂量下保护 CGN 免受 HO 和 6-OHDA 诱导的细胞死亡,抑制 Casp3 和 Bad 基因的表达,并上调 Cat 和 Gpx7 的表达。在体内,SSE 通过降低 caspase-3 的活性、抑制 Bax 和 Tp53 的表达、防止小脑皮质内颗粒细胞层厚度减少以及恢复运动功能,显著阻断了乙醇的有害作用。滇枣叶发挥着传统医学所宣称的神经活性作用,应该是开发针对神经退行性疾病的神经保护治疗的良好候选药物。