Chemistry of Natural Compounds Department, National Research Centre, Giza 12622, Egypt.
Pharmacology Department, National Research Centre, Giza 12622, Egypt.
Bioorg Chem. 2020 Dec;105:104444. doi: 10.1016/j.bioorg.2020.104444. Epub 2020 Nov 1.
Phytochemical investigation of the butanol fraction (BUF) derived from the 70% aqueous methanolic leaf extract of Barnebydendron riedelii led to the isolation of three flavonoid glycosides; kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-galactopyranoside and quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside. Docking studies were fulfilled to validate the possible bio-properties of BUF toward nuclear factorkappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). The protective role of BUF against behavioral, biochemical, molecular, histopathological and immunohistochemical alterations in thioacetamide (TAA)-induced hepatic encephalopathy in rats was investigated. The toxicological studies indicated that BUF was safe up to 2000 mg/kg bw. Prior to TAA intoxication, rats were orally treated with either BUF at multiple doses (70, 140 and 280 mg/kg bw) or lactulose (8 mL/kg bw) for 14 consecutive days. On the 13th and the 14th day, TAA (200 mg/kg bw/day) was intraperitoneally injected. The BUF significantly improved motor impairment, ameliorated cognitive deficits and attenuated TAA-induced hepatotoxicity. Moreover, BUF controlled the inflammatory processes by suppressing the hepatic inflammatory cytokine; interleukin-6 (IL-6) as well as its pro-inflammatory mediator; NF-κB supporting the molecular docking assessment. The brain neurotransmitters; dopamine, serotonin and noradrenaline, as well as ammonia levels were improved in BUF-treated TAA-intoxicated animals in a dose-dependent manner. Furthermore, BUF administration to TAA-intoxicated rats modulated the Nrf2 and heme oxygenase 1 (HO-1) genes expression in liver and brain tissues. The histological evaluation showed that pretreatment of TAA-intoxicated rats with BUF ameliorated the degenerative effects of TAA on liver and brain tissues as well as reduced the activation of cellular apoptotic marker; caspase-3 and glial fibrillary acidic protein (GFAP) astrocytes. In conclusion, the observed hepato-neuroprotective effect of BUF is attributed to its flavonoidal content through its modulatory effects on of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.
从 Barnebydendron riedelii 的 70%甲醇水叶提取物的正丁醇部分（BUF）进行植物化学研究，导致分离出三种类黄酮糖苷；山柰酚-3-O-α-l-鼠李吡喃糖苷基（1→6）-β-d-吡喃葡萄糖苷、槲皮素-3-O-α-l-鼠李吡喃糖苷基（1→6）-β-d-半乳糖吡喃糖苷和槲皮素-3-O-α-l-鼠李吡喃糖苷基（1→6）-β-d-吡喃葡萄糖苷。完成对接研究以验证 BUF 对核因子 kappa B (NF-κB) 和核因子红细胞 2 相关因子 2 (Nrf2) 的可能生物特性。研究了 BUF 对硫代乙酰胺 (TAA) 诱导的大鼠肝性脑病的行为、生化、分子、组织病理学和免疫组织化学改变的保护作用。毒理学研究表明，BUF 在高达 2000mg/kg bw 时是安全的。在 TAA 中毒之前，大鼠连续 14 天口服给予 BUF 多次剂量（70、140 和 280mg/kg bw）或乳果糖（8mL/kg bw）。在第 13 天和第 14 天，腹腔内注射 TAA（200mg/kg bw/天）。BUF 显著改善运动障碍，改善认知缺陷，并减轻 TAA 诱导的肝毒性。此外，BUF 通过抑制肝炎性细胞因子白细胞介素-6 (IL-6) 及其促炎介质核因子 kappa B (NF-κB) 来控制炎症过程，支持分子对接评估。BUF 处理的 TAA 中毒动物的大脑神经递质；多巴胺、血清素和去甲肾上腺素以及氨水平呈剂量依赖性改善。此外，BUF 给药于 TAA 中毒大鼠可调节肝和脑组织中的 Nrf2 和血红素加氧酶 1 (HO-1) 基因表达。组织学评价表明，BUF 预处理 TAA 中毒大鼠可改善 TAA 对肝和脑组织的退行性影响，并降低细胞凋亡标志物 caspase-3 和胶质纤维酸性蛋白 (GFAP) 星形胶质细胞的激活。总之，BUF 观察到的肝神经保护作用归因于其类黄酮含量，通过其对 NF-κB/IL-6 和 Nrf2/HO-1 信号通路的调节作用。
