Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Spleen and Stomach Diseases Department II, Longhua Hospital, Shanghai University of TCM, Shanghai, 200032, China.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2481-2494. doi: 10.1007/s00210-020-01814-4. Epub 2020 Mar 3.
This study sought to isolate active Flos lonicerae flavonoids and evaluate their anti-oxidative and anti-inflammatory effects as well as investigate the molecular mechanistic action of these flavonoids in the rat model of ulcerative colitis (UC). Total flavonoids and three flavonoids (hyperoside, lonicerin, and luteolin) were isolated from honeysuckle and purified via column purification. Rat model of UC was established via 2,4,6-trinitrobenzene sulfonic acid (TNBS) intoxication. The anti-oxidative and anti-inflammatory effects of the three flavonoids against TNBS-induced UC were evaluated by measuring appropriate biomarkers via assay kit. The effects of hyperoside, lonicerin, and luteolin on the regulation of nuclear factor-kappa B (NF-κB) pathway were investigated using Western blot (WB) and real-time polymerase chain reaction (RT-PCR) while their protective effects on UC were also elucidated. Pretreatment with flavonoids (hyperoside, lonicerin, and luteolin at 25-100 mg/kg) and sulfasalazine (SSZ, positive control at 100 mg/kg) substantially attenuated TBNS-induced UC. Also, the flavonoids significantly reduced the levels of respective serum oxidative and proinflammatory markers such as superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), prostaglandins E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-beta (IL-β), and C-reactive protein (CRP). In addition, the flavonoids remarkably inhibited the expression of NF-κB signaling pathway. F. lonicerae flavonoids (hyperoside, lonicerin, and luteolin) demonstrated potent anti-UC activities in TBNS-induced UC rat model via anti-oxidative and anti-inflammatory effects through the inhibition of NF-κB signaling pathway.
本研究旨在分离金银花中的活性黄酮类化合物,并评估其抗氧化和抗炎作用,以及研究这些黄酮类化合物在溃疡性结肠炎(UC)大鼠模型中的分子作用机制。采用柱层析法从金银花中分离得到总黄酮和 3 种黄酮类化合物(金丝桃苷、忍冬苷和木樨草素)。采用 2,4,6-三硝基苯磺酸(TNBS)灌胃法建立大鼠 UC 模型。通过试剂盒测定适当的生物标志物来评估三种黄酮类化合物对 TNBS 诱导的 UC 的抗氧化和抗炎作用。采用 Western blot(WB)和实时聚合酶链反应(RT-PCR)研究金丝桃苷、忍冬苷和木樨草素对核因子-κB(NF-κB)通路的调节作用,并阐明其对 UC 的保护作用。黄酮类化合物(金丝桃苷、忍冬苷和木樨草素,25-100mg/kg)和柳氮磺胺吡啶(SSZ,阳性对照,100mg/kg)预处理可显著减轻 TBNS 诱导的 UC。此外,黄酮类化合物显著降低了相应的血清氧化和促炎标志物水平,如超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、丙二醛(MDA)、前列腺素 E2(PGE2)、肿瘤坏死因子-α(TNF-α)、白细胞介素-β(IL-β)和 C 反应蛋白(CRP)。此外,黄酮类化合物还显著抑制了 NF-κB 信号通路的表达。金银花黄酮类化合物(金丝桃苷、忍冬苷和木樨草素)通过抑制 NF-κB 信号通路,在 TBNS 诱导的 UC 大鼠模型中表现出强大的抗 UC 活性,具有抗氧化和抗炎作用。