Liu Dan-Dan, Cao Gang, Han Li-Kai, Ye Yi-Lu, Zhang Qi, Sima Yu-Han, Ge Wei-Hong
Department of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Pathological Department, People's Hospital of Zhejiang, Hangzhou, Zhejiang 310046, P.R. China.
Mol Med Rep. 2016 Aug;14(2):1733-41. doi: 10.3892/mmr.2016.5412. Epub 2016 Jun 17.
Total flavonoids isolated from Radix Tetrastigmae (RTFs) possess immunomodulatory activity, particularly on inflammation. In mice with lipopolysaccharide (LPS)‑induced acute lung injury (ALI), treatment with RTFs at 40, 80 and 160 mg/kg significantly reduced leukocyte infiltration, improved histopathological changes in lung tissues and decreased the LPS‑induced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colony‑stimulating factor, monocyte inflammatory protein‑1α and B‑lymphocyte colony inflammatory cytokines, including interleukin (IL)‑1β, IL‑6, IL‑12p40 and tumor necrosis factor‑α, in a dose‑dependent manner. In addition, the expression of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor‑2 (MD‑2) compound, the phosphorylation of p38 mitogen‑activated protein kinase (p38MAPK), c‑Jun N‑terminal kinase (JNK) and nuclear transcription factor‑κB (NF‑κB), in addition to the DNA binding activity of NF‑κB p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signal‑regulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPS‑induced ALI through the TLR4/MD-2-mediated NF‑κB, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.
从四棱豆根中分离出的总黄酮（RTFs）具有免疫调节活性，尤其是对炎症的调节作用。在脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠中，以40、80和160mg/kg的剂量用RTFs治疗可显著减少白细胞浸润，改善肺组织的组织病理学变化，并降低LPS诱导的支气管肺泡灌洗液（BALF）中几种炎症介质的产生，这些炎症介质包括趋化因子、粒细胞集落刺激因子、单核细胞炎性蛋白-1α和B淋巴细胞集落炎性细胞因子，如白细胞介素（IL）-1β、IL-6、IL-12p40和肿瘤坏死因子-α，且呈剂量依赖性。此外，RTF治疗后，肺组织中Toll样受体4（TLR4）/髓样分化因子-2（MD-2）复合物的表达、p38丝裂原活化蛋白激酶（p38MAPK）、c-Jun氨基末端激酶（JNK）和核转录因子-κB（NF-κB）的磷酸化，以及NF-κB p65的DNA结合活性均减弱。然而，RTF治疗对细胞外信号调节激酶（ERK）没有影响。总之，RTFs通过TLR4/MD-2介导的NF-κB、JNK和p38MAPK途径对LPS诱导的ALI起到调节作用。这可能是治疗炎症性疾病的一种潜在治疗选择。
