Wu Yangping, Chen Xiangzheng, Ge Xiaojun, Xia Hongwei, Wang Yuxi, Su Siyuan, Li Wenting, Yang Tinghan, Wei Mingtian, Zhang Hang, Gou Lantu, Li Jiong, Jiang Xian, Yang Jinliang
State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 3-17 Renmin South Road, Chengdu, Sichuan, 610041, People's Republic of China.
Department of Laboratory Medicine, First Affiliated Hospital of Zun Yi Medical College, Zun Yi Medical College, Zun Yi, 563003, China.
J Mol Med (Berl). 2016 Feb;94(2):195-206. doi: 10.1007/s00109-015-1338-3. Epub 2015 Sep 18.
Isoliquiritigenin (ISL) is an important flavonoid component of licorice and has been reported to possess anti-inflammatory and antioxidant properties, but its exact mechanism of action remains poorly understood. Previously, we demonstrated that ISL could suppress IL-6 expression in multiple myeloma. Here, we further characterized the anti-inflammatory effects of ISL in several psoriasis models, including the keratin 14/vascular endothelial growth factor (VEGF) transgenic mouse, the imiquimod (IMQ)-induced psoriasis-like mouse, and the human keratinocytes HaCaT and NHEK in vitro. We found that ISL ameliorated the inflammatory process in psoriasis models but not in their respective controls. Moreover, the anti-inflammatory effects of ISL were attributed to the suppression of nuclear factor-κB (NF-κB) activity, which consequently resulted in the reduction of pro-inflammation cytokines IL-6 and IL-8 expression. In conclusion, ISL exhibited anti-inflammatory effects in psoriasis models, by downregulating IL-6 and IL-8 via suppression of NF-κB activity, suggesting that ISL might serve as a potential candidate for treatment of psoriasis and other autoimmune inflammatory diseases.
ISL could ameliorate the inflammatory process of psoriasis. ISL could suppress NF-κB and subsequent production of a series of pro-inflammatory cytokines. Dual-inhibitory activity against IL-6 and IL-8 of ISL is implemented via inhibiting NF-κB. ISL exerts no inhibitory effects on normal human keratinocytes or wild-type Balb/c mice, implying its low toxicity and safety.
异甘草素(ISL)是甘草的一种重要黄酮类成分,据报道具有抗炎和抗氧化特性,但其确切作用机制仍知之甚少。此前,我们证明ISL可抑制多发性骨髓瘤中白细胞介素-6(IL-6)的表达。在此,我们进一步在几种银屑病模型中表征了ISL的抗炎作用,包括角蛋白14/血管内皮生长因子(VEGF)转基因小鼠、咪喹莫特(IMQ)诱导的银屑病样小鼠以及体外培养的人角质形成细胞HaCaT和正常人表皮角质形成细胞(NHEK)。我们发现ISL改善了银屑病模型中的炎症过程,但对其各自的对照模型没有作用。此外,ISL的抗炎作用归因于对核因子-κB(NF-κB)活性的抑制,这进而导致促炎细胞因子IL-6和IL-8表达的减少。总之,ISL通过抑制NF-κB活性下调IL-6和IL-8,在银屑病模型中表现出抗炎作用,表明ISL可能是治疗银屑病和其他自身免疫性炎症疾病的潜在候选药物。
ISL可改善银屑病的炎症过程。ISL可抑制NF-κB及随后一系列促炎细胞因子的产生。ISL对IL-6和IL-8的双重抑制活性是通过抑制NF-κB实现的。ISL对正常人角质形成细胞或野生型Balb/c小鼠无抑制作用,这意味着其毒性低且安全性高。