Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 305-811, Republic of Korea.
Cells. 2023 Mar 20;12(6):941. doi: 10.3390/cells12060941.
A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.
变应性免疫反应的一个关键特征是 T 辅助细胞 2(Th2)介导的反应,伴有过敏原特异性 IgE 抗体的产生。已经表明,去除藏红花酸的姜黄提取物(GJExCR)可抑制 IgE 介导的过敏性疾病。为了评估这种抑制作用的疗效和作用机制,在 BALB/C 小鼠的卵清蛋白(OVA)诱导过敏模型中使用了 GJExCR。通过腹腔内注射在第 1 天和第 14 天对 BALB/C 小鼠进行 OVA 和氢氧化铝致敏,然后在去除前对背部皮肤进行 2 周的 OVA 挑战。在挑战后 7 天,每天用 GJExCR 对小鼠进行局部治疗 11 天。通过酶联免疫吸附试验、流式细胞术分析、实时 PCR 和 Western blot 来确定 IgE 和 Th2 细胞因子水平。在 OVA 挑战后,Th2 细胞因子表达和总 IgE 及 OVA 特异性 IgE 水平增加,其中 GJExCR 治疗后 OVA 特异性 IgE 和 Th2 细胞因子水平降低。流式细胞术分析显示 GJExCR 治疗降低了脾和淋巴结中 CD4+和 CD8+T 细胞群体。此外,与对照相比,GJExCR 治疗降低了信号转导和转录激活因子 1(STAT1)的激活和 Th2 细胞因子水平。含栀子苷的 GJExCR 下调了 HaCaT 细胞中的 STAT1 激活。这些发现表明,GJExCR 通过抑制 STAT1 激活发挥其抗过敏作用,从而通过调节 Th2 细胞因子释放和 IgE 水平来调节免疫反应。因此,我们提出 GJExCR 是治疗过敏反应的潜在方法。