School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China; Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 273400, China.
J Ethnopharmacol. 2023 Feb 10;302(Pt A):115913. doi: 10.1016/j.jep.2022.115913. Epub 2022 Nov 5.
Jingfang Granule (JFG) is a Traditional Chinese Medicine prescription to empirically treat skin disease such as urticaria in clinical practice. However, the potential mechanisms of JFG on urticaria are not fully defined.
The aim of this study is to investigate the mechanisms of JFG in treating urticaria through an OVA/aluminum hydroxide induced urticaria mice model.
KM mice were injected intraperitoneally (i.p.) with OVA/aluminium hydroxide to establish the model with urticaria. After the mice were administered JFG, itching degree and hematoxylin and eosin (H&E) staining were used to assess the protective effect of JFG on mice with urticaria. The regulatory networks were investigated by proteomics and central carbon metabolomics. Spleen T lymphocyte subsets were detected by flow cytometry. Peripheral blood cytokines were detected using ELISA kits or Cytometric Bead Array (CBA) kits. The protein expression of skin tissue was detected by western blot or immunohistochemical staining.
JFG significantly relived skin tissue lesions and skin pruritus in mice with urticaria. Meanwhile, JFG significantly decreased IgE, IL-1β, IL-6, IL-4, TNF-α and IL-17A levels and increased IFN-γ levels in the serum of urticaria mice by inhibiting the expression of inflammation associated proteins including TLR4 and p-NF-κB p65, p-ERK1/2, p-JNK and p-p38, NLRP3, ASC and cleaved caspase-1. The results of proteomics, central carbon metabolomics, western blot and immunohistochemical staining confirmed that JFG inhibited Glycolysis/Gluconeogenesis and Pentose phosphate pathway in the skin tissue of urticaria mice by activating the LKB1/AMPK/SIRT1 axis and then downregulating the protein expressions of Glut1, TORC2, p-CREB, PEPCK, HNF4α and G6Pase.
The current study demonstrates that JFG is effective in treating OVA/aluminum hydroxide-induced skin lesions and inflammation in mice, and JFG exhibits the clinical benefits via modulating LKB1/AMPK/SIRT1 axis, which in turn inhibits Glycolysis/Gluconeogenesis and Pentose phosphate pathway.
荆防颗粒（JFG）是一种中药方剂，临床上常用于治疗荨麻疹等皮肤病。然而，JFG 治疗荨麻疹的潜在机制尚未完全确定。
本研究旨在通过卵清蛋白/氢氧化铝诱导的荨麻疹小鼠模型探讨 JFG 治疗荨麻疹的作用机制。
KM 小鼠腹腔注射卵清蛋白/氢氧化铝建立荨麻疹模型。JFG 给药后，采用抓挠程度和苏木精-伊红（H&E）染色评估 JFG 对荨麻疹小鼠的保护作用。通过蛋白质组学和中心碳代谢组学研究调控网络。采用流式细胞术检测脾 T 淋巴细胞亚群。采用 ELISA 试剂盒或 Cytometric Bead Array（CBA）试剂盒检测外周血细胞因子。采用 Western blot 或免疫组化染色检测皮肤组织中蛋白的表达。
JFG 显著缓解了荨麻疹小鼠的皮肤组织损伤和皮肤瘙痒。同时，JFG 通过抑制 TLR4 和 p-NF-κB p65、p-ERK1/2、p-JNK 和 p-p38、NLRP3、ASC 和裂解的 caspase-1 等炎症相关蛋白的表达，显著降低了荨麻疹小鼠血清中的 IgE、IL-1β、IL-6、IL-4、TNF-α 和 IL-17A 水平，增加了 IFN-γ 水平。蛋白质组学、中心碳代谢组学、Western blot 和免疫组化染色结果证实，JFG 通过激活 LKB1/AMPK/SIRT1 轴，抑制荨麻疹小鼠皮肤组织中的糖酵解/糖异生和磷酸戊糖途径，从而下调 Glut1、TORC2、p-CREB、PEPCK、HNF4α 和 G6Pase 的蛋白表达。
本研究表明，JFG 对 OVA/氢氧化铝诱导的皮肤损伤和炎症具有治疗作用，通过调节 LKB1/AMPK/SIRT1 轴，抑制糖酵解/糖异生和磷酸戊糖途径，发挥临床疗效。
