Zhao Jingxia, Wang Yan, Chen Weiwen, Fu Jing, Liu Yu, Di Tingting, Qi Cong, Chen Zhaoxia, Li Ping
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing, China.
Front Pharmacol. 2021 Jun 8;12:626267. doi: 10.3389/fphar.2021.626267. eCollection 2021.
Clinical studies have demonstrated the anti-psoriatic effect of the LiangXueJieDu (LXJD) herbal formula. However, the systemic mechanism and the targets of the LXJD formula have not yet been elucidated. In the present study, a systems pharmacology approach, metabolomics, and experimental evaluation were employed. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, 144 active compounds with satisfactory pharmacokinetic properties were identified from 12 herbs of LXJD formula using the TCMSP database. These active compounds could be linked to 125 target proteins involved in the pathological processes underlying psoriasis. Then, the networks constituting the active compounds, targets, and diseases were constructed to decipher the pharmacological actions of this formula, indicating its curative effects in psoriasis treatment and related complications. The psoriasis-related pathway comprising several regulatory modules demonstrated the synergistic mechanisms of LXJD formula. Furthermore, the therapeutic effect of LXJD formula was validated in a psoriasis-like mouse model. Consistent with the systems pharmacology analysis, LXJD formula ameliorated IMQ-induced psoriasis-like lesions in mice, inhibited keratinocyte proliferation, improved keratinocyte differentiation, and suppressed the infiltration of CD3+ T cells. Compared to the model group, LXJD formula treatment remarkably reduced the expression of inflammatory cytokines and factors, such as IL-1β, IL-6, TNF-α, Cox2, and inhibited the phosphorylation of p-P65, p-IқB, p-ERK, p-P38, p-PI3K, p-AKT, indicating that LXJD formula exerts its therapeutic effect by inhibiting the MAPK, PI3K/AKT, and NF-қB signaling pathways. The metabolic changes in the serum of psoriasis patients were evaluated by liquid chromatography coupled with orbitrap mass spectrometry (LC-MS). The LXJD formula improved two perturbed metabolic pathways of glycerophospholipid metabolism and steroid hormone biosynthesis. Overall, this study revealed the complicated anti-psoriatic mechanism of LXJD formula and also offered a reliable strategy to elucidate the complex therapeutic mechanism of this Chinese herbal formula in psoriasis from a holistic perspective.
临床研究已证实凉血解毒（LXJD）中药配方具有抗银屑病作用。然而，LXJD配方的系统作用机制和靶点尚未阐明。在本研究中，采用了系统药理学方法、代谢组学和实验评估。首先，通过系统的吸收-分布-代谢-排泄（ADME）分析，使用中药系统药理学数据库（TCMSP）从LXJD配方的12味草药中鉴定出144种具有良好药代动力学性质的活性化合物。这些活性化合物可与125个参与银屑病病理过程的靶蛋白相关联。然后，构建了由活性化合物、靶点和疾病组成的网络，以解读该配方的药理作用，表明其对银屑病治疗及相关并发症的疗效。由多个调控模块组成的银屑病相关通路展示了LXJD配方的协同作用机制。此外，在银屑病样小鼠模型中验证了LXJD配方的治疗效果。与系统药理学分析一致，LXJD配方改善了咪喹莫特诱导的小鼠银屑病样皮损，抑制了角质形成细胞增殖，改善了角质形成细胞分化，并抑制了CD3 + T细胞浸润。与模型组相比，LXJD配方治疗显著降低了炎症细胞因子和因子如IL-1β、IL-6、TNF-α、Cox2的表达，并抑制了p-P65、p-IқB、p-ERK、p-P38、p-PI3K、p-AKT的磷酸化，表明LXJD配方通过抑制MAPK、PI3K/AKT和NF-қB信号通路发挥治疗作用。采用液相色谱-静电场轨道阱质谱联用（LC-MS）评估银屑病患者血清中的代谢变化。LXJD配方改善了甘油磷脂代谢和类固醇激素生物合成这两条紊乱的代谢途径。总体而言，本研究揭示了LXJD配方复杂的抗银屑病机制，也从整体角度为阐明该中药配方在银屑病中的复杂治疗机制提供了可靠策略。
