Du Qiyue, Yang Jiayong, Zhou Bangyan, Zeng Wenxuan, Huang Rui, Zhao Yun, Ren Jie, Qiu Yan
The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, China.
The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Xiamen Key Laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine, Xiamen, China.
J Ethnopharmacol. 2025 Feb 27;342:119368. doi: 10.1016/j.jep.2025.119368. Epub 2025 Jan 21.
Pseudostellaria heterophylla (Tài Zǐ Shēn, TZS) is a traditional Chinese medicine with spleen and qi benefits. Its immunomodulatory, anti-fatigue, anti-stress, and lipid metabolism regulation effects have been clinically confirmed, but its role in meibomian gland dysfunction (MGD) is still unclear.
This study aims to investigate the effect and mechanism of action of TZS in treating MGD.
Several therapeutic agents were used to predict MGD treatment using the "Disease-Syndrome-TCM" network mechanism. We then performed a network pharmacology analysis to identify possible targets and pathways for drug treatment of the disease. It was then validated by in vitro experiments. The animal models were taken and analyzed by slit lamp and stereo microscope. HE and ORO staining analysis were then performed. Next, the expressions of key protein indicators were tested by IF, and finally the metabolism of key substances such as lipids and ceramides were detected by SRS imaging.
The "Disease-Syndrome-TCM" network mechanism was used to predict several therapeutic agents for MGD treatment including TZS et al. Network pharmacology analysis revealed that the targets of active components in the total saponins of TZS (PHS) were significantly enriched in the pathways of PPAR and AMPK. Subsequently, seven targets of PHS were identified, which were enriched in signaling pathways associated with lipid metabolism and inflammation. Furthermore, in vivo experiments showed that PHS alleviated meibomian glands (MG) obstruction and atrophy induced by A939, a SCD1 inhibitor. PHS treatment significantly increased PPAR-γ proteins in MGs, contributing to the normal differentiation of acini. Additionally, PHS treatment resulted in a reduction in the number of K10-positive cells, which partially prevented keratinization and abnormal differentiation of acinar cells. TUNEL assay results indicated that PHS mitigated apoptosis in MGs. Detailed exploration using Raman spectroscopy imaging showed that PHS could enhance the expression of SCD1 protein and the unsaturation degree of fatty acids, which in turn downregulated SPT1 protein and endogenous ceramides de novo biosynthesis.
This study elucidated the effects of PHS in alleviating MGD and highlighted the pharmacological mechanisms involved, specifically the upregulation of SCD1 and inhibition of de novo ceramides biosynthesis. These findings provided a research basis for advancing its clinical application in MGD treatment.
太子参是一种具有健脾益气功效的传统中药。其免疫调节、抗疲劳、抗应激及脂质代谢调节作用已得到临床证实，但其在睑板腺功能障碍（MGD）中的作用仍不明确。
本研究旨在探讨太子参治疗MGD的作用及作用机制。
采用“疾病-证候-中药”网络机制，利用多种治疗药物预测MGD的治疗方法。然后进行网络药理学分析，以确定该疾病药物治疗的潜在靶点和途径。随后通过体外实验进行验证。建立动物模型，用裂隙灯和体视显微镜进行分析。接着进行苏木精-伊红（HE）和油红O（ORO）染色分析。之后，通过免疫荧光（IF）检测关键蛋白指标的表达，最后通过受激拉曼散射（SRS）成像检测脂质和神经酰胺等关键物质的代谢。
利用“疾病-证候-中药”网络机制预测了包括太子参等多种治疗MGD的药物。网络药理学分析表明，太子参总皂苷（PHS）中活性成分的靶点在过氧化物酶体增殖物激活受体（PPAR）和腺苷酸活化蛋白激酶（AMPK）途径中显著富集。随后确定了PHS的7个靶点，这些靶点富集于与脂质代谢和炎症相关的信号通路中。此外，体内实验表明，PHS可减轻硬脂酰辅酶A去饱和酶1（SCD1）抑制剂A939诱导的睑板腺（MG）阻塞和萎缩。PHS治疗显著增加了MG中PPAR-γ蛋白的表达，有助于腺泡的正常分化。此外，PHS治疗导致角蛋白10（K10）阳性细胞数量减少，部分防止了腺泡细胞的角化和异常分化。TUNEL检测结果表明，PHS可减轻MG中的细胞凋亡。利用拉曼光谱成像进行的详细研究表明，PHS可增强SCD1蛋白的表达和脂肪酸的不饱和度，进而下调丝氨酸棕榈酰转移酶1（SPT1）蛋白和内源性神经酰胺的从头生物合成。
本研究阐明了PHS在减轻MGD方面的作用，并突出了其涉及的药理机制，特别是SCD1的上调和神经酰胺从头生物合成的抑制。这些发现为推进其在MGD治疗中的临床应用提供了研究依据。
