Spleen qi deficiency (SQD) syndrome is one of the basic traditional Chinese medicine (TCM) syndromes related to various diseases including chronic inflammation and hypertension and guides the use of many herbal formulae. However, the biological basis of SQD syndrome has not been clearly elucidated due to the lack of appropriate methodologies. Here, we propose a network pharmacology strategy integrating computational, clinical, and experimental investigation to study the biological basis of SQD syndrome. From computational aspects, we used a powerful disease gene prediction algorithm to predict the SQD syndrome biomolecular network which is significantly enriched in biological functions including immune regulation, oxidative stress, and lipid metabolism. From clinical aspects, SQD syndrome is involved in both the local and holistic disorders, that is, the digestive diseases and the whole body’s dysfunctions. We, respectively, investigate SQD syndrome-related digestive diseases including chronic gastritis and irritable bowel syndrome and the whole body’s dysfunctions such as chronic fatigue syndrome and hypertension. We found innate immune and oxidative stress modules of SQD syndrome biomolecular network dysfunction in chronic gastritis patients and irritable bowel syndrome patients. Lymphocyte modules were downregulated in chronic fatigue syndrome patients and hypertension patients. From experimental aspects, network pharmacology analysis suggested that targets of Radix Astragali and other four herbs commonly used for SQD syndrome are significantly enriched in the SQD syndrome biomolecular network. Experiments further validated that Radix Astragali ingredients promoted immune modules such as macrophage proliferation and lymphocyte proliferation. These findings indicate that the biological basis of SQD syndrome is closely related to insufficient immune response including decreased macrophage activity and reduced lymphocyte proliferation. This study not only demonstrates the potential biological basis of SQD syndrome but also provides a novel strategy for exploring relevant molecular mechanisms of disease-syndrome-herb from the network pharmacology perspective.

中文翻译：

---

网络药理学揭示脾气虚证和草药治疗的生物学基础。

脾气虚（SQD）综合征是与多种疾病（包括慢性炎症和高血压）相关的基本中医（TCM）综合征之一，并指导许多草药配方的使用。但是，由于缺乏适当的方法，SQD综合征的生物学基础尚未明确阐明。在这里，我们提出了一种结合计算，临床和实验研究的网络药理策略，以研究SQD综合征的生物学基础。从计算方面来看，我们使用了功能强大的疾病基因预测算法来预测SQD综合征生物分子网络，该网络显着丰富了包括免疫调节，氧化应激和脂质代谢在内的生物学功能。从临床角度来看，SQD综合征与局部和整体疾病有关，即消化系统疾病和整个身体的功能障碍。我们分别研究与SQD综合征相关的消化系统疾病，包括慢性胃炎和肠易激综合症以及全身功能障碍，例如慢性疲劳综合征和高血压。我们发现慢性胃炎患者和肠易激综合征患者的SQD综合征生物分子网络功能异常先天性免疫和氧化应激模块。慢性疲劳综合征患者和高血压患者的淋巴细胞模块被下调。从实验方面，网络药理分析表明，调查与SQD综合征相关的消化系统疾病，包括慢性胃炎和肠易激综合症，以及全身功能障碍，例如慢性疲劳综合征和高血压。我们发现慢性胃炎患者和肠易激综合征患者的SQD综合征生物分子网络功能异常先天性免疫和氧化应激模块。慢性疲劳综合征患者和高血压患者的淋巴细胞模块被下调。从实验方面，网络药理分析表明，调查与SQD综合征相关的消化系统疾病，包括慢性胃炎和肠易激综合症，以及全身功能障碍，例如慢性疲劳综合征和高血压。我们发现慢性胃炎患者和肠易激综合征患者的SQD综合征生物分子网络功能异常先天性免疫和氧化应激模块。慢性疲劳综合征患者和高血压患者的淋巴细胞模块被下调。从实验方面，网络药理分析表明，慢性疲劳综合征患者和高血压患者的淋巴细胞模块被下调。从实验方面，网络药理分析表明，慢性疲劳综合征患者和高血压患者的淋巴细胞模块被下调。从实验方面，网络药理分析表明，黄芪和其他四种常用于SQD综合征的草药在SQD综合征生物分子网络中显着丰富。实验进一步验证了黄芪成分能促进免疫功能，例如巨噬细胞增殖和淋巴细胞增殖。这些发现表明，SQD综合征的生物学基础与免疫应答不足密切相关，包括减少的巨噬细胞活性和减少的淋巴细胞增殖。这项研究不仅证明了SQD综合征的潜在生物学基础，而且为从网络药理学角度探讨疾病-综合征-草药的相关分子机制提供了新的策略。