Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan Province, 671000, People's Republic of China.
National-Local Joint Engineering Research Center of Entomoceutics, Dali University, Dali, Yunnan Province, 671000, People's Republic of China.
Drug Des Devel Ther. 2024 Oct 24;18:4749-4778. doi: 10.2147/DDDT.S479341. eCollection 2024.
Hemsl (also known as ) is a traditional Chinese medicine commonly utilized as a medicinal herb with its rhizomes, mainly used to regulate the immune function of the human body. However, relatively few studies have investigated its active components and potential mechanisms of action in vivo.
First, the chemical composition in vitro was identified and analyzed using the UPLC-Q-TOF MS/MS technique. Cyclophosphamide (CTX) was then administered intraperitoneally to rats to establish an immunosuppression model. Physiological and biochemical parameters, organ indices, and histopathological findings were evaluated for efficacy. Subsequently, potential biomarkers in rat serum were identified using multivariate statistical analysis and enriched and topologized using online platforms such as MetaboAnalyst and KEGG to reveal the critical metabolic pathways and their roles in the immunomodulatory network. Finally, the integrated analysis of components in vivo and in vitro, along with metabolic pathways, was performed using network pharmacology and molecular docking technology to elucidate the mechanisms of their roles in organismal immunity.
A total of 28 chemical components in vitro were identified, while pharmacodynamic experiments confirmed the immunomodulatory effects of , especially in the high-dose administration group. Metabolomics analysis showed that 37 potential immune-related biomarkers were identified in positive and negative ion modes, involving 16 metabolic pathways such as arginine biosynthesis, pyrimidine metabolism, and riboflavin metabolism. The results of network pharmacology and molecular docking indicated that may affect 7-O-galloyl-catechin, Cynaroside, Quercetin-7-O-beta-D-glucopyranoside, and 1.6-bis-O-galloyl-beta-D-glucose through interactions with the immune system, with significant pathways of action including galactose metabolism, glycolysis/gluconeogenesis, pyrimidine metabolism, and riboflavin metabolism.
In our experiments, we confirmed the organismal modulatory effect of on immunocompromised rats, clarified the key components, target proteins, and pathways of its possible action, and provided possibilities for follow-up studies.
诃子（又称诃子）是一种常用的中药，其根茎作为药用，主要用于调节人体的免疫功能。然而，目前关于其体内的活性成分及其潜在作用机制的研究相对较少。
首先，采用 UPLC-Q-TOF MS/MS 技术对其体外化学成分进行鉴定和分析。然后，给大鼠腹腔注射环磷酰胺（CTX）建立免疫抑制模型。评估生理生化参数、器官指数和组织病理学疗效。接着，采用多元统计分析和在线平台（如 MetaboAnalyst 和 KEGG）对大鼠血清中的潜在生物标志物进行鉴定和富集及拓扑分析，以揭示关键代谢途径及其在免疫调节网络中的作用。最后，采用网络药理学和分子对接技术对体内和体外成分及其代谢途径进行整合分析，以阐明其在机体免疫中的作用机制。
共鉴定出 28 种体外化学成分，药效学实验证实了诃子的免疫调节作用，尤其是高剂量组。代谢组学分析显示，正、负离子模式下共鉴定出 37 个潜在的免疫相关生物标志物，涉及精氨酸生物合成、嘧啶代谢和核黄素代谢等 16 个代谢途径。网络药理学和分子对接结果表明，诃子可能通过与免疫系统相互作用影响 7-O-没食子酰儿茶素、獐牙菜苷、槲皮素-7-O-β-D-吡喃葡萄糖苷和 1,6-双-O-没食子酰基-β-D-吡喃葡萄糖，其作用的关键途径包括半乳糖代谢、糖酵解/糖异生、嘧啶代谢和核黄素代谢。
在本实验中，我们证实了诃子对免疫抑制大鼠的机体调节作用，阐明了其可能作用的关键成分、靶蛋白和途径，为后续研究提供了可能性。
