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Zedoary turmeric oil (ZTO) has been widely used in clinic. However, the unpleasant induced dyspnoea inevitably impedes its clinical application. Thus, it is urgent to elucidate the mechanism underlying the ZTO‐induced dyspnoea. In this study, network pharmacology was firstly performed to search the clue of ZTO‐induced dyspnoea. The key target genes of ZTO‐induced dyspnoea were analysed using GO enrichment analysis and KEGG pathway analysis. GO analysis suggested that haem binding could be a key molecular function involved in ZTO‐induced dyspnoea. Hence, the haemoglobin (Hb) was focused for its oxygen‐carrying capacity with haem as its critical component binding to the oxygen. Ultraviolet–visible absorption spectrum indicated that the ZTO injection (ZTOI) perturbed the Soret band of Hb, suggesting an interaction between ZTO and Hb. GC–MS analysis revealed that β‐elemene, germacrone, curdione and furanodiene were main components of ZTOI. Molecular docking was used to illustrate the high affinity between representative sesquiterpenes and Hb, which was finally confirmed by surface plasmon resonance, suggesting their potential roles in dyspnoea by ZTO. Following a network pharmacology‐driven strategy, our study revealed an intervened Hb‐based mechanism underlying the ZTO‐induced dyspnoea, providing a reference for elucidating mechanism underlying adverse drug reactions of herbal medicines in clinic. [ABSTRACT FROM AUTHOR]

Abstract: The human solute carrier family 19 member 1 (SLC19A1) is the gene coding for reduced folate carrier 1 (RFC1). In our previous work, we showed that the miR‐595‐related polymorphism, rs1051296 G>T, which was located in the 3′‐untranslated region (3′‐UTR) of SLC19A1, was associated with high methotrexate (MTX) plasma concentrations in patients with paediatric acute lymphoblastic leukaemia (ALL). This study aimed to investigate the role of miR‐595 in the regulation of SLC19A1 expression and its effects on the cellular uptake and cytotoxicity of MTX in ALL CEM/C1 cells. Luciferase reporter assay was performed to validate SLC19A1 as a miR‐595 target. RFC1 protein expression was determined via Western blotting. Intracellular MTX concentrations were measured by enzyme‐linked immunosorbent assay (ELISA). Cell viability and apoptosis were assessed using Cell Counting Kit‐8 (CCK‐8) assay and flow cytometer, respectively. Compared to the negative control, miR‐595 mimics induced a significant decrease in the relative luciferase activity by binding to the 3′‐UTR of SLC19A1 harbouring the rs1051296 T allele (p < 0.01). Treatment of CEM/C1 cells with miR‐595 mimics substantially reduced RFC1 protein expression, intracellular MTX levels, MTX‐induced cytotoxicity and apoptosis rates compared to those of negative control. However, opposite results were observed in cells transfected with a miR‐595 inhibitor. These findings suggested that miR‐595 acts as a phenotypic regulator of MTX sensitivity in CEM/C1 cells by targeting SLC19A1. This study helped us to understand the mechanisms underlying the variable MTX responses observed in patients with ALL. [ABSTRACT FROM AUTHOR]