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Purpose: This study aimed to investigate the potential mechanisms and related bioactive components of ZSS for the treatment of insomnia.Method: The insomnia model of rat induced by PCPA was established. After oral administration of ZSS extract, the general morphological observation, pentobarbital sodium-induced sleep test and histopathological evaluation were carried out. Network pharmacology, assisted by UHPLC-Q-Exactive-MS/MS analysis, was developed to identify the targets of ZSS in the treatment of insomnia, as well as the corresponding signaling pathways. In addition, we validated the identified targets and pathways by RT-qPCR and immunohistochemical analysis.Results: The pentobarbital sodium-induced sleep test, determination of 5-HT and GABA levles in hypothalamic tissues and HE staining showed that ZSS extract was an effective treatment for insomnia. Network pharmacology analysis identified a total of 19 candidate bioactive ingredients in ZSS extract, along with 433 potentially related targets. Next, we performed protein-protein interaction (PPI), MCODE clustering analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and ingredient-target-pathway (I-T-P) sub-networks analysis. These methods allowed us to investigate the synergistic therapeutic effects of crucial pathways, including the serotonergic and GABAergic synapse pathways. Our analyses revealed that palmitic acid, coclaurine, jujuboside A, N-nornuciferine, caaverine, magnoflorine, jujuboside B, and betulinic acid, all played key roles in the regulation of these crucial pathways. Finally, we used the PCPA-induced insomnia in rats to validate the data generated by network pharmacology; these in vivo experiments clearly showed that pathways associated with the serotonergic and GABAergic system were activated in the rats model. Furthermore, ZSS treatment significantly suppressed high levels of HTR1A, GABRA1, and GABRG2 expression in the hypothalamus and reduced the expression levels of HTR2A.Conclusion: Based on the combination of comprehensive network pharmacology and in vivo experiments, we successfully identified the potential pharmacological mechanisms underlying the action of ZSS in the treatment of insomnia. The results provide a theoretical basis for further development and utilization of ZSS, and also provide support for the development of innovative drugs for the treatment of insomnia.

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Curcuma aromatica Salisb. rhizome (CASR) has multifunctional characteristics worldwide and a long history of use as a botanical drug with. Currently, it is often used clinically to treat coronary heart disease (CHD) caused by blood stasis syndrome. However, the therapeutic mechanism of CASR in the treatment of CHD remains poorly understood. In study, the main chemical constituents of CASR were analyzed using UPLC-Q-TOF-MS/MS. Then, its potential therapeutic mechanism against CHD was predicted. Subsequently, pharmacological evaluation was performed using CHD rat model. Finally, a lipidomics approach was applied to explore the different lipid metabolites to verify the regulation of CASR on lipid metabolism disorders in CHD. A total of 35 compounds was identified from CASR. Seventeen active components and 51 potential targets related to CHD were screened by network pharmacology, involving 13 key pathways. In vivo experiments showed that CASR could significantly improve myocardial infarction, blood stasis, and blood lipid levels and regulate the PI3K/AKT/mTOR signaling pathway in CHD rats. Lipidomics further showed that CASR could regulate abnormal sphingolipid, glycerophospholipid, and glycerolipid metabolism in CHD rats. The therapeutic mechanism of CASR against CHD was initially elucidated and included the regulation of lipid metabolism. Its effects may be attributed to active ingredients, such as curzerene, isoprocurcumenol, and (+)-curcumenol. This study reveals the characteristics of multi-component and multi-pathway of CASR in the treatment of CHD, which provides a basis for the follow-up development and utilization of CASR.

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