Diroleuton

This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.

Jinkui Wenjing Tang (JKWJT), a Traditional Chinese Medicine prescription for gynecological menstrual adjustment, is also used to treat continuous uterine bleeding and abdominal pain. However, the mechanism of action, potential targets, and active ingredients of JKWJT in the treatment of anovulatory dysfunctional uterine bleeding (ADUB) remain unknown. Therefore, it is imperative to explore the molecular mechanism of JKWJT.

The chemical composition and target of JKWJT were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the SwissTargetPrediction website. ADUB-related targets were collected through the GeneCards database. The protein-protein interaction network was constructed from the target protein. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The binding of the compounds in JKWJT and the potential therapeutic target molecules was verified by molecular docking. Finally, immunohistochemistry, Western Blotting, and qPCR were used for target expression validation within ADUB patient tissues.

The putative targets of JKWJT for the treatment of ADUB mainly involve ESR1, VEGFA, TNF, AR, OXTR, and PCNA. Functional enrichment analysis showed that the therapeutic effect of JKWJT on ADUB was correlated to response to estradiol, gland development, regulation of hormone levels as well as endocrine resistance, estrogen signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, prolactin signaling pathway. Molecular docking showed that the target OXTR was expected to have a good binding affinity with 4 corresponding compounds (Girinimbin, icosa-11, 14, 17-trienoic acid methyl ester, Kanzonol F, and Obacunone). After treatment with JKWJT, OXTR relative protein expression and mRNA levels were significantly reduced in ADUB patients.

In this study, the basic pharmacological effects, and mechanisms of JKWJT in the treatment of ADUB were elucidated, thus providing a clinical basis for the treatment of ADUB by JKWJT.