Magnoflorine (Mag) has multiple pharmacological activities for the prevention and treatment of prostatitis. However, its molecular mechanisms andpharmacological targets are not clear. In this study, the ultra-performance liquid tandem mass spectrometry-based metabolomics method was used to clarify the intervention of Mag against prostatitis and the biological mechanism. A total of 25 biomarkers associated with the prostatitis model were identified by metabolomics, and a number of metabolic pathways closely related to the model were obtained by MetPA analysis. After given Mag treatment, the results of each indicator were shown that Mag alkaloid could inhibit the development of prostatitis effectively. We found that Mag had regulative effects on potential biomarkers of prostatitis model, which can regulate them to the control group. Our results indicated that alkaloids have an effective intervention therapy for prostatitis, and five types of metabolic pathways closely related to prostatitis model were obtained, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, tyrosine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism. This study has provided the basic experimental data for the development of Mag in the prevention and treatment of prostatitis.
Meili Zhu,Jiangbiao Hu,Yifan Pan,Qian Jiang,Chang Shu
Background Heart failure (HF) remains one of the most common events in the progression of hypertension. Magnoflorine (MNF) has been shown beneficial effects on the cardiovascular system. However, the action of MNF on angiotensin (Ang) II-induced cardiac remodeling and its underlying mechanisms have not yet been characterised. Here, we assessed the action of MNF in the development of hypertension-related HF. Methods C57BL/6 male mice were subjected to Ang II through a micro-osmotic pump infusion continuously for 4 weeks to induce hypertensive HF. MNF (10 and 20 mg/kg) was administered in the final 2 weeks. Ang II content was measured by enzyme-linked immunosorbent assay (ELISA) kit. Values of ejection fraction (EF) and fractional shortening (FS) were detected using an ultrasound diagnostic instrument. The mRNA levels of hypertrophic and fibrotic genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Haematoxylin and eosin (H&E), wheat germ agglutinin (WGA), Masson trichrome, and Sirius Red staining were used to analyse pathologic changes in heart tissues. The expression levels of phosphorylated AMP-activated protein kinase (AMPK), light chain 3 microtubule associated protein II (LC3 II) to LC3 I, and p62 were detected by western blot assay. Results MNF significantly improved cardiac dysfunction and the content of creatine kinase-MB without altering blood pressure in Ang II-challenged mice. MNF obviously corrected the phenotypes of cardiac hypertrophy and fibrosis, including the high mRNA levels of atrial natriuretic peptide ( Anp ), brain natriuretic peptide ( Bnp ), collagen1a ( Col1a1 ), transforming growth factor beta ( Tgfb1 ), enlarged myocardial areas, and increased positive areas of Masson trichrome and Sirius Red staining. In addition, MNF alleviated oxidative injury, reflected by the upregulation of glutathione and the downregulation of reactive oxygen species and malondialdehyde. The activation of AMPK was elevated accompanied by an increased level of autophagy by MNF in hypertensive heart tissues. The therapeutic action of MNF was confirmed in Ang II-challenged H9c2 cells. Specifically, the AMPK inhibitor could eliminate the autophagy pathway in which MNF is involved. Conclusions MNF has benefits in hypertension-induced cardiac remodeling, which was partially associated with the improvement of oxidative stress via the mediation of the AMPK/autophagy axis.
Magnoflorine alleviates depression-like behaviors in a chronic stress model • Magnoflorine modulates serotonergic signaling involving 5-HT 1A receptor and SERT • Neuroprotective effects are associated with regulation of BDNF and ERK pathways • Magnoflorine restores monoamine neurotransmitter levels and neuroplasticity • Findings suggest potential therapeutic relevance for depression treatment Depression is a prevalent and debilitating psychiatric disorder characterized by dysregulation of monoaminergic neurotransmission and impaired neuroplasticity, and current antidepressants are limited by delayed onset and suboptimal efficacy, necessitating novel multi-target therapeutics. Magnoflorine, an alkaloid derived from Ziziphi Spinosae Semen (Suanzaoren), has been reported to possess antianxiety and neuroprotective activities, but its antidepressant effects and underlying mechanisms remain unclear. This study employed an integrated strategy combining network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation to investigate the antidepressant effects of magnoflorine. The effects of magnoflorine were evaluated in corticosterone (CORT)-induced HT-22 cells and a chronic unpredictable mild stress (CUMS) mouse model using behavioral tests, neurochemical analysis, histological analysis, and Western blotting. Network pharmacology analysis suggested that magnoflorine may regulate multiple targets involved in depression, particularly serotonergic signaling pathways. Molecular docking and molecular dynamics simulations suggested potential interactions between magnoflorine and 5-HT 1A R/SERT. In vitro and in vivo experiments demonstrated that magnoflorine ameliorated CORT-induced neuronal injury and CUMS-associated depression-like behaviors, restored hippocampal monoamine levels, and alleviated neuronal damage. These effects were accompanied by alterations in 5-HT 1A R and SERT expression and enhanced ERK phosphorylation and BDNF expression. Collectively, these findings suggest that the antidepressant-like effects of magnoflorine are associated with modulation of serotonergic and neurotrophic signaling. Download: Download high-res image (261KB) Download: Download full-size image
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