Dihydromyricetin attenuates intracerebral hemorrhage by reversing the effect of LCN2 via the system Xc- pathway.

BACKGROUND: The limited understanding of the pathological mechanisms of intracerebral hemorrhage (ICH) and the absence of successful therapies lead to poor prognoses for patients with ICH. Dihydromyricetin (DMY) has many physiological functions, such as regulating lipid and glucose metabolism and modulating tumorigenesis. Moreover, DMY has been proven to be an effective treatment of neuroprotection. However, no reports to date have been made regarding the impact of DMY on ICH. PURPOSE: This investigation aimed to identify the role of DMY on ICH in mice and the underlying mechanisms. METHODS/RESULTS: This study demonstrated that DMY treatment effectively reduced hematoma size and cell apoptosis of brain tissue, and improved neurobehavioral outcomes in mice with ICH. Transcriptional and network pharmacological analyses revealed that lipocalin-2 (LCN2) was a potential target of DMY in ICH. After ICH, LCN2 mRNA and protein expression in brain tissue increased and DMY could inhibit the expression of LCN2. The rescue experiment with the implementation of LCN2 overexpression verified these observations. Furthermore, after DMY treatment, there was a significant decrease in cyclooxygenase 2 (COX2), phospho-extracellular regulated protein kinase (P-ERK), iron deposition, and the number of abnormal mitochondria, which were reversed by the overexpression of LCN2. Proteomics analysis suggests that SLC3A2 may be the downstream target of LCN2, promoting ferroptosis. Finally, LCN2 was shown to bind to SLC3A2 and regulate the downstream glutathione (GSH) synthesis and Glutathione Peroxidase 4 (GPX4) expression and glutathione (GSH) synthesis, as determined by molecular docking and co-immunoprecipitation analysis. CONCLUSION: Our study confirmed for the first time that DMY might offer a favorable treatment for ICH through its action on LCN2. The possible mechanism for this could be that DMY reverses the inhibitory effect of LCN2 on the system Xc-, lessening ferroptosis in brain tissue. The findings of this study offer a greater understanding of how DMY affects ICH at a molecular level and could be conducive to developing therapeutic targets for ICH.

A woman with premature ovarian failure induced by Tripterygium wilfordii Hook.f. gives birth to a healthy child.

OBJECTIVE: To inform clinicians about the reproductive damage of Tripterygium wilfordii Hook.f. (TW) associated with subsequent premature ovarian failure. DESIGN: Case report. SETTING: Reproductive medicine center in a university-affiliated hospital. PATIENT(S): A 36-year-old infertile woman presenting amenorrhea and elevated FSH levels (65.56 mIU/mL) after using TW. INTERVENTION(S): Estradiol valerate, two month course of oral contraceptives, GnRH agonist, stimulation cycle with urine FSH, triggered ovulation using 5000 IU of hCG and IVF-ET. MAIN OUTCOME MEASURE(S): Serum hormone levels, antral follicle count (AFC), oocyte retrieval number, embryo quality and birth. RESULT(S): Serum hormone levels and AFC of the POF woman were restored, and she gave birth to a healthy child after IVF-ET. Through IVF-ET she was found to have had oocyte and granulosa cell damage because of TW. CONCLUSION(S): This is a real-life manifestation of reproductive damage of TW. The medicamentous amenorrhea, hormone levels and AFC decline induced by TW are reversible, but oocyte and granulosa cell damage may be irreversible. This will help clinicians to avoid using TW for nulligravida.