Yifeng Zhou,Liling Wang,Yuchuan Qin,Lichun Chen,Qing Ge,Jianwei Mao
Linderane (LDR) and norisoboldine (NOR) are two typical active compounds in Lindera aggregate (Sims.) Kosterm. In this study, a new method of sequential extraction of LDR and NOR from L. aggregate was developed by supercritical fluid extraction (SFE) and ionic liquid-based ultrasonic-assisted extraction (IL-UAE) for the first time. The suitable SFE with CO2 conditions for LDR were 60 min dynamic extraction time, 40°C temperature and 30 MPa pressure. And the optimal IL-UAE factors for NOR were 2.06 mol/L 1-butyl-3-methylimidazolium bromide ([Bmim] Br) aqueous solution, 44 mL/g liquid–solid ratio, and 67 min ultrasonic time. Compared with the traditional extraction process, the sequential methods not only can obtain higher extraction efficiency, but also can realize the selective extraction for two different kinds of constituents with less consumption of traditional organic solvent. In addition, this environmentally friendly method could be used in a large-scale industry.
Norisoboldine (NIB) displays beneficial effects on cardiovascular diseases, although its protective role and underlying mechanisms in myocardial ischemia (MI) injury remain elusive. The aim of this study is to explore the potential cardioprotective mechanism of NIB on MI injury caused by isoproterenol (ISO). We administered NIB to SD rats at 20 and 40 mg/kg daily for 7 days in this study; this was followed by an ISO injection to induce MI injury. Parameters such as electrocardiogram readings, heart rate, serum concentrations of creatine kinase (CK) and creatine kinase-MB (CK-MB), levels of inflammatory markers, some histopathological assessments and oxidative stress markers were evaluated. We conducted Western blot analyses to evaluate protein expression related to apoptosis and the TLR4–MyD88-mediated NF-κB activation pathway. The L-type Ca 2+ current (ICa-L) and contraction of isolated ventricular cells from rats were identified using patch-clamp methods and the IonOptix detection system. The treatment with NIB resulted in improvements in heart rate and ST-segment changes, a reduction in CK and CK-MB levels, the restoration of superoxide dismutase, catalase and glutathione levels and a decrease in malondialdehyde accumulation. Furthermore, NIB reduced the expression of inflammatory markers, lowered Ca 2+ levels and reactive oxygen species production and improved myocardial tissue morphology. It also countered ISO-induced alterations in apoptosis and the TLR4–MyD88-dependent NF-κB activation pathway. Additionally, NIB considerably attenuated ICa-L and reduced the contractile function of cardiomyocytes. These results suggest that NIB effectively mitigates ISO-induced MI injury through anti-inflammatory, antioxidative, and anti-apoptotic mechanisms, potentially involving the TLR4–MyD88-dependent NF-κB activation pathway and calcium balance.
Depression is a common mental and mood disorder. Norisoboldine (NIB) has been shown to provide neuroprotective benefits. However, its potential antidepressant effects and underlying mechanisms remain to be elucidated. Our findings indicated that NIB ameliorates depressive behaviors and mitigates hippocampal neuronal damage induced by chronic unpredictable mild stress (CUMS). Numerous studies have corroborated the neuroprotective effects of gastrointestinal hormones such as ghrelin and its endogenous receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a). Notably, NIB demonstrated minimal impact on the expression levels of ghrelin and GHSR-1a. We furtherly investigated whether NIB could directly activate GHSR-1a in vitro . Treatment with NIB increased cell viability and inhibited CORT-induced apoptosis in HT-22 cells in a dose-dependent manner. The use of a GHSR-1a antagonist and GHSR-1a knockdown weakened the inhibitory effect of NIB on cell apoptosis. NIB attenuated endoplasmic reticulum (ER) stress via GHSR-1a in HT-22 cells, thereby protecting against cell apoptosis and loss. Molecular docking results showed an interaction between NIB and GHSR-1a, and CESTA results showed that NIB increased the thermal stability of GHSR-1a. In conclusion, NIB can reduce ER stress-induced injury to hippocampal neurons through GHSR-1a and improve depressive behavior in mice induced by CUMS. Download: Download high-res image (317KB) Download: Download full-size image
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