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MOLECULAR NEUROBIOLOGY · 2025 · IF 4.3

Mechanisms of Senegenin in Regulating Oxidative Stress and Mitochondria Damage for Neuroprotection in Insomnia: Evidence from In Vivo and In Vitro Models

Jia Honglin,Liang Zhengting,Yan Deqi,Chen Xu,Liang Ruining,Wu Jinhong,Zhang Xingping

Insomnia is a common sleep disorder worldwide, and oxidative stress and mitochondrial damage are closely related to insomnia. This study aimed to investigate the mechanism by which senegenin exerts neuroprotective effects in regulating oxidative stress and mitochondrial damage in insomnia. In vivo, EEG/EMG analysis confirmed the successful establishment of insomnia rat models; Nissl and HE staining and electron microscopy were used to evaluate the pathological changes of neurons and mitochondria in rat brain tissue. The expression of oxidative stress and sleep factors was assessed. In vitro, an oxidative damage cell model was established to measure oxidative stress–related parameters; the protective concentration of senegenin against oxidative damage was determined using the CCK-8 assay, and the effects of senegenin on the expression of Keap1/Nrf2 and PINK1/Parkin, key signaling pathways involved in oxidative stress and mitochondrial damage, were analyzed. During insomnia, wake is prolonged, and NREM and REM are shortened; learning memory and exploration behavior are impaired, oxidative stress factor expression is changed, and mitochondria are damaged. Brain tissue from insomnia rats showed decreased BDNF, 5-HT1A, GABA-T, and GAD and increased expression of 5-HT2A and Glu. Keap1, PINK1, Parkin, and LC3 expression increased and Nrf2, NQO1, HO-1, and p62 expression decreased in oxidatively injured cells. Senegenin showed a dose–response regulatory effect after the intervention. Senegenin may exert neuroprotective effects in insomnia by improving oxidative stress and mitochondrial damage.

CAS / MDL: 7424-00-2
研究领域: 神经生物学 · 药理学 · 细胞生物学 · 睡眠医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Chinese Journal of Chromatography · 2022 ·Vol. 40 ·期 5 ·433-442 · IF 0

[Fast screening and confirmation of 73 common prohibited compounds in cosmetics by ultra performance liquid chromatography-quadrupole-time-of-flight high resolution mass spectrometry].

Yangjie LI,Jiaying HUANG,Jihui FANG,Zhiye HUANG

A high throughput screening method based on ultra performance liquid chromatography-quadrupole-time-of-flight high resolution mass spectrometry (UPLC-Q-TOF HRMS) was developed for the simultaneous and rapid confirmation of 73 prohibited compounds in cosmetics. The sample was dispersed in a saturated sodium chloride solution and ultrasonically extracted using acetonitrile containing 0.2% (v/v) formic acid. The resultant solution was centrifuged and then cleaned using dispersive solid phase extraction using a primary secondary amine (PSA) sorbent. The purified solution was centrifuged, and the supernatant was filtered through a 0.22 μm membrane before determination. The optimal pretreatment method was determined by comparing the recovery rates obtained using different extraction solvents and different amounts of purifying agents. The chromatographic separation conditions and mass spectrometry scanning mode were also optimized. Chromatographic separation was performed on an Acquity UPLC HSS T3 column (100 mm×2.1 mm, 1.8 μm) with gradient elution using 0.1% (v/v) formic acid aqueous solution and methanol as mobile phases. The eluent from the column was further detected using Q-TOF HRMS with the high resolution multiple reaction monitoring (MRM HR) scanning mode. Retention time, precise mass of parent ion, isotope abundance ratio, and precise mass of fragment ions were the parameters considered for rapid untargeted screening and confirmation. The matrix effects of water- and cream-based cosmetics were investigated. The matrix effects could be addressed using the matrix matched standard curve method. The correlation coefficients for the 73 prohibited compounds were all >0.99 in the corresponding linear concentration range. The limits of detection (LODs) were in the range of 5-150 μg/kg, and the limits of quantification (LOQs) were in the range of 15-450 μg/kg. Average recoveries were in the range of 60.3%-130.3% at three spiked levels, and the intra-day and inter-day precisions were 0.8%-10.0% ( n =6) and 1.1%-15.0% ( n =3), respectively. A total of 692 cosmetics samples were screened; 16 positive samples were detected, namely, sulfamethoxazole, meprednisone, lincomycin, 4-acetamidophenol, trimethoprim, alfacalcidol, betamethasone 17-valerate, brimonidine, chloramphenicol, chlorpheniramine, clobetasol propionate, crotamiton, econazole, ketoconazole, prednisone 21-acetate, and prednisone, with content in the range of 0.5-1136.1 mg/kg. The optimized method is accurate, fast, and simple, and it is suitable for the routine detection and rapid screening of common prohibited compounds in cosmetics. In addition, a screening and confirmation library was established for the 650 prohibited compounds using SCIEX OS and Library View software, using information-dependent acquisition (IDA)-MS/MS mode for MS data acquisition. The database contains multiple types of information, including formulas, theoretical exact mass, retention time, precise mass of parent ion, isotope abundance ratio, and fragment ion distribution. The library can be used for the simultaneous and rapid confirmation of prohibited compounds in cosmetics.

✓ 已验证 产品关联 DOI PubMed
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

Microliquid/Liquid Interfacial Sensors: Biomimetic Investigation of Transmembrane Mechanisms and Real-Time Determinations of Clemastine, Cyproheptadine, Epinastine, Cetirizine, and Desloratadine

Zhidan Xu,Yongtao You,Silan Bai,Lishi Wang,Cheng Liu

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I–t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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