MOLECULAR NEUROBIOLOGY
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2023
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IF 5.1
Guo Xiying,Lei Min,Ma Guandi,Ouyang Changhan,Yang Xiaosong,Liu Chao,Chen Qingjie,Liu Xiufen
Clinical and epidemiological research shows that people with diabetes mellitus frequently experience diabetic cognitive impairment. Schisandrin A (SchA), one of the lignans found in the dried fruit of Schisandra chinensis, has a variety of pharmacological effects on immune system control, apoptosis suppression, anti-oxidation and anti-inflammation. The goal of the current investigation was to clarify the probable neuro-protective effects of SchA against streptozotocin-induced diabetes deficiencies of the spatial learning and memory in rats. The outcomes show that SchA therapy effectively improved impaired glucose tolerance, fasting blood glucose level and serum insulin level in diabetic rats. Additionally, in the Morris water maze test, diabetic rats showed deficits in spatial learning and memory that were ameliorated by SchA treatment. Moreover, giving diabetic rats SchA reduced damage to the hippocampus structure and increased the production of synaptic proteins. Further research revealed that SchA therapy reduced diabetic-induced hippocampus neuron damage and the generation of Aβ, as demonstrated by the upregulated phosphorylation levels of insulin signaling pathway connected proteins and by the decreased expression levels of inflammatory-related factors. Collectively, these results suggested that SchA could improve diabetes-related impairments in spatial learning and memory, presumably by reducing inflammatory responses and regulating the insulin signaling system.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Guangxu Cao,Shuang Li,Hezhan Shi,Peidi Yin,Jialing Chen,Huifeng Li,Ying Zhong,Li-Ting Diao,Bin Du
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Jinpeng,Cui Xinyuan,Zhao Shuo,Chang Zenghui,Zhang Junshuo,Chen Yufeng,Liu Jiale,Sun Guohao,Wang Yiyuan,Liu Yuanyuan
Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer’s disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model.Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group.Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.
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JOURNAL OF CHROMATOGRAPHY A
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2024
·
IF 3.8
Jiaming Yuan,Jincai Wang,Zhixu Chen,Yuexiang Chang,Litong Chen,Zhizeng Gao,Jacques Crommen,Tingting Zhang,Zhengjin Jiang
In this study, a novel at-line nanofractionation platform was established for screening SARS-CoV-2 fusion inhibitors from natural products for the first time by combining HPLC-MS/MS with high-throughput fluorescence polarization (FP) bioassay. A time-course FP bioassay in 384 well-plates was conducted in parallel with MS/MS to simultaneously obtain chemical and biological information of potential fusion inhibitors in Lonicerae Japonicae Flos (LJF) and Lianhua Qingwen capsules (LHQW). Semi-preparative liquid chromatography and orthogonal HPLC separation were employed to enrich and better identify the co-eluted components. After comprehensive evaluation and validation, 28 potential SARS-CoV-2 fusion inhibitors were screened out and identified. Several compounds at low micromolar activity were validated by in vitro inhibitory assay, molecular docking, cytotoxicity test, and pseudovirus assay. Moreover, four potential dual-target inhibitors against influenza and COVID-19 were discovered from LJF using this method, offering novel insights for the development of future pharmaceuticals targeting epidemic respiratory diseases.
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FITOTERAPIA
·
2012
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IF 1.848
Cong Liu,Yun-Feng Cao,Zhong-Ze Fang,Yan-Yan Zhang,Cui-Min Hu,Xiao-Yu Sun,Ting Huang,Jia Zeng,Xu-Ran Fan,Mo Hong
Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructus schisandrae which has been widely used as a tonic in traditional Chinese medicine for many years. Inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb–drug interaction. The aim of the present study is to investigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGT isoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM of deoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligible inhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin A were demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC 50 value of 10.8 ± 0.4 μM and 12.5 ± 0.5 μM, respectively. Dixon and Lineweaver–Burk plots showed that inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, and inhibition kinetic parameter (K i ) was calculated to be 0.48 μM. Inhibition of UGT1A3 by schisantherin A gave the best fit for types of noncompetitive inhibition, and the results showed K i to be 11.3 μM. All these experimental data suggested that herb–drug interaction might occur when deoxyschizandrin or schisantherin A containing herbs were co-administered with drugs which mainly undergo UGT1A3-mediated metabolism. However, given that many in vivo factors could influence the in vitro – in vivo extrapolation (IVIVE), these in vitro inhibitory parameters should be considered with caution.
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Waste and Biomass Valorization
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2024
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IF 2.6
Zhao Zijia,Gao Yan,Yuan Min,Ye Cai,Guo Yingxue,Zhao Yanli,Li Jinlian,Cui Jiwen,Dong Tianwei,Wu Dongmei
A significant quantity of residues will produce when volatile oil in Schisandra chinensis fruit is extracted by steam distillation. It is important to investigate the residues for potential use. Currently, there is an increasing demand for anti-photoaging products due to the skin damage caused by UV radiation. In this paper, the ingredients of the residues were investigated, and the anti-photoaging activities of residues extracts were studied. The results showed that the residues still contained notable amounts of lignans, flavonoids, and organic acids. In the extracted fraction of dichloromethane (DE), the residues contained higher amounts of schizandrol B and schisantherin A compared to the fresh fruit. The levels were particularly high at 17.39 ± 0.02 and 52.58 ± 0.04 mg/ml, respectively. By lowering the amount of matrix metalloproteinase-1 (MMP-1), reactive oxygen species (ROS) accumulation, and type I collagen (COL-I) loss in fibroblasts, the residues showed targeted benefits in the fight against skin photoaging. In particular, the DE-R phase of residues was very successful in raising the level of COL-I, matching or even exceeding that of retinol (ROL) and undistilled fresh fruits. Protocatechuic acid, schizandrol A, schizandrol B, schisantherinA, schisandrin A and schizandrin B were found to have a significant correlation with the anti-photoaging ability of residues. Particularly, there was a strong and significant correlation between an increase in COL-I and schizandrol B (|ρ| = 0.829*) and schisantherin A (|ρ| = 0.928**), and the distillation procedure has the potential to increase the amount of schizandrol B and schisantherin A in the residues. Graphical
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ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2025
·Vol. 57
·期 10
·1647
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IF 3.4
Guandi Ma,Min Lei,Shuang Guo,Yuqing Zhang,Yixuan Sun,Huimin Ji,Changhan Ouyang,Xiaosong Yang,Youzhi Zhang,Xiufen Liu,Baoqing Zhao,Xiying Guo
Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis , has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ 42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.
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Biology-Basel
·
2024
·Vol. 13
·期 8
·597
·
IF 3.6
Pengyu Wang,Qing Lan,Qi Huang,Ruyi Zhang,Shuo Zhang,Leiming Yang,Yan Song,Tong Wang,Guandi Ma,Xiufen Liu,Xiying Guo,Youzhi Zhang,Chao Liu
Simple SummaryEnd-stage renal disease is mainly caused by diabetic nephropathy, which has a complex pathogenesis and currently has no effective treatment. Schisandrin A has a wide range of pharmacological activities, including antioxidant, apoptosis inhibition, and immune regulation, but its pharmacological mechanism of action on diabetic nephropathy is still unclear. This study aimed to explore the pharmacological mechanism of Schisandrin A in the treatment of diabetic nephropathy using a network pharmacology approach. Through in vivo experiments, hub genes and related signaling pathways were verified based on the results of network analysis. The results showed that Schisandrin A had a protective effect on diabetic nephropathy, EGFR might be a potential therapeutic target, and AKT/GSK-3β might be involved in this process. This will provide a certain theoretical basis for the further clinical application of Schisandrin A in the treatment of diabetic nephropathy.AbstractDiabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein–protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3β signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3β pathway.
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FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Tian-Xiu Qiu,Lei Liu,Huan Wang,Yang Hu,Jiong Chen
Spring viraemia of carp virus (SVCV) is a major threat to the aquaculture industry, causing severe economic losses and significantly impacting fish health. Despite this, no approved antiviral treatments are currently available for use in aquaculture, underscoring the urgent need for effective interventions. This study evaluated the antiviral and immunomodulatory potential of Schisandrin A (SA), a bioactive compound derived from the traditional Chinese medicinal herb Schisandra chinensis , against SVCV. Through a combination of in vitro and in vivo experiments, SA was found to significantly inhibit SVCV replication, lower the viral titer, and improve survival rates in infected juvenile carp. Mechanistically, SA enhanced the host’s innate immune response, as demonstrated by the upregulation of key antiviral genes including interferon-alpha1 ( ifna1 ), interferon-gamma ( ifnγ ), interferon-stimulated gene 15 ( isg15 ), and myxovirus resistance 1 ( mx1 ). Additionally, SA exhibited potent antioxidative properties, preserving mitochondrial integrity and reducing oxidative stress in SVCV-infected cells. These findings showed the dual role of SA in both directly suppressing viral replication and modulating the immune response, offering a multifaceted approach to managing SVCV infection. Given its low toxicity and biodegradability, SA emerges as a promising, sustainable antiviral agent for aquaculture. This study highlights the potential of SA to enhance biosecurity and promote sustainability in the industry, paving the way for the development of eco-friendly antivirals that could improve the management of viral diseases, ensuring healthier fish populations and greater economic stability.
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