Pharmaceuticals
·
2021
·Vol. 14
·期 3
·198
·
IF 5.863
Qingfeng He,Fengjiao Bu,Hongyan Zhang,Qizhen Wang,Zhijia Tang,Jing Yuan,Hai-Shu Lin,Xiaoqiang Xiang
Wuzhi capsule (WZC) is commonly prescribed with tacrolimus in China to ease drug-induced hepatotoxicity. Two abundant active ingredients, schisantherin A (STA) and schisandrin A (SIA) are known to inhibit CYP3A enzymes and increase tacrolimus’s exposure. Our previous study has quantitatively demonstrated the contribution of STA and SIA to tacrolimus pharmacokinetics based on physiologically-based pharmacokinetic (PBPK) modeling. In the current work, we performed reversible inhibition (RI) and time-dependent inhibition (TDI) assays withCYP3A5genotyped human liver microsomes (HLMs), and further integrated the acquired parameters into the PBPK model to predict the drug–drug interaction (DDI) in patients with differentCYP3A5alleles. The results indicated STA was a time-dependent and reversible inhibitor of CYP3A4 while only a reversible inhibitor of CYP3A5; SIA inhibited CYP3A4 and 3A5 in a time-dependent manner but also reversibly inhibited CYP3A5. The predicted fold-increases of tacrolimus exposure were 2.70 and 2.41, respectively, after the multidose simulations of STA. SIA also increased tacrolimus’s exposure but to a smaller extent compared to STA. An optimized physiologically-based pharmacokinetic (PBPK) model integrated withCYP3A5polymorphism was successfully established, providing more insights regarding the long-term DDI between tacrolimus and Wuzhi capsules in patients with differentCYP3A5genotypes.
研究领域:
药理学
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临床医学
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遗传学
✓ 已验证
DOI
高影响因子
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.
研究领域:
药理学
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内分泌学
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肾病学
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2025
·Vol. 57
·期 10
·1647
·
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.
研究领域:
药理学
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神经科学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xiaohong Xu,Vinothakumar Rajamanicham,Sujing Xu,Zhoudi Liu,Tao Yan,Guang Liang,Guilong Guo,Huiping Zhou,Yi Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2024
·
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.
研究领域:
水产养殖
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病毒学
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免疫学
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药理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2024
·
IF 4.8
Bo Li,Wuming Zhou,Jiacheng Zhang,Nan Wang,Xingguan Yang,Xin Ge
Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae , exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. However, the effect of Sch A on HS-caused cardiac injury and its underlying mechanism still lack research. In this study, we established an HS rat model through blood loss from the femoral artery and monitoring mean arterial pressure (MAP) followed by fluid resuscitation. Our findings suggested that cardiac dysfunction and pathological injury were induced by HS and attenuated by Sch A treatment in a dose-dependent manner. Apoptosis in cardiac tissue was promoted by HS, but suppressed after administration of Sch A by decreasing the protein expressions of cleaved-caspase-3 and -9. Moreover, excessive ROS production induced by HS was mitigated by Sch A, and the levels of oxidative stress indicators were improved by Sch A. Additionally, HS triggered the reduction of mitochondrial membrane potential (MMP), and led to mitochondrial dysfunction. Sch A reversed this effect of HS on mitochondria. The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.
研究领域:
药理学
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心脏病学
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急诊医学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Daozheng Fang,Qixiang Shang,Zhihao Liu,Xinyue Li,Quanrun He,Yining Liu,Yong Zhu,Haimeng Li,Tong Wu,Yan-Fang Xian,Jianping Chen,Jihang Chen
Schisandra berry , an edible fruit of the Schisandra genus, produces two main lignans known as Schisandrin A (SchA) and Schisandrin B (SchB). These compounds have garnered significant attention for their beneficial effects in alleviating diabetes and its complications, such as diabetic nephropathy and diabetic neuropathy. However, their protective effects and mechanisms of action against diabetic cardiomyopathy remained largely unknown. In this study, the diabetic cardiomyopathy in vivo model was established by intraperitoneal injection of streptozotocin (STZ) in mice, followed by 2 months of continuous oral administration of SchA and SchB. A positive control group receiving dapagliflozin (DAP) treatment was also included. We conducted a comprehensive evaluation of the protective effects of SchA and SchB against diabetic cardiomyopathy in Type 1 diabetes mellitus (T1DM) mice through a series of experiments, including echocardiography, immunofluorescence staining, immunohistochemistry, western blotting, transcriptomics, and molecular docking simulations, etc. Both SchA and SchB treatment significantly reduced fasting blood glucose level and inhibited dysfunction of pancreatic β-cells. Echocardiography revealed that both SchA and SchB substantially improved cardiac function, including changes in left ventricular muscle thickening, ejection fraction, and fractional shortening. This was accompanied by a reduction in ventricular hypertrophy and myocardial fibrosis following SchA or SchB treatment. Additionally, SchA and SchB treatment exhibited anti-inflammatory and antioxidant effects in mouse heart tissues. Transcriptomics analysis suggested that SchA and SchB may exert their protective effects against diabetic cardiomyopathy by inhibiting the complement cascade, as evidenced by decreased expression levels of genes such as C3, C3a, and C5a. Docking simulations further supported complement factor B as a potential target of SchA and SchB. Our study demonstrated that SchA and SchB exerted protective effects within the framework of T1DM on pancreatic tissues by suppressing apoptosis and preserving the ability of insulin secretion of β-cells. In addition, both SchA and SchB could protect against diabetic cardiomyopathy by inhibiting the complement pathway. These findings highlight the potential therapeutic applications of SchA and SchB in managing diabetic cardiomyopathy in the future.
研究领域:
药理学
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心脏病学
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糖尿病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2023
·
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.
研究领域:
神经科学
·
药理学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）