BIOMEDICAL CHROMATOGRAPHY
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2025
·Vol. 39
·期 5
·e70068
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IF 1.7
Sanwen Li,Qing Shao,Hongqun Qiao
Schisandrin B (Sch B), a natural lignan extracted from schisandra chinesis, has exhibited various pharmacological activities including anticancer effects. However, studies on the preclinical toxicokinetic profile of Sch B have not been publicly reported. This study aimed to investigate the preclinical concomitant toxicokinetics of multiple administration of Sch B. Sch B was administered orally to rats and dogs at 150, 300, and 600 mg/kg/day and 50, 100, and 200 mg/kg/day, respectively, for 26 weeks. Plasma concentrations of Sch B were determined by a validated HPLC–MS/MS method. According to the toxicokinetic results, significant gender differences were observed in the rats, and females had higher exposures than males for each dosing group. Toxicokinetic analysis demonstrated a notable accumulation in the plasma of dogs during the repeated administration of Sch B, and the degree of accumulation increased with the increase of the dose. The findings of this study indicated that there were differences in the concomitant toxicokinetics of Sch B between rats and dogs. These results can inform clinical studies and provide valuable insights for future human Sch B risk assessments.
研究领域:
药理学
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毒理学
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分析化学
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PubMed
高影响因子
International Journal of Nanomedicine
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2017
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IF 4.3
Mingfeng Shao,Wenfang Yang,Guangying Han
Purpose Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model.Methods PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats.Results The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent.Conclusion The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction.
研究领域:
药剂学
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心血管病学
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纳米医学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Zi-Kun Lin,Cheng Chen,Jia-Hui Hong,Ping Tan,Yao Yuan,Peng Wang,Xue-Sen Yang,Ya Liu,Hai-Gang Zhang
Heat stroke (HS) represents a severe public concern due to its high mortality rate, with cardiac injury recognized as a critical pathological process. Schisandra chinensis has been utilized in traditional Chinese prescription to prevent and treat heat stroke, but the underlying mechanism is unclear. The present study was designed to explore the cardioprotective effect of its main component, Schisandrin B (SchB). We analyzed cardiac RNA sequencing differentially expressed genes (DEGs) between HS and control mice to initially evaluate SchB's potential in attenuating HS-induced cardiac injury and its relation with ferroptosis. Using murine (core temperature reaching 42 °C) and cellular HS models (42 °C exposure for 5 h), we verified the cardiac preventive effects of SchB against HS-induced injury and its role in the modifying of ferroptosis. Bioinformatic analysis suggested SchB could modulate ferroptosis during HS. SchB pretreatment significantly prolonged time to reach HS in mice, alleviated cardiomyocyte injury, decreased Fe 2+ and malondialdehyde (MDA) levels while elevated glutathione (GSH) levels. Additionally, SchB downregulated acyl-CoA synthetase long chain family member 4 (ACSL4) expression and upregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in both murine and H9c2 cells HS models. Concurrently, SchB upregulated sirtuin 1 (SIRT1) expression while inhibiting the nuclear translocation of high mobility group box 1 (HMGB1). These findings suggest that SchB pretreatment may attenuate HS-induced cardiac ferroptosis and the associated myocardial injury through modulation of the SIRT1/HMGB1/ACSL4 pathway.
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JOURNAL OF CHROMATOGRAPHY A
·
2026
·
IF 4
Xuhua Qi,Zengbo Fang,Siqi Li,Shuyao Wang,Nan Tao,Huarong Xu,Yan Cui
Chiral HPLC-MS/MS developed for axial chiral Sch B in diverse complex matrices. • Coated Chiralcel OD-RH showed superior selectivity for rigid axial enantiomers. • Stereoselective BBB permeability of Sch B was identified using the new platform. • Neuroprotective effect and BBB permeability of Sch B enantiomers were first compared. Schisandrin B (Sch B), a major dibenzocyclooctadiene lignan from Schisandra chinensis , possesses a unique form of axial chirality and exhibits significant neuropharmacological properties. To address the formidable analytical challenge of resolving this rigid axial chiral scaffold in complex biological environments, a high-performance chiral HPLC platform was systematically developed. Superior resolution ( Rs = 2.93) was achieved on a Chiralcel OD-RH column using a methanol-water (90:10, v/v ) mobile phase. By coupling experimental optimization with molecular docking simulations, the separation mechanism was elucidated, revealing that specific hydrogen bonding and π-σ hydrophobic interactions between the cellulose-based chiral stationary phase (CSP) and the axial chiral framework are the primary driving forces for stereoselective recognition. To overcome the matrix-resolution trade-off, the method was optimized to ensure high sensitivity and minimal Ion Suppression in five distinct biological matrices, including lipid-rich brain tissue. Under multiple reaction monitoring (MRM) mode, the analytes were measured with high specificity ( m/z 401.2→285.2). This robust analytical platform was then applied to investigate the stereoselective blood-brain barrier permeability and neuroprotective efficacy of Sch B. While R -Sch B showed superior antioxidant efficacy in PC12 cells, S -Sch B exhibited significantly higher brain-to-plasma ratios (2.31 vs. 1.49) and preferential central nervous system accumulation. These findings, facilitated by enantiomer-specific interactions with efflux transporters such as P-glycoprotein, highlight the critical role of chirality in drug disposition and provide a reliable analytical framework for the development of enantiomer-specific neuroprotective agents.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Zhenxin Mou,Zhiguo Feng,Zheng Xu,Fei Zhuang,Xuyong Zheng,Xiaokun Li,Jianchang Qian,Guang Liang
Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients, with inflammation and oxidative stress implicated as crucial pathogenic factors. There is an urgent need to develop effective therapeutic drug. Natural medicines are rich resources for active lead compounds. They would provide new opportunities for the treatment of DN. The present study was designed to investigate the protective effects of Schisandrin B ( SchB ) on DN and to delineate the underlying mechanism. Oral administration of SchB in the diabetic mouse model significantly alleviated hyperglycemia-induced renal injury, which was accompanied by maintenance of urine creatinine and albumin levels at similar to those of control non-diabetic mice. Histological examination of renal tissue indicated that both development of fibrosis and renal cell apoptosis were dramatically inhibited by SchB . The protective effect of SchB on DN associated with suppression of inflammatory response and oxidative stress. These results strongly suggested that SchB could be a potential therapeutic agent for treatment of DN. Moreover, our findings provided a fuller understanding of the regulatory role of NF-κB and Nrf2 in DN, indicating that they could be important therapeutic targets.
研究领域:
药理学
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糖尿病学
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肾病学
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2019
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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
研究领域:
肾病学
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分子生物学
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药理学
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2018
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IF 3.616
Xuanxuan Dai,Changtian Yin,Guilong Guo,Yi Zhang,Chenguang Zhao,Jianchang Qian,Ouchen Wang,Xiaohua Zhang,Guang Liang
Triple negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. In this study, we have examined the potential of Schisandrin B (Sch B), a bioactive chemical compound found in Schisandra chinensis , against TNBC. We used MDA-MB-231, BT-549, and MDA-MB-468 TNBC cells and immunodeficient mice to study the effect of Sch B. Our results show that Sch B inhibits TNBC growth by inducing cell cycle arrest and by triggering apoptotic death. Sch B also inhibited the migration and colony formation of tumor cells, and prevented the growth of TNBC cells in mice. We found that these inhibitory activities were mediated through suppression of signal transducer and activator of transcription-3 (STAT3) phosphorylation and nuclear translocation. Taken together, our studies show that Sch B has potent anti-tumor activity against TNBC via a novel mechanism involving STAT3 inactivation.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 1
·1-8
·
IF 2.447
Heng Tang,Junhao Zhao,Rui Feng,Peng Pu,Li Wen
The cardiotoxicity of pirarubicin (THP) seriously affects its clinical application, which cannot be ignored. The antioxidant effect of schisandrin B (SchB) has been extensively reported in the context of dietotherapy. However, whether this antioxidant effect can protect the heart from THP damage remains unknown. The aim of the present study was to investigate whether the antioxidant effect of SchB can antagonize the cardiotoxicity of THP. Changes in electrocardiogram (ECG), echocardiography and serum lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB and cardiac troponin T levels were used to detect the degree of cardiac damage. The levels of superoxide dismutase (SOD), malondialdehyde, catalase and total antioxidant capacity in the serum and heart were measured to observe the oxidative stress state of rats. Primary cardiomyocytes were cultured, and cell viability and reactive oxygen species (ROS) production were detected. Western blotting was used to detect the expression levels of SOD2, NOX2, pro/cleaved‑caspase3 and Bcl‑2/Bax in heart tissue and primary cardiomyocytes to verify the related signaling pathways. THP‑treated rats showed a range of cardiac damage, including an abnormal ECG, echocardiography and myocardial enzymes. In the cellular experiments, cell viability decreased and ROS increased. However, this damage was alleviated after SchB treatment. Further studies demonstrated that SchB antagonized THP cardiotoxicity via its antioxidant effect. In conclusion, SchB protects the heart from THP damage in rats, and the mechanism may be closely associated with its antioxidant effect.
研究领域:
药理学
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心脏病学
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肿瘤学
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分子生物学
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PubMed
高影响因子
MEDICAL SCIENCE MONITOR
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2018
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IF 1.894
Zeng Li,Xiao-chang Liu,Rui Li,Jun Chang
Background Beta-secretase 1 (BACE1) is a rate-limiting enzyme in the generation of amyloid beta peptides, which are associated with Alzheimer’s disease (AD). It has been reported that Schisandrin B could improve cognitive functions in animal models of AD, but the underlying mechanisms are not completely understood. Material/Methods In this research, in order to investigate the effects of Schisandrin B on amyloid-β (Aβ) metabolism and its mechanisms, amyloid precursor protein (APP) and its proteolytic products were determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and RT-PCR after incubation of N2a/Swe cells with Schisandrin B. Results The results indicated that Schisandrin B can significantly reduce the level of secretion of Aβ 40 and Aβ 42 secreted in N2a/Swe cells. Additionally, there was nonsignificant change in APP level after Schisandrin B treatment. Treatment of Schisandrin B dramatically reduced the mRNA and protein expression levels of BACE1. Moreover, Schisandrin B treatment resulted in a reduction of protein level of sAPPβ, an APP fragment cleavage by BACE1. Conclusions These results suggest that Schisandrin B inhibits the transcription and translation of BACE1, suppresses the activity of BACE1, and ultimately attenuates Aβ generation, which provides a novel mechanism for the regulation of Aβ metabolism by Schisandrin B.
研究领域:
神经生物学
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分子药理学
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神经退行性疾病研究
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药物代谢
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生物化学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
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IF 8.5
Pui-Kei Lee,Co Vanessa Anna,Yang Yang,Murphy Lam Yim Wan,Hani El-Nezami,Danyue Zhao
Schisandrin B (Sch B) is a predominant bioactive lignan from the fruit of a Chinese medicine food homology plant, Schisandra chinensis . Previously, we observed potent anti-tumor effect of Sch-B in colorectal cancer (CRC) and enhanced chemotherapy efficacy with fluorouracil (5-FU). However, their bioavailability and reciprocal interactions under CRC conditions are unclear. In this study, we first compared the bioavailability, metabolism and tissue distribution of Sch-B between non-tumor-bearing and xenograft CRC tumor-bearing mice. Next, we examined SchB-5-FU interactions via investigating alterations in drug metabolism and multidrug resistance. Using a validated targeted metabolomics approach, five active metabolites, including Sch-B and fluorodeoxyuridine triphosphate, were found tumor-accumulative. Co-treatment resulted in higher levels of Sch-B and 5-FU metabolites, showing improved phytochemical and drug bioavailability. Multidrug resistance gene (MDR1) was significantly downregulated upon co-treatment. Overall, we demonstrated the potential of Sch-B to serve as a promising chemotherapy adjuvant via improving drug bioavailability and metabolism, and attenuating MDR.
研究领域:
药理学
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肿瘤学
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代谢组学
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药物递送系统
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高影响因子
Biomed Research International
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2022
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IF 3.246
Hongwei Shi,Yue Yan,Hong Yang,Peng Pu,Heng Tang
Objective. Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver-protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP-induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP-induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP-induced hepatotoxicity. Methods. The rat model of THP-induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis-related protein GPX4 and oxidative stress-related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer-1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results. THP rats showed a series of THP-induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP-induced hepatotoxicity. Conclusion. SchB has obvious protective effect on THP-induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Qiao Lai,Zhengzhong Luo,Chunying Wu,Sisi Lai,Hanmei Wei,Tongming Li,Qing Wang,Yang Yu
Cyclosporine A (CsA) is a potent immunosuppressive agent whose clinical usage is limited by nephrotoxicity . Schisandrin B (SchB), isolated from the fruit of Schisandra chinensis , is a natural compound with multiple pharmacological activities that has been shown to attenuate organ injury caused by CsA. Hence, the primary objective of the current study was to evaluate whether SchB has a cytoprotective effect on CsA-induced nephrotoxicity in human proximal tubular epithelial cell line (HK-2). This study demonstrated that pre-incubation of HK-2 cells with 2.5–10.0 μM SchB ameliorated CsA induced cytotoxicity caused by oxidative stress as evidenced by reduced levels of intracellular reactive oxygen species (ROS) and LDH release along with increased levels of mitochondrial membrane potential (ΔΨm) and glutathione (GSH). Also, it was demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) activation was involved in modulating cellular oxidative stress, where SchB promoted Nrf2 translocation into the nucleus and downstream target gene expression of heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and Glutamate-cysteine ligase modifier subunit (GCLM). Additionally, SchB was found to enhance cell survival via reducing apoptosis rate as well as recover the CsA induced blockade of autophagic flux. Collectively, these findings demonstrated that SchB mediated alleviation of CsA induced nephrotoxicity by preventing the accumulation of ROS by way of suppressing oxidative stress, apoptosis and autophagy.
研究领域:
药理学
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肾病学
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细胞生物学
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免疫学
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PubMed
高影响因子
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