NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 7
·1662-1672
·
IF 2.472
Song Xiaoyu,Zhou Biao,Zhang Pingping,Lei Di,Wang Yubin,Yao Guodong,Hayashi Toshihiko,Xia Mingyu,Tashiro Shin-ichi,Onodera Satoshi,Ikejima Takashi
Silibinin, a flavonoid derived from the herb milk thistle ( Silybum marianum ), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1β and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS–BDNF–TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.
研究领域:
神经科学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2019
·
IF 5.808
Yayun Liu,Wei Xu,Ting Zhai,Jiaojiao You,Yong Chen
Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro . The in vivo study was performed using male C57BL/6 mice fed with methionine– choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp , reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo . These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the β -oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress.
研究领域:
药理学
·
肝病学
·
代谢性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Zebin Huang,Wanying Zhang,Qi Shu,Xiao-Chun Guo,Xi Zheng,YuJing Lu
Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin has excellent anti-inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti-inflammatory benefits of silibinin (SB). The synergistic effects of DBM and SB in combination were evaluated in LPS-induced RAW264.7 cells and TPA-induced mice. In addition, a network pharmacology approach and molecular docking were used to explore the key targets and signaling pathways of DBM and SB in combination. The results showed that DBM and SB synergistically inhibited the production of NO, ROS, IL-1β, and TNF-α in a 1:1 concentration ratio. These two compounds may exert their synergistic effects by modulating the NF-κB and HIF-1 signaling pathways, among others. Molecular docking revealed that both compounds exhibited high binding affinities to iNOS and COX-2. Compared with single compound use, the two compounds in combination significantly reduced ear edema and inflammatory cell infiltration, and inhibited the protein expression of iNOS and COX-2 in TPA-induced mice. This research provides a rationale for the combination of DBM and SB as an effective anti-inflammatory agent.
研究领域:
药理学
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免疫学
·
分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 42
·期 4
·1073-1083
·
IF 2.472
Song Xiaoyu,Zhou Biao,Cui Lingyu,Lei Di,Zhang Pingping,Yao Guodong,Xia Mingyu,Hayashi Toshihiko,Hattori Shunji,Ushiki-Kaku Yuko,Tashiro Shin-ichi,Onodera Satoshi,Ikejima Takashi
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ 25-35 -injected rats. Results demonstrated that silibinin significantly attenuated Aβ 25-35 -induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ 25-35 -injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ 25-35 -injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Jingwen Luo,Zhiwei Zhang,Yingchun Zeng,Yanming Dong,Lixin Ma
Components of the extracellular matrix (ECM) are overexpressed in fibrotic liver. Collagen is the main component of the liver fibrosis stroma. Here we demonstrate that chondroitin sulfate coated multilayered 50-nm nanoparticles encapsulating collagenase and silibinin (COL + SLB-MLPs) break down the dense collagen stroma, while silibinin inhibits activated hepatic stellate cells. The nanoparticles were taken up to a much greater extent by hepatic stellate cells than by normal hepatocytes, and they down-regulated production of type I collagen. In addition, chondroitin sulfate protected the collagenase from premature deactivation. COL + SLB-MLPs were delivered to the cirrhotic liver, and the collagenase and silibinin synergistically inhibited fibrosis in mice. Immunofluorescence staining of liver tissues revealed that CD44, mediated by chondroitin sulfate, delivered the nanoparticles to hepatic stellate cells. This strategy holds promise for degrading extracellular stroma and thereby facilitating drug penetration into fibrotic liver and related diseases such as liver cirrhosis and liver cancer.
研究领域:
药学
·
生物医学工程
·
肝脏疾病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2017
·
IF 2.341
Xiaoyu Song,Bo Liu,Lingyu Cui,Biao Zhou,Weiwei Liu,Fanxing Xu,Toshihiko Hayashi,Shunji Hattori,Yuko Ushiki-Kaku,Shin-ichi Tashiro,Takashi Ikejima
Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin , a flavonoid derived from milk thistle ( Silybum marianum ), has been used as a hepato-protectant in the clinical treatment of liver diseases. In this study, the effect of silibinin on Aβ-induced anxiety/depression-like behaviors in rats was investigated. Silibinin significantly attenuated anxiety/depression-like behaviors caused by Aβ1-42-treatment as shown in tail suspension test (TST), elevated plus maze (EPM) and forced swimming tests (FST). Moreover, silibinin was able to attenuate the neuronal damage in the hippocampus of Aβ1-42-injected rats. Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Our study provides a new insight into the protective effects of silibinin in the treatment of anxiety/depression.
研究领域:
神经科学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yulu Wang,Minghao Yuan,Sihui Li,Jiamei Tang,Yan Wan,Xue Liang,Yiping Guo,Li Guo
Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.
研究领域:
药理学
·
肝病学
·
药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yanan Wang,Huichao Wei,Keyang Li,Liru Liu,Yingfei Zhu,Xinyuan Wang,Jiahui Yan,Liangmin Yu,Xuefeng Yan,Zhiyu He
Calcium overload in hepatocytes mediates the crosstalk and amplification loop with oxidative stress and severe inflammation that initiate pro-apoptotic and necrotic signaling pathways in acute liver injury (ALI). In this study, an N-acetylgalactosamine-modified amphiphilic dextran-silibinin conjugate (GalNAc-Dex-Sil) with ROS-sensitive phenylboronic acid (PBA) linkage was synthesized. The as-prepared amphiphilic polymer was self-assembled into GalNAc-Dex-Sil nanoparticles, which efficiently encapsulated the membrane-permeable calcium chelator BAPTA-AM (BA), achieving GalNAc-mediated hepatocyte-specific targeting and ROS-responsive release in injured hepatocytes through PBA cleavage. Accordingly, a single low-dose injection of formulation (BA: 150 μg·kg −1 ) significantly alleviated hepatocyte oxidative stress and inflammation, rescued dying hepatocytes, prevented further hepatocyte damage, and ultimately restored liver function in the ALI mouse model by 1) rapidly and effectively eliminating the overloaded calcium and scavenging excessive ROS via released BA to block the feed-forward vicious cycles of the cell damage, 2) inhibiting the inflammatory cascade by decreasing the expression of the key factor of the NF-κB/NLPR3 axis, 3) inhibiting the key branch of the mitochondrial apoptotic pathway (Cyt C/Bcl-2 family/caspase-3 axis) and death receptor pathway (TNFα/Caspase-8 axis), and 4) stabilizing hepatocyte membranes through the synergistic hepatoprotective effect of silibinin. Taken together, this formulation exhibited great potential as a potent and effective ALI treatment strategy.
研究领域:
药理学
·
纳米技术
·
肝病学
·
炎症
·
细胞凋亡
✓ 已验证
产品关联
DOI
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Qingqing Du,Xiaoyun Wu,Kai Ma,Weiwei Liu,Panwen Liu,Toshihiko Hayashi,Kazunori Mizuno,Shunji Hattori,Hitomi Fujisaki,Takashi Ikejima
Type 2 diabetes (T2DM) is induced by the abundance of glucose and lipids , which causes glucolipotoxicity to the pancreatic β-cells. Silibinin is a natural flavonoid possessing the regulatory activity on insulin production and therapeutic activity in diabetic mice; however, its effect on glucolipotoxicity is not fully explained. This in vitro study investigates the effects of silibinin on palmitic acid (PA) and high glucose (HG)-induced cell loss and ferroptosis of rat insulinoma INS-1 cells. In the cells treated with PA and HG, expressions of glucose transporter 4 (Glut4) and carnitine acyltransferase I (CPT1) for β-oxidation of fatty acids are reduced. Mitochondria are the metabolic organelles for glucose and fatty acids. The mitochondrial membrane potential (MMP) and ATP production were decreased, while the ROS level was elevated in the cells treated with PA and HG, indicating an induction of mitochondrial disorder . Cell loss was partially rescued by ferroptosis inhibition, suggesting an involvement of ferroptosis in the cells treated with PA and HG. More importantly, the increases in total iron, lipid ROS, MDA and COX-2, and the decrease in ferroptosis inhibitory molecules GSH, GPX4 and FSP1 appeared in the cells treated with PA and HG, confirming the occurrence of ferroptosis. Moreover, PINK1/parkin-mediated mitophagy , a vital process for selective elimination of damaged mitochondria, was blocked. Interestingly, silibinin rescued the mitochondria, restricted the ferroptosis and restored the mitophagy. By using the pharmacological stimulator and inhibitor of mitophagy, and si-RNA transfection to silence PINK1 expression, silibinin's protective effect against ferroptosis caused by PA and HG treatment was found to depend on mitophagy. Collectively, our current study reveals the new mechanisms for the protection of silibinin against the injury of INS-1 cells treated with PA and HG, elucidates the participation of ferroptosis in glucolipotoxicity, highlighting the involvement of mitophagy in defense against ferroptotic cell death.
研究领域:
糖尿病
·
细胞生物学
·
药理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Science
·
2025
·
IF 8.3
Yong Li,Youdong Zhou,Yinqiu Tan,Gang Deng
Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and high mortality. Early brain injury (EBI) is the main cause of high mortality and delayed neurological dysfunction in patients with SAH. Neuroinflammation is the important pathological processes of EBI.We prepared Silymarin nanoparticles (SIM NPs) through the solvent precipitation method and investigated their role in combating EBI following SAH in mice. We found that SIM NPs with a diameter of 150 nm have the strongest ability to cross the blood-brain barrier. SIM nanoparticles are spherical and contain irregular particles inside, which may be composed mainly of silibinin and assembled through hydrogen bonding. Further in vivo experiments showed that SIM NPs improved short-term neurological dysfunction in SAH mice, reduced cortical neural damage, and reduced EBI inflammation through the Nrf2/STING pathway. Finally, water maze experiments showed that SIM NPs can improve long-term memory and learning ability in SAH mice. Based on the above results, we conclude that silymarin nanoparticles can reduce EBI after SAH by inhibiting the Nrf2/STING pathway, inhibiting neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 7
·e5887
·
IF 1.8
Shuai-nan Zhang,Qi Liu,Xu-zhao Li
Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl 4 -induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)–extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH 3 , and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.
研究领域:
中药学
·
生物信息学
·
肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Yuanbin Li,Wu Yi,Haowei Chen,Bao Han,Bo Ruan,Zhong Xiaoyu,Li ShanShan,Yifan Chen,Tao Peng,Jiaheng Zhang,Fang Wang
Betaine/ascorbyl glucoside (Bet/AA-2G) deep eutectic solvents (DES) composed of betaine and ascorbyl glucoside had been successfully used to improve the solubility of silymarin in this study. Under appropriate conditions, the solubility of silymarin in a 5 wt% Bet/AA-2G DES solution increased by 17.7% and 60.9% compared to a 50 wt% 1,3-butanediol solution and a 50 wt% ethanol solution, respectively. In addition, quantum chemical simulations showed that silymarin has a strong binding capacity to Bet/AA-2G DES and can remain stable after binding. The combination of Bet/AA-2G DES with silymarin enhanced the skin permeability and antioxidant capacity of silymarin. Moreover, SM-DES promoted the synthesis of type I collagen and significantly reduced the expression of MMP-1, indicating potential anti-wrinkle and firming properties. Overall, Bet/AA-2G DES showed great potential for improving the solubility and stabilizing the bioactivity of silymarin.
研究领域:
药学
·
化学
·
化妆品科学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）