INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Can Wang,Jia-Jun Cui,Tao Sheng,Shuai Xia,Jia-Min Li,Bing-Feng Zhang
Oral nanoparticles coated with chitosan (CS) exhibited improvement of gastrointestinal therapeutics delivery and enhancement of liver fibrosis therapy. Here, chitosan-modified silibinin-hyaluronic acid nanoparticles (CS/HA-SLB NPs) was fabricated. The silibinin (SLB) was linked with hyaluronic acid (HA) by ester bond to from HA-SLB conjugates, and then self-assembled by dialysis to form silibinin-hyaluronic acid nanoparticles (HA-SLB NPs), finally coated with CS through electrostatic attraction. The prepared CS/HA-SLB NPs had a particle size about 220 nm, approximate spherical profile, positive potential and drug loading 3.71 % or so. The in vitro release of CS/HA-SLB NPs showed sustained release feature, and the NPs were stable in simulated gastric fluid with minimal release. The results of in vivo pharmacokinetic experiments showed CS/HA-SLB NPs had longer t l/2 and larger AUC than that of others group (Free SLB, HA-SLB NPs). Moreover, the intestinal loop absorption and in vivo drug distribution study exhibited that CS/HA-SLB NPs had better enhancement intestine absorption and liver targeting ability. In CCl 4 -induced liver fibrosis mice, CS/HA-SLB NPs group had a better anti-liver fibrosis effect than that of others group. Taken together, these findings suggested that CS-decorated silibinin prodrug self-assembled nanoparticles were expected to improve the bioavailability and anti-hepatic fibrosis effect of SLB.
研究领域:
药剂学
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纳米技术
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肝病学
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药物递送系统
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生物药剂学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jichen Yang,Huan Li,Xiaoli Wang,Chuanying Zhang,Guo Feng,Xin Peng
As a natural flavonolignan, silibinin is reported to possess multiple biological activities, while the inhibitory potential of silibinin on carbohydrate-hydrolyzing enzymes is still unclear. Therefore, in this study, the inhibitory effect and underlying mechanism of silibinin against α-amylase/α-glucosidase were investigated. The results indicated that silibinin showed a strong inhibitory efficiency against α-amylase/α-glucosidase in noncompetitive manners and exhibited synergistic inhibition against α-glucosidase with acarbose. However, interestingly, the inhibitory effect of silibinin was significantly hindered in various milk protein-rich environments, but this phenomenon disappeared after simulated gastrointestinal digestion of milk proteins in vitro. Furthermore, silibinin could combine with the inactive site of α-amylase/α-glucosidase and change the microenvironment and secondary structure of the enzymes, thereby influencing the catalytic efficiency of enzymes. This research suggested that silibinin could be used as a novel carbohydrate-hydrolyzing enzyme inhibitor, and milk beverages rich in silibinin had the potential for further application in antidiabetic dietary or medicine.
研究领域:
食品科学
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生物化学
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药理学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 4
·796-805
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IF 2.772
Song Xiaoyu,Liu Bo,Cui Lingyu,Zhou Biao,Liu Lu,Liu Weiwei,Yao Guodong,Xia Mingyu,Hayashi Toshihiko,Hattori Shunji,Ushiki-Kaku Yuko,Tashiro Shin-ichi,Ikejima Takashi
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is characterized by a cascade of pathologic changes. A widely discussed theory indicates that amyloid β (Aβ) peptides are the causative agents of AD. Silibinin, a flavonoid derived from milk thistle, is well known for its hepato-protective activities and we have reported the neuroprotective effects of silibinin. In this study, we investigated the role of estrogen receptors (ERs) in silibinin’s neuroprotective effect on Aβ 1−42 -injected rats. Results of Morris water maze and novel object-recognition tests demonstrated that silibinin significantly attenuated Aβ 1−42 -induced memory impairment. Silibinin attenuated ERs and PI3K-Akt pathways, as well as modulated mitogen-activated protein kinases in the hippocampus of Aβ 1−42 -injected rats. Taken together, silibinin is a potential candidate in the treatment of Alzheimer’s disease.
研究领域:
神经科学
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药理学
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DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2023
·
IF 2.7
Meiqing Mai,Ya Wang,Mengliu Luo,Zhongxia Li,Di Wang,Yongdui Ruan,Honghui Guo
Nonalcoholic steatohepatitis (NASH) represents an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD). The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome triggers pyroptosis, thus propelling the progression from simple steatosis to NASH. Silibinin, a hepatoprotective compound derived from milk thistle, exerts diverse hepatoprotective effects. However, the direct impact of silibinin on NLRP3 inflammasome activation and its ability to mitigate pyroptosis remain uncertain. To address this, we utilized an in vitro model of NASH, employing HepG2 cells treated with deoxycholic acid (DCA) and free fatty acids. Subsequently, we treated these model cells with silibinin for 24 h. Our findings demonstrated that, although there were no significant changes in cellular lipid content, silibinin effectively ameliorated hepatocyte injuries. Silibinin treatment inhibited the activation of the NLRP3 inflammasome and suppressed DCA-induced pyroptosis. Additionally, molecular docking analysis revealed that silibinin exhibited a binding affinity to components of the NLRP3 inflammasome similar to that of MCC950, a selective NLRP3 inhibitor. These results suggest that silibinin may alleviate inflammation in DCA-exposed HepG2 cells by mitigating pyroptosis, possibly through its binding affinity and inhibition of the NLRP3 inflammasome. Overall, our study indicates that silibinin holds promise as a therapeutic agent for NASH by modulating pyroptosis and inhibiting NLRP3 inflammasome activation.
研究领域:
药理学
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细胞生物学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2023
·
IF 2.3
Omidi-Shahsavandi M.,Yaghmaei P.,Ahmadian S.,Ebrahim-Habibi A.
Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
·
IF 4.389
Weiwei Wu,Lingling Wang,Siying Wang
In the present study, the silibinin (SLB) was loaded into porous starch (PS) in the form of nanoparticles (SNPS) by the liquid antisolvent precipitation (LAP) method, so as to improve its solubility and bioavailability. Firstly, the different experimental parameters on drug loading (DL) of the SLB in the LAP process were optimized through the single-factor experiments. Under the optimum conditions, the DL and the encapsulation efficiency (EE) of the SNPS were 9.49 ± 0.37 % and 89.93 ± 0.64 %, respectively. Compared with free SLB and SLB nanoparticles (SN), the SNPS had a higher solubility, and was about 180.81 ± 5.32 μg/mL in artificial gastric juice (AGJ) and was about 88.91 ± 4.14 μg/mL in artificial intestinal juice (AIJ), respectively. The in vitro release study demonstrated a slow and sustained ± release of SLB from the SNPS with the SN and free SLB as controls. The pharmacokinetic results showed that the C max and AUC (0–t) of the SNPS (87.71 ± 7.24 μg/L, 439.55 ± 8.76 μg/L*h) increased when compared with the SN (60.31 ± 8.98 μg/L, 206.51 ± 12.24 μg/L*h) and free SLB (26.08 ± 1.43 μg/L, 102.63 ± 7.15 μg/L*h), showing its ability to improve SLB’s pharmacokinetic properties.
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2019
·Vol. 44
·期 8
·1818-1829
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IF 2.782
Liu Bo,Liu Weiwei,Liu Panwen,Liu Xiumin,Song Xiaoyu,Hayashi Toshihiko,Onodera Satoshi,Ikejima Takashi
Excessive physical exercise (overtraining; OT) increases oxidative stress and induces damage in multiple organs including the brain, especially the hippocampus that plays an important role in learning and memory. Silibinin, a natural flavonoid derived from milk thistle of Silybum marianum , has been reported to exert neuroprotective effect. In this study, rats were subjected to overtraining exercise, and the protective effects of silibinin were investigated in these models. Morris water maze and novel object recognition tests showed that silibinin significantly attenuated memory defects in overtrained rats. At the same time, the results of Nissl, TUNEL and SA-β-gal staining showed that silibinin reversed neuronal loss caused by apoptosis, and delayed cell senescence of the hippocampus in the overtrained rats, respectively. In addition, silibinin decreased malondialdehyde (MDA) levels which is associated with reactive oxygen species (ROS) generation. Silibinin prevented impairment of learning and memory caused by excessive physical exercise in rats, accompanied by reduced apoptosis and senescence in hippocampus cells.
研究领域:
神经科学
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药理学
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运动生理学
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2017
·Vol. 38
·期 12
·1655-1662
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IF 3.223
Dong Xin-yue,Lang Tian-qun,Yin Qi,Zhang Peng-cheng,Li Ya-ping
Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 86
·54379-54390
·
IF 3.108
Weiwei Wu,Yuangang Zu,Lingling Wang,Li Wang,Yuanyuan Li,Yanjie Liu,Mingfang Wu,Xiuhua Zhao,Xinxin Zhang
Silibinin (SLB) is reported to possess multiple biological activities. However, due to its poor water solubility and poor absorption after oral administration, its clinical therapeutic effects have been limited. Thus, an experiment is designed to prepare SLB nanoparticles by the liquid antisolvent precipitation (LAP) technique to improve its solubility and bioavailability. Firstly, we applied single-factor experiments to investigate the effects of various factors on the mean particle size (MPS) of SLB nanoparticles in the LAP process, and the optimal conditions obtained were: HPMC concentration 3 mg mL−1, precipitation temperature 55 °C, SLB concentration 35 mg mL−1, antisolvent/solvent volume ratio 10, dropping speed 1 mL min−1, stirring speed 800 rpm and stirring time 5 min. A SLB nanosuspension with a MPS of 132.3 nm was obtained under the optimum conditions. The SLB nanoparticles were obtained by the freeze-drying method, and characterized using various analytical techniques such as SEM, FTIR, XRD DSC, and TG. The experimental data revealed that SLB nanoparticles were transformed into an amorphous form without changing the chemical structure, and had a higher solubility, and were about 36.9 mg mL−1 (free SLB was about 0.09 mg mL−1) in artificial gastric juice (AGJ) and about 59.71 mg mL−1 (free SLB was about 0.03 mg mL−1) in artificial intestinal juice (AIJ). The dissolution rate of SLB nanoparticles was also obviously higher than that of free SLB, and was about 48.2 times and 153.8 times that of free SLB in AGJ and in AIJ. Furthermore, the results of a bioavailability study in rats showed that the Cmax value of SLB nanoparticles (398.580 ng mL−1) was apparently higher than that of free SLB (26.070 ng mL−1), and the AUC (0 → t) value of SLB nanoparticles (965.666 ng mL−1 h−1) was about 6.48 times greater than that of free SLB (149.124 ng mL−1 h−1), so the SLB nanoparticles had a higher bioavailability than free SLB. The inhibitory effect of SLB nanoparticles on HepG2 cells was also higher by lower IC50 than that of free SLB. Taken together, the present study suggests that the SLB nanoparticles can become a new oral drug formulation with high bioavailability and produce a better response for its clinical applications.
研究领域:
药剂学
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药物化学
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生物医学
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产品关联
DOI
高影响因子
ACS Pharmacology & Translational Science
·
2023
·
IF 6
Baofei Yan,Xian Zheng,Yun Wang,Jingwen Yang,Xingyu Zhu,Mengmeng Qiu,Kexin Xia,Yongan Wang,Mian Li,Sipan Li,Xinai Ma,Jianjun Xie,Fengtao Li,Tingming Fu,Wei Li
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity that is typically characterized by intrahepatic ectopic steatosis. Nowadays, NAFLD has surpassed viral hepatitis and become the most common chronic liver disease worldwide, which poses a great threat to human health. Silibinin (Sil), a well-known natural product, has been widely used in clinical treatment for liver disorders and exhibited therapeutic potential for NAFLD. However, the suitability of Sil for NAFLD treatment still requires further investigation due to its limited absorption and low bioavailability. This study aimed to construct a Sil-loaded liposome (Sil-Lip) to overcome the limitations of Sil, thereby enhancing its beneficial effects on NAFLD and then investigate the underlying mechanisms of action of Sil-Lip. Herein, Sil-Lip was fabricated by a well-established thin-film dispersion method and carefully characterized, followed by evaluating their therapeutic efficacy using high-fat diet-induced NAFLD mice and free fatty acid -stimulated HepG2 cells. Then, liver transcriptome analysis and 16S ribosomal RNA (16S rRNA) sequencing were utilized to elucidate the potential mechanisms of action of Sil-Lip. Our data indicated that Sil-Lip harbored good gastrointestinal tract stability, mucus layer permeation, and excellent oral absorption and bioavailability. In vivo and in vitro NAFLD models demonstrated that Sil-Lip had better effects in alleviating lipid metabolism disorders, insulin resistance, and inflammation than did Sil alone. Further investigations revealed that the beneficial effects of Sil-Lip were mediated by modulating intrahepatic insulin resistance-related and nuclear factor-kappa B (NF-κB) signaling pathways and extrahepatic gut microbiota. Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.
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PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Feifei Han,Haiping Wang,Li Wang,Limei Fan,Sibei Peng,Xiaoying Hou,Xiji Shu,Binlian Sun,Yuchen Liu
Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excessive fat accumulation in the liver, is the most prevalent cause of chronic liver disease globally. The clinical use of pharmacological agents such as silibinin and sorafenib is limited due to poor water solubility, low bioavailability, and potential side effects, necessitating innovative therapeutic approaches.Methods In this study, we developed self-assembled, carrier-free microparticles of silibinin and sorafenib (SIL-SOR-MPs) using magnetic stirring and evaluated their therapeutic effects on MASLD both in vitro and in vivo.Results Compared to free SIL and free SOR, SIL-SOR-MPs significantly reduced lipid accumulation in HepG2 cells and effectively alleviated hepatic steatosis and liver damage in mice. Mechanistic investigations further showed that SIL-SOR-MPs more effectively down-regulated lipid synthesis genes and up-regulated genes involved in lipid oxidation.Discussion In summary, our study highlights that carrier-free SIL-SOR-MPs demonstrate the ability to reverse the progression of MASLD and present a promising therapeutic strategy.
研究领域:
药理学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2019
·
IF 2.635
Panwen Liu,Lingyu Cui,Bo Liu,Weiwei Liu,Toshihiko Hayashi,Kazunori Mizuno,Shunji Hattori,Yuko Ushiki-Kaku,Satoshi Onodera,Takashi Ikejima
Alzheimer's disease (AD) is a neurodegenerative disease, mainly characterized by cognitive dysfunction and memory impairment. Due to its pathological similarities to type 2 diabetes mellitus (T2DM), such as β-amyloid deposition, oxidative stress, inflammation, disordered glucose metabolism, impaired signaling pathways of insulin and insulin-like growth factor-1 (IGF-1), we speculate that AD is another form of brain diabetes. Clarifying the relationship between T2DM and AD is important for us to better understand the exact pathological mechanisms of AD. Silibinin, a polyphenolic flavonoid extracted from the seeds of Silybum marianum , exerts hepatoprotective, anti- diabetic and neuroprotective effects. Streptozotocin (STZ), which is used to disrupt the insulin signal transduction pathway, could well mimic the sporadic AD models by intracerebroventricular (ICV) injection. Therefore, we selected ICV injection of STZ (ICV-STZ) to investigate the neuroprotective effects of silibinin in rats and to make a foundation for further exploring the relationship between AD and T2DM. ICV-STZ obviously caused memory damage, sharply reduced the number of nissl bodies and destroyed morphological structure of hippocampal neuronal cells, while silibinin attenuated the damages. Moreover, silibinin significantly decreased STZ-induced tau hyperphosphorylation (ser404) in hippocampus and cerebral cortex, markedly inhibited apoptosis of neurons induced by STZ, and up-regulated insulin signal transduction pathway. Silibinin exerts neuroprotective effect in STZ-treated rats, indicating the potential of silibinin for the treatment of AD patients with T2DM in future.
研究领域:
神经科学
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药理学
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内分泌学
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分子生物学
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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）