JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Jiaoxiang Chen,Xin Gan,Shenkai Su,Sizhe Jiao,Zailing Gong,Ziqiang Liu,Xiaopei Wu,Jun Jiang,Jiaming Zhang,Junlai Wan
Intervertebral disc degeneration (IVDD) is a multifaceted and complex condition primarily driven by excessive inflammation, degradation of the extracellular matrix (ECM), and dysfunction of nucleus pulposus cells (NPCs). Despite extensive exploration of various therapeutic agents targeting IVDD, their efficacy remains disappointingly limited. This study underscores the efficacy of ginkgetin (GK), a natural bioflavonoid with potent anti-inflammatory properties, in mitigating inflammation as well as ECM degradation and NPC dysfunction triggered by interleukin-1β (IL-1β). However, GK alone cannot fully address the persistent obstruction in autophagic flux induced by IL-1β. To overcome this limitation, an innovative MMP13-responsive nanoplatform was developed, orchestrating the sequential delivery of GK and rapamycin (RA), targeting distinct phases of IVDD progression. In this design, GK is progressively released from exosomes during the initial phase, while RA is released from mesoporous silica nanoparticles during the mid-phase to enhance autophagic flux. This staged release approach leverages the strengths of both agents, addressing inflammation and restoring autophagy more effectively. In vivo experiments confirmed the substantial therapeutic benefits of this staggered delivery strategy in IVDD. The engineered MMP13-responsive nanoplatform represents a significant advancement in controlled, sequential drug delivery systems, offering a promising therapeutic avenue to effectively regulate inflammation and autophagy, thereby ameliorating IVDD.
研究领域:
医学
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生物材料学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Liangrong Wu,Chenchen Qian,Weiqi Zhang,Mengyun Shi,Xiuxiu Chen,Yi Wang,Feng Lin
Background Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). Hypothesis/Purpose OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. Methods The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo . Results We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo . Conclusion Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.
研究领域:
肿瘤学
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药理学
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分子生物学
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中药学
✓ 已验证
产品关联
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
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2017
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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
Acta Biomaterialia
·
2022
·
IF 10.633
Yang Wang,Yunfei Yi,Jie Yao,Haoqiang Wan,Mian Yu,Lanlan Ge,Xiaobin Zeng,Meiying Wu,Lin Mei
Doxorubicin (DOX) widely used in hepatocellular carcinoma (HCC) can induce serious side effects and drug resistance. Herein, we aimed to seek a strategy to improve the efficacy and reduce the side effects of DOX in HCC based on an autophagy inducer drug called isoginkgetin (ISO). The design of multifunctional nanocarriers based on hyaluronic acid-conjugated and manganese-doped mesoporous silica nanoparticles (HM) for the co-delivery of antitumor drugs against HCC provided an effective and promising antitumor strategy. Our results showed that [email protected] @DOX could efficiently inhibit HCC cell proliferation through activating autophagy through AMPKa-ULK1 pathway. Moreover, intravenous injection of [email protected] @DOX significantly suppressed HCC tumor progression in nude mouse HCC model. Collectively, our findings revealed an anti-HCC mechanism of [email protected] @DOX through autophagy and provide an effective therapeutic strategy for HCC. Statement of significance In our study, we constructed a co-delivery system by loading ISO and DOX in the mesoporous channels of manganese-doped mesoporous silica nanoparticles, which could be further conjugated with hyaluronic acid to obtain [email protected] @DOX. The nanocarriers had been demonstrated to be biodegradable under the acidic and reducing tumor microenvironment, as well as to possess the tumor targeting capability via the conjugated hyaluronic acid. In addition, [email protected] @DOX enhanced the therapeutic efficacy against human HCC tumor through the combinatorial therapies of chemotherapeutics, Mn 2+ -mediated chemodynamic therapeutics and autophagic cell death, which might be achieved through AMPK-ULK1 signaling. This work revealed that such a nanomedicine exhibited superior tumor accumulation and antitumor efficiency against HCC with extremely low systemic toxicity in an autophagy-boosted manner.
研究领域:
肿瘤学
·
药学
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纳米技术
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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