COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
·
IF 5.6
Wenbin Nan,Hao Wang,Linxiao Li,Jiulong Du,Xiangjuan Wei,Dongmei Wang,Yan Yang,Yongxue Wang,Dan Ding,Hongli Chen
The persistence of non-healing diabetic wounds is frequently attributed to excessive inflammation and bacterial infections. Therefore, strategies that target the reduction of inflammation while simultaneously inhibiting bacterial proliferation may offer an effective approach to overcoming this clinical challenge. In this study, we have developed an innovative formulation of hyaluronic acid (HA)-based dissolving microneedles (Cu(II)-PDA/ORI MNs) that incorporate oridonin (ORI) and Cu(II)-PDA nanoparticles, specifically designed for the treatment of chronic wounds in diabetic murine models. Our findings demonstrate that the composite MNs exhibit robust mechanical properties, facilitate drug delivery to the deeper layers of the skin, and exhibit favorable cytocompatibility and hemocompatibility. The encapsulation of ORI within the MNs effectively modulates the phenotype of RAW264.7 macrophages and exhibits significant anti-inflammatory properties, thereby contributing to the reduction of excessive inflammation within the wound microenvironment. Cu(II)-PDA nanoparticles significantly mitigate the toxicity associated with Cu(II) while retaining substantial antibacterial efficacy. Furthermore, they effectively promote wound angiogenesis, thereby expediting the wound healing process. Consequently, these Cu(II)-PDA/ORI MNs emerge as promising candidates for multifunctional wound dressing applications.
研究领域:
生物医学工程
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 8
·4480-4493
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IF 4.486
Linhao Xu,Yanli Bi,Yizhou Xu,Zhuocheng Zhang,Wenjie Xu,Sisi Zhang,Jian Chen
Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E-cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition (EMT) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety.
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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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2016
·
IF 0
Lifei Zhu,Miao Li,Xiaoyan Liu,Lina Du,Yiguang Jin
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic- co -glycolic)acid (PLGA) large porous microparticle (LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.
研究领域:
药学
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肿瘤学
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药物递送系统
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呼吸科医学
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产品关联
DOI
PubMed
Oncology Letters
·
2017
·Vol. 15
·期 1
·1362-1372
·
IF 1.39
Chun‑Yu Li,Qi Wang,Shen Shen,Xiao‑Lu Wei,Guo‑Xia Li
Epithelial‑mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti‑metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16‑F10 melanoma cells. The transforming growth factor‑β1 (TGF‑β1)‑induced EMT was also inhibited in ORI‑treated cells, as reflected in the upregulation of E‑cadherin, and downregulation of vimentin and Snail. Similar results were observed in A375 and B16‑F10 melanoma cells treated with ORI. Furthermore, pre‑treatment with ORI blocked the TGF‑β1‑induced phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt)/glycogen synthase kinase (GSK)‑3β signaling pathway activation. These effects mimicked PI3 kinase inhibitor LY294002 treatment. ORI interfered with the PI3K/Akt/GSK‑3β pathway, and reversed TGF‑β1‑induced EMT, which suppressed the invasion and metastasis of melanoma cells. Taken together, the present study demonstrated that ORI inhibits melanoma cells migration, invasion, and adhesion and TGF‑β1‑induced EMT through the PI3K/Akt/GSK‑3β signaling pathway. These findings suggest that ORI is a promising anti‑metastasis agent for melanoma.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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