International Journal of Analytical Chemistry
·
2020
·
IF 1.678
Zhenzhen Ying,Jingyao Wei,Ruijuan Liu,Fang Zhao,Yifang Yu,Xin Tian
Osimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and minimize adverse reactions. In the present study, a highly sensitive UPLC-MS/MS method was established and validated for analysis of osimertinib in rat plasma according to US FDA guideline. Separation was performed on a C18 (2.1 × 50 mm, 2.6 μm) column using a gradient elution of ammonium formate (10 mM) with 0.1% formic acid buffer (A) and ACN (B) at a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization in the MRM mode. The method was validated over a concentration range of 1–400 ng/mL for osimertinib. The intra- and interday accuracy and precision values were within ±15%. No significant degradation occurred under the experimental conditions in stability assays. There was a further investigation on the effects of multiple doses of ginsenoside Rg3 on the pharmacokinetics of osimertinib in rats for the first time. The results implied that osimertinib exhibited a slow absorption and moderate-rate elimination in rats following oral administration. Coadministeration with ginsenoside Rg3 (5 mg/kg, 7 days, i.g.) may have no effect on the pharmacokinetics of osimertinib in rats. The results provide a reference for the clinical concomitant medications of Rg3 and osimertinib.
研究领域:
药物分析
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2025
·
IF 8.1
Zheng Zhang,Jiaxing Wang,Xiaofang Li,Lingzhou Zhao,Junwei Zhao,Mengjiao Su,Xiangxiang Wu,Huahui Zeng
Celastrol (Cel) is a potential anticancer therapeutic candidate, but its limited practical applicability is due to its low solubility, poor tumor selectivity, and cytotoxicity. Clinically, ginsenoside Rg3 (RG3) is typically combined with chemotherapy to enhance antitumor effects and reduce side effects. Herein, we developed novel pH-sensitive prodrug nanoparticles (NPs) containing RG3 and Cel for the synergistic treatment of pancreatic cancer (PC). Amphiphilic prodrug, a PEGylated chitosan oligosaccharide coupled with RG3 via Schiff base bond, was self-assembled with hydrophobic Cel into NPs with drug loadings of 2.12% (Cel) and 1.63% (RG3). NPs exhibited a suitable particle size of 124.01 nm, zeta potential of −39.89 mV and good physical stability. In addition, NPs also showed a controlled drug release when the Schiff base bonds were hydrolyzed in the acidic environment. In Pan02 tumor-bearing mice, NPs exhibited a high accumulation in tumor tissues and prolonged blood circulation time. Furthermore, NPs could more effectively inhibit tumor growth and reduce systemic toxicity, compared with the free Cel, RG3, prodrug, and Cel + RG3. The results indicated that the NPs could provide a safe and promising nanoplatform for PC therapy.
CAS / MDL:
研究领域:
药剂学
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 8
·2001-2009
·
IF 3.641
Ma Jun,Yu Da-Hai,Zhao Di,Huang Teng,Dong Min,Wang Ting,Yin Hai-Tao
Radiotherapy is an effective anti-cancer therapy for patients with non-small cell lung cancer (NSCLC), however, the prognosis is unsatisfactory owing to radio-resistance and toxicity. It is crucial to improve radiotherapy efficacy. Ag nanoparticles (NPs) and ginsenoside Rg3 (Rg3) exerted
antitumor and radio-sensitization effects. Therefore, we investigated whether poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG)-Rg3-Ag will function as a noninvasive, tracing, radiotherapy sensitizer. The morphology of NPs was visualized with transmission electron microscopy (TEM).
The drug loading content, encapsulation efficiency, and cumulative drug release of Rg3 was determined by HPLC. Cellular uptake of NPs in A549 and SPCA-1 was measured by immunostaining. The radio-sensitization effect of PLGA-PEG-Rg3-Ag in vitro was determined in A549 by detecting proliferation,
colony formation, and apoptosis with CCK-8, clonogenic survival assay, and flow cytometry, while in vivo was determined in nude mice by testing the body weight and tumor volume. PLGA-PEG-Rg3-Ag exerted radio-sensitization effect by reducing cell proliferation and colony formation while
enhancing cell apoptosis in A549; reduced tumor volume in nude mice. PLGA-PEG-Rg3-Ag exhibits radio-sensitization effects in NSCLC.
研究领域:
肿瘤学
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药剂学
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放射治疗学
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Tianhua Liu,Ling Zuo,Dongqing Guo,Xinlou Chai,Jie Xu,Zhaorui Cui,Zhiyi Wang,Chunying Hou
Lung cancer is the leading cause of cancer-related deaths. Ginsenoside Rg3 is the main ingredient of Ginseng which is used to treat non-small cell lung cancer (NSCLC). It has been found to enhance the efficiency of chemotherapy thereby reducing its side effects. Previous studies found that ginsenoside Rg3 can reduce the occurrence of NSCLC by inducing DNA damage. Yet, its anti-DNA damaging effects and mechanisms in tumor cells are still not fully understood. This study explored the effect of ginsenoside Rg3 on DNA repair and VRK1/P53BP1 signaling pathway. Ginsenoside Rg3 treatment significantly decreased the incidence and invasionin a mouse model of lung cancer induced by urethane. The results of cell survival assay and single cell gel electrophoresis showed that ginsenoside Rg3 protected lung adenocarcinoma cells from DNA damage as well as inhibited the proliferation of tumor cells. Ginsenoside Rg3 increased the mRNA and protein expression of VRK1 in NSCLC cells as measured by RT-qPCR and western blot, respectively. These findings suggests that ginsenoside Rg3 regulates VRK1 signaling. Immunofluorescence assays showed that P53BP1 and VRK1 protein level increased, and the VRK1 protein translocated between the nuclei and cytoplasm. Finally, this conclusion was confirmed by the reverse validation in VRK1-knockdown cells. Taken together, these results show that ginsenoside Rg3 upregulate VRK1 expression and P53BP1 foci formation in response to DNA damage thereby inhibiting the tumorigenesis and viability of cancer cells. These findings reveal the role of Rg3 in lung cancer and provides therapeutic targets for developing new drugs in the prevention and treatment of lung cancer.
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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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2022
·Vol. 102
·期 10
·4140-4150
·
IF 4.125
Huan Liu,Xueyi Hu,Lei Li,Xinyu Meng,Yun Fang,Yongmei Xia
BACKGROUND Unsaturated fatty acids used to form unstable micro-vesicles, while conjugate linoleic acid (CLA)-sodium dodecyl sulfate (SDS) can self-assembly to stable nano-conjugate linoleic acid vesicles (nano-CLAVs). Generally, micro-capsule could geometrically provide higher loading capacity but also generate concerns in construction convenience, sustained release, bioaccessibility and stability. Hence there is a contradiction between loading capacity and encapsulation efficiency. Therefore, the study of the factors that decide the capsule size falling in nano or micron size with same capsule material would be a benefit to food or drug delivery science. RESULTS The micron- and nano-CLAVs were constructed for encapsulation and sustained release of ginsenoside Rg3. The formation mechanism of nano or micron capsule,s the effect of vesicle sizes on encapsulation efficiency, drug loading efficiency and stability of the encapsulated Rg3 were investigated. It was found that with the addition of salt (PBS), the size of CLAVs jumped from nano to micron. Furthermore, the salt concentration is the key factor that decides the vesicle size of nano or micron. The pH at fabrication triggers the vesiculation and dramatically affects the vesicle size over the nano and micron scales. CONCLUSION Compared to the nano-CLAVs, micron vesicles enhanced the loading capacity to 137.6% and the encapsulation efficiency to 138.4%, respectively. Meanwhile, the micron-CLAVs performed similar sustained release of Rg3 as the nano-CLAVs did, and was stable for 120 days at room temperature or sustained 98.9% of capsules after centrifuge at 6090 × g for 20 min. © 2022 Society of Chemical Industry.
研究领域:
食品科学
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药物递送
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 81
·期 7
·875-884
·
IF 1.902
Xiaonan Zhang,Fenglan Huang,Xiaoyong Chen,Xiaoqing Wu,Jinyu Zhu
Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng , can regulate autophagy via AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. AMPK/mTOR signaling and autophagy have been reported to be involved in osteogenesis. Here, the effect of Rg3 on ovariectomy (OVX)-induced osteoporosis is explored. In vivo, rats were treated with 20 mg/kg Rg3 after OVX and the body weight (BW) was monitored. Bone mineral density (BMD), hematoxylin–eosin staining of femur tissues, osteogenesis, autophagy, and AMPK/mTOR signaling were analyzed. In vitro, MC3T3-E1 cells were treated with 0, 1, 5, 10, 20, and 100 μmol/L Rg3. 10 and 20 μmol/L Rg3, which had no significant effect on cell viability and significantly affected AMPK/mTOR signaling, were chosen for further analysis. Then osteogenic differentiation was induced with Rg3 or/and AMPK inhibitor (Compound C). AMPK/mTOR signaling, autophagy, osteogenic differentiation, and mineralization by Alizarin Red staining were analyzed. The expression or activity of AMPK/mTOR signaling-related proteins, autophagy markers, and osteogenesis markers was measured by western blotting or commercial kits, and cell viability by cell counting kit-8 assay kits. Rg3 significantly alleviated OVX-induced BW increases, BMD declines and histological changes of femur tissues, promoted osteogenesis, autophagy, and AMPK signaling, but inhibited mTOR signaling in vivo. Moreover, Rg3 significantly enhanced AMPK signaling, autophagy, osteogenic differentiation, and mineralization, but suppressed mTOR signaling in vitro. However, Compound C significantly reversed Rg3-induced alterations in vitro, indicating that Rg3 regulated autophagy, osteogenic differentiation, and mineralization via AMPK/mTOR signaling. Hence, it was speculated that Rg3 might attenuate OVX-induced osteoporosis via AMPK/mTOR signaling pathway.
研究领域:
药理学
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内分泌学
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骨科
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2016
·Vol. 68
·期 1
·1-13
·
IF 2.363
Li Jianying,Hu Meina,Xu Huan,Yu Xiu,Ye Feifei,Wang Kaiqian,Luan Xiaojiao,Li Ling,Zhang Di
ObjectivesTo improve stability and shelf life, lyophilized formulations of 20(R)-Ginsenoside Rg3 liposomes (G-Rg3-Ls) were prepared.MethodsGlucose, trehalose, sucrose, maltose, lactose, mannitol, inositol, hydroxypropyl-β-cyclodextrin and polyethylene glycol were used as single lyoprotectant and then compared in terms of their ability to protect lyophilized G-Rg3-Ls. Further, a glucose–mannitol complex was used to determine the optimal lyophilized preparation. The analysis of lyophilized liposomes or lyoprotectant was further investigated by scanning electron microscopy, thermogravimetry-differential thermal analysis, X-ray diffractometry and Fourier transform infrared spectroscopy. Cytotoxicity assay was used to assess the cyto-inhibition of freshly prepared and lyophilized liposomes.Key findingsWhen the ratio of glucose–mannitol to phospholipids was 4 : 2 : 1 (w/w) the lyophilized G-Rg3-Ls exhibited good appearance, high DRR (86.52% ± 5.02%), small change in particle size (45.83 ± 0.50%) and short rehydration reconstruction time (8.3 ± 1.5 s). All indices were considerably better than those of each single protective agent. Results indicated that when the two lyoprotectants were combined, the stabilizing effect of glucose and shaping effect of mannitol were well maintained. The cyto-inhibition of freshly prepared and lyophilized G-Rg3 liposomes showed that lyophilization did not affect the bioactivity of G-Rg3.ConclusionsThe application of glucose–mannitol composite lyoprotectants can obtain a good G-Rg3 lyophilized preparation.
研究领域:
药学
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药理学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xufan Cai,Zhaohong Wang,Shengzhang Lin,Hui Chen,Heqi Bu
Background Vasculogenic mimicry (VM) is an angiogenesis-independent process that potentially contributes to the poor clinical outcome of anti-angiogenesis therapy in multiple malignant cancers, including pancreatic adenocarcinoma (PAAD). Several studies have shown that ginsenoside Rg3, a bioactive component of ginseng, holds considerable potential for cancer treatment. Our previous work has proved that Rg3 can inhibit VM formation in PAAD. However, its underlying mechanism remains unclear. Purpose To explore the underlying mechanism by which Rg3 affects VM formation in PAAD. Methods We first investigated the effects of Rg3 on the cellular phenotypes of two PAAD cell lines (SW-1990 and PCI-35), and the expression of EMT- and stemness-related proteins. SW-1990 cells were adopted to construct xenograft models, and the anti-tumor effects of Rg3 in vivo were validated. Subsequently, we isolated the exosomes from the two PAAD cell lines with Rg3 treatment or not, and explored whether Rg3 regulated VM via PAAD cell-derived exosomes. MiRNA sequencing, clinical analysis, and rescue experiments were performed to investigate whether and which miRNA was involved. Subsequently, the target gene of miRNA was predicted using the miRDB website ( https://mirdb.org/ ), and rescue experiments were further conducted to validate those in vitro and in vivo . Results Rg3 indeed exhibited excellent anti-tumor effects both in vitro and in vivo , with inhibitory effects on EMT and stemness of PAAD cells. More interestingly, Rg3-treated PAAD cell-derived exosomes suppressed the tube-forming ability of HUVEC and PAAD cells, with a decrease in stemness-related protein expression, indicating that Rg3 inhibited both angiogenesis and VM processes. Subsequently, we found that Rg3 induced the up-regulation of miR-204 in PAAD cell-derived exosomes, and miR-204 alone inhibited tube and sphere formation abilities of PAAD cells like exosomes. Specifically, miR-204 down-regulated DVL3 expression, which was involved in regulating cancer cell stemness, and ultimately affected VM. The in vivo experiments further indicated that Rg3-treated SW-1990 cell-derived exosome-inhibited tumor growth, VM formation, and stemness-related protein expression can be abrogated by DVL3 overexpression. Conclusion Ginsenoside Rg3 increased the PAAD cell-derived exosomal miR-204 levels, which subsequently inhibited its target genes DVL3 expression in the receptor PAAD cells, and the down-regulated DVL3 broke stemness maintenance, ultimately suppressing VM formation of PAAD. Our findings revealed a novel mechanism by which Rg3 exerted its anti-tumor activity in PAAD via inhibiting VM, and provided a promising strategy to make up for the deficiency of anti-angiogenesis therapy in cancer.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 7
·1077
·
IF 4.8
Xinyi Lv,Yuehan Song,Tianhua Liu,Dingdan Zhang,Xinpeng Ye,Qingqing Wang,Rongrong Li,Jiayi Chen,Shujing Zhang,Xue Yu,Chunying Hou
Background : Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, there is an urgent need to find strategies to increase their efficacy and reduce the incidence of drug resistance. Methods : In this study, we examined the distribution and probability of EGFR mutations in non-small cell lung cancer patients in the cBioPortal database and compared the survival prognosis of patients with normal and abnormal EGFR, NSCLC patients treated with and without TKI, and NSCLC patients with different EGFR gene copy numbers. We established a mouse lung cancer model and examined the histomorphological characteristics of lung tissues via hematoxylin and eosin staining. Additionally, changes in the copy number of the EGFR gene and its protein expression levels were detected using RT-qPCR and Western blotting. Furthermore, we quantified the concentration of the EGFR protein using ELISA. Results : We found no significant advantage of EGFR-TKI therapy over first-line chemotherapeutic agents in patients with EGFR-abnormal NSCLC. The reason for this may be related to the abnormal EGFR gene copy number; the higher the copy number increases, the worse the survival prognosis of the patients. In molecular biology experiments, we demonstrated that ginsenoside Rg3 down-regulated the copy number of 18, 19, 20, and 21 exons and protein expression of EGFR in lung adenocarcinoma cells. The results of in vivo pharmacodynamic assays confirmed that sequential administration of ginsenoside Rg3 with TKI drugs could achieve a gainful complementary effect. Conclusions : Ginsenoside Rg3 down-regulates the copy number of EGFR important exons in EGFR-mutant cells of lung adenocarcinoma and reduces EGFR protein expression, thus providing a high gainful complementary effect in combination with EGFR-TKI.
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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遗传学
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药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xusen Wang,Pengyu Wei,Cewen Hu,Huajing Zeng,Zengjie Fan
During the process of wound healing, the stimulation of inflammatory factors often leads to abnormal proliferation of blood vessels and collagen, ultimately resulting in scar formation. To address this challenge, we fabricate a novel dermal extracellular matrix (DECM) hydrogel scaffold loaded with ginsenoside Rg3 (Rg3) using 3D printing technology. Mesoporous silica nanoparticles (MSNs) are introduced into the system to encase the Rg3 to control its release rate and enhance its bioavailability. We systematically evaluate the biological, physicochemical, and wound healing properties of this scaffold. In vitro studies demonstrate that the hydrogel exhibits excellent biocompatibility and solid-like rheological properties, ensuring its successful printing. In vivo studies reveal that the composite hydrogel scaffolds effectively accelerate wound healing and achieve scar-free wound healing within three weeks. Histological and immunohistochemical (IHC) analyses show that the composite hydrogel scaffolds reduce the inflammatory response and inhibit excessive collagen accumulation. These combined effects underscore the potential of our approach in effectively inhibiting scar formation.
研究领域:
生物医学工程
·
组织工程
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伤口愈合
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Weili Yang,Min Cao,Wenxin Wang,Ningning Diao,Xiaowei Liu,Yue Hu,Xinxin Wang,Tianying Sun,Chunjing Guo,Daquan Chen
The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the “one stone, three birds” strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.
研究领域:
药学
·
材料科学
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生物医学工程
·
伤口护理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2016
·
IF 2.618
Xiaonan Zhang,Kang Chen,Bo Wei,Xingwang Liu,Zeming Lei,Xizhuang Bai
Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX)-induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone-alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy.
研究领域:
药理学
·
骨科
·
分子生物学
✓ 已验证
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）