Asian Journal of Pharmaceutical Sciences
·
2013
·
IF 0
Ting Yuan,Lingzhen Qin,Zhouhua Wang,Jinyuan Nie,Zhefei Guo,Ge Li,Chuanbin Wu
Solid dispersion of calcitriol with lipophilic surfactants and triglycerides was developed by melt-mixing method to modify the release and enhance stability of the drug. The solid dispersions were characterized by differential scanning calorimetry (DSC), hot stage polarized optical microscopy (HSPM), infrared spectroscopy (FTIR) and stability studies. The solid dispersion significantly enhanced the stability of calcitriol, which could be attributed to the high antioxidant activity of the solid lipid dispersion. The rapid dissolution rate from the solid dispersion was attributed to the amorphous or solid solution state of drug with improved specific surface area and wettability than the drug crystals. Therefore, solid dispersion of calcitriol with d -a-tocopheryl polyethylene glycol 1000 succinate (TPGS) offers a good approach to modify the release and enhance stability of calcitriol. The influence of lipophilic solid dispersion on drug bioavailability needs further investigation.
研究领域:
药剂学
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药物化学
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产品关联
DOI
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2020
·
IF 2.169
Xiao Yue,Yingtong Cui,Ting Yuan,Zhengwei Huang,Ying Huang,Xuejuan Zhang,Chen Wang,Guanlin Wang,Ruifeng Liang,Chunxia Liu,Xin Pan,Chuanbin Wu
Calcitriol, as the biologically active form of vitamin D3, is essential for patients with renal osteopathy. The solubilization, stabilization, and content uniformity are key issues in its formulation development. In our previous study, the incomplete release of calcitriol was solved by using the hybrid lipid-based solid dispersion (SD) for calcitriol. However, good stability and content uniformity are still urgently needed. In this study, solid lipid with antioxidant properties and liquid lipid compatible with calcitriol were employed as hybrid lipid carrier (HLC) to establish a solid dispersion. Moreover, the content uniformity of tablets with hybrid lipid carrier based SDs (HLCTs) was further guaranteed due to the multi-dispersion of calcitriol in HLC, solidification, and blank granules. Additionally, the compression of the blank granules was adjusted by the water content. The mixing method of calcitriol-containing and blank granules was also optimized. The obtained HLCTs were evaluated for hardness, disintegration time, in vitro drug dissolution, content uniformity, and stability. Satisfactory HLCTs were developed successfully in this study with superior content uniformity and better stability than the commercial soft capsule (Rocaltrol®). It was proved to be a promising formulation for drugs with poor water-solubility, instability to oxygen and heat, and dose-related toxicity.
研究领域:
药剂学
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生物医学工程
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DOI
PubMed
高影响因子
APPLIED CLAY SCIENCE
·
2021
·
IF 5.467
Xingchen Wang,Huilin Song,Siyu Hou,Yuqi Zhang,Xi Luo,Guanwei Tao,Feng Zheng,Shunli Ji
An environmentally friendly, simple and reliable method to quantify calcitriol in soft capsules was developed. Calcitriol with strong physiological activity has a low content (1.55 μg·g −1 ) in calcitriol soft capsules. Due to the poor stability of calcitriol, a large amount of medium chain triglycerides (>99.99%) need to be used as excipients to protect it. Herein, to achieve accurate quantification of the active ingredients in the calcitriol soft capsules, removing the interference of fat-soluble matrix is the main challenge. This experiment developed a cost-effective solid-phase extraction (SPE) clean-up method based on natural kaolinite (Kaol), which is followed by liquid chromatography coupled with Photodiode array detector (HPLC-DAD) analysis. In the self-made Kaol-SPE, calcitriol could remain on the Kaol sorbent (Al 2 O 3 : 39.5%, SiO 2 : 46.5% and H 2 O: 14.0%) by polar interactions, n-π interaction and lewis acid base interaction, whereas the hydrophobic medium chain triglycerides could be sufficiently washed off by n-hexane. Thus, the selective extraction of calcitriol and clean-up of fat-soluble matrix were achieved. Kaol was characterized by Fourier transform infrared spectrometry, scanning electron microscopy, transmission electron microscopy , X-ray diffraction and nitrogen adsorption-desorption. Adsorption isotherms were determined to infer the adsorption mechanism and adsorption capacity of calcitriol on Kaol. The fitting results showed that it was followed Langmuir model and the maximum adsorption capacity was 5.495 mg·g −1 (fast adsorption rate, 1 min). Various parameters such as SPE cartridges, Sorbent dosage (20–120 mg), washing solvent, eluting solvent and its volume (0.2–4.0 mL) were investigated. Under optimized conditions, good linear range was 0.15–2.99 μg∙g −1 . Recoveries is satisfactory (98.15–101.64%), and the relative standard deviations (RSDs) are only 1.22%. Minor matrix effect was 96.72%, which was excellent. Moreover, low quantitation limit (LOQ) of calcitriol is 0.015 μg·g −1 . This method was further validated to determine the content of calcitriol in different batches of commercial calcitriol capsules. The method can directly process diluted samples without liquid-liquid extraction, and has the feature of automation. Thus, this work provides a simple, convenient and economical platform for the determination of calcitriol in complex matrices on a large scale and promotes natural-based materials in pharmaceutical analysis field.
研究领域:
药物分析
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环境科学
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2021
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IF 3.935
Huilin Song,Xingchen Wang,Siyu Hou,Yuqi Zhang,Xi Luo,Tengfei Li,Shunli Ji
Calcitriol is an active product of vitamin D produced by the liver and kidney hydroxylase metabolism with strong physiological activity. It is the preferred form of medicine for patients with insufficient bone mineralization due to chronic kidney disease. Calcitriol soft capsule is one of the common preparation forms, the main drug content of which is very low (1.55 μg g −1 ), and the pharmaceutical excipients interfere greatly, especially the oily matrix medium-chain triglycerides. Therefore, removing the interference of oily matrix is the main challenge in the content determination. At present, the commonly used sample purification method for the determination of calcitriol in soft capsules is liquid-liquid extraction, but it usually consumes a lot of toxic organic solvents and it is costly. The adoption of SPE purification method, on the one hand, requires specific experimental equipment, and on the other hand, the organic solvent used in the experiment may cause the dissolution of SPE column tube materials, which will interfere with the subsequent detection. Herein, in order to achieve a cost-effective and reliable determination of calcitriol soft capsule content, we developed a dispersive solid-phase (DSPE) extraction method that directly uses irregular silica as sorbent , which is followed by high-performance liquid chromatography equipped with a UV detector(HPLC-UV)analysis. Selective retention of calcitriol is achieved by the polar interaction between calcitriol and silica, what’s more, sufficient contact between washing solvent and sorbent can be guaranteed. Therefore, after pretreatment with DSPE, the interference of oily matrix on detection can be mostly removed and then improve the accuracy of the method compared to the SPE method. Under the optimal conditions of DSPE, calcitriol showed a good linear relationship in the range of 0.15−2.99 μg g −1 , the R 2 was 0.997. Satisfactory recoveries ranging from 101.1%–102.0% for calcitriol were achieved in the oily matrix at the levels of 0.75, 1.50 and 2.24 μg g −1 . And the intra-day and inter-day RSD were less than 2.5 % and 3.2 %. Meanwhile, the LOD and LOQ of calcitriol was 0.01 μg g −1 and 0.02 μg g −1 , which is in full compliance with the regulatory level fixed by the EU, China or other countries. This method was further verified to determine the content of calcitriol in commercial calcitriol soft capsules and the recoveries of three batches of products was 86.2 %–94.4 %. Based on these characteristics, the proposed method makes it possible to determine the low content of weakly polar drugs in the oily matrix in a simple, low-cost and reliable way.
研究领域:
药学
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分析化学
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DOI
高影响因子
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
·
2025
·
IF 2.4
Jingjing Lu,Dongxuan Wang,Hongjin Huo,Hao Jiang,Wei Wei,Jie Sun,Fei Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high metastatic potential and limited therapeutic options. This study investigates the effects of calcitriol, an active metabolite of vitamin D, on TNBC progression by targeting the vitamin D receptor (VDR)-mediated hypoxia-inducible factor-1α (HIF-1α) axis. We established in vivo TNBC xenograft models using 4T1 cells and in vitro models with MDA-MB-231 and 4T1 cells overexpressing HIF-1α. Results showed that calcitriol inhibited lung metastasis and downregulated glycolytic activity in TNBC xenografts without affecting primary tumor growth. In vitro, calcitriol reduced cell viability, migration, and invasion by suppressing HIF-1α expression. It also decreased glucose uptake, lactate production, and ATP levels while downregulating key glycolytic regulators. VDR knockdown abolished these effects, confirming VDR as the critical mediator. Our findings suggest that calcitriol exerts anti-metastatic effects in TNBC by modulating the VDR-HIF-1α axis, inhibiting glycolysis, and suppressing the epithelial-mesenchymal transition. This study highlights the potential therapeutic role of calcitriol in TNBC treatment by targeting both metabolic reprogramming and invasive capacity. Future research should further explore the mechanisms underlying calcitriol-mediated HIF-1α suppression and its clinical application in TNBC.
研究领域:
肿瘤学
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分子生物学
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内分泌学
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癌症代谢
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转化医学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 7
·1-18
·
IF 8.1
Wang Sikai,Cheng Hongxia,Li Miaomiao,Gao Dongmei,Wu Haoran,Zhang Shanshan,Huang Yilan,Guo Kun
An increasing evidence supports that cell competition, a vital selection and quality control mechanism in multicellular organisms, is involved in tumorigenesis and development; however, the mechanistic contributions to the association between cell competition and tumor drug resistance remain ill-defined. In our study, based on a contructed lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obvious competitive growth dominance over sensitive cells through reprogramming energy metabolism. Mechanistically, the hyperactivation of BCL2 interacting protein3 (BNIP3) -mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis, by regulating AMP-activated protein kinase (AMPK) -enolase 2 (ENO2) signaling, which perpetually maintaining lenvatinib-resistant HCC cells’ competitive advantage over sensitive HCC cells. Of note, BNIP3 inhibition significantly sensitized the anti-tumor efficacy of lenvatinib in HCC. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism reprogramming; meanwhile, this work recognizes BNIP3 as a promising target to overcome HCC drug resistance.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Xiaoqin Zhang,Jiale Mao,Lu Shao,Shuang Liu,Jiwang Zhou,Mingrong Mei,Zunjing Zhang
Background: Melastoma dodecandrum Lour. (MD), a traditional botanical drug known for its hypoglycemic, antioxidant, and anti-inflammatory properties, is commonly used to treat diabetes, osteoarthritis, and osteoporosis. However, its specific active components against diabetic osteoporosis remain unclear.Purpose: This study aimed to identify the key active components in MD using cell membrane chromatography coupled with mass spectrometry and validate their effects in vitro.Methods: An AGEs-induced osteoblast injury model was established. MTT assays measured cell viability, and ALP activity was assessed using a biochemical kit. Western blotting was employed to detect the expression levels of osteoblast-related proteins OCN and RUNX2 and the AGE receptor protein RAGE. ELISA was used to determine the levels of SOD, MDA, CAT, and GPx. PCR quantified TNF-α expression to evaluate the protective effects and potential mechanisms of MD. The AGEs-induced osteoblast cell membrane chromatography-mass spectrometry method facilitated the rapid identification of potentially active compounds based on their affinity for the osteoblast cell membrane. Cell experiments further validated the activity of the characteristic component isovitexin.Results: MD significantly improved cell viability in AGEs-damaged osteoblasts, enhanced ALP, SOD, CAT, and GPx activities, reduced MDA levels, increased OCN and RUNX2 protein expression, and decreased TNF-α mRNA and RAGE protein expression. Cell membrane chromatography identified 20 chemical constituents, including 13 flavonoids, 4 organic acids, 1 phenylpropanoids, 1 terpenoids, and 1 alkaloid. Cell experiments have confirmed that isovitexin has significant protective activity against osteoblasts and can inhibit the expression of specific receptor RAGE on the osteoblast membrane, consistent with the effect of MD.Conclusion: MD and its active component, isovitexin, provide protective effects against AGEs-induced osteoblast injury, offering a basis for subsequent drug development.
研究领域:
药理学
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生物化学
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细胞生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jiale Mao,Houxing Lei,Pingcui Xu,Shuang Liu,Jiwang Zhou,Mingrong Mei,Nani Wang,Xiaoqin Zhang
Ethnopharmacological relevance Melastoma dodecandrum (MD), a traditional ethnomedicine, has been widely used for the treatment of fractures, osteoarthritis, and osteoporosis due to its remarkable anti-inflammatory activity. However, the specific active components responsible for its therapeutic effects on orthopedic conditions remain unidentified. Aim of the study This study aimed to screen and identify key active components in MD using a combination of cell membrane chromatography and mass spectrometry, followed by cellular validation. Materials and methods A TNF-α-induced osteoblast injury model and an osteoblast membrane chromatography screening system were established to select and identify chemical components of MD that directly act on osteoblasts. The protective effects of MD on osteoblasts were assessed by evaluating cell viability, alkaline phosphatase (ALP) activity, cell mineralization and the expression of osteogenesis-related proteins OCN, RUNX2, and the TNF-α receptor protein TNFR1. Validation of the activity of individual components was also conducted. Results MD significantly improved the viability of osteoblasts under TNF-α-induced injury, enhanced ALP activity, stimulated the expression of OCN and RUNX2 proteins, and decreased the expression of TNFR1. Cell membrane chromatography screening identified 32 chemical components, including 21 flavonoids, 6 organic acids, 2 phenylpropanoids, 2 terpenes, and 1 nucleotide. Molecular docking revealed that isovitexin could bind to the specific receptor TNFR1 on the cell membrane. Furthermore, cellular validation demonstrated that isovitexin significantly protected osteoblasts. Conclusions MD and its pharmacologically active component, isovitexin, exhibit protective effects against TNF-α-induced inflammatory injury in osteoblasts, laying a solid foundation for future drug development.
研究领域:
药理学
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民族药理学
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细胞生物学
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质谱学
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色谱学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PATHOLOGY
·
2025
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IF 5.2
Fang Liu,Qingchun Liang,Li Li,Yuan Gong,Mingxi Li,Liyun Feng,An Chen,Yuanzhi Ye,Zirong Lan,Yining Li,Jing-Song Ou,Lihe Lu,Jianyun Yan
Vascular calcification is an important risk factor related to all-cause mortality of cardiovascular events in patients with chronic kidney disease (CKD). Vascular extracellular matrix (ECM) proteins have been demonstrated to regulate vascular calcification. ECM protein thrombospondin 1 (THBS1/TSP-1) plays a critical role in the regulation of vascular diseases. However, whether THBS1 is involved in vascular calcification in CKD patients remains unclear. In this study, RNA sequencing datasets from the Gene Expression Omnibus (GEO) database GSE146638 showed that THBS1 was upregulated in the aortas of CKD rats. Enzyme-linked immunosorbent assay (elisa) revealed that serum THBS1 levels were increased in CKD patients with thoracic calcification. Western blotting and immunofluorescence analysis showed that THBS1 expression was increased in calcified vascular smooth muscle cells (VSMCs) and arteries. THBS1 knockdown exacerbated rat VSMC calcification induced by high phosphorus and calcium, as shown by Alizarin red staining and calcium content assays. Conversely, THBS1 overexpression attenuated VSMC calcification and abdominal aortic calcification in rats with CKD. Moreover, addition of recombinant THBS1 protein inhibited calcification of VSMC S and human arterial rings. Smooth muscle cell-specific knockout of THBS1 mice treated with vitamin D3 displayed aggravated aortic calcification. Mechanistically, the protein–protein interaction database STRING ( http://string-db.org/ ) analysis and coimmunoprecipitation assays revealed THBS1 bound to integrin β3. Reduction of integrin β3 levels abrogated the protective effect of THBS1 on vascular calcification. RNA-seq analysis revealed that THBS1 overexpression modulated the nuclear factor-kappa B (NF-κB) signaling pathway. Of note, the inhibitory effect of THBS1 overexpression on the NF-κB signal was abolished by knockdown of integrin β3. In conclusion, THBS1 interacts with integrin β3 to inhibit vascular calcification through suppression of NF-κB signal, suggesting a promising therapeutic target for vascular calcification in CKD. © 2025 The Pathological Society of Great Britain and Ireland.
研究领域:
医学
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分子生物学
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心血管研究
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2026
·Vol. 105
·期 11
·107437
·
IF 4.5
Zhanbang Ma,Fangfang Wang,Bing Wang,Zhihui Zuo,Zongxi Han,Huixin Li,Deying Ma
Vitamin D is increasingly recognized as an important regulator of innate and adaptive immunity, yet its antiviral role in chickens during fowl adenovirus serotype 4 (FAdV-4) infection remains unclear. In this study, we investigated the effects of oral vitamin D 3 supplementation on humoral immunity, tissue viral load, and immune-related gene expression in FAdV-4-infected chickens. Ninety 8-day-old specific pathogen-free chickens were randomly divided into two groups (n = 45/group) and fed a basal diet. The experimental group received oral vitamin D 3 dissolved in 0.1 mL soybean oil at a dose equivalent to 3000 IU/kg diet daily for 3 weeks, whereas the control group received soybean oil alone. After supplementation, all birds were challenged with FAdV-4. Vitamin D 3 supplementation significantly reduced tissue viral loads and increased serum antibody levels compared with the control group. At the transcriptional level, vitamin D 3 modulated key innate and adaptive immune markers, including Toll-like receptors (TLRs), avian β-defensins, and cytokines. It downregulated several TLRs and reduced the pro-inflammatory cytokines interleukin (IL)-6 and IL-8, while increasing the antiviral cytokines interferon-γ and IL-1β. Vitamin D 3 also increased vitamin D receptor expression, decreased inducible nitric oxide synthase, and reduced the apoptosis regulators B-cell lymphoma-2 (BCL-2) and Bcl2-associated X protein in selected tissues. In conclusion, vitamin D 3 supplementation enhanced antiviral defense against FAdV-4 infection, possibly by promoting humoral immunity and modulating innate immune and apoptosis-related responses. These findings provide new insight into the role of vitamin D 3 in limiting FAdV-4 infection and support its potential as a nutritional strategy for controlling viral diseases in poultry.
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产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2026
·Vol. 105
·期 5
·106672
·
IF 4.5
Guangxiao Zhang,Yawen Sun,Ling He,Bowen Zhao,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Min Liu,Kelin Li,Hai Lin,Haifang Li
Vitamin D 3 (VD 3 ) is an essential fat-soluble micronutrient that regulates diverse biological processes. However, its long-term impact on avian intestinal development remains largely unknown. In this study, we detected that the VD 3 content was significantly lower in late-cycle production eggs (68 weeks old, termed “LP eggs”) compared to the peak-cycle production eggs (44 weeks old, named “PP eggs”) ( P < 0.05). Notably, the intestine index was reduced ( P < 0.05), and the intestinal expression of tight junction (TJ) proteins (Occludin and ZO-1) was decreased for chicks hatched from LP eggs versus those from PP eggs ( P < 0.05). Thus serial dosages of VD 3 (2.5, 5.0, or 7.5 μg VD 3 /egg) were injected into the amniotic cavity of embryos hatched from LP eggs on embryonic day 17 (E17). This intervention effectively improved hatchability, promoted intestinal development that persisted through 14-days post-hatch, and showed immuno-modulatory effects manifesting as Interleukin-6 ( IL-6 ) downregulation and Interleukin-10 ( IL-10 ) upregulation. Further in vivo and in vitro analysis revealed that VD 3 improved intestinal development by activating TJ-related genes ( P < 0.05), with vitamin D receptor (VDR) mediating these effects. Chromatin immunoprecipitation (ChIP) assays confirmed that 1,25-(OH) 2 D 3 strengthened VDR binding to promoter regions of Occludin and ZO-1 but decreased the interaction degree of VDR with the IL-6 promoter ( P < 0.05). These findings establish that in ovo injection of VD 3 is an efficacious perinatal intervention strategy, which significantly mitigates developmental constraints in late-phase poultry production through VDR-dependent intestinal barrier potentiation and immuno-homeostasis modulation.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Chengsi Li,Jing Li,Chengyingjie Yang,Zhenghao Zhu,Yachen Zhang,Yin Xiang
Chronic kidney disease (CKD) is a condition characterized by progressive loss of kidney function. Vascular calcification is not only a common late-stage complication of CKD but also serves as an independent predictor of cardiovascular events and mortality in CKD patients. This study investigates the mechanism by which vericiguat (VER), a soluble guanylyl cyclase (sGC) sensitizer, attenuates CKD-associated vascular calcification. The hypothesis that vericiguat alleviates the decrease of sGC activity mediated by calcium and phosphorus metabolism was verified in both in vitro and in vivo experimental models. The calcium levels were increased in the aorta of CKD rats and VSMCs in vitro, and the expression of osteogenic differentiation-related markers, eNOS and PKG was upregulated. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were downregulated, while VER significantly improved calcification by activating the NO/cGMP/PKG pathway. Meanwhile, L-NAME antagonized the positive effects of VER in either CKD rats or calcified VSMCs.
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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）