Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Hui Ni,Zijia Zhang,Ye Lu,Yaowen Liu,Yang Zhou,Wenyong Wu,Xinqin Kong,Liling Shen,Sihan Chen,Huali Long,Cheng Luo,Hao Zhang,Jinjun Hou,Wanying Wu
The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C 18 column and a conventional C 18 column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, thirteen 2D fractions of Uncaria alkaloids were prepared, and their components were characterized using mass spectrometry. Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the thirteen 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine, corynoxeine N -oxide, and cadambine demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H 2 O 2 measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H 2 O 2 clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.
研究领域:
药理学
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分析化学
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传统医学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2019
·
IF 2.705
Jinyue Zhu,Weiqing Wang,Xia Wu
Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway.
研究领域:
药理学
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免疫学
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分子生物学
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2021
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IF 3.269
Chuanfeng Lv,Hui Li,Hongxia Cui,Qianyu Bi,Meng Wang
Allergic asthma is one of the most common chronic airway diseases, and there is still a lack of effective drugs for the treatment of allergic asthma. The purpose of this work is to formulate rhynchophylline (Rhy)-solid lipid nanoparticles (SLNs) to improve their therapeutic efficacy in a mice allergic model of asthma. A solvent injection method was employed to prepare the Rhy-SLNs. Physicochemical characterization of Rhy-SLNs was measured, and the release assessment was investigated, followed by the release kinetics. Next, a model of murine experimental asthma was established. Mice were subcutaneously injected with 20 μg ovalbumin mixed with 1 mg aluminum hydroxide on days 0, 14, 28, and 42 and administrated aerosolized 1% ovalbumin (w/v) by inhalation from day 21 to day 42. Mice were intraperitoneally injected with 20 mg/kg Rhy-SLNs or Rhy at one hour before the airway challenge with ovalbumin. The results showed that Rhy-SLNs revealed a mean particle size of 62.06 ± 1.62 nm with a zeta potential value of −6.53 ± 0.04 mV and 82.6 ± 1.8% drug entrapment efficiency. The release curve of Rhy-SLNs was much higher than the drug released in phosphate buffer saline at 0, 1, 1.5, 2, 4, or 6 h. Moreover, Rhy-SLNs exerted better effects on inhibiting ovalbumin-induced airway inflammation, oxidative stress, airway remodeling (including collagen deposition and mucus gland hyperplasia) than Rhy in murine experimental asthma. Subsequently, we found that Rhy-SLNs relieved allergic asthma via the upregulation of the suppressor of cytokine signaling 1 by repressing the p38 signaling pathway.
研究领域:
药学
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免疫学
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纳米技术
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2021
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IF 4.219
Qiang Zheng,Yuan Zhang,Zheng Zhao,Haitao Shen,Hongyu Zhao,Min Zhao
Isorhynchophylline (IRN) is an alkaloid with anti-inflammatory and anti-oxidative activities in cardiovascular and brain diseases, but its role in paraquat (PQ)-induced acute kidney injury (AKI) is yet unknown. The model of PQ-induced AKI in rats was established by intraperitoneal injection of PQ (25 mg/kg). We found that the tail vein injection of IRN (4 mg/kg) significantly increased the survival rate of PQ-intoxicated rats. IRN administration alleviated PQ-induced renal injury and renal dysfunction in rats, as evidenced by decreased apoptosis in renal cortex and reduced serum creatinine, serum BUN , and urine NGAL levels. Furthermore, IRN treatment improved the PQ-triggered oxidative stress in renal cortex by increasing the levels of anti-oxidant indicators (SOD activity, GSH/GSSG ratio, levels of Nrf-2, NQO-1, and HO-1 in renal cortex) and decreasing the levels of oxidative stress indexes (ROS and MDA levels in renal cortex). Interestingly, toll-interacting protein (Tollip), a negative regulator of interleukin 1 receptor associated kinase 1 (IRAK1) phosphorylation, was demonstrated to be increased by IRN injection in the renal cortex of PQ-intoxicated rats. In vitro experiments revealed that IRN protected renal tubular epithelial cells against PQ toxicity through suppressing oxidative stress and mitochondrial damage, and these protective effects were reversed by Tollip shRNA . Collectively, the present study demonstrated that IRN ameliorated PQ-induced AKI by attenuating oxidative stress and mitochondrial damage through upregulating Tollip, which provides new insights into the pathogenesis and treatment of PQ poisoning.
研究领域:
药理学
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毒理学
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肾脏生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
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IF 8.663
Lukuan Xie,Honglei Lin,Lingrui Lv,Wenxin Zhang,Feng Feng,Fulei Liu,Wenyuan Liu,Lingfei Han
Parkinson's disease (PD), one of common neurodegenerative diseases, afflicts many elderly people lacking of effective treatment strategies. Rhynchophylline (RIN) is an anti-PD natural active compound. However, RIN can hardly cross the blood-brain barrier (BBB) and is easily excreted as a substrate of P-glycoprotein (P-gp), making it difficult to exert anti-PD efficacy in brain. Nanocarrier-based brain targeting strategies provide an attractive platform to address brain distribution problems of drugs. In this work, we designed a brain-targeting core-shell nanoparticle (RIN/TAR-A2-CSN) for the programmed co-delivery of RIN and P-gp inhibitor Tariquidar (TAR). It was composed of Angiopep-2 (A2) modified reduction-responsive PEG shell material and thiamine disulfide system (TDS) grafted polyglutamate core material. After entering the body, first RIN/TAR-A2-CSN crossed the BBB into the brain via A2-receptor-mediated transport. Subsequently, the shell material disintegrated under reducing conditions, and the TDS-grafted core material was reduced to become hydrophilic, thereby leading to the drugs "locked-in" the brain. Finally, the released TAR inhibits P-gp-mediated RIN efflux, increases the retention time of RIN in the brain, and fully exerts the anti-PD effect of RIN. The brain targeting efficiency of RIN/TAR-A2-CSN was improved to 5.8 times that of free RIN. In addition, the therapeutic effect on the MPTP-induced PD mice model was significantly improved. This work develops a novel brain targeting strategy for drugs to overcome BBB and inhibit efflux. RIN/TAR-A2-CSN nanoparticles show the potential to become PD therapeutics.
研究领域:
神经药理学
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纳米技术
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药学
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神经退行性疾病
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产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 17
·期 1
·251-259
·
IF 1.41
Meng Wang,Hui Li,Yaxin Zhao,Chuanfeng Lv,Guanghua Zhou
Rhynchophylline (Rhy) is a major active component of Uncaria rhynchophylla and exhibits the potential to inhibit the proliferation of airway smooth muscle cells (ASMCs). In the current study, it was hypothesized that Rhy serves a key role in the anti‑asthma effect of Uncaria rhynchophylla by inhibiting transforming growth factor‑β1 (TGF‑β1)‑mediated activation of Smad and mitogen‑activated protein kinase (MAPK) signaling. Allergic asthma was induced in mice using ovalbumin (OVA), and the effect of Rhy treatment on inflammatory and allergic responses in the bronchoalveolar lavage fluid (BALF) and serum of mice was determined. Subsequently, the changes in TGF‑β1‑induced Smad and MAPK signaling following Rhy administration were detected to determine the mechanism associated with this treatment. In addition, TGF‑β1 was employed to induce hyperplasia of ASMCs, and the effect of Rhy on proliferation of ASMCs, and Smad and MAPK signaling in vitro was also assessed. The administration of Rhy attenuated the recruitment of eosinophils in BALF induced by OVA, which was associated with the suppressed production of immunoglobulin E, interleukin (IL)‑13, IL‑4 and IL‑5. At the molecular level, the administration of Rhy suppressed the expression levels of TGF‑β1, Smad4, p‑Smad2 and p‑Smad3, while it induced the expression of Smad7, indicating the inhibitory effect of Rhy on TGF‑β1‑mediated Smad and MAPK signaling. Furthermore, Rhy inhibited the proliferation of ASMCs and, similar to the results of the in vivo assay, it blocked the pro‑hyperplasia signaling transduction in vitro. In conclusion, the current study demonstrated the anti‑asthma effect of Rhy, which depended on the inhibition of TGF‑β1‑mediated Smad and MAPK signaling.
研究领域:
药理学
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免疫学
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呼吸医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Honglei Lin,Lukuan Xie,Lingrui Lv,Jianrong Chen,Feng Feng,Wenyuan Liu,Lingfei Han,Fulei Liu
The aim of this study is to overcome the obstacle of the blood-brain barrier (BBB) in therapeutic drugs of Parkinson's disease (PD), like rhynchophylline (RIN) entry by intranasal administration and to solve the problem of short residence time of drugs in the nasal cavity by the dosage form design of thermosensitive gel . We first conducted a study of the screening of absorption enhancers and 3% hydroxypropyl-β-cyclodextrin (HP-β-CD) was effective to improve the nasal mucosal permeability of RIN. By adjusting the ratio of different components in order to make the gel with adhesion and rapid gelation which were determined to be Poloxamer 407 (P407) 20%, Poloxamer 188 (P188) 1%, polyethylene glycol 6000 (PEG-6000) 1% and HP-β-CD 3%. In addition, the characterization showed that the thermosensitive gel was network cross-linked, rapidly gelation upon entry into the nasal cavity and was stable as semi-solid state with adhesion as well as sustained release properties. Moreover, pharmacokinetic study was performed to evaluate the bioavailability and brain targeting of RIN thermosensitive gel and which were 1.6 times and 2.1 times higher than those of oral administration. We also evaluated the anti-PD effects of RIN thermosensitive gel in-vitro as well as in-vivo . The results showed that RIN thermosensitive gel was effective in repairing the motor function impairment, dysregulated expression levels of oxidative stress factors, and positive neuronal damage within the substantia nigra and dopamine caused by PD. The constructed intranasal drug administration strategy through thermosensitive gel provided a new choice for targeted treatment of PD together with other central nervous system diseases.
研究领域:
药剂学
·
神经学
·
药理学
·
药物递送系统
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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）