Advanced Science
·
2025
·
IF 14.1
Yanan Wang,Xutao Ma,Xinyuan Wang,Liru Liu,Xue Zhang,Qiuyue Wang,Yingfei Zhu,Huanhua Xu,Liangmin Yu,Zhiyu He
The scarcity of effective neuroprotective agents and the presence of blood-brain barrier (BBB)-mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS-responsive borneol-based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain-targeting ligand, inner hydrophobic core for efficient drug loading of membrane-permeable calcium chelator BAPTA-AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA-AM: 400 µg·kg −1 ) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl-2/Bax/Cyto-C/Caspase-3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over-activation, reprogramming microglia polarization toward an anti-inflammatory phenotype, and blocking NF-κB/TNF- α /IL-6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple-stage sequential treatment strategy for clinical CIS.
研究领域:
药学
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神经科学
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药物递送系统
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传统中药
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中风治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2019
·
IF 2.813
Jian Ren,Chang-Liang Hu,Zheng-Ping Zhang,Rong Chen,Shi-Bao Yang,Zhen-Yu Miao,Lu-Ning Sun,Yong-Qing Wang
(+)-Borneol, a bicyclic monoterpene , has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m / z [M + H] + 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol.
研究领域:
药理学
·
分析化学
·
药物代谢
✓ 已验证
DOI
高影响因子
XENOBIOTICA
·
2020
·
IF 1.902
Qun Ma,Manman Dai,Huimin Zhang,Luyu Bai,Ning He
The effect of different doses of borneol on the pharmacokinetics of vinpocetine after intraocular administration in the rat plasma and the brain was investigated.Intraocular administration of vinpocetine (3 mg/kg) was performed, in combination with different doses (0, 5, 10, and 20 mg/kg) of borneol. Intravenous administration of vinpocetine was used as a control (1 mg/kg). The concentrations of vinpocetine in the rat plasma and the brain were determined using a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. Using the non-compartmental models with the DSA 2.0 software, the main pharmacokinetics parameters and the brain-targeting effect evaluated.In comparison with intravenous administration, after intraocular administration of vinpocetine alone, the absolute bioavailability (F) of vinpocetine was 43.82% for the plasma, and the drug target index (DTI) was 1.05 for the brain. After intraocular administration of vinpocetine combined with different doses of borneol, the relative bioavailability (Fr) of vinpocetine in the plasma was increased by 130.46–182.90%. The relative bioavailability (Fr) of vinpocetine in the brain was improved (147.19–225.36%). The DTI was 1.12, 1.18, and 1.21 for 5, 10, and 20 mg/kg of borneol, respectively.Compared with the intraocular administration of vinpocetine alone, the co-administration of different doses of borneol resulted in an obvious brain targeting effect.
研究领域:
药理学
·
药物代谢动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Fanchang Wu,Mingjun Huang,Xue Zuo,Ruiye Xie,Jinman Liu,Junyu Ke,Weirong Li,Qi Wang,Yong Liang
Alzheimer’s disease (AD) poses a significant threat to the global elderly population. Traditional Chinese medicine (TCM) has been widely utilized in the treatment of AD. Osthole, a bioactive ingredient classified as an “emperor” in many TCM formulas, has been demonstrated to effectively alleviate AD symptoms. However, its low bioavailability in the brain has limited its clinical application. This study aimed to increase the intracerebral bioavailability of osthole by using borneol as a “courier,” based on the classical “Emperor–Minister–Assistant–Courier” model, and to investigate the enhanced pharmacological performance of osthole on AD. Results indicated that a suitable in situ thermosensitive gel matrix for intranasal administration mixed with osthole and borneol consists of P407 at 20%, P188 at 7%, and PEG300 at 6%. The concentration of osthole in the cerebrospinal fluid increased almost tenfold after intranasal administration of osthole/borneol compared to oral administration. Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression, thereby expediting the nose-to-brain route and guiding osthole as “emperor” to its target in the brain. Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio, improving T-SOD and catalase expression, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice compared to osthole alone. Overall, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol and provided a wider application of TCM for AD treatment with higher intracerebral bioavailability.
研究领域:
药理学
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神经科学
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传统中药
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Tianyi Xu,Qilei Yang,Yue Peng,Congcong Xie,Huimin Yu
Rheumatoid arthritis (RA) therapy demands agents that are both effective and safe, yet many natural products with promising bioactivity, such as curcumin, face major translational challenges due to poor solubility and bioavailability. To overcome these limitations, we designed and synthesized a series of dual-functional curcumin-borneol prodrugs via a succinate ester linkage, including the parent ester (CBS), its water-soluble sodium salt (CBS-Na), and a disubstituted analog (DCBS), to enhance delivery and synergize therapeutic action. These derivatives markedly improved cellular uptake and nuclear localization, potently scavenged reactive oxygen species, and effectively suppressed the MAPK/AP-1 signaling axis by inhibiting ERK and p38 phosphorylation and c-Fos expression, leading to downregulation of matrix metalloproteinase MMP9 and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In a collagen-induced arthritis rat model, the derivatives demonstrated superior efficacy over native curcumin in alleviating joint inflammation and destruction, while exhibiting an excellent safety profile, thus representing a novel and promising therapeutic strategy for RA.
✓ 已验证
DOI
PubMed
高影响因子
ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING
·
2025
·
IF 2.9
Liu Zaizhi,Liao Haibin,Li Hualan,Zou Zhengrong
Cinnamomum camphora chvar. Borneol essential oil (CBEO), a potential antibacterial ingredient, faces challenges in widespread use for food preservation due to its high volatility and low stability. This study aimed to enhance the stability and release properties of CBEO by preparing CBEO/β-cyclodextrin microcapsules. The ultrasound-assisted complexation (UACP) method has been developed to fabricate microcapsules containing CBEO , with β -cyclodextrin used as the wall material. The UACP process was optimized using the Box–Behnken response surface methodology. Under optimal conditions—a wall–core ratio of 4.09, ultrasound time of 52 min, ultrasound power of 617 W, and embedding temperature of 32 °C—the maximum microcapsule yield (84.93 ± 2.21%) and encapsulation efficiency (60.20 ± 1.56%) were achieved. Analysis through scanning electron microscopy, Fourier transform infrared spectroscopy, particle size distribution analysis, thermogravimetric analysis, and X-ray diffraction revealed the effective encapsulation of CBEO by UACP method. Furthermore, CBEO microcapsules exhibited favorable thermal stability and a slow-release effect. This study presents a promising approach to microencapsulation technology for the preparation of plant essential oil microcapsules.
研究领域:
食品科学
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植物化学
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材料科学
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Yuhsien Lai,Xuesong Wu,Zhuoyu Jiang,Yifei Fang,Xiuting Liu,Dan Hong,Yanyun Jiang,Guozhen Tan,Shiqi Tang,Siyao Lu,David Wei,Sam T. Hwang,Kit S. Lam,Liangchun Wang,Yanyu Huang,Zhenrui Shi
Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes ( p < 0.0001), PSI ( p < 0.0001) and epidermal thickness ( p < 0.05). Moreover, a strengthened anti-inflammatory effect caused by TYK2i-BO-gel is seen in a human skin explant model, implying its potential application for human patients. With the addition of BO, the TYK2i-BO-gel not only increases skin permeability but also inhibits the expression of antimicrobial peptides in keratinocytes and facilitates the anti-Th17 response of TYK2i with suppressed activation of STAT3. Therefore, this work represents the accessibility and effectiveness of TYK2i-BO-hydrogel as a new topical formulation for anti-psoriasis management and shows great potential for clinical application.
研究领域:
皮肤病学
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Xiaoyu Yang,Jidong Zhang,Jitang Chen,Yunxuan Xie,Tianci Hu,Qin Luo,Tianhao Peng,Han Luo,Linlin Shi,Jiangling Wan,Jianxin Wang,Xiangliang Yang,Jianyong Sheng
Oral protein drugs’ delivery faces challenges due to multiple absorption barriers for macromolecules. Co-administration with permeation enhancers and encapsulation in nano-carriers are two promising strategies to enhance their oral absorption. Herein, the poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are decorated with polyethylene glycol (PEG) and a traditional Chinese medicine-derived permeation enhancer borneol (BO) for oral insulin delivery. Compared with a physical mixture of BO and PEG-decorated PLGA NPs, PLGA–PEG–BO NPs significantly facilitate insulin permeation across intestinal epithelia through various transcytosis pathways. The relationship among the BO surface density, physico-chemical properties and multiple barriers penetration ability is further investigated. Increasing the BO density boosts penetration through the epithelial cell layer but reduces enzyme and mucus barrier penetration. When the surface PEG density is at 90% and BO density is at 10%, the NPs possess the strongest overall ability to overcome both the mucus layer barrier and epithelial cell barrier, as illustrated by the highest permeation efficiency through Caco-2/HT29-MTX cell co-cultural monolayers. In diabetic rodents, PLGA–PEG90%–BO10% NPs exhibit high intestinal safety and a substantial hypoglycemic effect, with insulin availability at 6.22 ± 2.30%, double that of orally delivered insulin PLGA–PEG NPs and far superior to a physical mixture with BO. This study reveals the importance of tailored absorption enhancer decoration for oral protein delivery.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Catalysis
·
2022
·
IF 5.089
Xiaoxiang Hu,Huaxiang Deng,Yajun Bai,Tai-Ping Fan,Xiaohui Zheng,Yujie Cai
Arabidopsis has attracted increasing attention to biotechnology as a model plant. Among, many of studies have focused on monoterpenoids metabolism. Borneol is a typical representative of monoterpenoids and widely applied in fragrances and pharmaceuticals. And (+)-camphor also is also attracting more and more interest in the field of pharmaceutical. However, the enzyme involved the conversion of borneol and camphor in Arabidopsis is still unknown. In this study, a borneol dehydrogenase (BDH) from Arabidopsis lyrate was overexpressed in Escherichia coli BL21 (DE3). The optimum pH for reduction and oxidation were 7.5 and 9.0, respectively, and the optimum temperature was 45 ℃. The specific activity of reduction reaction for (-)-camphor and (+)-camphor were 1.09 and 0.76 U·mg −1 which were the highest so far. The AlBDH coupled with glucose dehydrogenase (GDH) of coenzyme regeneration could efficiently convert rac -camphor, yielding 4.64 mM rac -borneol within 3.5 h with a conversion of 92.8%. A single point mutation L205F could successfully be used for enzymatic resolution of 2 mM rac -camphor, yielding 95.9% of (+)-camphor with an ee s of > 99%. It also could respectively reduce (+)-camphor and (-)-camphor to optically pure (+)-borneol and (+)-isoborneol. The study of the enzymatic properties of AlBDH lay an important foundation for further studies on the conversion of borneol and camphor in Arabidopsis and provide potential industrial application value for the optically pure enantiomers borneol sustainable synthesis in the future.
研究领域:
生物化学
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生物技术
·
酶学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2024
·
IF 3.9
Zhenlong Zhou,Shengli Wang,Penghui Fan,Xiaofeng Meng,Xinyu Cai,Wen Wang,Lin Ma,Hang Ma,Jianyu Su
Candida albicans ( C. albicans ), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans . This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.
研究领域:
微生物学
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药理学
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分子生物学
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真菌病理学
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光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2023
·
IF 10.2
Xin Shen,Zhixiang Cui,Yidan Wei,Yingnan Huo,Duo Yu,Xin Zhang,Shirui Mao
The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. In vivo behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VIN NE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.
研究领域:
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 6
·e4210
·
IF 1.688
Weiguo Liao,Xiaojie Huang,Yongxin Yin,Bin Liu,Runzhi Zhu
Tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic cerebrovascular disease. However, the mechanism of TMP and how to increase its bioavailability need to be further explored. In our study, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography–mass spectrometry method was developed to investigate the pharmacokinetic properties of TMP and its interaction with different doses of borneol (BO) in rats. Linearity of TMP in brain and blood dialysates exhibited good linear relationships over the concentration range of 0.991–555.14 ng/mL. The specificity, linearity, accuracy, precision, matrix effect and stability were within acceptable ranges. The results demonstrated that BO had a marked impact on the pharmacokinetic properties of TMP. After co-administration, the areas under the concentration–time curve (AUC) of TMP in brain and blood were significantly increased. Meanwhile, the peak concentration of TMP in brain was also enhanced. The AUC Brain /AUC Blood of TMP, increased from 44% to 56 and 60.8% after co-administration with BO (15 and 30 mg/kg). The pharmacodynamic results showed that TMP co-administration with BO enhanced the cerebral blood flow during the period of ischemia and reduced the infarct volume. Overall, it might be an effective way to treat stroke to use TMP co-administered with BO.
研究领域:
药理学
·
神经科学
·
分析化学
✓ 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）