Drug Delivery and Translational Research
·
2017
·Vol. 8
·期 1
·83-96
·
IF 3.094
Pan Linmei,Zhou Jing,Ju Feng,Zhu Huaxu
Alpha-asarone is a bioactive component of Acorus tatarincuii Schott with low bioavailability, which is often used for treatments of various brain diseases in clinical setting. This study was to formulate biodegradable methoxy polyethylene glycol-polylactic acid (mPEG-PLA) nanoparticles (NPs) surface-modified by lactoferrin (Lf), for delivering α-asarone into the brain following intranasal administration. Alpha-asarone NPs were prepared by premix membrane emulsification. The relative parameters were optimized by a Box-Behnken experimental design. The particle size, zeta potential, and dispersibility index of NPs and Lf-NPs were characterized. Their ex vivo permeation, pharmacokinetics, distribution in the brain and other tissue, brain targeting, and toxicity were investigated. Following intranasal administration, Lf-NPs had a better permeability and no significant poor bioavailability compared to NPs; the area under curve from 0 to 12 h of α-asarone in Lf-NPs of the olfactory bulb, hippocampus, olfactory bundles, and thalamus were 2.14-, 4.17-, 3.62-, and 1.96-fold of those in NP group, respectively. Lactoferrin could enhance the efficacy of brain targeting with NPs and reduce its liver accumulation. Toxicity of NPs on nasal mucosal cilia and epithelial cells was also decreased by Lf. To summarize, these results demonstrate that Lf-NPs of α-asarone have potential as a carrier for nose-to-brain delivery of α-asarone for brain diseases.
研究领域:
药剂学
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神经科学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Wei Wei,Qiang Han,Sheng Tian,Yanping Wang,Huiying Zhang,Haibo Wang,Qionglin Liang
The separation of active ingredients in traditional Chinese medicine (TCM) is of great significance in determining the efficacy of TCM as well as the pharmacological study of active ingredients, improving the scope of application of TCM and the efficiency of disease prevention and treatment. In the current study, we have successfully synthesized a core–shell structure magnetic microsphere Fe 3 O 4 -COF for the separation of α-asarone and β-asarone in the combined decoction of Acorous Tatarinowii Rhizoma (ATR) and Polygalae Radix (PR). The successful synthesis of Fe 3 O 4 -COF was demonstrated chemically and morphologically by using five characterizations such as Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM). Extraction conditions were investigated and optimized, including adsorbent dosage, adsorption time, sample pH value, elution solvent, elution time and volume of elution solution. Under the optimal experimental conditions, we got a low limit of detection (LOD) of α-asarone and β-asarone were 0.0379 μg/mL and 0.0432 μg/mL, and the relative standard deviations (RSD) were less than 2.3%. And the number and intensity of impurity peaks in the chromatogram after extraction of complex samples were significantly reduced and the good recoveries were still maintained after multiple extractions of complex samples, which showed satisfied specific adsorption and excellent resistance to matrix interference. The successful establishment of this method will provide a new direction for the separation and analysis of active ingredients in traditional Chinese medicine.
研究领域:
药学化学
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分析化学
·
中药学
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DOI
高影响因子
METABOLIC BRAIN DISEASE
·
2025
·Vol. 40
·期 2
·1-16
·
IF 3.5
Yan Xiao-dan,Fan Rong-hua,Wang Yu,Duan Xiao-xu,Wei Xuan,Li Lin-sen,Yu Qing
Diabetic encephalopathy (DE) is a common complication of diabetes that may result in cognitive impairment. Currently, there is limited effective therapy for DE. Herein, we explored the beneficial effect of α-Asarone on DE and its potential mechanisms. DE was induced in Type 2 diabetes mellitus mice and high-glucose (HG)-exposed PC-12 cells. Cognitive function was evaluated by MWM test. Pathological changes in the brain tissues were observed by HE staining. Cell viability was detected by CCK-8. Apoptosis was assessed by Hoechst 33,342 staining, Annexin V/PI staining and TUNEL. Mitochondrial membrane potential was analyzed by JC-1 probe. ROS production was measured by DCFH-DA staining. Target protein levels were analyzed by Western blotting. Network pharmacology was used to elucidate the beneficial mechanisms of α‐Asarone in DE. Our study showed that α‐Asarone enhanced cell viability and suppressed apoptosis in HG-stimulated PC-12 cells. Furthermore, α‐Asarone relieved HG-induced reduction in mitochondrial membrane potential and ROS overproduction. In addition, mitophagy was triggered by α‐Asarone, which was responsible for the inhibitory effect of α‐Asarone on apoptosis and oxidative stress. Consistently, the in vivo experiments showed that α‐Asarone treatment relieved cognitive dysfunction, apoptosis, and oxidative stress of DE mice via mitophagy induction. However, inhibition of mitophagy by Mdivi-1 counteracted the beneficial action of α‐Asarone. Mechanistically, network pharmacology analysis identified 10 key targets of α‐Asarone. Molecular docking substantiated a strong affinity of α‐Asarone with CASP3, EGFR, NFKB1, and ESR1 proteins. Taken together, α‐Asarone protected against mitochondrial dysfunction, oxidative stress and apoptosis via activating mitophagy, thereby alleviating DE. Our findings suggest α‐Asarone as a potential drug for DE. Graphical
研究领域:
神经生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2016
·
IF 3.926
Xiao-Fei Gu,Yue Zhao,Kan Li,Meng-Xiang Su,Fang Yan,Bo Li,Ying-Xiang Du,Bin Di
Structure elucidation of volatile aromatic isomers at trace level has long been considered as an elusive task, due to their structural similarities and similar polarities, even with the aid of many spectroscopic techniques such as mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Single-crystal X-ray diffraction (SCD) is recognized as one of the most powerful structural elucidation techniques. The recently developed crystalline sponge method overcomes the intrinsic limitation of SCD that the target molecules must be single crystals, being able to analyze non-crystalline and trace-amount compounds without any special treatment. In order to investigate whether the crystalline sponge method could be used for the structure elucidation of closely related isomers or other volatile and even oily compounds in complex mixtures at trace level, we combined HPLC separation with the crystalline sponge method for X-ray crystallographic analysis. In this paper, two pairs of volatile aromatic isomers including cis / trans isomers of asarone and positional isomers of carvacrol and thymol, as well as the main volatile component in essential oil extracted from Acorus Tatarinowii , were first isolated by HPLC and encapsulated into the crystalline sponge then elucidated by X-ray crystallographic analysis. Direct observation of these volatile compounds by X-ray crystallography was achieved using only microgram quantities without crystallization or derivatization. Unambiguous identification of these compounds was realized without reference standards. This strategy offers a promising platform capable of providing high-confidence detailed structural information of closely related isomers as well as other volatile and even oily compounds in complex mixtures in microgram quantities.
研究领域:
分析化学
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晶体学
·
药学
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产品关联
DOI
PubMed
高影响因子
ANESTHESIA AND ANALGESIA
·
2018
·Vol. 127
·期 3
·775
·
IF 3.463
Gui Yulong,Li Aiyuan,Zhang Jie,Li Guan,Ruan Xia,Guo Qulian,Zou Wangyuan
BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent studies have shown a close relationship between endoplasmic reticulum (ER) stress and neuropathic pain. Here, we investigated the effect of α-asarone, an ER stress inhibitor, on chronic constriction injury (CCI)–induced neuropathic pain. METHODS: Two parts were included in this study. In part 1, rats were assigned to 7 groups: the sham group, the sham + α-asarone 20 mg/kg group, the CCI group, the CCI + vehicle group, the CCI + α-asarone 5 mg/kg group, the CCI + α-asarone 10 mg/kg group, and the CCI + α-asarone 20 mg/kg group. After surgery, the rats were treated with α-asarone or normal saline daily. Pain thresholds were measured, and samples of the L3–6 spinal cord were taken for western blotting and immunofluorescence on day 7. In part 2, rats were intrathecally implanted with PE-10 tubes and divided into 4 groups: the CCI + α-asarone 20 mg/kg group, the CCI + α-asarone 20 mg/kg + vehicle group, the CCI + α-asarone 20 mg/kg + SR9243 group, and the CCI group. Five rats in each group were separated for behavioral tests 1 hour after intrathecal injection. The rest of them were killed for western blotting on day 7. RESULTS: In this study, CCI surgery significantly induced mechanical allodynia and thermal hyperalgesia. CCI surgery significantly induced activation of ER stress (PERK-eIF2α, IRE1α, CHOP, and XBP-1s) in rats. However, treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced activation of ER stress. Behavioral results showed that daily treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced nociceptive behaviors, on day 7 (mechanical allodynia, P = .016, 95% confidence interval, 0.645–5.811; thermal hyperalgesia, P = .012, 95% confidence interval, 0.860–6.507). Furthermore, α-asarone induced upregulated expression of liver X receptor β (LXRβ) and downstream proteins in the spinal cord. The LXR antagonist SR9243 completely inhibited the anti-ER stress and antinociceptive effects of α-asarone in rats. CONCLUSIONS: α-Asarone relieved CCI-induced neuropathic pain in an LXR-dependent manner. α-Asarone may be a potential agent for treatment of neuropathic pain.
研究领域:
神经科学
·
药理学
·
疼痛管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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