Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 47
·9770-9783
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IF 6.331
Linhua Li,Chong Chen,Chunle Zhang,Rifang Luo,Xiaorong Lan,Fan Guo,Liang Ma,Ping Fu,Yunbing Wang
Thrombus, bacterial infections, and severe inflammation are still serious problems that have to be faced with blood-contacting materials. However, it is a great challenge to simultaneously meet the above functional requirements in a simple, economical and efficient method. As such, we put forward a robust and versatile coating strategy by covalently modifying the multi-pharmacological drug honokiol (HK) with an amine-rich polydopamine/polyethyleneimine coating, through which anticoagulant, antibacterial and anti-inflammatory properties were obtained (DPHc) simultaneously. The amine content in the DPHc coating was lower than the detection limit, while it contained abundant phenolic hydroxyl groups (49 μmol cm−2). Meanwhile, the 30 day drug release test confirmed that the drug was firmly modified on the surface of the coating without release. A systematic in vitro and ex vivo evaluation confirmed that the coating had significant anti-thrombotic properties. The antibacterial rates of the DPHc coating against Staphylococcus aureus and Escherichia coli reached 99.98% and 99.99%, respectively. In addition, subcutaneous implantation indicated that the DPHc coating also has excellent histocompatibility. To the best of our knowledge, this is the first study using HK as a coating material that can not only combat thrombosis and infection but also significantly inhibit inflammation associated with the use of blood-contacting materials, thus expanding the application of HK in the field of biomaterials.
研究领域:
生物材料
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药学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF FISH DISEASES
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2022
·Vol. 45
·期 11
·1599-1607
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IF 2.58
Xin-Yuan Jiang,Zong-Yi Ren,Nian-Kun Zhang,Ke-Chen Yang,Gao-Xue Wang,Hai-Feng Jiang
Nocardiosis caused by Nocardia seriolae is a major threat to the aquaculture industry. Given that prolonged therapy administration can lead to a growth of antibiotic resistant strains, new antibacterial agents and alternative strategies are urgently needed. In this study, 80 medicinal plants were selected for antibacterial screening to obtain potent bioactive compounds against N. seriolae infection. The methanolic extracts of Magnolia officinalis exhibited the strongest antibacterial activity against N. seriolae with the minimal inhibitory concentration (MIC) of 12.5 μg/ml. Honokiol and magnolol as the main bioactive components of M. officinalis showed higher activity with the MIC value of 3.12 and 6.25 μg/ml, respectively. Sequentially, the evaluation of antibacterial activity of honokiol in vivo showed that honokiol had good biosafety, and could significantly reduce the bacterial load of nocardia-infected largemouth bass ( p < .001). Furthermore, the survival rate of nocardia-infected fish fed with 100 mg/kg honokiol was obviously improved ( p < .05). Collectively, these results suggest that medicinal plants represent a promising reservoir for discovering active components against Nocardia , and honokiol has great potential to be developed as therapeutic agents to control nocardiosis in aquaculture.
研究领域:
水产养殖学
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药用植物学
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微生物学
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高影响因子
PHARMACEUTICAL RESEARCH
·
2022
·Vol. 39
·期 9
·2263-2276
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IF 4.58
He Xiaoshuang,Wei Yuanfeng,Wang Shiru,Zhang Jianjun,Gao Yuan,Qian Shuai,Pang Zunting,Heng Weili
Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed to improve its physicochemical properties. The binary mixture of HK and MEG was obtained by anti-solvent method and characterized by TGA, DSC, FTIR, and PXRD. The SCXRD analysis showed that two HK − molecules and two MEG + molecules were coupled in each unit cell via the ionic interaction along with intermolecular hydrogen bonds, suggesting the formation of a salt, which was further confirmed by the XPS measurements. However, the ∆pK a value between HK and MEG was found to be less than 1, which did not follow the oft-quoted ∆pK a rule for salt formation. After salification with MEG, the solubility and dissolution rate of HK exhibited 3.50 and 25.33 times improvement than crystalline HK, respectively. Simultaneously, the powder flowability, tabletability and stability of HK-MEG salt was also significantly enhanced, and the salt was not more hygroscopic, and that salt formation did not compromise processability in that regard. Further, in vivo pharmacokinetic study showed that C max and AUC 0-t of HK-MEG salt were enhanced by 2.92-fold and 2.01-fold compared to those of HK, respectively, indicating a considerable improvement in HK oral bioavailability.
研究领域:
药学
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药物制剂
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药物递送
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PubMed
高影响因子
Natural Product Communications
·
2022
·
IF 1.496
Yuyan Zhu,Lixia Zhang,Xiyuan Zhou
The prevalence of acne vulgaris is high, but the topical retinoids used as the foundation of treatment have teratogenic and photosensitivity properties. Previous studies have suggested that honokiol, a small-molecule compound extracted from Magnolia officinalis, could effectively inhibit Cutibacterium acnes (C acnes) and inflammation in vitro. However, the effect in vivo is unclear. The rabbit ear acne model that we created showed obvious comedones and hyperkeratosis. These lesions were repeatedly measured and recorded by dermatoscopy (ultraviolet light). Compared with the control group, topical 2.5% honokiol cream obviously improved the comedones and hyperkeratosis and effectively reduced sebum secretion, as shown by Oil Red O staining. The effects were equivalent to those of adapalene gel without local side effects. We added honokiol's other functions to acne treatment in addition to antiinflammation, but further studies are needed.
研究领域:
皮肤病学
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分子生物学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2023
·
IF 5.3
Fei Li,Chunyu Ye,Xiuli Wang,Xinting Li,Xiaoxia Wang
Cigarette smoking can cause damage of airway epithelial cells and contribute to chronic obstructive pulmonary disease (COPD). Honokiol is originally isolated from Magnolia obovata with multiple biological activities. Here, we investigated the protective effects of honokiol on cigarette smoke extract (CSE)-induced injury of BEAS-2B cells. BEAS-2B cells were treated with 300 mg/L CSE to construct an in vitro cell injury model, and cells were further treated with 2, 5 and 10 μM honokiol, then cell viability and LDH leakage were analysed by CCK-8 and LDH assay kits, respectively. Apoptosis was detected by flow cytometry analysis. ELISA was used to measure the levels of tumour necrosis factor (TNF)-ɑ, IL-1β, IL-6, IL-8 and MCP-1. The results showed that honokiol (0.5–20 μM) showed non-toxic effects on BEAS-2B cells. Treatment with honokiol (2, 5 and 10 μM) reduced CSE (300 mg/L)-induced decrease in cell viability and apoptosis in BEAS-2B cells. Honokiol also decreased CSE-induced inflammation through inhibiting expression and secretion of inflammatory cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-8 and MCP-1. Moreover, honokiol repressed CSE-induced reactive oxygen species (ROS) production, decrease of ATP content and mitochondrial biogenesis, as well as mitochondrial membrane potential. Mechanistically, honokiol promoted the expression of SIRT3 and its downstream target genes, which are critical regulators of mitochondrial function and oxidative stress. Silencing of SIRT3 reversed the protective effects of honokiol on CSE-induced damage and mitochondrial dysfunction in BEAS-2B cells. These results indicated that honokiol attenuated CSE-induced damage of airway epithelial cells through regulating SIRT3/SOD2 signalling pathway.
研究领域:
肺病学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2020
·
IF 6.205
Xiaojia Shi,Tao Zhang,Hongxiang Lou,Huina Song,Changhao Li,Peihong Fan
Mitochondrion is a favorable therapeutic target in cancer, given its regulation of bioenergetics and cell death. Honokiol exhibits antiproliferative effects through mitochondria-mediated death signaling. To enhance its anticancer potential and selectivity, we conjugated honokiol to berberine, a mitochondria-targeting carrier. All designed derivatives displayed 1 order of magnitude increased cytotoxicity compared with the parent compounds, especially with massive cytoplasmic vacuoles. Biological evaluation demonstrated the representative compound 6b localized within the mitochondria, and mitochondrial dilation resulted in vacuolization. 6b induced vacuolation-associated cell death and apoptosis with obvious mitochondrial dysfunction, as demonstrated by booming reactive oxygen species generation, opening mitochondrial permeability transition pore, and reducing mitochondrial membrane potential. The targeting property also conferred 6b with selectivity for tumor cells compared to normal cells. 6b inhibited cancer cell proliferation in the zebrafish xenograft model. These results demonstrate that berberine-linked honokiol derivatives open up a direction for novel mitochondrial-targeting antitumor agents.
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高影响因子
JOURNAL OF FISH DISEASES
·
2024
·Vol. 47
·期 4
·e13915
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IF 2.2
Fei Yang,Bin Yang,Kaige Song,Yingjie Jin,Gaoxue Wang,Pengfei Li,Qing Yu,Fei Ling
Micropterus salmoides rhabdovirus (MSRV) is a formidable pathogen, presenting a grave menace to juvenile largemouth bass. This viral infection frequently leads to epidemic outbreaks, resulting in substantial economic losses within the aquaculture industry. Unfortunately, at present, there are no commercially available vaccines or pharmaceutical treatments to combat this threat. In order to address the urgent need for therapeutic strategy to resist MSRV infection, the antiviral activity of natural product honokiol against MSRV was explored in this study. Firstly, cellular morphology was directly observed in an inverted microscope when treated with honokiol after MSRV infection. The results clarified that honokiol significantly lessened cytopathic effect (CPE) induced by MSRV and protected the integrity of GCO cells. Furthermore, the viral nucleic acid expression (G gene) was detected by reverse transcription real-time quantitative PCR (RT-qPCR) and the results indicated that honokiol significantly decreased the viral loads of MSRV in a concentration-dependent manner, and honokiol showed a high antiviral activity with IC 50 of 2.92 μM. Besides, honokiol significantly decreased the viral titre and suppressed apoptosis caused by MSRV. Mechanistically, honokiol primarily inhibited the initial replication of MSRV and discharge of progeny virus to exert anti-MSRV activity. More importantly, in vivo experiments suggested that honokiol (40 mg/kg) expressed a fine antiviral activity against MSRV when administrated with intraperitoneal injection, which led to a notable 40% improvement in the survival rate among infected largemouth bass. In addition, it also resulted in significant reduction in the viral nucleic acid expression within liver, spleen and kidney at 2, 4 and 6 days following infection. What is more, 100 mg/kg honokiol with oral administration also showed certain antiviral efficacy in MSRV-infected largemouth bass via improving the survival rate by 10.0%, and decreasing significantly the viral nucleic acid expression in liver, spleen and kidney of largemouth bass on day 2. In summary, natural product honokiol is a good candidate to resist MSRV infection and has promising application prospects in aquaculture.
研究领域:
水产养殖学
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病毒学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Plant Science
·
2026
·
IF 5.9
Zhangguang Cao,Guoyu Wei,Amir Khan,Anlong Hu,Zhenxiang Guo
IntroductionRoot diseases in crops are increasingly becoming the most difficult to control due to the challenge of fungicides reaching infection sites. Honokiol, a natural fungicidal product derived from Magnolia officinalis, is primarily biosynthesized in leaves and subsequently translocated to roots to resist pathogen infection.MethodsIn this study, honokiol applied to the leaves of Polygonatum cyrtonema Hua (PCH) could be transported downward to the roots and exhibited a control effect against root rot disease.ResultsSubsequent research showed that concentration, temperature, pH, energy inhibitors (DNP, CCCP) and other agents (AgNO3, BaCl2, CaCl2) significantly affect basipetal translocation of honokiol, suggesting that its translocation from leaves to roots is mediated by transport proteins. The distribution of honokiol in various parts of PCH was found as leaf > stem > root, indicating that honokiol was absorbed by the leaves and transferred to the roots through phloem. Translocation factorroot/stem value of honokiol in PCH was more than 1, indicating that honokiol was easy to transfer to the root. Subsequently, four potential transporter proteins, ABCB11, ABCG24, TIP1–2 and PIP1-3, were screened from Arabidopsis thaliana for molecular docking analysis, indicating a significant binding affinity between honokiol and transporter proteins having a binding energy of −12.83 kcal mol-1, −10.70 kcal mol-1, −9.38 kcal mol-1 and −10.67 kcal mol-1, respectively.DiscussionFoliar-applied honokiol exhibited pronounced basipetal translocation, efficiently moving from leaves to root tissues where root rot pathogens reside. This systemic redistribution enables targeted delivery of the antifungal compound honokiol to the infection site without direct soil application, minimizing environmental exposure.
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高影响因子
Nanomedicine
·
2019
·
IF 4.717
Xin Jin,Qing Yang,Ning Cai,Zhenhai Zhang
Aim: Lung cancer has a very high incidence rate, and thus, there is an urgent need for novel and effective therapies. Materials & methods: In this study, we proposed a potential treatment option by combining four natural products in liposome systems. Results:In vitro studies indicated that the combination of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 exhibited a synergistic action. When these four natural products were loaded into liposome systems, we observed an increased effect. The relative action was also observed in vivo. The cisplatin group presented obvious kidney damage, whereas both cocktail therapy and cocktail liposome therapy were safer. Conclusion: Therefore, we propose cocktail liposome systems may provide a more efficient and safer treatment for lung cancer.
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高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 11
·573
·
IF 4.773
Li Wang,Weiwei Wu,Lingling Wang,Lu Wang,Xiuhua Zhao
Honokiol (HK), a well-tolerated natural product, has many multiple pharmacological activities. However, its poor water solubility and low bioavailability limit its clinical application and development. The aim of this research was to prepare the solid dispersion (SD) formulation of honokiol (HK) with poloxamer-188 (PLX) as the carrier, thereby improving its solubility and oral bioavailability. Firstly, by investigating the relationship between the addition amount of the PLX and the solubility of HK, and the effects of solid dispersions with different ratios of HK–PLX on the solubility of HK, we determined that the optimum ratio of PLX to HK was (1:4). Then, the HK–PLX (1:4) SD of HK was prepared using the solvent evaporation method. The morphology of the obtained HK–PLX (1:4) SD was different from that of free HK. The HK in the HK–PLX (1:4) SD existed in amorphous form and formed intermolecular hydrogen bonds with PLX. Additionally, the solubility values of the HK–PLX (1:4) SD were about 32.43 ± 0.36 mg/mL and 34.41 ± 0.38 mg/mL in artificial gastric juice (AGJ) and in artificial intestinal juice (AIJ), respectively. Compared with free HK, the release rate and the bioavailability was also substantially improved for HK in its SD form. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the HK–PLX (1:4) SD showed higher inhibition of HepG2 cells than free HK. Taken together, the present study suggests that the HK–PLX (1:4) SD could become a new oral drug formulation with high bioavailability and could produce a better response for clinical applications of HK.Keywords:honokiol;solid dispersion;solubility;bioavailability;antitumor activity
研究领域:
药剂学
·
肿瘤学
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2023
·
IF 7.4
Yuan Hu,Miao Zhang,Bihan Liu,Yingying Tang,Zhuo Wang,Tao Wang,Jiaxin Zheng,Junjian Zhang
Alzheimer's Dementia (AD) and Vascular Dementia (VaD) are two main types of dementias for which no specific treatment is available. Chronic Cerebral Hypoperfusion (CCH) is a pathogenesis underlying AD and VaD that promotes neuroinflammatory responses and oxidative stress . Honokiol (HNK) is a natural compound isolated from magnolia leaves that can easily cross blood brain barrier and has anti-inflammatory and antioxidant effects. In the present study, the effects of HNK on astrocyte polarization and neurological damage in in vivo and in vitro models of chronic cerebral hypoperfusion were explored. We found that HNK was able to inhibit the phosphorylation and nuclear translocation of STAT3 , A1 polarization, and reduce conditioned medium's neuronal toxicity of astrocyte under chronic hypoxia induced by cobalt chloride ; STAT3 phosphorylation inhibitor C188-9 was able to mimic the above effects of HNK, suggesting that HNK may inhibit chronic hypoxia-induced A1 polarization in astrocytes via STAT3. SIRT3 inhibitor 3-TYP reversed, while Sirt3 overexpression mimicked the inhibitory effects of HNK on oxidative stress, STAT3 phosphorylation and nuclear translocation, A1 polarization and neuronal toxicity of astrocyte under chronic hypoxic conditions. For in vivo research, continuous intraperitoneal injection of HNK (1 mg/kg) for 21 days ameliorated the decrease in SIRT3 activity and oxidative stress, inhibited astrocytic STAT3 nuclear translocation and A1 polarization, and prevented neuron and synaptic loss in the hippocampal of CCH rats. Besides, HNK application improved the spatial memory impairment of CCH rats, as assessed with Morris Water Maze . In conclusion, these results suggest that the phytochemical HNK can inhibit astrocyte A1 polarization via regulating SIRT3-STAT3 axis, thus improving CCH-induced neurological damage. These results highlight HNK as novel treatment for dementia with underlying vascular mechanisms.
研究领域:
神经科学
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药理学
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神经退行性疾病
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分子生物学
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植物化学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 3.616
Jiahui Sun,Jing Li,Qi Liu,Min Jiang,Mengjia Yang,Siwen Zhan,Tong Qiu,Kaiyong He,Xueqiong Zhang
This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis . The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm , with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .
研究领域:
药剂学
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肿瘤学
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生物医学工程
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PubMed
高影响因子
危险品化学品经营许可证（带存储）