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dihydromyricetin‑Incorporated Multilayer Nanofibers Accelerate Chronic Wound Healing by Remodeling the Harsh Wound Microenvironment

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Advanced Fiber Materials 2022年第6期4卷 1556-1571页

作者： Zijian Wang Wenjie You Wang Wang Weiqun Tian Fangjin Chen Yu Xiao Yun Chen Xinghuan Wang Department of Urology Zhongnan Hospital of Wuhan University430071 WuhanChina Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Disease School of Basic Medicine SciencesTaiKang Medical SchoolWuhan University430071 WuhanChina Center for Quantitative Biology School of Life SciencesPeking University100871 BeijingChina

The harsh microenvironment in wound(HMW)remains a major obstacle to chronic wound *** a series of bioactive materials have been developed,few of them are multi-functional and able to accelerate wound healing via precisely remodeling the ***,a series of dihydromyricetin(DHM)-incorporated multilayer nanofibers(termed DQHP-n,n=0,2,6 and 10)are fabricated using a layer-by-layer(LBL)self-assembly *** average diameters of DQHP-n significantly increase from 0.30±0.16μm to 0.84±0.28μm(P<0.05)along with the n value increased from 0 to 10,the tensile strength of that is also significantly improved from 1.12±0.15 MPa to 2.16±0.30 MPa(P<0.05),and the water contact angle of that significantly decreases from 129.1±1.5°to 76.6±3.9°(P<0.05).The DQHP-n are found to be biocompatible,in which DQHP-6 promoted cell migration through activation of the epithelial–mesenchymal transformation(EMT)pathway and reconstruction of the HMW by stopping bleeding,killing bacteria,eliminating inflammation,and scavenging reactive oxygen species(ROS).The in vivo evaluation is carried out via an ***-infected rat skin regeneration *** DQHP-6 group demonstrates the best effect,as it healed up to 98.5±1.0%of the wound area at day ***-6 differentially regulates the mRNA expressions of several cytokines(FGF2,PDGF,IL-1α,IL-6,IL10,and TGF-β),which ends to reductions of total inflammatory cells(CD45^(+) cells)and M1 macrophages(CD80^(+) and CD86^(+) cells),proliferation of host cell(Ki67^(+) cells),and enhancement of collagen *** conclusion,DQHP-6 exhibits multifunctional properties for HMW,and can serve as a promising wound dressing for clinical transformation.

关键词： dihydromyricetin Quaternized chitosan Hyaluronic acid Nanofiber Wound dressing

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dihydromyricetin promotes apoptosis, suppresses proliferation and tumor necrosis factor-α-mediated nuclear factor kappa-B activation in nasopharyngeal carcinoma CNE-2 cells

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Journal of Traditional Chinese Medicine 2021年第3期41卷 367-375页

作者： LI Caihong SHI Jinlian HUANG Bo DING Hang LIN Hanguang ZENG Jincheng ZHAO Yang LUO Guoqing Institute of Biochemistry and Molecular Biology Guangdong Medical UniversityZhanjiang 524023China Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsGuangdong Medical UniversityDongguan 523808China Department of Otolaryngology of Shenzhen Longhua New District Central Hospital Shenzhen 518109China Department of Otolaryngology of The Third People's Hospital of Longgang Shenzhen 518115China Faculty of Forensic Medicine of Guangdong Medical University Dongguan 523808China Department of Otolaryngology of the Second Affiliated Hospital of Guangdong Medical University Zhanjiang 524023China Department of Otolaryngology of the Affiliated Hospital of Guangdong Medical University Zhanjiang 524023China

OBJECTIVE: To investigate the efficacy of dihydromyricetin(DMY) on nasopharyngeal carcinoma(NPC) cell proliferation, apoptosis and to reveal the underlying mechanism in vitro ***: The CNE-2 cell line was treated with different concentrations of DMY and the effects of DMY on cell viability and proliferation were evaluated using cell counting kit-8(CCK-8) assay and plate colony formation assay. Cellular apoptosis was detected by flow cytometry following Annexin V fluorescein isothiocyanate/propidine iodide *** morphology was observed under a fluorescence microscope following Hoechst 333258 staining. The expression of phosphorylated inhibitor of nuclear factor kappa-B kinase subunit beta(p-IKKβ), phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha(p-IKKα), inhibitor of nuclear factor kappa-B alpha(IκB-α), nuclear factor kappa-B(NF-κB)/p65 was examined by Western blot analysis and the nuclear translocation of NF-κB/p65 was observed using a confocal laser scanning ***: DMY inhibited the proliferative capability and colony formation of NPC CNE-2 cells. Meanwhile, DMY induced apoptosis of CNE-2 cells in a dose and time-dependent manner via upregulating B-cell lymphoma-2 associated X, but downregulating B-cell lymphoma-2 and pro-caspase-3. Importantly, we found that DMY suppressed tumor necrosis factor alpha(TNF-α)-mediated NF-κB activation via inhibiting p-IKKβ, p-IKKα and blocking NF-κB subunit ***: Our experiments demonstrated that DMY had significant antiproliferative and apoptosisinducing effects on CNE-2 cells. Additionally, DMY promoted inactivation of p-IKKβ, p-IKKα,and blocked the nuclear translocation of NF-κB subunit p65. These results suggest that DMY may be an important therapeutic approach for NPC.

关键词： dihydromyricetin Nasopharyngeal carcinoma Cell proliferation Apoptosis I-kappa B kinase NF-kappa B Signal transduction

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dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway

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Chinese Journal of Integrative Medicine 2023年第5期29卷 434-440页

作者： ZHANG Zhi-ying LIU Chao WANG Peng-xiang HAN Yi-wei ZHANG Yi-wen HAO Mei-li SONG Zi-xu ZHANG Xiao-ying Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region School of MedicineXizang Minzu UniversityXianyangShaanxi Province(712082)China Key Laboratory of High Altitude Environment and Gene Related to Disease of Tibet Ministry of Education School of MedicineXizang Minzu UniversityXianyangShaanxi Province(712082)China School of Finance Economics Xizang Minzu UniversityXianyangShaanxi Province(712082)China School of Information Engineering Xizang Minzu UniversityXianyangShaanxi Province(712082)China

Objective: To investigate the effect and potential mechanism of dihydromyricetin(Dmy) on H9C2 cell proliferation, apoptosis, and autophagy. Methods: H9C2 cells were randomly divided into 7 groups, namely control, model, EV(empty p CDH-CMV-MCS-EF1-Cop GFP-T2A-Puro vector), IV(circHIPK3 interference), Dmy(50 μmol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ), phospho-phosphoinositide 3-kinase(p-PI3K), protein kinase B(p-AKT), and phospho-mammalian target of rapamycin(p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells. Results: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly(P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3Ⅱ/Ⅰ significantly increased(all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3Ⅱ/Ⅰ decreased significantly(all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced(P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed(P<0.05). Conclusion: Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

关键词： dihydromyricetin circHIPK autophagy cell apoptosis PI3K/AKT/mTOR

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dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression

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World Journal of Gastroenterology 2014年第29期20卷 10082-10093页

作者： Qing-Yu Zhang Ran Li Guo-Fang Zeng Bin Liu Jie Liu Yang Shu Zhong-Kao Liu Zhi-Dong Qiu Dong-Jun Wang Hui-Lai Miao Ming-Yi Li Run-Zhi Zhu Key Laboratory of Hepatic Disease Affiliated Hospital of Guangdong Medical College Department of General Surgery Jiamusi University

AIM: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human hepatic cancer cells.

关键词： dihydromyricetin Migration Invasion Hepatic cancer Matrix metalloproteinase-9

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dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and Hep G2 hepatoma cells

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World Journal of Gastroenterology 2017年第34期23卷 6242-6251页

作者： Cai-Jie Lu Yi-Feng He Wei-Zhuang Yuan Li-Jun Xiang Jian Zhang Yan-Rui Liang Juan Duan Yun-He He Ming-Yi Li Laboratory of Hepatobiliary Surgery Affiliated Hospital of Guangdong Medical University the First Clinical Medical College Southern Medical University Department of Gastrointestinal Surgery. The Second Affiliated Hospital of Guangzhou Medical University TCM-Integrated Hospital Southern Medical University

AIM To investigate whether dihydromyricetin(DHM) inhibits cell proliferation and promotes apoptosis by downregulating Notch1 *** The correlation between Notch1 and Hes1(a Notch1 target molecule) expression in hepatoma samples was confirmed by q RT-PCR. In addition, MTT assays, flow cytometry and TUNEL analysis showed that DHM possessed strong anti-tumor properties, evidenced not only by reduced cell proliferation but also by enhanced apoptosis in QGY7701 and Hep G2 hepatocellular carcinoma(HCC) cells. The expressions of Notch1, Hes1, Bcl-2 and Bax were determined by Western *** Among the tested samples(n = 64), the expression levels of Notch1(75% of patients) and Hes1(79.7% of patients) m RNA in tumor tissues were higher than in the normal liver tissues. There was a negative correlation between the expression of Notch1 and the degree of differentiation and positively correlated with the Alpha Fetal Protein concentration. The viability of HCC cells treated with DHM was significantly inhibited in a dose and time-dependent manner. Apoptosis was induced in Hep G2 and QGY7701 cell lines following 24 h of DHM treatment. After treatment with DHM, the protein expression of Notch1 was downregulated, the apoptosis-related protein Bax was upregulated and Bcl2 was downregulated. Notch1 si RNA further enhanced the anti-tumor properties of DHM. CONCLUSION Notch1 is involved in the development of HCC and DHM inhibits cell proliferation and promotes apoptosis by down-regulating the expression of Notch1.

关键词： dihydromyricetin Apoptosis Hepatocellular carcinoma Notch1

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dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice

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World Journal of Gastroenterology 2015年第18期21卷 5473-5481页

作者： Jun Xie Jie Liu Tu-Ming Chen Qing Lan Qing-Yu Zhang Bin Liu Dong Dai Wei-Dong Zhang Li-Ping Hu Run-Zhi Zhu Clinical Research Center Xuyi People’s Hospital Department of Hepatobiliary Surgery of Affiliated Hospital of Guangdong Medical College Zhanjiang Key Laboratory of Hepatobiliary Diseases Department of Stomatology Affiliated Hospital of Guangdong Medical College

AIM: To assess the effects of dihydromyricetin(DHM) as a hepatoprotective candidate in reducing hepatic injury and accelerating hepatocyte proliferation after carbon tetrachloride(CCl4) ***: C57 BL/6 mice were used in this study. Mice were orally administered with DHM(150 mg/kg) for 4 d after CCl4 treatment. Serum and liver tissue samples were collected on days 1, 2, 3, 5 and 7 after CCl4 treatment. The anti-inflammatory effect of DHM was assessed directly by hepatic histology detection and indirectly by serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), albumin, and superoxide dismutase(SOD). Inflammatory cytokines, such as interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α), were detected using ELISA kits. Proliferating cell nuclear antigen(PCNA) staining was used to evaluate the role of DHM in promoting hepatocyte proliferation. Hepatocyte apoptosis wasmeasured by TUNEL ***,apoptosis proteins Caspases-3,6,8,and 9 were detected by Western ***600125 were used to confirm whether DHM regulated liver regeneration through JNK/TNF-α***:DHM showed a strong anti-inflammatory effect on CCl4-induced liver injury in *** could significantly decrease serum ALT,AST,IL-1β,IL-6 and TNF-αand increase serum albumin,SOD and liver SOD compared to the control group after CCl4 treatment(P<0.05).PCNA results indicated that DHM could significantly increase the number of PCNA positive cells compared to the control(348.9±56.0 vs 107.1±31.4,P<0.01).TUNEL assay showed that DHM dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control(365.4±99.4 vs 90.5±13.8,P<0.01).Caspase activity detection showed that DHM could reduce the activities of Caspases-8,3,6 and 9 compared to the control(P<0.05).The results of Western blot showed that DHM increased the expression of JNK and decreased TNF-α***,DHM could not affect TNF-αexpression after SP600125 ***

关键词： dihydromyricetin Liver regeneration Tumor necrosis factor-α

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dihydromyricetin ameliorates chronic liver injury by reducing pyroptosis

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World Journal of Gastroenterology 2020年第41期26卷 6346-6360页

作者： Quan-Cheng Cheng Jing Fan Xin-Wei Deng Huai-Cun Liu Hui-Ru Ding Xuan Fang Jian-Wei Wang Chun-Hua Chen Wei-Guang Zhang Department of Anatomy Histology and EmbryologySchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Xin Hua Hospital Shanghai Jiaotong University School of MedicineShanghai 202155China

BACKGROUND Chronic liver injury(CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. dihydromyricetin(DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosisrelated molecules. Therefore, we studied the influence of DHM on CLI and *** To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of *** Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride(CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-β-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related *** Serum total cholesterol, low density lipoprotein, aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR-and pyrin domain-containing 3(NLRP3) and gasdermin D(GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these prot

关键词： Chronic liver injury dihydromyricetin Pyroptosis Carbon tetrachloride Pathogenesis Steatosis

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Recent advances in research on vine tea,a potential and functional herbal tea with dihydromyricetin and myricetin as major bioactive compounds

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Journal of Pharmaceutical Analysis 2021年第5期11卷 555-563页

作者： Qili Zhang Yanfang Zhao Meiyan Zhang Yalu Zhang Hongfang Ji Liang Shen College of Life Sciences Shandong University of TechnologyZiboShandong 255000China Department of Pharmacy The First Hospital of Hebei Medical UniversityShijiazhuangHebei 050000China Department of Pharmacy The Affiliated Hospital of Jining Medical CollegeJiningShandong 272100China

Vine tea has been used as an herbal tea by several ethnic minorities for hundreds of years in ***,a kind of indispensable component in a variety of nutraceutical,pharmaceutical and cosmetic applications,are identified to be the major metabolites and bioactive ingredients in vine ***,vine tea exhibits a wide range of significant bioactivities including anti-oxidant,anti-inflammatory,anti-tumor,antidiabetic,neuroprotective and other activities,but no *** bioactivities,to some extent,enrich the understanding about the role of vine tea in disease prevention and *** health benefits of vine tea,particularly dihydromyricetin and myricetin,are widely ***,there is currently no comprehensive review available on vine ***,this report summarizes the most recent studies investigating bioactive constituents,pharmacological effects and possible mechanisms of vine tea,which will provide a better understanding about the health benefits and preclinical assessment of novel application of vine tea.

关键词： Vine tea Flavonoids dihydromyricetin Myricetin Pharmacological effects Molecular mechanism

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Comparison of eugenol and dihydromyricetin loaded nanofibers by electro-blowing spinning for active packaging

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Food Bioscience 2023年第1期51卷 676-686页

作者： Songqi Liu Zaihan Chen Huange Zhang Yuanli Li Taxipalati Maierhaba Jianhui An Zhi Zhou Lingli Deng College of Biological and Food Engineering Hubei Minzu UniversityEnshi445000China Turpan Vocational and Technical College Turpan838000China

To explore the dihydromyricetin or eugenol loaded nanofiber’s potential as food active packaging,0%,0.1%,0.5%,and 1.0%dihydromyricetin or eugenol loaded nanofibers were fabricated by electro-blowing spinning,which increased the yield of nanofibers by a factor of 10 times compared to that of traditional *** morphology observation by scanning electron microscopy showed similar morphology and diameter distribution of the dihydromyricetin or eugenol *** transform infrared spectra analysis indicated that eugenol or dihydromyricetin interacted with proteins through hydrogen bonding.X-ray diffraction profiles of the nanofibers indicated that dihydromyricetin was uniformly distributed within the *** encapsulated with various concentrations of eugenol or dihydromyricetin showed better barrier properties against water vapors than the free nanofibers,which indicated that the hydrophobic eugenol and dihydromyricetin inhibited the permeation of water molecules through the *** tests showed that the nanofibers loaded with 0.5%eugenol or 1.0%dihydromyricetin exhibited relatively higher elastic moduli and lower elongation at *** nanofibers loaded with dihydromyricetin showed comparable antioxidant activity to that with eugenol in the aspect of ferric and cupper reducing activity,while that with 0.1%-1.0%dihydromyricetin showed superior DPPH radical scavenging ***,both eugenol and dihydromyricetin loaded gelatin/zein nanofibers showed effective antimicrobial activities against Escherichia coli and Staphylococcus ***,the dihydromyricetin loaded gelatin/zein nanofibers showed comparable physical and functional properties compared to eugenol,which suggests the application of dihydromyricetin nanofibrous films on food active packaging and the potential application of dihydromyricetin on functional food delivery systems.

关键词： Electro-blowing spinning Eugenol dihydromyricetin Nanofibers Antimicrobial activities Active packaging

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Analysis of the role of dihydromyricetin derived from vine tea(Ampelopsis grossedentata)on multiple myeloma by activating STAT1/RIG-I axis

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Oncology Research 2024年第8期32卷 1359-1368页

作者： WEI JIANG MEI ZHOU Department of Hematology Shaoxing Shangyu People’s HospitalShaoxing312000China Department of Hematology Zhuji People’s HospitalShaoxing311800China

Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately *** study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its *** MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro *** counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,*** real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo ***,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 *** DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in ***,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in ***,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 ***,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in ***,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.

关键词： dihydromyricetin Multiple myeloma Epithelial-mesenchymal transition Tumor growth

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