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Screening potential mitochondria-targeting compounds from traditional Chinese medicines using a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method

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Journal of pharmaceutical Analysis 2018年第4期8卷 240-249页

作者： Xing-Xin Yang Yu-Zhen Zhou Feng Xu Jie Yu Gegentana Ming-Ying Shang Xuan Wang Shao-Qing Cai Department of Natural Medicines School of Pharmaceutical Sciences Peking University Department of Chemical Biology School of Pharmaceutical Sciences Peking University College of pharmaceutical Science Yunnan University of Traditional Chinese Medicine

Mitochondria regulate numerous crucial cell processes, including energy production, apoptotic cell death, oxidative stress, calcium homeostasis and lipid metabolism. Here, we applied an efficient mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry（LC/MS） method,also known as screening method for mitochondria-targeted bioactive constituents（SM-MBC）. This method allowed searching natural mitochondria-targeting compounds from traditional Chinese medicines（TCMs）, including Puerariae Radix（PR） and Chuanxiong Radix（CR）. A total of 23 active compounds were successfully discovered from the two TCMs extracts. Among these 23 hit compounds, 17 were identified by LC/MS, 12 of which were novel mitochondria-targeting compounds. Among these, 6 active compounds were analyzed in vitro for pharmacological tests and found able to affect mitochondrial functions. We also investigated the effects of the hit compounds on Hep G2 cell proliferation and on loss of cardiomyocyte viability induced by hypoxia/reoxygenation injury. The results obtained are useful for in-depth understanding of mechanisms underlying TCMs therapeutic effects at mitochondria level and for developing novel potential drugs using TCMs as lead compounds. Finally, we showed that SM-MBC was an efficient protocol for the rapid screening of mitochondria-targeting constituents from complex samples such as PR and CR extracts.

关键词： Mitochondria Bioactive constituents Traditional Chinese medicines Centrifugal ultrafiltration Liquid chromatography/mass spectrometry

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Based on non-targeted metabolomics for differential components screening of Rosae Chinensis Flos and Rosae Rugosae Flos and their quality evaluation

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Traditional Medicine Research 2025年第2期10卷 1-15页

作者： Xu Liang Ni-Hui Zhang Zhi-Lai Zhan Guang-Lu Chang Yan Gao Xia Li Wen-Yuan Gao school of pharmaceutical Science and Technology Faculty of MedicineTianjin UniversityTianjin 300193China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs China Academy of Chinese Medical SciencesBeijing 100700China Key Laboratory of Modern Chinese Medicine Resources Research Enterprises Tianjin 300402China

Background:Rosa chinensis *** Rosa rugosa *** not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional *** two plants have some differences in efficacy,but the flower buds are easily confused for similar *** addition,large-scale cultivation of ornamental rose flowers may lead to a decrease in the effective components of medicinal ***,it is necessary to study the chemical composition and make quality evaluation of Rosae Chinensis Flos(Yueji)and Rosae Rugosae Flos(Meigui).Methods:In this study,40 batches of samples including Meigui and Yueji from different regions in China were collected to establish high-performance liquid chromatography ***,the fingerprints data was analyzed using principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis analysis chemometrics to obtain information on intergroup differences,and non-targeted metabolomic techniques were applied to identify and compare chemical compositions of samples which were chosen from groups with large *** compounds were screened by orthogonal partial least-squares discriminant analysis and S-plot,and finally multi-component quantification was performed to comprehensively evaluate the quality of Yueji and ***:The similarity between the fingerprints of 40 batches roses and the reference print R was 0.73 to 0.93,indicating that there were similarities and differences between the *** principal component analysis and hierarchical cluster analysis of fingerprints data,the samples from different origins and varieties were intuitively divided into four *** least-squares discriminant analysis analysis showed that Meigui and Yueji cluster into two categories and the model was reliable.A total of 89 compounds were identified by high resolution mass spectrometry,mainly were flavonoids and flavon

关键词： Rosa chinensis Jacq. Rosa rugosa Thunb. metabolomics chemometrics multiple component quantification quality evaluation

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Moxibustion Promotes Formation of Granulation in Wound Healing Process through Induction of Transforming Growth Factor-β in Rats

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Chinese Journal of Integrative Medicine 2020年第1期26卷 26-32页

作者： Hiroshi Kawanami Hirohisa Kawahata Hiroko-Miyuki Mori Motokuni Aoki graduate school of Health sciences Morinomiya University of Medical Sciences

Objective:To examine the effect of moxibustion on the wound healing process and its mechanism using a rat wound ***:Sixty male Sprague-Dawley rats were randomly divided into a sham-treated group(n=30,wound surgery only)and a moxibustion group(n=30,wound treated with moxibustion).Circular fullthick ness skin wounds were produced in *** was applied to the edge of wound and was continued on alternating days till 14 days after surgery,followed by measurement of wound *** of collagens,prolyl-4-hydroxylase(P4H)and transtorming growth factor-β(TGF-β)were evaluated by histochemical study and real-time polymerase chain ***:The size of the wound lesion was significantly reduced in rats treated with moxibustion as compared to that in sham-treated rats at 4-10 days after wounding(P<0.01).Moxibusti on stimulated mRNA expressi on of collage ns at 4 days(P<0.01),but not at 7 days,accompa nied by enhanced proliferation of P4H-positive *** importanee,expression of TGF-β in tissue from the wound lesio n treated with moxibusti on was sign ifica ntly in creased as compared to that in sham-treated rats at 4 days(P<0.01 or P<0.05),but not at 7 ***:The treatment with moxibustion promoted the wound healing process in the early phase through proliferation of fibroblasts and rapid formation of granulation,possibly mediated by induction of TGF-β which is a key molecule in the physiological process of wound *** can be expected to be effective as complementary treatment for intractable ulcers.

关键词： compleme ntary and alter native medicine moxibusti on wound healing granulation tran storming growth factor-β collagen

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Emerging prospects of protein/peptide-based nanoassemblies for drug delivery and vaccine development

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Nano Research 2022年第8期15卷 7267-7285页

作者： Taiyu Liu Lu Li Cheng Cheng Bingfang He Tianyue Jiang school of pharmaceutical sciences Nanjing Tech UniversityNanjing 211816China

Proteins have been widely used in the biomedical field because of their well-defined architecture,accurate molecular weight,excellent biocompatibility and biodegradability,and *** by the wisdom of nature,increasing proteins/peptides that possess self-assembling capabilities have been explored and designed to generate nanoassemblies with unique structure and function,including spatially organized conformation,passive and active targeting,stimuli-responsiveness,and high *** characteristics make protein/peptide-based nanoassembly an ideal platform for drug delivery and vaccine *** this review,we focus on recent advances in subsistent protein/peptide-based nanoassemblies,including protein nanocages,virus-like particles,self-assemblable natural proteins,and self-assemblable artificial *** origin and characteristics of various protein/peptide-based assemblies and their applications in drug delivery and vaccine development are *** the end,the prospects and challenges are discussed for the further development of protein/peptide-based nanoassemblies.

关键词： drug delivery vaccine protein/peptide self-assembly targeting controlled release

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Immunosuppressive terpenoids from Tripterygium wilfordii

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Chinese Chemical Letters 2008年第4期19卷 453-456页

作者： Qian Shen ZhiYao Yoshihisa Takaishi Yan Wen Zhang Hong Quan Duan school of pharmaceutical sciences Basic Medical Research Center of TianjinTianjin Medical UniversityTianjin 300070China Department of Immunology Tianjin Medical UniversityTianjin 300070China Faculty of pharmaceutical sciences University of TokashimaTokushima 770-8505Japan

Two new terpenes,triptobenzene P（1）and wilforone（2）were isolated from Tripterygium wilfordii,as well as 10 known *** structures were elucidated by spectroscopic *** 2-4,8,10,and 11 showed significant immunosuppres... 详细信息

关键词： Tripterygium wilfordii Diterpene Triterpene Immunosuppressive activity

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New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury

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World Journal of Gastroenterology 2015年第45期21卷 12778-12786页

作者： Naoki Sano Takafumi Tamura Naoyuki Toriyabe Takeshi Nowatari Ken Nakayama Tomohito Tanoi Soichiro Murata Yu Sakurai Mamoru Hyodo Kiyoshi Fukunaga Hideyoshi Harashima Nobuhiro Ohkohchi Department of Surgery Doctoral Program in Clinical Science Graduate School of Comprehensive Human Sciences University of Tsukuba Faculty of pharmaceutical sciences Hokkaido University

AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid(HA) and sphingosine ***: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate(S1P), and HA-S1 P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase(ALT), histological findings, Td T-mediated d UTP-biotin nick end labeling(TUNEL) staining, and transmission electron microscopy(TEM). We also investigated the expressionof proteins associated with apoptosis, hepatoprotection, and S1 P accumulation. RESULTS: S1 P accumulated in the HA-S1 P group livers more than S1 P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1 P group. TEM revealed that the liver sinusoidal endothelial cell(LSEC) lining was preserved in the HA-S1 P group. Moreover, the HA-S1 P group showed a greater increase in the HO-1 protein levels compared to the S1 P ***: Our results suggest that HA-S1 P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1 P is an effective agent for hepatic ischemia/reperfusion injury.

关键词： Hyaluronic acid Sphingosine 1-phosphate Liver sinu

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Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system:the relationship of hydrogen bonding strength and controlled release capacity

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Acta Pharmaceutica Sinica B 2020年第5期10卷 928-945页

作者： Zheng Luo Chao Liu Peng Quan Degong Yang Hanqing Zhao Xiaocao Wan Liang Fang Department of pharmaceutical sciences School of PharmacyShenyang Pharmaceutical Universityshenyang 110016China

Background:Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal ***,the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported,and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive(PSA)was not well *** present study shed light on this ***:Acrylate PSAs with amide group were synthesized by a free radical-initiated solution *** drugs,i.e.,etodolac,ketoprofen,gemfibrozil,zolmitriptan,propranolol and lidocaine,were selected as model *** vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were *** correlation analysis,fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA *** test,rheology study,and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of ***:Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations;however,only zolmitriptan and propranolol showed decreased skin permeation *** was found that drug release was controlled by amide group through hydrogen bonding,and controlled release extent was positively correlated with hydrogen bonding ***:From these results,we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

关键词： Controlled release Polar functional group Hydrogen bonding strength Pharmacokinetics Pressure sensitive adhesive Hydrogen bonding interaction Transdermal patch Stratum corneum

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Use of potentially inappropriate medications for heart failure according to the three sets of heart failure-specific criteria in Thai older patients with heart failure

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Journal of Geriatric Cardiology 2022年第7期19卷 498-510页

作者： Jidapha Duangsong Panida Samansaplert Yosita Khamkong Kittipak Jenghua Department of pharmaceutical Care School of Pharmaceutical SciencesUniversity of PhayaoPhayao ProvinceThailand

OBJECTIVE To study the prevalence of potentially inappropriate medications for patients with heart failure(PIMHF) use and to identify factors associated with PIMHF use in Thai older HF *** This cross-sectional analytical survey included data on older(≥ 60 years) HF patients obtained from the electronic medical record databases of secondary-and tertiary-care hospitals. The medication profiles of patients were assessed to examine whether they were prescribed any PIMHF after an HF diagnosis. For PIMHF detection, the HF-specific criteria, including 2014 St Vincent criteria, 2019 Beers criteria, and 2021 Thailand criteria were applied. The prevalence of PIMHF use was expressed as percentages. The associated factors were identified using a binary logistic regression analysis, expressed as the adjusted odds ratio(aOR) and 95% confidence interval(95% CI).RESULTS A total of 2,639 patients were included in the study. Thirty-two PIMHF were found to have been prescribed to these patients. The prevalence of PIMHF use identified by the ST Vincent criteria, the Beers criteria, the Thailand criteria, and the three combined criteria was 23.76%, 19.67%, 21.18%, and 25.16%, respectively. The factors associated with PIMHF use were secondarycare hospital(aOR = 1.54, 95% CI: 1.26-1.87), HF with preserved ejection fraction(HFp EF)(aOR = 1.81, 95% CI: 1.38-2.38), hypertension(HTN)(aOR = 1.24, 95% CI: 1.02-1.51), diabetes mellitus(DM)(aOR = 1.39, 95% CI: 1.10-1.75), chronic pulmonary diseases(CPD)(aOR = 2.09, 95% CI: 1.56-2.80), and connective tissue diseases(CTD)(aOR = 5.10, 95% CI: 2.20-11.83).CONCLUSIONS PIMHF are commonly used in Thai older HF patients. The factors associated with PIMHF use identified in this study include secondary-care hospital, HFp EF, HTN, DM, CPD, and CTD.

关键词： prescribed specific criteria

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Liposome cocktail activator modulates hepatocytes and remodels the microenvironment to mitigate acute liver failure

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Asian Journal of pharmaceutical sciences 2022年第6期17卷 867-879页

作者： Na Yin Wenjun Zhang Runxiu Wei Qiang Yang Fengming He Ling Guo Min Feng school of pharmaceutical sciences Sun Yat-Sen UniversityGuangzhou 510006China school of pharmaceutical sciences Hainan UniversityHaikou 570228China school of pharmaceutical sciences Xiamen UniversityXiamen 361102China

Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the ***,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the *** this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced *** results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage *** cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for *** importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ***,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival *** summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.

关键词： Cocktail activator Dimethyl itaconate Dodecyl gallate Hepatocyte Microenvironment modulation

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Development and optimization of nanoemulsion gel for topical delivery of imiquimod

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Journal of Chinese pharmaceutical sciences 2018年第1期27卷 31-39页

作者： Gurvinder Kaur Tanurajvir Kaur Deepak N.Kapoor school of pharmaceutical sciences Lovely Professional University school of pharmaceutical sciences Shoolini University of Biotechnology and Management Sciences

In the present study,we aimed to formulate,optimize and characterize nanoemulsion-based gel of imiquimod for its topical administration and to improve the drug *** were prepared by the aqueous phase titration method and spontaneously formed by mixing specific fractions of oil phase:Smix:*** nanoemulsion formulations were optimized by response surface methodology(RSM) using mixture design,Scheffe *** formulated nanoemulsion was incorporated into 0.5% Carbopol 934(w/v) to enhance convenience in superficial application of the *** nanoemulsions were characterized in terms of droplet size,zeta potential,TEM,DSC and in vitro drug *** vesicle size was 113.6 nm with polydispersity index of *** zeta potential was 34 m *** spherical droplet shape was confirmed by TEM *** drug permeation from the diffusion membrane was 73.67% in 6 h for the optimized *** optimized nanoemulsion gel formulation of imiquimod was successfully developed with improved permeation using experimental design *** developed formulation could be further explored as a potential alternate to currently available topical formulations for the treatment of genital warts.

关键词： Imiquimod Condyloma acuminata Human papilloma virus Genital warts Nanoemulsions

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