Berberine(BBR)is a major bioactive alkaloid found in Coptis chinensis Franch.,Coptis deltoidea C.Y.Cheng et Hsiao,Coptis teeta Wall.,and Phellodendron chinense Schneid.of the Rutaceae family,as well as in certain species of the Brassicaceae.Extensive studies have demonstrated that BBR exerts a broad spectrum of pharmacological activities,including anti-inflammatory,antioxidant,antitumor,hypoglycemic,antihypertensive,hypolipidemic,and antibacterial effects.Nevertheless,its clinical application has been hampered by intrinsic limitations such as a short biological half-life,poor water solubility,and low bioavailability.In recent years,nanotechnology-based delivery systems for BBR have attracted considerable attention as promising strategies to overcome these barriers.This review systematically summarizes the classification and preparation methods of BBR nanoformulations,highlights their potential in enhancing drug targeting and improving tissue distribution,and discusses future perspectives to inform the development and therapeutic applications of BBR-based nanomedicines.
1.范围《中国药学》（英文版）为中国科协主管,中国药学会主办,北京大学药学院承办的英文药学综合性期刊,现为月刊。本刊主要报道药学领域各学科进展及科研成果,旨在促进学术交流。本刊登载药学研究各学科,包括药物化学、生药学、天然产物、药物分析、药剂学、生物制剂学、药理学、药物代谢与处置、药物基因组学以及临床药学等方面,同时报道
The aluminum hydroxide adjuvant possesses a poorly crystalline boehmite(PCB)structure,the stability of which is significantly affected by storage conditions.In the present study,we conducted a comprehensive investigation into the structural and quality alterations of aluminum hydroxide adjuvants under varying temperature conditions over time.Three batches of the adjuvant were stored at 2-8 ℃,18-25 ℃,and 37 ℃,respectively,for 6 months.Key parameters,including X-ray diffraction patterns,pH,isoelectric point(pI),adsorption capacity,and average particle size,were analyzed to assess the impact of storage temperatures.X-ray diffraction analysis confirmed the PCB structure of the aluminum hydroxide adjuvant.Notably,after 1 month of storage at 37 ℃,new diffraction peaks emerged at 18.2 °2θ,with their intensity increasing progressively over time.Concurrently,the largest decreases in pI and pH were observed,measuring 0.78 and 1.33,respectively.In contrast,adjuvants stored at 2-8 ℃ for 6 months exhibited only faint diffraction peaks at 18.2 °2θ,indicating minor structural changes.Under these conditions,the reductions in pI and pH were comparatively smaller,at 0.43 and 0.80,respectively.The average particle size of the adjuvants remained within 110-140 nm across all storage conditions.Additionally,the aluminum hydroxide adjuvant consistently demonstrated a high protein adsorption capacity,approximately 8 mg BSA/mg Al3+,with no statistically significant differences in adsorption rates observed among the different temperature conditions(P>0.05).These findings highlighted the remarkable adsorption efficiency of nanoparticle aluminum hydroxide adjuvants throughout storage,reinforcing their potential as superior vaccine adsorbents.However,elevated storage temperatures were shown to accelerate structural aging,promoting the formation of highly crystalline phases such as gibbsite or bayerite,which could compromise the stability and quality of the adjuvant.
Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-a (TNF-a), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension. (c) 2023 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
To establish a model with a short modeling period and consistent with the pathogenesis of IBS,chronic stimulation and chemical stimulation were combined.In the present study,we aimed to establish a novel model of irritable bowel syndrome(IBS)and investigate its feasibility.Chronic unpredictable stimulation was used as a single factor model,and its addition with glacial acetic acid stimulation was used as a comprehensive factor model.The symptoms of the IBS model were analyzed from a collection of tests,including body weight,essential food consumption,sucrose consumption,fecal grain number,Bristol score,abdominal withdrawal reflex,open field tests,elevated cross-maze tests,intestinal transportation time,and H&E staining.The results showed that compared with the single-factor model and the control groups,the rats in the comprehensive model group exhibited less body weight,reduced food consumption,decreased sucrose consumption,increased fecal grain number,decreased Bristol score and pain threshold,and significantly reduced physical activity.The comprehensive factor group model conformed to the complex pathogenesis of IBS and thus had a significant effect on it,which could be used to establish an effective IBS model.Furthermore,the modeling effect was significantly evident in male rats compared with female ones.
In the present study,we aimed to explore the anti-inflammatory mechanism of acetylcholine(ACh)and to provide further evidence for the investigation of the inflammatory pathogenesis of Alzheimer's disease(AD)and its therapeutic drugs.The in vitro model of Aβ25-35-induced inflammatory injury in microglial cell line BV-2 cells was established to observe the anti-inflammatory effect of ACh chloride.In the presence or absence of α7 nAChR blocker(α-bungarotoxin),the expressions of IL-1β and IL-1RA and their ratio after ACh treatment were evaluated by ELISA.The expression and phosphorylation levels of MAPK(JNK,p38,and ERK1/2)and NF-κB pathway molecules were determined by Western blot analysis or EMSA,respectively.The results showed that ACh could significantly reduce the ratio of IL-1β/IL-1RA,antagonize the inflammatory activity of the IL-1 system induced by Aβ25-35,and restore the viability of BV-2 cells.Pretreatment with α7 nAChR blocker could block the inhibitory effect of ACh on the IL-1β/IL-1RA ratio.Meanwhile,α7 nAChR blocker could block the phosphorylation level of ERK1/2 MAPK protein and NF-κB activation downstream.Our study suggested that ACh could regulate IL-1 system inflammatory response induced by Aβ25-35 in BV-2 cells and maintain IL-1 subfamily balance,which was mediated by α7 nAChR and involved ERK1/2 MAPK and NF-κB pathways.This study provided a basis for exploring AD inflammatory pathogenesis and also a reference for discovering new targets for AD treatment.
In the present study,we aimed to prepare,characterize,and evaluate the capability of solid dispersion(SD)for resveratrol(RES)with low solubility and high melting points.A sustained-release solid dispersion(SRSD)was prepared by hot melt extrusion(HME).The release of RES was controlled using a hydrophobic-hydrophilic polymer mixture(Eudragit RS and Poloxamer 188).The effects of formula and process parameters were systematically studied by univariate analysis.Then the Box-Behnken design(three factors,three levels)was used to optimize the preparation process of SRSD.Differential scanning calorimetry and X-ray diffraction were adopted to determine the physical state of SD.Scanning electron microscopy was used to observe its surface properties,and Fourier transform infrared spectroscopy was used to explore chemical interactions between excipients.Dissolution studies were carried out to investigate the kinetics and drug release time.In vitro studies showed that RES release followed the Weibull model kinetic.RES SRSD(RESRS P188-SRSD)was successfully prepared using HME,in which the mass ratio of the drug to the carrier was 1∶3,the release regulator was P188,and the dosage was 10％.The stability of the preparation was good,and the dissolution was increased by 10 times.
11％的单基因遗传疾病是由人类基因中的过早终止密码子(PTC)引起的,其中突变的转录本会生成功能受损的截短蛋白质,从而导致无义突变PTC疾病[1].近期,北京大学药学院天然药物及仿生药物国家重点实验室夏青团队基于蛋白质翻译提前终止的机制,应用基因密码子扩展技术中的重要元件,即工程化"tRNA—氨酰tRNA合成酶"正交系统对模型小鼠中致病基因的无义突变进行通读治疗.实验不仅验证了"tRNA—酶"能够在动物体内稳定表达,而且可以精准通读内源性的发病位点,从而能够恢复蛋白的全长表达,缓解疾病的症状.此项研究从突变类型的角度,提出了通用型治疗无义突变的方法,是一种治疗单基因遗传疾病的新策略[2].为推进这种新型疗法的转化研究,亟需建立动物水平的实验流程和评价标准,为临床前研究提供坚实的基础.
近日,北京大学药学院药事管理与临床药学系史录文教授/管晓东副教授团队在医学权威期刊柳叶刀·发现科学系列eClinicalMedicine在线发表 了题为"Evidence of clinical benefit of WHO essential anticancer medicines for children,2011-2021"的最新研究成果.
由清华大学药学院刘刚教授主编、清华大学出版社出版的《药物化学及药物研发案例》正式与读者见面.该书是我国第一部以案例为基础的药学教材,并辅以教学PPT、试题及参考答案、参考文献等内容,将药物化学的教学思政体现在了具体药物的研发案例中.该书由教育部高等学校药学类专业教学指导委员会牵头组织,以适应基础药学拔尖人才培养的教学要求.
In the present study,we investigated the effects of human β-defensin-3(hBD3)on the proliferation,cell cycle,and migration of HCT116 cells.The eukaryotic expression vector pcDNA3.1-hBD3 was transfected into human colon cancer HCT116 cells.The transfection efficiency was detected by qPCR and Western blotting analysis.The expressions of β-catenin,E-cadherin,and N-cadherin at the protein level were assessed by Western blotting analysis.Single-channel Hoechst33342 was used to detect the number of nuclei and calculate the proportion of proliferating cells.The cell cycle was detected by flow cytometry.The migration ability of HCT116 cells was detected by wound-healing and transwell assays.The results showed that the ability of migration and proliferation was inhibited,and the cell cycle G2/M phase was blocked.The expressions of β-catenin and N-cadherin at the protein level in HCT116-hBD3 cells were lower than those in HCT116 and HCT116-Blank cells,while the expression of E-cadherin at the protein level in HCT116-hBD3 cells was higher than that in HCT116 and HCT116-Blank cells.These findings suggested that hBD3 could regulate the migration and proliferation of HCT1 16 cells by regulating the Wnt/β-catenin signaling pathway.
In the present study,we aimed to investigate the effect of midazolam combined with dezocine on anesthesia induction before laparoscopic appendectomy.A total of 107 patients with appendicitis in our hospital from June 2018 to March 2021 were randomly divided into the control group(53 cases)and the observation group(54 cases).The control group was given midazolam,and the observation group was given midazolam combined with dezocine.The vitals,analgesia,sedation indexes,and adverse reactions of the two groups were compared.Compared with time T0,HR and MAP at T1,T2,T3,and T4 in both groups were decreased(P＜0.05),while there was no significant change in T1-T4 in the two groups,respectively(P＞0.05).MAP of the observation group was lower than that of the control group at the T1-T4 time points(P＜0.05).SPO2 showed no significant change at all time points(P＞0.05).The NRS score at 6 h after surgery of the observation group(3.52±1.28 scores)was significantly lower compared with the control group(4.26±1.76 scores,P＜0.05).The Ramsay sedation score at 1 h after surgery of the observation group(2.32±0.78 scores)was significantly higher compared with the control group(1.73±0.65 scores,P＜0.05).Moreover,there was no significant difference in the incidence of adverse reactions between the observation group(7.4％)and the control group(11.3％,P＞0.05).Collectively,midazolam combined with dezocine could better reduce postoperative MAP and postoperative pain in patients with laparoscopic appendectomy,showing good postoperative sedation effect and safety.
In the present study,we aimed to study the action mechanism of Mongolian medicine Herba Lomatognii on acute liver injury(ALI)using network pharmacology and bioinformatics methods to provide a reference for further study of Herba Lomatognii on metabolic diseases.Herba Lomatognii showed protective effects on D-GlaN-induced ALI model rats,which were used to analyze serum transaminase and enzyme-linked immunosorbent assay changes.The chemical constituents of Herba Lomatognii and their corresponding targets were collected by TCMSP database and literature search.ALI targets were compiled by GenCards and DisGeNet disease databases,and the targets of active constituents of Herba Lomatognii were interesting ALI targets.The obtained targets were targets of Herba Lomatognii against ALI.The Metascape database was used to do a Go function and KEGG pathway enrichment analysis of consensus targets,and Cytoscape software was used to create a correlation network diagram.Validation of molecular docking was carried out by analyzing important core components and significant targets.In addition,Western blotting analysis was utilized to detect transcription activator 3(STAT3),AKT1,and CASP3 expressions in the rat liver.Serum transaminases and enzyme-linked immunostaining assay demonstrated that Herba Lomatognii had preventive and anti-inflammatory effects on D-GlaN-induced ALI in rats.From network pharmacology screening,a total of 10 active ingredients of Herba Lomatognii and 289 corresponding targets were identified,843 targets of ALI and 89 targets of both,and GO enrichment and KEGG pathway analysis revealed that the common targets were mostly related to cancer,PI3K-Akt signaling pathway,Ras signaling pathway,HIF-1 signaling pathway,TNF-α signaling pathway,toll-like receptor signaling pathway,MAPK signaling pathway,VEGF signaling pathway,p53 signaling pathway,and NF-κB signaling pathway.Molecular docking results showed that the core components,such as swetiamain,luteolin,and kaempferol,could dock well with the targets of EGFR,SRC,AKT1,STAT3,and CASP3.The expressions of AKT1,STAT3,and CASP3 proteins in the liver tissues of model rats were considerably higher compared with the normal control rats based on Western blotting data(P＜0.05).In contrast to the model group,the AKT1 and STAT3 protein expressions in the liver tissues of the positive group and the Herba Lomatognii low-,medium-,and high-dose groups were significantly decreased(P＜0.05).Compared with the model group,the CASP3 protein expression in the liver tissue of the middle-and high-dosage groups of Herba Lomatognii was significantly lower,and no significant difference was observed in the liver tissue of the low-dosage group of Herba Lomatognii(P＞0.05).Herba Lomatognii contained potential therapeutic agents for ALI and could interfere with the development of ALI through multi-target and multi-pathway approaches.
In the present study,we aimed to evaluate the efficacy and safety of immune checkpoint inhibitors(ICIs)in treating malignant pleural mesothelioma(MPM).The PubMed,Embase,Web of science,and Cochrane Library databases were searched for prospective clinical trials evaluating the efficacy and safety of ICIs for the treatment of advanced MPM.The primary outcomes included objective response rate(ORR),overall survival(OS),progression-free survival(PFS),and adverse events(AEs).Eight single-arm studies and three randomized controlled trials were included,including 839 patients.Meta-analysis results showed that the pooled overall ORR of the studies receiving ICIs was 37％(95％confidence interval(CI),23％-51％),the median OS was 14.02 months(95％CI,11.40-17.64 months),and the median PFS was 4.72 months(95％CI,3.62-6.16 months).Subgroup analysis was made according to the type of treatment methods:ICI single-agent immunotherapy or ICI combination therapy(combining ICIs or ICI with chemotherapy).It was suggested that the combination therapy of ICI was superior to the single-agent immunotherapy of ICI in ORR,OS,and PFS.The results were ORR 51％(95％CI,39％-62％)vs.19％(95％CI,8％-29％),OS 18.30 months(95％CI,16.42-20.40 months)vs.11.03 months(95％CI,9.46-12.86 months),and PFS 6.78 months(95％CI,6.18-7.44 months)vs.3.40 months(95％CI,2.41-4.79 months).The incidence of grade 3-4 AEs in all studies was 30％.The most common AEs of ICI treatment were fatigue,diarrhea,and rash.The level 3-4 AEs of the combination group were higher than those of the single-agent group(37％vs.22％).The combination therapy of ICI had clinical application value in MPM patients and supported large-scale clinical application in MPM patients.However,regarding safety,ICI combination therapy had a higher incidence of grade 3-4 AEs than first-line chemotherapy.
近日,北京大学药学院药事管理与临床药学系史录文教授/管晓东副教授团队与北京大学第一医院郑波教授联合在公共卫生权威期刊Bulletin of the World Health Organization在线发表 了题为"Inpatient antibacterial use trends and patterns in China's hospitals,2013-2021"的最新研究成果.
3月6日,北京大学药学院召开主题为"重基础求创新推动新时代北大药学高质量发展"的2023年新学期发展战略研讨会,共谋下一学年学院各项事业发展大计.学院党政班子成员、党委委员、各系室负责人、教代会代表和学院各行政办公室负责人近60人参加会议.会议还特别邀请了中国科学院院士张礼和教授和离退休党支部书记、学院原党委书记解冬雪老师.研讨会分两组进行,分别由药学院院长周德敏和党委书记焦宁主持.
The specific structure of the blood-brain barrier(BBB)leads to the low permeability of central nervous system(CNS)drugs.Many cell-based in vitro BBB models have been developed to aid the study of CNS drug delivery.Mouse,rat,bovine,pig,and human brain endothelial cells are mainly used to build in vitro BBB models.However,interspecies differences in the expressions of transporters,receptors,and tight junction proteins are significant.In this review,several commonly used cell-based in vitro BBB models were introduced.The transendothelial electrical resistance and permeability coefficients of the representative substances,as well as specific endothelial markers,were highlighted.The review provided a clearer overview of these common models and a reference for readers when choosing BBB models.
Nitrosamine impurities being reported to potentially present in medicinal products are the new hot issues in the pharmaceutical field during recent years.Five classes of medicinal products are being reported due to the possible presence of nitrosamine impurities:Sartan medicines,Metformin-containing medicines,Ranitidine medicines,Rifampicin medicines,and Champix.In this paper,we introduced the source and potential root causes of nitrosamine formation,potential or founded nitrosamine impurities in API and medicinal products,and acceptable intake limits recommended for those impurities.Moreover,we also summarized the current nitrosamine impurities concerned with medicinal products and corresponding control strategies adopted by the FDA and EMA,and it is expected to give reference for the Chinese or foreign pharmaceutical enterprises,as well as the regulatory authority,to get the comprehensive understanding of the nitrosamine impurities in the medicinal products.
The antitumor potential of warfarin is demonstrated in different experimental cancer model systems.However,the mechanism of warfarin in reducing the incidence of lung cancer is unclear.In the present study,we aimed to investigate the effect and the possible mechanism of warfarin on the proliferation and apoptosis of lung cancer cell line H226.It was an in vitro experiment.The lung cancer cell line H226 was intervened with warfarin at the concentrations of 128,256,and 512 μmol/L.The cell proliferation was determined by CCK8 assay,and the cell apoptosis was evaluated by flow cytometry and Western blotting analysis.The effects of warfarin on Gas6/Axl/PI3K/Akt/NF-κB protein and gene expression were determined by Western blotting analysis and RT-PCR,respectively.Warfarin inhibited the growth of H226 cells at 24,48,and 72 h,showing a dose-and time-dependent manner.Flow cytometry results showed that the apoptosis rate of H226 cells was significantly increased when treated with 128,256,and 512 μmol/L warfarin.Meanwhile,the expression of Bcl-2 protein was decreased,and the expressions of Bax protein and Caspase 3 protein were increased,showing significant differences compared with the blank group(P＜0.05).Compared with the control group,warfarin and Axl inhibitor BGB324 could inhibit the protein expression of the Gas6/Axl pathway and its downstream pathway(P＜0.05)significantly and decrease the gene expression of the Gas6/Axl/PI3K/Akt/NF-κB pathway significantly(P＜0.05).Warfarin could inhibit the proliferation and induce the apoptosis of the lung cell line.The possible mechanism might be related to the inhibitory effect on Gas6/Axl/PI3K/Akt/NF-κB pathway proteins and genes.
In China,generic drug substitution is affected by multiple factors.However,existing studies mainly focus on policy analysis and clinical use.Therefore,we aimed to investigate the influencing factors in psychiatric patients in China's"4+7"pilot cities.The demographic characteristics,willingness to use Chinese generic drugs,and influencing factors of psychiatric patients in four pilot cities were investigated by questionnaire,and the results were statistically analyzed.Univariate analysis revealed that the willingness to use the selected generic drugs was significantly correlated with educational background,age,average monthly income,time of illness,and severity of illness.Furthermore,logistic regression analysis indicated that the willingness to use the selected generic drugs was significantly associated with patients'age.Therefore,the government should pay attention to the role of young and middle-aged groups in the substitution of generic drugs,carry out differential management,strengthen education and propaganda to all parties,adjust the standard of medical insurance payment for the selected generic drugs,and ask doctors to make suggestions on the use of selected generic drugs to target patients.
