Chronic pain represents a significant global health concern, posing a severe threat to human wellbeing and affecting up to 20% of the adult population. Bulleyaconitine A (BLA), a diterpenoid alkaloid derived from plants of the Aconitum genus with in the Ranunculaceae family, demonstrates remarkable analgesic properties with a low potential for addiction, thus broad clinical application prospects compared to opioids. Extensive research has elucidated multiple pharmacological mechanisms underlying the analgesic effects of BLA, including state-dependent blockade of voltage-gated sodium channels, activation of the κ-opioid receptor pathway in spinal microglia, and anti-inflammatory immunomodulatory effects through inhibition of the NF-κB pathway. These mechanisms have been validated in various pain models, including neuropathic pain, cancer pain, rheumatoid arthritis pain, and visceral pain. However, BLA still faces pharmacokinetic challenges in clinical translation, including a narrow therapeutic window, low bioavailability, and potential neurotoxicity. In recent years, the development of novel drug delivery systems, structural modifications targeting the C-8 and C-14 sites to separate toxicity from efficacy, and advances in artificial intelligence-assisted drug design have provided effective solutions to overcome these limitations. Emerging research suggests that BLA has potential new indications in areas such as visceral hypersensitivity, irritable bowel syndrome, and pain-related anxiety disorders. This article provides a comprehensive review of the ion channel targets, central and peripheral mechanisms of action, pharmacokinetic characteristics, innovative drug delivery strategies, structural optimization pathways, and current clinical application of BLA. It aims to offer valuable references for the further development and rational clinical application of BLA as a non-opioid analgesic with multi-target therapeutic potential.

As consumer demand for functional dairy products continues to rise, there is growing interest in formulations that provide both nutritional value and added health benefits. In this study, a novel supramolecular hybrid hydrogel was developed from phlorizin (PHL) and diosmetin (DIO), two natural bioactive flavonoids, to enhance the texture and antioxidant properties of dairy products. The hydrogel was formed via co-assembly through non-covalent interactions such as hydrogen bonding and π-π stacking. Optimized at a 1:2 PHL:DIO molar ratio and 2 % concentration, the hydrogel exhibited improved solubility, thermal stability, and mechanical strength, with a storage modulus exceeding 2.8 kPa, pronounced shear-thinning behavior (viscosity 976,000 to 330 mPa·s at 0.1-10 s-1), and rapid self-healing (103 % recovery). In vitro antioxidant assessments showed significantly enhanced activity compared to individual flavonoids, including 74.43 % DPPH, 57.65 % hydroxyl radical, 80 % ABTS, and 94.92 % superoxide anion scavenging. In vivo experiments using Caenorhabditis elegans demonstrated improved locomotion, a 28.6 % extension in lifespan under oxidative stress, and a 9-fold reduction in ROS levels. When applied in dairy systems, the hydrogel increased milk viscosity by 230-fold at low shear (0.5 % w/v) and improved yogurt texture, achieving 98.89 % water-holding capacity while promoting beneficial Lactobacillus growth. These findings highlight the potential of this dual-function hydrogel as a natural, multifunctional additive for enhancing both the sensory quality and health value of dairy products.

Doxorubicin (DOX) was an anticancer drug that had widespread use in treating tumor cells, its excessive use leaded to several adverse effects, including hair loss, cardiotoxicity, and suppression of bone marrow hematopoiesis. Herein, we designed and prepared ultrathin Pd-Au NPs anchored on the surfaces of flower-like MoS2/GO to formation Pd(4)-Au(3)/MoS2/GO nano-catalysts. The obtained Pd(4)-Au(3)/MoS2/GO nano-catalysts were characterized by scanning electron microscope (SEM) and X-ray diffractometer (XRD). The numerous ultrathin walls containing both GO and MoS2 nanolayers were interconnected to form flower-like MoS2/GO. The large specific surface area and interwoven pore structure were conducive to the loading of a large number of Pd and Au nanoparticles (NPs). The excellent hierarchical structure could possess more active sites and transportation channels to adsorb and diffuse of target analyte. Then Pd(4)-Au(3)/MoS2/GO nano-catalysts was used as sensing materials for sensitive DOX detection. The Pd(4)-Au(3)/MoS2/GO electrochemical-sensing properties and detection mechanism to DOX were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results showed that Pd(4)-Au(3)/MoS2/GO possessed excellent electrochemical catalysts activity and the electrode reaction was a an adsorption controlled process. The linear detection ranges of 0.11-127.5 mu M, the detection limits was 0.042 mu M. The prepared electrode had been successfully applied to the determination of DOX in urine sample with the recoveries were between 101.5 % and 106.4 %.

The study aimed to construct saikosaponin D (SSD)-based liposomes modified with phosphatidic acid (PA) and poloxamer 407 (P407) (termed P407-SSD-Lps), and to evaluate their tumor-targeting ability and antitumor efficacy through in vitro and in vivo experiments. The preparation process and formulation of the P407-SSD-Lps were optimized using single-factor and orthogonal experimental designs, followed by systematic characterization. Their antitumor activity and targeting specificity were assessed through in vitro experiments. Additionally, the tumor-targeting capability, therapeutic efficacy, and biocompatibility of the P407-SSD-Lps were investigated in murine orthotopic hepatocellular carcinoma transplantation models. The P407-SSD-Lps optimized through single-factor and orthogonal experiments exhibited ideal physicochemical properties. In vitro results demonstrated that the P407-SSD-Lps enhanced cell membrane permeability and promoted cellular uptake in the HepG2 cells. Additionally, they significantly inhibited the HepG2 cells proliferation and induced apoptosis. In murine orthotopic hepatocellular carcinoma transplantation models, the P407-SSD-Lps exhibited prolonged tumor accumulation and demonstrated potent antitumor efficacy with favorable biocompatibility. When delivering doxorubicin (DOX), the system not only retained high biocompatibility but also exhibited enhanced therapeutic efficacy. Employing the SSD as both a liposomal membrane stabilizer and a therapeutic agent constituted a novel expansion of “drug-excipient integration” material applications. Moreover, the SSD-based P407-SSD-Lps system functioned as a stable and efficient multifunctional liposomal delivery system, offering innovative therapeutic avenues for hepatocellular carcinoma treatment.

IntroductionA series of oridonin hybrids were synthesized and evaluated for anti-inflammatory potential, focusing on their ability to inhibit NO production in RAW264.7 cells and their therapeutic prospects for NLRP3-driven disorders.MethodsAnti-inflammatory activity was assessed by measuring NO inhibition in LPS-stimulated RAW264.7 cells. The most active compound, 4c, was further analyzed using ELISA and WB to evaluate its effects on inflammatory proteins (p-NF-κB, p-IκB, NLRP3, IL-6, IL-1β, COX-2, iNOS). In vivo efficacy was tested in a murine acute lung injury model, with RT‒qPCR and WB used to assess inflammatory markers in lung tissues. Molecular docking predicted 4c’s binding mode with NLRP3, while RNA-seq and RT‒qPCR identified differentially expressed genes.ResultsCompound 4c significantly inhibited NO production and suppressed key inflammatory proteins in vitro. In vivo, it alleviated acute lung injury, reduced IL-6 and TNF-α mRNA levels, and inhibited NLRP3, p-NF-κB, and IL-6 protein expression. Docking suggested covalent binding to NLRP3. RNA-seq revealed 4c upregulated Trdc, Stfa2, and Gsta2 while downregulating Spib, Csf2, and Nr4a1.DiscussionCompound 4c demonstrates potent anti-inflammatory effects via NLRP3 pathway inhibition and modulation of inflammatory genes. These findings highlight oridonin hybrids, particularly 4c, as promising candidates for NLRP3-driven inflammatory disorders, warranting further investigation.

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of chalcone analogues were designed and synthesized. The figure was drawn by Figdraw (http://www.figdraw.com).

Dysfunction of the Nav1.5, Cav1.2, and Kv channels could interfere with the AP and result in arrhythmias and even heart failure. We herein present a novel library of nuciferine analogs that target ion channels for the treatment of arrhythmias. Patch clamp measurements of ventricular myocytes revealed that 6a dramatically blocked both the INa and ICa without altering the currentvoltage relationship (including the activation potential and peak potential), accelerated the inactivation of Nav and Cav channels and delayed the resurrection of these channels after inactivation. Additionally, 6a significantly decreased the APA and RMP without affecting the APD30 or APD50. The IC50 values of 6a against Nav1.5 and Cav1.2 were 4.98 μM and 4.62 μM, respectively. Furthermore, 6a (10 μM) blocked IKs, IK1, and Ito with values of 17.01 %±2.54 %, 9.09 %±2.78 %, and 11.15 %±3.52 %, respectively. Surprisingly, 6a weakly inhibited hERG channels, suggesting a low risk of proarrhythmia. The cytotoxicity evaluation of 6a with the H9c2 cell line indicated that this compound was noncytotoxic. In vivo studies suggested that these novel nuciferine analogs could shorten the time of arrhythmia continuum induced by BaCl2 and normalize the HR, QRS, QT and QTc interval and the R wave amplitude. Moreover, 6a dose-dependently affected aconitine-induced arrhythmias and notably improved the cumulative dosage of aconitine required to evoke VP, VT, VF and CA in rats with aconitine-induced arrhythmia. In conclusion, nuciferine analogs could be promising ion channel blockers that could be further developed into antiarrhythmic agents.

目的:分析丁香-肉桂药对共提取挥发油(丁香-肉桂挥发油)的成分及其抗氧化作用,为该药对临床合理应用于关节炎性病症提供实验依据.方法:通过GC-MS分析丁香-肉桂挥发油成分,DPPH、ABTS+自由基清除实验及总还原力测定丁香-肉桂挥发油的抗氧化能力,MTT法测定丁香-肉桂挥发油对RAW264.7细胞的细胞活力影响;H202刺激RAW264.7细胞建立氧化损伤模型,试剂盒检测丁香-肉桂挥发油对细胞CAT、SOD、GSH-PX、MDA水平的影响.结果:GC-MS分析鉴定出丁香-肉桂挥发油20种成分,其中丁香酚、α-古巴烯、β-石竹烯、肉桂醛等成分相对含量较高,丁香-肉桂挥发油对ABTS+自由基和DPPH自由基都有较好的清除作用,其IC50分别为(24.15±1.03)μg/mL和(47.23±1.89)μg/mL,其总抗氧化能力FRAP值与丁香-肉桂挥发油浓度呈现量效关系;10～80 μg/mL 丁香-肉桂挥发油对RAW264.7细胞活性没有影响;40 μg/mL的丁香-肉桂挥发油能显著提高抗氧化因子SOD、GSH水平,并降低过氧化脂质产物LDH、MDA水平(P＜0.01).结论:丁香-肉桂挥发油通过提高抗氧化因子活性,抑制脂质过氧化酶反应,改善细胞氧化损伤,具有较好的抗氧化能力.

目的:通过建立高效液相色谱(HPLC)法,测定昭通产三七剪口、根茎、须根以及三七茎叶中的5种皂苷:三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和人参皂苷Rd的含量,为昭通产三七药材质量控制奠定基础.方法:采用HPLC法,以乙腈-水为流动相,进行梯度洗脱.结果:在所建立的色谱条件下,三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和人参皂苷Rd有较好的分离度,线性关系、稳定性、精密度和加样回收试验均符合中药质量分析的要求;昭通三七剪口中以上5种皂苷含量最高,其总含量为6.709％,其中人参皂苷Rg1、人参皂苷Rb1以及三七皂苷R13种皂苷总含量为5.720％,茎叶中仅含有人参皂苷Rb1、人参皂苷Rd两种皂苷,其总含量为0.2539％.结论:昭通产三七剪口的总皂苷含量符合现行版《中国药典》要求、根茎总皂苷含量略低于《中国药典》标准,昭通引种三七值得进一步探讨.

药事管理学是药学专业的主干课程之一,旨在帮助学生正确处理和解决药事工作中的各类实际问题.在教学过程中,药事管理学课堂的案例教学难以满足现代企事业单位的实际需求,多数学生毕业工作后发现绝大多数的药事主干知识仍然需要不断补充学习才能适应岗位需要.以能力为核心、以成果为导向的OBE教育教学理念已成为教育改革的主流理念和重要的质量考核标准,该理念以强调"以学生为中心"的"价值塑造、能力培养、知识传授".基于此,结合案例教学和OBE理念,该文从案例教学现状、案例教学的新要求、案例教学实践等方面入手,探讨基于OBE理念的案例教学模式的改革实践.

Swertia patens Burk. is a commonly used herbal medicine of the Yi nationality in Yunnan, China. It is widely used in the treatment of children with spastic abdominal pain, cholecystitis, and other diseases, mainly containing iridoid glycosides and ketone compounds. The highest and most significant pharmacological activity, with antispasmodic, analgesic, sedative, anti-inflammatory, liver-protecting, stomach-protecting, and other effects, is closely related to its effects of soothing the liver, clearing heat, and relieving stomach pain. As a very distinctive pediatric folk medicine, the related quality standards of Swertia patens Burk. have not been perfected, and the development of preparations is relatively lagging.

目的 制备DiR(1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanineiodide)脂质体荧光探针(DiR-LP),研究柴胡作为引经药对其在小鼠体内分布的影响,初步验证柴胡引药入肝性能.方法 薄膜分散法制备DiR-LP,以包封率为主要指标,通过单因素试验确立DiR-LP最佳处方与制备工艺,并进行表征.30只SPF级昆明种小鼠随机分为5组:对照组、DiR-LP组和柴胡水提液低、中、高剂量(0.5、1.0、2.0 mg·kg-1)+DiR-LP组,柴胡水提液+DiR-LP组小鼠预先连续3 d按10 mL·kg-1体积ig相应的柴胡水提液,对照组和DiR-LP组小鼠ig相同体积的生理盐水;除对照组外,各组小鼠以10 mL·kg-1尾ivDiR-LP,对照组小鼠尾iv相同剂量的生理盐水;利用小动物活体成像仪在不同时间点(4、5、6、8h)拍照,示踪小鼠体内DiR-LP的分布情况;8h时经解剖取出心、肝、脾、肺、肾等器官进行拍照,观察各器官的荧光强度.结果 DiR-LP最佳处方与制备工艺:精密称取大豆卵磷脂120 mg、胆固醇12 mg、DiR 0.375 mg于100 mL茄形瓶中,加入10 mL无水乙醇溶解,于40℃恒温水浴中,30r.min-1旋转减压蒸发1 h,形成均匀透明薄膜;再加入聚山梨酯80 12 mg、溶于纯净水10 mL,于150 r·min-1旋转常压水化1 h后,置于冰水浴中超声10 min(功率100 W),分别过0.45、0.22μm微孔滤膜整粒3次,即得DiR-LP.制得的DiR-LP包封率为95.2％,粒径为254.1 nm,聚合物分散性指数(PDI)为0.196,Zeta电位-5.21 mV,14 d内无沉淀或浑浊现象.DiR-LP经尾iv后主要在肝脏中分布,柴胡水提液+DiR-LP组肝脏部位荧光信号明显比DiR-LP组强,且荧光信号强度与柴胡水提液剂量呈正相关.结论 使用薄膜分散法制备的DiR-LP包封率高、粒径适宜、稳定性较好;在小鼠体内,柴胡对DiR-LP具有肝脏导引作用,且与剂量相关,初步验证了柴胡"引药入肝"的肝靶向性.

Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity.

Carbapenem-resistant Enterobacterales (CRE) has emerged as a worldwide spread nosocomial superbug exhibiting antimicrobial resistance (AMR) to all current antibiotics, leaving limited options for treating its infection. To discovery novel antibiotics against CRE, we designed and synthesized a series of 14 isothiazol-3(2H)-one analogues subjected to antibacterial activity evaluation against Escherichia coli ( E. coli ) BL21 (NDM-1) and clinical strain E. coli HN88 for investigating their structure–activity relationships (SAR). The results suggested that 5-chloroisothiazolone core with an N-(4-chlorophenyl) substitution 5a was the most potent antibacterial activity against the E. coli BL21 (NDM-1) with MIC value of less than 0.032 μg/mL, which was at least 8000-fold higher than the positive control Meropenem (MRM). It also displayed 2048-fold potent than the positive control MRM against E. coli HN88. Additionally, SAR analysis supported the conclusion that compounds with a chloro-group substituted on the 5-position of the heterocyclic ring was much more potent than other positions. The board spectrum analysis suggested that compound 5a showed a promising antimicrobial activity on MRSA and CRE pathogens. Meanwhile, cytotoxicity study of compound 5a suggested that it had a therapeutic index value of 875, suggesting future therapeutic potential. In vivo efficacy study declared that compound 5a could also protect the BALB/c mice against American type culture collection (ATCC) 43,300. Further screening of our compounds against a collection of CRE strains isolated from patients indicated that compound 5 g displayed much stronger antibacterial activity compared with MRM. In conclusion, our studies indicated that isothiazolones analogues could be potent bactericidal agents against CRE and MRSA pathogens.

Novel selective [3 + 2] cycloaddition reactions between in situ formed nonstabilized azomethine ylide generated from N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine enabled by Lewis acids and bioactive molecules isothiazol-3(2H)-ones have been developed. The reaction selectively afforded novel thiazolidines or cyclo-fused oxazolidinones depending on Lewis acid catalyst system of reaction used.

目的 研究除湿通痹颗粒对以尿酸钠(MSU)为诱导因素的急性痛风性关节炎模型大鼠右后足踝关节肿胀指数、炎症指数、关节功能障碍、炎症细胞因子以及踝关节滑膜组织切片的影响,探讨除湿通痹颗粒治疗急性痛风性关节炎的部分作用机制.方法 选用Wistar雄性大鼠48只,随机分成3组,包括生理盐水组(A)、模型组(B)、秋水仙碱组(C)、除湿通痹颗粒低(D)、中(E)、高(F)剂量组.各组给予相应药物灌胃,2次/d,第3天灌胃1.5h后于大鼠右后足内踝的胫跗关节注射MSU晶体形成大鼠急性痛风性关节炎模型,并于10,24,72h分别观察测量大鼠右后足踝关节肿肿胀指数、炎症指数、关节功能障碍等;注射MSU3天后,ELISA法检测腹主动脉血清中大鼠白介素-4(IL-4)和白介素-1β(IL-1β)浓度,HE染色法观察右后足踝关节滑膜组织切片的病理变化.结果 对比A组,B组造模后4,10,24,72 h关节肿胀指数明显增加(P＜0.05).对比B组,C、E、F组各时段关节肿胀指数显著减轻(P＜0.05),且E、F组较D组关节肿胀指数有降低趋势.与B组比较,C、D、E、F组关节炎症指数和功能障碍明显减轻.对比B组,C、D、E、F组的IL-1β的浓度明显减低.HE染色显示模型组(B)大鼠踝关节滑膜具有明显的炎性症状,滑膜细胞具有一定的增生,伴炎细胞、小血管具有明显的浸润与增生,而C、D、E、F组上述病理改变减轻.结论 除湿通痹颗粒可明显缓解MSU导致的大鼠后足踝关节肿胀、红肿及功能障碍,降低IL-1β的表达,缓解滑膜组织炎症病理组织切片变化.

课程思政在大学生培养中有着举足轻重的作用,为了开拓新的教育形式、提高教育效果,在专业课程教学中融入思政元素已取得一定成效.药剂学是药学专业的主干专业课,教学中融入思政内容,有助于在教授专业知识的同时实现“立德树人”教育.

目的:为探讨傣药和拉祜族药的药用资源、炮制及制剂特点,促进民族药的合理保护与开发利用.文章对目前傣族和拉祜族传统药物的应用与研究进行了系统阐述和整理分析.方法:通过查阅大量的相关文献及实地考察,收集整理并归纳总结傣药、拉祜族药的药用资源、炮制和制剂研究应用.结果:初步总结出我国傣药、拉祜族药的应用与研究进展.结论:为进一步研究和开发我国傣药、拉祜族药的药用资源、炮制及制剂提供一定的参考依据.

目的:提高克淋通胶囊的质量标准,便于控制其质量.方法:采用薄层色谱法(TLC)法鉴别黄柏,并检查关黄柏;采用高相液相色谱法(HPLC)法测定克淋通胶囊中没食子酸的含量.结果:TLC方法斑点清晰,专属性强;HPLC法测定没食子酸在0.04242～0.6363 μg范围内线性关系良好,平均加样回收率为99.76％,RSD值0.25％.结论:该方法操作简便、结果准确可靠、专属性及重现性好,可用于有效地控制克淋通胶囊的质量.

中药药剂学是我校中药学、中药资源与开发、中草药栽培与鉴定等专业的核心主干课程.历时数十余载,完成万余人的教学任务,但也存在部分课堂教学效果不佳、教学资源有限、缺乏全面有效的评价体系等问题.经过教研室和教学团队的总结和创新设计,在依旧贯彻课堂讲授"抓主线、破难点"、线上资源"做补充、开眼界"、实践训练"铸基础、重应用"的原则上,针对性地提出"一个中心、二个层次、三个创新教学方法"的设计思路重构课程,实现显隐式课程思政融入、线上线下混合教学、有限资源产出最大化、国际化培养的部分创新成果,培养"四能"复合应用型人才.