Tetramethylpyrazine (TMP), a potent coronary vasodilator, enhances myocardial perfusion and shows promise for treating cardiovascular disorders. Its clinical utility is limited, however, by the short half-life of conventional tablets and injections, which necessitates frequent dosing. To overcome this drawback, we developed a transdermal patch that co-loadsTMP and borneol (BO-TMP). After optimization, patches containing 3

Medicinal plant-derived extracellular vesicles (MPDEVs) are nanoscale vesicles secreted by medicinal plant cells. They are enriched in diverse functional components and function as natural mediators that facilitate intercellular communication and regulate multiple physiological processes. Owing to their unique biological activities and delivery capabilities, these vesicles have emerged as a frontier research hotspot. Recent studies have demonstrated that MPDEVs exhibit excellent biocompatibility and cross-species delivery potential and can be engineered to encapsulate small-molecule compounds for use as drug delivery vectors. Remarkably, MPDEVs also display notable intrinsic therapeutic effects and can be directly applied as natural therapeutic agents in various disease models. Furthermore, MPDEVs can be co-administered with conventional therapeutic drugs to strengthen their efficacy and improve bioavailability. This article systematically summarizes the biogenesis, composition, and functional properties of MPDEVs and emphasizes their broad application potential, characterized by a triple identity as intelligent carriers, natural therapeutic agents, and synergistic treatment systems. Nonetheless, the translation of MPDEVs from laboratory research to clinical application is impeded by several critical challenges, including source heterogeneity, the absence of specific biomarkers for efficient purification and identification, and a lack of standardized quality control procedures. Accordingly, this paper also highlights these core limitations and outlines future development directions aimed at facilitating clinical translation and industrial deployment. The objective is to provide a comprehensive reference and theoretical framework to support overcoming these constraints and to contribute to the advancement of MPDEVs into reliable and scalable biomedical tools.

The limited aqueous solubility and transdermal permeability of rotundine (RTD) constrain its therapeutic utility in pain management. To address these challenges, a co-amorphous formulation incorporating RTD and syringic acid (SA) were designed to improve solubility, dermal permeation, and pharmacological efficacy. The system's solid-state and molecular attributes were rigorously evaluated via PXRD, DSC, FTIR, NMR, and molecular docking simulations. Findings revealed ion-pair complexation between SA and RTD within the amorphous matrix, yielding enhanced solubility, synchronized dissolution, and modulated stratum corneum lipid organization to promote permeation. In vitro assessments demonstrated an 867-fold solubility enhancement for RTD and a 12-fold increase for SA relative to their crystalline counterparts. Ex vivo Franz cell studies confirmed superior transdermal flux and coordinated release profiles for the co-amorphous formulation. Molecular dynamics simulations elucidated reduced free energy barriers for the neutral ion-pair, corroborating the observed permeation synergy. In vivo analgesic evaluations in acetic acid-induced zebrafish nociception and mouse hot-plate models evidenced rapid, sustained pain relief with the co-amorphous system, mitigating RTD's sedative effects while preserving efficacy. This study highlights co-amorphous drug-drug systems as a versatile, excipient-free platform for transdermal delivery of poorly soluble bioactives, offering a promising strategy for improving the efficacy and safety of pain management treatments.

Autophagy is a highly conserved cellular degradation and recycling process that plays a pivotal role in maintaining cartilage homeostasis. Normal autophagy is essential for the survival of chondrocytes and the preservation of the extracellular matrix (ECM); however, a decline in autophagic function may lead to the accumulation of damaged organelles and macromolecules, thereby reducing chondrocyte vitality and promoting apoptosis, which in turn contributes to the development of osteoarthritis (OA). This review summarizes the biological processes of autophagy, the interaction between autophagy and cartilage degeneration, as well as the interplay between autophagy and cellular senescence, apoptosis, inflammation, and oxidative stress. Furthermore, we explore key autophagic targets for the regulation of OA and discuss autophagy-targeting therapies, including mTOR inhibitors, AMPK activators, and natural products that target autophagy, along with emerging strategies aimed at modulating autophagy. Finally, the article highlights the challenges in the development of autophagy-targeting drugs for OA treatment and presents important scientific issues that warrant further investigation to guide future research.

Introduction: The currently available therapies for acute lung injury (ALI), including gluco-corticoids, protease inhibitors, and heparin, have limited clinical efficacy and are often associated with significant side effects. Cepharanthine (CEP) has demonstrated effectiveness in treating pulmonary dis-eases, but its clinical application is restricted by low solubility and poor bioavailability. This study aimed to develop mannosylated cepharanthine-loaded polymeric micelles (MA-CEP-PMs) to improve CEP bio-availability and enhance lung-targeted delivery for the treatment of ALI. Methods: The pharmacokinetics of MA-CEP-PMs in rats were assessed using Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). Lung-targeting ability was evaluated through tissue distribution studies and near-infrared imaging. In a rat model of ALI induced by lipopolysaccharide (LPS), anti-ALI effects were assessed via general physiological indicators, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot analysis. Hematoxylin-eosin (HE) staining was used to examine hepatotoxicity and nephrotoxicity of MA-CEP-PMs in normal rats. Cyto-toxicity of the mannosylated polyethylene glycol-poly(lactic-co-glycolic acid) copolymer (MA-PEG-PLGA) on NR8383 cells was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake experiments were performed to determine the targeting ability of MA-PEG-PLGA in NR8383 cells, and the effects of MA-CEP-PMs on inflammatory cytokines were analyzed using ELISA. Results: MA-CEP-PMs significantly increased the AUC and exhibited better lung targeting ability com-pared to the unmodified micelles (P < 0.01). In the ALI model, MA-CEP-PMs improved the thymus and spleen indices, decreased the lung wet-to-dry weight ratio (P < 0.05), alleviated model animal damage, and inhibited inflammatory factor and nuclear factor-κB (NF-κB)-related protein levels (P < 0.05). MA-CEP-PMs exhibited no significant hepatotoxicity or nephrotoxicity. MA-PEG-PLGA exhibited low tox-icity against NR8383 cells and greater cell uptake, indicating stronger targeting of the lung. MA-CEP-PMs also exhibited more potent anti-inflammatory effects. Discussion: This study focused on the short-term therapeutic effects of ALI, whereas the clinical man-agement of lung injury often requires long-term intervention. Future research should therefore assess the long-term efficacy of this delivery system in chronic lung injury, along with determining its safety profile and potential impacts on extra-pulmonary organs. While the involvement of the NF-κB pathway in the anti-inflammatory effects has been confirmed, it remains to be deciphered whether mannose modification synergistically regulates other signaling pathways and what the specific intracellular targets of CEP are, which would require further exploration through detailed molecular biology experiments. Conclusion: The MA-CEP-PMs significantly improved CEP bioavailability and increased lung targeting. They exhibited good safety and had a significant effect on ALI management. .

ETHNOPHARMACOLOGICAL RELEVANCE:Huli San (HLS) is a classic compound formulation long utilized by ethnic minorities such as the Yi and Miao peoples in Southwest China. Its composition blends traditional medicinal herbs including Aconitum vilmoriniannum Kom (AK), Panax notoginseng (Burk.) F. H. Che (PN), Cynanchum wallichii Wight (CW), and Campanumoea javanica BI (CJ), creating a formula deeply rooted in the rich tradition of ethnic pharmacology. This compound is renowned for its ability to dispel wind and dampness, invigorate blood, and alleviate pain. It is commonly used to treat rheumatic pain, numbness of muscles and bones, and injuries from falls and bruises, reflecting the indigenous understanding of the interplay between "wind-damp-stasis" as the core pathological mechanism. Traditionally, Huli San is prepared through processes such as grinding, resulting in either a powder or tincture for oral administration. Its clinical efficacy is centered around the relief of wind-damp conditions, promoting blood circulation, and alleviating pain, particularly in the treatment of rheumatic disorders, musculoskeletal numbness, and traumatic injuries. AIM OF THE STUDY:The study aimed to comprehensively analyze the chemical components, acute toxicity, as well as anti-inflammatory and analgesic effects of the HLS ethanol extract (HLS-EE) and compare it with the commercial drug Hulisan capsules (HLS-C). MATERIALS AND METHODS:The chemical composition of HLS-EE was characterized using UPLC-MS/MS, and its median lethal dose (LD50) was determined to establish a safe dosage range. Toxicological assessment included observation of pathological alterations in major organs. The anti-inflammatory efficacy of HLS-EE and HLS-C was evaluated utilizing three classical models: xylene-induced ear edema, carrageenan induced paw edema, and acetic acid-induced vascular permeability in mice. Their analgesic activity was assessed via the acetic acid-induced writhing test, hot plate test, and formalin-induced biphasic pain test. RESULTS:The UPLC-MS/MS analysis showed that there were 156 kinds of chemicals in HLS-EE. The LD50 value is 2.962 g/kg. Histopathological examination showed no major abnormalities in the heart, liver, spleen, lungs, and kidneys at 15 times the clinical dose (CLD); at 90 times and 120 times the CLD, there were inflammatory cell infiltrations in multiple organs. HLS-EE showed great activity on anti-inflammatory testing. It significantly inhibited xylenc-caused ear swelling, carragenan-caused paw swelling and aceticacid-caused vascular leakage tests. Middle and high-dose HLS-EE groups exhibited stronger inhibition than HLS-C. Mechanistically, HLS-EE reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) in serum from ear edema model.In the paw edema model, it decreased IL-1β, IL-6, TNF-α, prostaglandin E2 (PGE2), nitric oxide (NO), and malondialdehyde (MDA), while increasing superoxide dismutase (SOD) activity. Additionally, HLS-EE downregulated protein and mRNA expression of cyclooxygenase-2 (COX-2), IL-6, TNF-α, and extracellular signal-regulated kinase 1/2 (Erk1/2) in paw tissues. In analgesic tests, HLS-EE markedly reduced writhing responses, prolonged thermal pain latency, and suppressed formalin-induced biphasic pain, with middle and high doses outperforming HLS-C. Serum analysis showed decreased 5-hydroxytryptamine (5-HT), IL-1β, and PGE2 in writhing-test mice and reduced IL-1β and IL-6 in formalin-test rats. Spinal cord analysis further indicated downregulated mRNA expression of cellular oncogene fos (c-Fos), 5-hydroxytryptamine 2A receptor (5-HT2A), kappa opioid receptor (KOR), and prodynorphin (PDYN), suggesting central analgesic mechanisms. CONCLUSION:A total of 156 chemical components were identified in HLS-EE. The LD50 of HLS-EE is 2.962 g/kg. HLS-EE exhibits good anti-inflammatory and analgesic effects, which are superior to those of the commercially available HLS-C. This study provides a basis for further research and formulation development of HLS-EE and contributes to the promotion of the development and utilization of ethnic medicine.

Purpose:To investigate the synergistic protective effects and underlying mechanisms of combining Acorus gramineus rhizoma volatile oil (VOA), known for its "Cardiotropic-channel-directing" properties, with Crebanine (Cre) in MIRI. Patients and Methods:An MIRI model was established in Sprague-Dawley rats to evaluate the synergistic cardioprotective effects of VOA combined with Cre. Myocardial injury was assessed by measuring the infarct size, apoptotic cardiomyocytes, myocardial injury biomarkers, and histopathological changes. Proinflammatory mediators and oxidative stress markers and results of Western blotting were analyzed to determine the underlying cardioprotective mechanisms of Cre and VOA. In addition, metabolomic analysis was conducted to identify alterations in relevant metabolic pathways. Results:Cre and VOA alleviated MIRI in rats by reducing infarct size, lowering the levels of myocardial injury biomarkers (Lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase (CK), and creatine kinase-myocardial band (CK-MB)), and ameliorating histopathological damage. Mechanistically, Cre and VOA attenuated oxidative stress by enhancing the activity of the antioxidant enzyme superoxide dismutase (SOD) and suppressing the expression of the oxidative stress marker malondialdehyde (MDA). In addition, they downregulated proinflammatory cytokines (interleukin-6 (IL-6) and interleukin-1β (IL-1β)) by inhibiting the MAPK/NF-κB/TNF-α signaling pathway. They mitigated endoplasmic reticulum (ER) stress and apoptosis by modulating the GRP78-PERK/ATF6-CHOP pathway. Metabolomic analysis identified 13 potential biomarkers, and glutamic, pantothenic, and oleic acids were the key metabolites. The glycine, serine, and threonine metabolism pathway, glutathione metabolism, the pentose phosphate pathway, and the biosynthesis of unsaturated fatty acids were the most relevant metabolic pathways involved in the cardioprotective effects of Cre and VOA. Conclusion:Cre and VOA may alleviate MIRI by modulating energy metabolism and suppressing apoptosis and inflammatory responses triggered by oxidative and ER stress. This effect is mediated by GRP78-PERK/ATF6-CHOP and MAPK-NF-κB-TNF-α signaling pathways. Moreover, the volatile oil of Acorus tatarinowii significantly enhanced the cardioprotective effects of Cre against ischemia-reperfusion injury.

Osteoarthritis (OA) is a chronic degenerative joint disease, primarily characterized by the degradation of the ECM and cartilage degeneration. Articular cartilage is maintained by chondrocytes, which secrete the ECM, making the stability of these cells crucial for joint function. Research has shown that in the later stages of OA, cartilage cavities form, indicating a decline in chondrocyte function. Chondrocyte death is considered a central feature of cartilage degeneration. Apoptosis, a form of programmed cell death, plays a key role in this process. While controlled apoptosis helps remove damaged chondrocytes and protects the cartilage from injury, excessive apoptosis disrupts the balance of the cartilage microenvironment and accelerates OA progression. Therefore, regulating chondrocyte apoptosis may offer a novel approach for preventing and treating cartilage degeneration. This review examines the apoptosis pathways, the interaction between apoptosis and OA, the key regulatory factors of chondrocyte apoptosis, and analyzes current drug interventions targeting apoptosis in both preclinical and clinical studies. It also discusses the challenges in treating OA and outlines future research directions to guide upcoming studies.

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.

Objective To investigate pharmacokinetic characteristics of sinoacutine transdermal patch by pharmacological effect method,and to provide an experimental basis for the clinical application of sinoacutine transdermal patch.MethodsUsing the analgesic effect in the hot-plate test as indicator,we calculated the net rise rates of pain threshold at different time points,obtained the dose-effect relationship and draw systemic cumulationtime curve.The pharmacokinetic parameters of sinoacutine transdermal patch in mice were computed.A model of adjuvant arthritis rats was used,and TNF-α inhibition rate was investigated,the content of TNF-α was determined by ELISA method at different time points to obtain the dose-effect relationship.Then,systemic cumulation-time curve was drawn,and the pharmacokinetic parameters of sinoacutine transdermal patch in rats was computed.ResultsThe main pharmacokinetic parameters of sinoacutine transdermal patch in mice and rats were as following:AUC 0-t =（2 721.114±620.672）,（4 158.542±89.465）mg·h·kg -1 ;AUC 0-∞ =（2 968.194±534.247）,（7 088.899±2 173.940）mg·h·kg -1 ;t max =9 h;C max =（247.604±129.485）,（179.091±7.503）mg·kg -1 ;MRT 0-t =（10.776±0.408）,（21.424±0.804）h;MRT 0-∞ =（12.855±2.870）,（53.798±24.543）h;t 1/2z =（14.219±2.660）,（35.531±17.760）h;CL z /F=（0.104±0.019）,（0.045±0.012）L·h -1 ·kg -1 ;V z /F=（0.785±0.442）,（2.078±0.451）L·kg -1 .ConclusionThe pharmacokinetic process of sinoacutine turbodermal patch is in line with non-compartment model in mice and rats.Linear dynamics feature was observed in the range of administered doses.Sinoacutine turbodermal patch showed a longer arrived peak time and higher peak concentration,which can continuously control the release rate of sinoacutine and thereby prolong the effect.

目的:探讨香果健消片治疗肠易激综合征(irritable bowel syndrome,IBS)的作用机制.方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology data-base and analysis platform,TCMSP)和基因与化学物质相互作用预测数据库(STITCH)检索,以及文献挖掘收集香果健消片配方中草果、木香、蜘蛛香的有效成分与潜在靶点,借助人类基因数据库(the human gene database,GeneCards)预测IBS作用靶点,通过VENNY平台得到IBS与中药有效成分的共同作用靶点,借助String数据库平台筛选人类且置信度高于0.4的靶点,采用Cytoscape软件构建中药有效成分靶点互作网络图,通过R软件进行GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)通路富集分析,利用CB-Dock数据库对中药治疗IBS的核心靶点与有效成分进行分子对接.结果:通过筛选得到有效活性成分草果8个,木香7个,蜘蛛香3个,IBS相关靶点2027个,中药与IBS共同靶点73个,主要通过作用于TP53基因、白细胞介素6、血管内皮生长因子A、胱天蛋白酶3、表皮生长因子受体等关键基因参与调控肿瘤坏死因子、Hepatitis B等信号通路,发挥治疗IBS的作用.与关键靶点对接较好的成分是表儿茶素和橙皮苷.结论:草果、木香、蜘蛛香3药配方治疗IBS的主要药效物质及其可能的分子作用机制印证了香果健消片多成分、多靶点的整体调节作用特点.

苄基异喹啉类生物碱（Benzylisoquinoline alkaloids，BIAs）属于异喹啉类生物碱中的一类，根据其化学结构特点可分为小檗碱和原小檗碱类、阿朴菲类、苄基四氢异喹啉类、普罗托品类、双苄基异喹啉类等。此类生物碱来源中药及中药组方在治疗心悸、怔忡、厥证、胸痹等心血管相关疾病方面也有着丰富的临床用药经验，现代研究表明苄基异喹啉类生物碱具有较强的抗心律失常活性，从中药中开发抗心律失常单体活性成分，毒性、副作用更清楚，开发成本更低。基于心律失常发病机制复杂的特点，通过多途径，多靶点作用的抗心律失常药物具有更高的安全性和有效性，现在临床使用的抗心律失常药物大多属于单离子通道阻滞剂，具有致心律失常风险，而苄基异喹啉类生物碱可通过影响Na + 、K + 、Ca 2+ 多条离子通道、抗炎及氧化应激途径达到治疗多种心律失常的目的，极具开发前景。本文通过查阅、整理近40年的国内外文献，结合中医药理论对苄基异喹啉类生物碱的抗心律失常离子机制进行总结，可为开发安全高效的抗心律失常药物和治疗手段提供参考。

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.

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 对不同产地的瓜子金药材进行质量评价.方法 利用高效液相色谱-蒸发激光散射检测法(HPLC-ELSD)建立瓜子金皂苷己含量测定方法,并测定13批不同产地瓜子金药材中瓜子金皂苷己的含量,各产地样品分析采用ZORBAX Eclipse Plus C18色谱柱(4.6 mm×250 mm,5μm);流动相:水-乙腈,梯度洗脱,流速:1 min/ml,柱温:30℃,进样量:10μl,漂移管温度70℃,喷雾器温度40℃,气体流速:1.64 L/min.参照2020年版《中国药典》方法对不同产地瓜子金药材进行薄层色谱鉴别.结果 不同产地瓜子金药材中瓜子金皂苷含量排名:广西贵港(0.60％)＞贵州毕节(0.39％)＞安徽阜阳(0.37％)＞贵州安顺(0.29％)＞贵州兴义(0.23％)＞云南双江(0.20％)＞湖北随州(0.11％),其余产地未检出瓜子金皂苷己.不同产地13批瓜子金药材薄层色谱鉴别结果与高效液相色谱结果具有一致性.结论 本研究建立的方法准确、科学、稳定,适用于瓜子金皂苷己的含量测定;不同产地13批瓜子金药材中仅广西贵港药材达到药典要求.

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy. Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved. Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels. Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages ( p < .01). Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

目的 比较克班宁经皮和灌胃2种给药途径在大鼠体内的药动学差异性,评价克班宁贴剂经皮给药抗大鼠心律失常的效果,以及克班宁对钙离子通道的作用机制.方法 采用HPLC法测定大鼠血浆中克班宁的浓度;采用氯化钡(BaCl2)致大鼠心律失常的模型观察克班宁经皮给药的抗心律失常效果,采用Whole Cell记录检测克班宁对钙通道电流的影响.结果 克班宁贴剂经皮给药(400 mg·kg-1)的主要药动学参数为:AUC0-∞=(204.500±170.496)mg·h·L-1;Tmax=(10.333±0.745)h;Cmax=(1.968±0.147)mg·L-1(n=6).克班宁溶液灌胃给药(40 mg·kg-1)的主要药动学参数为:AUC0-∞=(26.980±6.672)mg·h·L-1;Tmax=(0.086±0.024)h;Cmax=(8.991±2.343)mg·L-1(n=6).与阴性组比较,79、158、316 mg·kg-1三个剂量克班宁贴剂组大鼠经皮给药后,恢复窦性心律所需的时间均显著缩短(P<0.01),恢复窦性心律的鼠数均明显增多(P<0.01);给药后≤20 min能够恢复窦性心律的鼠数均明显增多(P<0.001);恢复窦性心律后维持时间>20 min的鼠数显著增多(P<0.01).克班宁对T型钙通道和L型钙通道均有较明显的抑制作用.结论 克班宁贴剂给药在大鼠体内消除慢,具有缓释作用,可通过抑制钙离子通道发挥对BaCl2致大鼠心律失常的明显抑制作用,显著延长作用时间,达到减毒增效的目的.

目的:建立不同产地、批次草果挥发油气相色谱-质谱联用(GC-MS)指纹图谱,并评价其质量.方法:采用GC-MS技术建立不同产地、批次的草果挥发油指纹图谱并评价其相似度,结合聚类分析、主成分分析以及熵权TOPSIS法比较不同产地、批次草果挥发油的化学成分差异,并对其品质优劣进行评价.结果:16批次草果挥发油有19个共有峰,相似度在0.967～0.996之间.聚类分析结果显示,16批草果挥发油可以分为3类.主成分分析结果显示共提取出3个主成分,累计方差贡献率为92.500％,16批草果挥发油可以分为3类,最优样品为S11.熵权TOPSIS法结果显示,最优样品同样为S11.结论:建立的GC-MS方法准确可行,可用于评价草果挥发油的质量优劣.