Toxicological evaluation of Yulangsan polysaccharide in Wistar rats: A 26-week oral gavage study

Although numerous studies have proven the medicinal values of Yulangsan polysaccharide (YLSP), the toxicity of this active ingredient is unknown. In the acute toxicity study, a single oral administration of 24 g/kg YLSP caused neither toxicological symptoms nor mortality, and the LD₅₀ was estimated >24 g/kg. In the chronic toxicity study, we administered doses of 0, 0.6, 1.2 and 2.4 g/kg YLSP in rats by oral gavage for 26 weeks followed by a 3-week recovery period. There was no mortality or remarkable clinical signs observed during this 26-week study. Additionally, there were no toxic differences in the following parameters: body weight, food consumption, hematology, clinical biochemistry, organ weight, and macroscopic findings. There were no adverse effects on histopathology observed in males or female rats treated with YLSP. Based on the results, the no-observed-adverse-effect-level of YLSP in rats is greater than 2.4 g/kg when administered orally for 26 consecutive weeks.     

生物样品中天麻素测定方法及药代动力学研究进展＊

天麻素是从兰科植物天麻的块茎中提取分离而得，现已人工合成。天麻素药理作用广泛，如镇痛、镇静安眠、促智、保护神经元、降血压、抗惊厥、抗癫痫、抗氧化、抗衰老、改善微循环等，且安全、无明显毒副作用，其相关制剂在临床上亦被广泛用于心脑血管及神经精神系统疾病，如头痛、冠心病、高血压、后循环缺血性眩晕、突发性耳聋、癫痫、神经衰弱及脑卒中等。考虑到天麻素临床治疗上述疾病常与其他药物或治疗方法联用，故其体内过程及其药代动力学性质不容忽视。目前，有关天麻素综述多集中于药理作用和临床应用方面，而其药代动力学综述鲜见报道。随着天麻素药代动力学研究日渐深入，本研究将从其样品前处理、测定方法、药物ADME过程及影响体内过程的因素等方面较系统全面地对天麻素近年来的药代动力学研究作一综述，以期对天麻素制剂工艺及临床联合配伍应用有所裨益。     

Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.

Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma

ObjectiveAlthough there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.MethodsSmall interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2′-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.ResultsJAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.ConclusionJAML is a novel target for kaempferol against LUAD cells.Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268–276.     

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation

ObjectiveTo investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca²⁺ channels, and insulin secretion.MethodsWe studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca²⁺ channels and insulin secretion, respectively.ResultsFerulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca²⁺ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca²⁺ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca²⁺-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca²⁺ influx through L-type Ca²⁺ channel. Our data also suggest that this may be a direct, nongenomic action.ConclusionThis is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca²⁺ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.     

云南萝芙木根中吲哚生物碱及其抗菌活性

目的 研究云南萝芙木Rauvolfia yunnanensis根中的吲哚类生物碱化学成分及抗菌活性,明确该植物抗菌活性成分。方法 采用硅胶柱色谱、RP-C₁₈、Sephadex LH-20、半制备HPLC等方法进行分离纯化,结合波谱数据及文献参数对化合物进行结构鉴定,并采用微量肉汤稀释法对单体化合物进行抗菌活性评价。结果 从云南萝芙木根醋酸乙酯部位共分离得到20个吲哚类生物碱化合物,分别鉴定为维诺任碱（1）、霹雳萝芙木碱（2）、四叶萝芙木新碱（3）、萝加灵（4）、西特斯日钦碱（5）、缝籽木醇（6）、柯楠醇（7）、二氢柯楠醇（8）、毛茶碱（9）、异毛茶碱（10）、佩立任碱（11）、10-羟基-16-表-花菊醇（12）、育亨宾（13）、降马枯星碱B（14）、洛柯碱（15）、阿枯米定碱（16）、去乙酰阿枯米灵（17）、利血平（18）、哈尔满碱（19）、梅林诺宁F（20）。其中化合物20对白色念球菌表现出较好的抗菌活性,最低抑菌浓度（minimum inhibitory concentration,MIC）值为3.12μg/mL,与临床抗真菌药物氟康唑的MIC值相同。化合物1、11对大肠杆菌,化合物11、13、20对枯草芽孢杆菌均表现出一定的抗菌活性,MIC值为6.25～12.50 μg/mL,活性与植物源抗菌药物小檗碱相当。结论 化合物20为首次从萝芙木属中分离得到,化合物6、8～13、16～18均为首次从该植物中分离得到,部分单体化合物表现出潜在抗菌活性。     

基于网络药理学整合体内实验探究脉络舒通丸抗血栓性浅静脉炎的作用机制

目的 基于网络药理学整合体内实验方法探究脉络舒通丸抗血栓性浅静脉炎（superficial thrombophlebitis,STP）的作用机制。方法 借助网络药理学方法,从药物及疾病相关数据库筛选脉络舒通丸的成分作用靶点及STP疾病相关靶点,根据拓扑特征值筛选关键靶点后,进行基因本体（gene ontology,GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。将日本大耳白兔随机分为对照组、模型组、地奥司明（0.168 g/kg）组和脉络舒通丸低、中、高剂量（0.56、1.68、5.04 g/kg）组。除对照组外,其余各组均采用耳缘iv 20%甘露醇建立STP兔模型。造模同时各给药组连续ig给药14 d。采用苏木素-伊红（HE）染色法检测各组兔耳组织病理变化;ELISA检测各组血清中白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和IL-6水平;Western blotting检测耳组织蛋白激酶B(pr...     

八珍益智合剂3种成分的含量测定及稳定性考察

目的 建立一测多评法同时测定八珍益智合剂中甘草苷、芹糖甘草苷和橙皮苷3种成分的含量，并对八珍益智合剂3种成分的稳定性进行考察。方法 采用HPLC-DAD法，以橙皮苷为参照物，测定其他2种成分的相对校正因子和相对保留时间，并计算各成分含量；以外标法为对照，比较一测多评法（single marker，QAMS）与外标法（external standard method，ESM）实测值的差异，探讨一测多评法的可行性。同时测定八珍益智合剂在高温、强光照射、加速试验和长期室温条件下的稳定性，为其贮藏条件和保质期提供数据。结果 经过方法学验证，3种成分在4.512~108.2，10.13~101.30，4.496~107.90 μg·mL^-1内线性关系良好（r>0.999）；平均加样回收率为95.9%~104.7%，RSD ≤ 3%；2种成分相对橙皮苷的相对校正因子分别为0.49和0.38，且在不同实验条件下相对校正因子重复性良好；含量测定QAMS计算结果与ESM实测值无明显差异。稳定性考察结果表明，在高温条件下长时间放置芹糖甘草苷和橙皮苷含量下降速度较快，甘草苷含量下降较为平缓，提示中药合剂在高温条件下不宜放置过长时间。结论 本研究所建方法准确可靠、重复性好，可用于八珍益智合剂的质量控制，本合剂应密封置阴凉处保存。     

Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system

We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action.Oral administration of EET (1, 3, 10 and 30 mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10 mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10 mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30 mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin–Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.