Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular remodeling.Potassium dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections.This study investigates the potential of PDA in regulating pathological vascular remodeling.The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice.Experimental approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions.The results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima formation.PDA treatment significantly increased the proliferation and migration of SMCs.Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular remodeling.Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

Potassium dehydroandrographolide succinate injection for treatment of infantile pneumonia:a systematic review and Meta-analysis

OBJECTIVE:To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection(PDS) in treatment of infantile pneumonia.METHODS:Randomized controlled trials(RCTs) of infantile pneumonia treated by PDS were searched in China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,Chinese Biomedical Literature Database,PubMed,and Cochrane Library,from January 1979 to July 2013.Two reviewers independently retrieved the RCTs and extracted the information.The quality of included studies was assessed by the Cochrane risk of bias,and a Meta-analysis was conducted with Review Manager 5.2 software.RESULTS:A total of 9 studies with 1056 participants were included.The quality of the studies was generally no high,only one study mentioned the random method.The Meta-analysis indicated that PDS was significantly superior to the conventional therapy in the total effective rate[relative risk(RR)=1.21,95%CI(1.14,1.27),P<0.000 01],the time of temperature recovery[mean difference(MD)=-1.43,95%CI(-1.75,-1.11),P<0.000 01],rale disappeared and cough relieving[MD=-1.44,95%CI(-1.93,-0.90),P<0.000 01].Six adverse drug reactions from five studies mainly represented rash and diarrhea,and no serious ADRs were reported.CONCLUSION:Based on this systematic review,PDS was proved effective and relatively safe in treatment of infantile pneumonia.However the articles enrolled in the study were not high in quality,studies with higher quality should be conducted for assessment of efficacy and safety of PDS in treatment of infantile pneumonia.

Potassium Dehydroandrographolide Succinate Injection for the Treatment of Child Epidemic Parotitis:A Systematic Review and Meta-Analysis

Objective： To systematically evaluate the clinical efficacy and safety of Potassium Dehydroandrographolide Succinate Injection （PDSI） in the treatment of child epidemic parotitis （EP）. Methods： Randomized controlled trials （RCTs） regarding PDSI in the treatment of child EP were searched in China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from inception to July 30, 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of included studies, and a meta- analysis was conducted with RevMan 5.2 software. Results： A total of 11 studies with 818 participants were included. The quality of the studies was generally low, among which only one study mentioned the random method. The meta-analysis indicated that PDSI was more effective than the conventional therapy with Western medicine for EP in the outcomes of the total effective rate [relative risk （RR）=1.23, 95% confidence interval （CI） [1.14, 1.33], P〈0.01], the time of temperature return to normal, the time of detumescence [mean difference （MD）=-2.10, 95% CI [-2.78, -1.41], P〈0.01], and the incidence of complications （RR=0.14, 95% CI [0.03, 0.72], P=0.02）. There were 6 adverse drug reactions （ADRs） in this systematic review, 2 of which were mainly represented rash and diarrhea in the experiment group, while another 4 ADRs occurred in the control group. Conclusions： Based on the systematic review, PDSI was effectiveness and relatively safety in the treatment of child EP. But further rigorously designed trials are warranted to determine its effectiveness.

炎琥宁联合干扰素治疗小儿手足口病的临床效果

目的观察炎琥宁联合干扰素治疗小儿手足口病的临床效果。方法选取2021年1月至2023年1月商河县人民医院收治的62例手足口病患儿为研究对象,按照随机数字表法将其分为对照组(31例)、治疗组(31例)。对照组采用干扰素治疗,治疗组在对照组基础上采用炎琥宁治疗,比较两组的治疗总有效率、症状消失时间及炎症因子水平。结果治疗组治疗总有效率高于对照组(P<0.05);治疗组退热、皮疹消失及口腔溃疡愈合时间短于对照组(P<0.05);治疗后,治疗组C反应蛋白、白细胞介素-6、肿瘤坏死因子-α水平低于对照组(P<0.05)。结论炎琥宁联合干扰素治疗小儿手足口病的临床效果显著,能够促进症状缓解,减轻炎症反应,值得推广。

基于TLR3/TRIF通路分析重组人干扰素α2b联合炎琥宁对病毒性肺炎患儿的疗效与作用机制

目的基于Toll样受体3(TLR3)/β干扰素TIR结构域衔接蛋白(TRIF)通路分析重组人干扰素α2b联合炎琥宁对病毒性肺炎(VP)患儿的疗效与作用机制。方法选取2020年1-5月收治的VP患儿200例,根据治疗方法不同分为观察组和对照组,每组100例。对照组给予重组人干扰素α2b治疗,观察组在对照组基础上加用炎琥宁治疗。治疗7 d后,比较2组临床疗效、临床症状改善时间、住院时间及不良反应发生情况,比较2组治疗前后外周血单个核细胞(PBMC)中TLR3/TRIF通路相关因子[TLR3、TRIF、核因子-κBp65(NF-κBp65)]mRNA表达量、血清免疫球蛋白(IgG、IgA、IgM)水平及呼吸功能[呼吸频率(RR)、潮气量(VT)、呼气达峰时间(TPTEF)/呼气时间(TE)]。结果观察组临床总有效率高于对照组,退热时间、咳嗽消失时间、呼吸困难消失时间、肺啰音消失时间及住院时间均短于对照组(P<0.01)。治疗7 d后,观察组PBMC中TLR3、TRIF、NF-κBp65 mRNA表达量以及RR低于对照组,血清IgG、IgA、IgM水平以及VT、TPTEF/TE高于对照组(P<0.05)。2组不良反应总发生率比较差异无统计学意义(P>0.05)。结论重组人干扰素α2b联合炎琥宁治疗VP患儿的效果显著,可改善临床症状、呼吸功能,提高免疫球蛋白含量,其作用机制与抑制TLR3/TRIF通路活化有关。

Andrographolide and Its Derivative Potassium Dehydrographolide Succinate Suppress PRRSV Replication in Primary and Established Cells via Differential Mechanisms of Action

Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited protection against PRRSV infection, and consequently, new antiviral strategies are urgently required. Andrographolide(Andro) and its derivative potassium dehydrographolide succinate(PDS) have been used clinically in China and other Asian countries as therapies for inflammation-related diseases, including bacterial and viral infections, for decades. Here, we demonstrate that Andro and PDS exhibit robust activity against PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages(PAMs). The two compounds exhibited broad-spectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, XH-GD, and NADC30-like HNhx strains in China. The EC_(50)values of Andro against three tested PRRSV strain infections in Marc-145 cells ranged from 11.7 to 15.3 lmol/L, with selectivity indexes ranging from 8.3 to10.8, while the EC_(50)values of PDS ranged from 57.1 to 85.4 lmol/L, with selectivity indexes ranging from 344 to 515.Mechanistically, the anti-PRRSV activity of the two compounds is closely associated with their potent suppression on NFj B activation and enhanced oxidative stress induced by PRRSV infection. Further mechanistic investigations revealed that PDS, but not Andro, is able to directly interact with PRRSV particles. Taken together, our findings suggest that Andro and PDS are promising PRRSV inhibitors in vitro and deserves further in vivo studies in swine.

穿琥宁原料药及其注射液的有关物质检查和含量测定方法研究

目的:建立穿琥宁原料药及其注射液的有关物质检查及含量测定方法。方法:采用高效液相色谱法,色谱柱为ODS柱(Shimpack CLC—ODS 150 mm×6.0 mm,5 μm),流动相为甲醇-水-磷酸(60:40:0.1),检测波长为251 nm。结果:能有效检查有关物质。有关物质检查的检测限为1.6 ng(S/N=3),线性范围约0.039-0.79μg(r=0.9978);含量测定方法的平均回收率为100.6%(n=9),线性范围0.48—2.40μg(r=0.9999)。结论:所建立的方法简便、灵敏、准确,可用于原料及其注射液的有关物质检查和含量测定。

穿琥宁脂质体包封率的测定

采用乙醇注入法制备穿琥宁脂质体。分别采用葡聚糖凝胶过滤法、透析法、超速冷冻离心法分离脂质体和游离药物,计算脂质体包封率。结果表明,3种方法中超速冷冻离心法测得的平均包封率最高。4℃离心(268000×g)2h后,测得平均包封率为96.9%。

新药炎琥宁的碳氢NMR信号全归属(英文)

炎琥宁为中药提取物穿心莲内酯经结构改造后获得的一个抗菌、抗病毒新药,本文应用1D NMR和脉冲梯度场2D NMR实验技术(gCOSY,gHSQC,gHSQC-TO-COSY,gHMBC)对其结构进行了研究,并首次对其1H NMR、13C NMR谱信号进行了全归属.

羟丙基-β-环糊精对穿琥宁溶液稳定性的影响

目的:研究羟丙基-β-环糊精(HP-β-CD)对穿琥宁溶液稳定性的影响。方法:以穿琥宁含量变化为指标,以未加HP-β-CD的穿琥宁溶液为对照,采用恒温加速试验考察试验组(穿琥宁溶液+HP-β-CD)的稳定性。结果:与对照组比较,试验组含量变化更小,2组有效期分别为0.657y、3.40y。结论:穿琥宁溶液中可加入HP-β-CD,以提高其稳定性。

高效液相色谱法-二极管阵列检测器考察炎琥宁在更昔洛韦葡萄糖注射液中的配伍稳定性

目的考察室温（20±1）℃下,注射用炎琥宁与更昔洛韦葡萄糖注射液配伍的稳定性,为临床合理用药提供依据。方法采用反相高效液相色谱法-二极管阵列检测器同时测定炎琥宁与更昔洛韦配伍后0-6 h内的含量变化,并观察配伍液的外观及pH值。结果6 h内混合液外观、pH及含量均无明显变化。结论在室温（20±1）℃条件下,注射用炎琥宁与更昔洛韦葡萄糖注射液6 h内可以配伍使用。

反相高效液相色谱法测定穿琥宁含量

目的： 建立反相高效液相色谱法测定穿琥宁及其注射液的含量。方法： 采用μＢｏｎｄｐａｋ Ｃ１８ 色谱柱， 甲醇－水（７０∶３０） 为流动相，２５０ ｎｍ 为检测波长， 室温下对穿琥宁及其注射剂进行含量测定。结果： 能将穿琥宁及其主要杂质穿心莲内酯进行分离； 穿琥宁在２５ ～４００ μｇ·ｍＬ－ １ 范围内， 峰面积与其浓度线性关系良好（ｒ＝ ０－９９９ ９） ； 样品平均回收率为１００－６ ％ ； 日内精密度ＲＳＤ 为１－０８％ （ｎ ＝ ５）， 日间（１０ ｄ 内） 精密度ＲＳＤ为２－０６ ％ （ｎ＝ ５） 。结论： 该法简便、快速、专属性强， 可以满足其原料和制剂的质量控制要求。

RP-HPLC法测定穿琥宁氯化钠注射液中穿琥宁含量及有关物质

目的:建立反相高效液相色谱法测定穿琥宁氯化钠注射液中穿琥宁含量及有关物质的方法。方法:采用RP-HPLC法,使用Shim-pack CLC-ODS柱(6.0 mm × 150 mm,5μm),以0.01 mol·L-1磷酸二氢钾溶液(用磷酸调pH至2.5)-甲醇-四氢呋喃(9:6:4)为流动相,流速为1.0 mL·min-1,在251 nm波长处,测定穿琥宁氯化钠注射液中穿琥宁含量及有关物质。结果:该方法的线性范围为0.02～0.20μg(r=0.9993)、0.50～10.0μg(r=0.9992);平均回收率为99.35%,RSD=0.79%(n=9)。结论:该方法测定样品分离效果佳,灵敏度高,重现性好,结果准确可靠。

穿琥宁溶液的稳定性研究

目的研究穿琥宁溶液在不同条件下的稳定性。方法采用经典恒温法考察了穿琥宁在不同pH值的磷酸盐缓冲液,相同pH值的不同缓冲盐溶液及不同浓度的枸橼酸盐缓冲液中的稳定性。结果穿琥宁在pH6.5时最为稳定;枸橼酸盐缓冲液能延缓其水解;枸橼酸盐的浓度不影响药物稳定性。结论穿琥宁溶液在不同条件下稳定性不同,该结果为穿琥宁的分析及相关制剂的研究提供了参考。

穿琥宁中空栓在兔体内的药物动力学及绝对生物利用度

目的:研究穿琥宁中空栓在兔体内的药物动力学及绝对生物利用度。方法:取健康家兔30只,随机分为3组。第1组为静脉注射组;第2组为聚乙二醇300穿琥宁中空栓组;第3组为1,2丙二醇穿琥宁中空栓组,分别静脉注射穿琥宁100 mg或直肠给予穿琥宁中空栓1枚。用HPLC法测定血药浓度。按统计矩的非隔室动力学理论计算药物动力学参数。结果:聚乙二醇300穿琥宁中空栓和1,2丙二醇穿琥宁中空栓的C_(max)分别为(37.4±5.3)和(20.2±4.6)μg·ml^(-1);AUC_(0-inf)分别为(2885.92±214.578)和(1960.98±111.194)μg·min·ml^(-1);绝对生物利用度分别为18.33%和12.45%。结论:聚乙二醇300穿琥宁中空栓组和1,2丙二醇穿琥宁中空栓组的C_(max)和AUC_(0-inf)有统计学差异。

炎琥宁的合成工艺研究

目的研究炎琥宁的合成工艺。方法以脱水穿心莲内酯二琥珀酸半酯为起始原料,用KHCO3和Na2CO3混合溶液一步成盐法合成炎琥宁。结果总收率为80.6%。结论合成工艺操作简便,提高了收率,降低了成本,适合于工业化生产。

注射用炎琥宁与注射用头孢曲松钠配伍的稳定性研究

目的:考察注射用炎琥宁与注射用头孢曲松钠在0.9%氯化钠注射液中的配伍稳定性。方法:采用高效液相色谱法,以Venusil XBP-C_(18)色谱柱,乙腈-0.02 mol·L^(-1)磷酸二氢钾-10%四丁基氢氧化铵(pH 5.0)(38:60.5:1.5)为流动相,252 nm为检测波长,测定注射用炎琥宁与注射用头孢曲松钠配伍后在室温下6 h内的含量变化,并观察和检测配伍液的外观及pH值变化。结果:配伍液pH值及含量无明显变化,但颜色随时间变化逐渐加深。结论:注射用炎琥宁与注射用头孢曲松钠在0.9%氯化钠注射液可配伍使用,但应在4 h内用完。

注射用炎琥宁与头孢呋辛钠配伍的稳定性考察

目的:考察注射用炎琥宁与注射用头孢呋辛钠在0.9%氯化钠注射液中的配伍稳定性。方法:采用高效液相色谱法,测定注射用炎琥宁与注射用头孢呋辛钠配伍后在室温下8 h内的含量变化,并观察和检测配伍液的外观及pH值变化。结果:配伍液pH值无明显变化,颜色随时间变化逐渐加深,头孢呋辛钠相对百分含量在5 h后降至95%以下,4 h后降解产物峰面积占总峰面积百分比超过1%。结论:注射用炎琥宁与注射用头孢呋辛钠在0.9%氯化钠注射液可配伍使用,但应在4 h内用完。

穿琥宁在3种不同包装输液中的稳定性

目的 :考察穿琥宁在PVC袋 (聚氯乙烯输液袋 )、三层复合膜输液袋及玻璃瓶中的稳定性是否存在差异。方法 :穿琥宁分别以NS液及 5 %GS配制于PCV袋、三层复合膜输液袋及玻璃瓶中 ,于 4℃ ,2 5℃ ,37℃下放置 2 4h ,分别于 0 ,0 5 ,1,3,6 ,8,12 ,2 4h时取样检测其外观、pH值、含量 ,其中含量以HPLC法进行检测。结果 :穿琥宁在各种条件下于PVC袋、三层复合膜输液袋及玻璃瓶中各检测项目均无明显变化 ,3组之间无显著性差异 (P >0 0 5 )。结论 :穿琥宁在各条件下均较稳定。

反相高效液相色谱法考察注射用炎琥宁与注射用更昔洛韦配伍稳定性

目的 考察注射用炎琥宁与注射液用更昔洛韦在5%葡萄糖注射液中的配伍稳定性.方法 在室温[（20±1）℃]下,采用反相高效液相色谱法-二极管阵列检测器同时测定炎琥宁与更昔洛韦配伍后0～8 h内的含量变化,并观察配伍液的外观及pH值.结果 检测波长为251 mm,炎琥宁的平均回收率为99.8%,峰面积相对标准偏差（RSD）为0.84%（n=9）,更昔洛韦的平均回收率为99.7%,RSD为0.68%（n=9）.8 h内配伍液的颜色、pH值以及炎琥宁与更昔洛韦的含量均变化较大.结论 在室温条件下,注射用炎琥宁与注射液用更昔洛韦不可以在5%葡萄糖注射液中配伍使用.