HPLC-MS/MS法同时测定薄荷药材中4种黄酮苷的含量

目的 建立HPLC-MS/MS同时测定薄荷药材中橙皮苷、香叶木苷、香蜂草苷、蒙花苷4种黄酮苷含量的方法.方法 采用Inertsil ODS-3色谱柱(4.6×150 mm,5μm),柱温30℃,流动相为甲醇-0.1％甲酸水,以0.5 mL/min的流速梯度洗脱,进样量2μL;质谱条件:采用电喷雾离子源进行正离子模式检测,多反应监测模式(MRM)用于定量测定.结果 薄荷药材中4种成分橙皮苷、香叶木苷、香蜂草苷和蒙花苷能完全分离;峰面积与浓度呈良好的线性关系.平均回收率(n=6)分别为99.40％、98.63％、99.08％、98.62％,RSD分别为2.5％、2.7％、2.6％、2.4％.结论 该方法简便、快速、准确、专属性高,适用于薄荷药材中橙皮苷、香叶木苷、香蜂草苷、蒙花苷含量的同时测定.     

地奥司明对肾缺血／再灌注大鼠肾组织PECAM-1表达的影响

摘要：目的观察地奥司明（diosmin,DOSM）对肾缺血／再灌注（ischemia／reperfusion,I／R）大鼠肾组织PECAM一1表达水平的影响,并探讨其对肾脏的保护机制。方法150只SD大鼠随机分成3组：假手术（shamoperation,SO）组、肾缺血／再灌注模型组（I／R）和地奥司明＋肾缺血／再灌注模型组（DOSM＋I／R）。在再灌注不同时间点分别采用免疫组化及Western免疫印迹方法测定肾脏组织中PECAM-1的表达水平。结果在1h、6h、12h、24h和48h不同时间点的肾组织中,I／R和DOSM＋I／R两组PECAM-1的表达水平均随时间逐渐上调,并于48h达最高。而在DOSM组显著低于I／R组俨〈0．05或P〈0．01）。Western免疫印迹与免疫组织化学检测结果基本一致。结论DOSM可显著降低肾I／R病理过程中PECAM-1的表达,有助于减轻I／R时炎性细胞的浸润,从而减轻缺血再灌注损伤,保护肾功能。     

复方爱脉朗防治包皮环切术后水肿的疗效观察

目的 探讨复方地奥斯明对于防治包皮环切术后包皮水肿的预防和治疗效果。 方法 152例拟行包皮环切术患者随机分成2组,实验组78例,术后给予抗感染、镇痛及抗搏起药物外,另给予复方地奥斯明（爱脉朗）口服7d,对照组74例,术后仅给予抗感染及镇痛药。术后1、3、7、14d随访观察,记录水肿发生情况。 结果 实验组5例出现水肿,对照组13例出现水肿。两组水肿发生率有显著性差异。 结论 爱脉朗对于防治包皮环切术后水肿具有明显的疗效,值得临床推广。     

地奥司明联合氨甲环酸治疗老年股骨转子间骨折术后隐性失血的疗效分析

目的探讨地奥司明联合氨甲环酸治疗老年股骨转子问骨折术后隐性失血及肢体肿胀的疗效。方法将采用近端防旋髓内钉（PFNA）的75例老年股骨转子间骨折患者随机分为2组,治疗组38例入院后即给予地奥司明,手术开始时给予氨甲环酸,静脉滴注,对照组37例术中按照相同方法给予氨甲环酸。分别计算2组可见失血量、总失血量及隐性失血量,并比较患肢膝关节上方10CITI肢体周径差值。结果治疗组隐性失血量及总失血量均明显少于对照组,差异有统计学意义;术后3、5、7d时,治疗组肢体周径缩小值及肿胀减轻程度上明显优于对照组,差异有统计学意义;治疗组未发现静脉血栓形成,对照组4例出现肌间静脉血栓形成,2组均未出现下肢深静脉血栓、肺栓塞等严重并发症。结论地奥司明联合氨甲环酸能有效减少转子问骨折PFNA术后隐性失血及肢体肿胀,疗效优于单纯氨甲环酸,值得临床推广。     

Efficacy of a Low-Dose Diosmin Therapy on Improving Symptoms and Quality of Life in Patients with Chronic Venous Disease: Randomized,Double-Blind,Placebo-Controlled Trial

Chronic Venous Disease (CVD) is a common medical condition affecting up to 80% of the general population. Clinical manifestations can range from mild to more severe signs and symptoms that contribute to the impairment of the quality of life (QoL) of affected patients. Among treatment options, venoactive drugs such as diosmin are widely used in the symptomatic treatment in all clinical stages. The aim of this study is to determine the effectiveness of a new formulated diosmin in relieving symptoms and improving QoL in patients suffering from CVD. In this randomized, double-blind, placebo-controlled, multicenter clinical study, CVD patients with a Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system between C2 and C4 were randomized to receive a bioavailable diosmin (as μsmin^® Plus) 450 mg tablet once daily or a placebo for 8 weeks. Clinical symptoms and QoL were monitored using the measurement of leg circumference, visual analogue scale (VAS) for pain, Global Index Score (GIS) and Venous Clinical Severity Score (VCSS). A total of 72 subjects completed the study. From week 4, leg edema was significantly decreased in the active group (p < 0.001). An improvement in the VAS score was observed in the active group compared to placebo at the end of treatment (p < 0.05). GIS and VCSS scores were significantly improved in the active group at week 8 (p < 0.001). No treatment related-side effects were recorded. The results of this study showed that the administration of low-dose μsmin^® Plus was safe and effective in relieving symptoms and improving QoL in subjects with CVD.     

Antihyperglycaemic action of diosmin,a citrus flavonoid,is induced through endogenous β‐endorphin in type I‐like diabetic rats

Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin‐induced diabetic rats (STZ‐diabetic rats). Diosmin lowered hyperglycaemia in a dose‐dependent manner in STZ‐diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β‐endorphin‐like immunoreactivity (BER) using enzyme‐linked immunosorbent assay (ELISA). Diosmin also increased BER dose‐dependently in the same manner. Repeated treatment of STZ‐diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ‐diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β‐endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ‐diabetic rats.     

Influence of diosmin on the metabolism and disposition of carbamazepine in healthy subjects

1.?Carbamazepine (CBZ) is an antiepileptic drug with narrow therapeutic window and administration in humans receiving long-term therapy with diosmin (DSN) may occur, which leads to CYP3A4-mediated drug interactions. The purpose of the present study was to assess the influence of DSN on the metabolism and pharmacokinetics of CBZ in healthy volunteers.

2.?An open-label, sequential, two-period study was conducted in 12 healthy male volunteers. A single dose of DSN 500?mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200?mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC-MS/MS.

3.?Treatment with DSN significantly enhanced the maximum plasma concentration (C_max)_, area under the curve (AUC), half-life (t_1/2) and significantly decreased the apparent oral clearance (CL/F) and elimination rate constant (K_el) of CBZ. On the other hand, treatment with DSN significantly decreased the C_max and AUC of carbamazepine 10, 11-epoxide (CBZE). Furthermore, treatment with DSN significantly decreased the metabolite to parent ratios of C_max and AUC, indicating the reduced metabolism of CBZ to CBZE.

4.?The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to DSN-mediated inhibition of CYP3A4 enzyme, which indicates pharmacokinetic interaction present between DSN and CBZ. Therefore, we conclude that DSN has an inhibiting effect on the metabolism and disposition of CBZ.     

The Growth Suppression Activity of Diosmin and PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins

Objective: We aim to enhance the effectiveness of curcumin analog PGV-1 through co-treatment with diosmin, a citrus flavonoid, on 4T1 cells and evaluate the molecular targets underlying its effect on the cell cycle. Methods: Cytotoxic effects were performed by MTT assay against 4T1 cells. The May Grünwald-Giemsa staining was used to observe cell cycle arrest. The senescence was assayed with SA-ß-gal staining. Bioinformatic studies were utilized to discover protein targets of PGV-1 and diosmin on triple-negative breast cancer (TNBC) using SwissTargetPrediction, then exploration of protein targets was performed using the TCGA dataset via the UALCAN website. Kaplan-Meier was performed using GraphPad with data from the TCGA dataset via Oncoln. Using MOE 2010, we conducted the binding affinity between PGV-1 and diosmin to protein targets. Results: PGV-1 and diosmin showed cytotoxic effect with IC50 values of 9 µM and 389 µM, respectively, and the combined cytotoxic assay exhibited a synergistic effect with a combination index (CI) of <1. PGV-arrested 4T1 cells in pro-metaphase and induced mitotic catastrophe, while the combination of diosmin with PGV-1 increased the number of mitotic catastrophes. The SA-ß-gal assay revealed that both compounds were capable of inducing senescence in 4T1 cells. Study bioinformatics and molecular docking showed that PGV-1 and diosmin target cell cycle regulatory proteins in TNBC, namely CDK1, KIF11, and AURKA. Thus, the combination of diosmin and PGV-1 modulating the cell cycle that causes senescence and catastrophic death of 4T1 cancer cells is related to the inhibition of these cell cycle proteins. Conclusion: Diosmin enhances the cytotoxic effect of PGV-1 synergistically on 4T1 cancer cells, which correlates to the increasing senescence and mitotic catastrophe. The synergistic effect of the co-treatment is likely to target AURKA, CDK1, and KIF11. The combination of PGV-1 and diosmin performs a potential as a combinatorial anticancer drug for TNBC.     

头颈部肿瘤术后放疗后淋巴水肿发生的影响因素

目的 探讨头颈部肿瘤患者术后放疗后淋巴水肿发生的影响因素.方法 收集接受术后放疗的128例头颈部肿瘤患者,随访1年~2年7个月.回顾性分析年龄、性别、颈部淋巴结清扫术、放疗剂量、同步化疗、放射性皮炎以及预防性使用改善微循环药物与放疗后淋巴水肿的关系.结果 颈部淋巴结清扫术、放疗剂量和预防性使用改善微循环药物是影响淋巴水肿发生的重要因素(均P<0.05).结论 接受颈部淋巴结清扫术以及术后放疗剂量60 Gy的头颈部肿瘤患者发生局部淋巴水肿的风险较高,而预防性使用改善微循环药物可以有效预防水肿的发生.     

地奥司明治疗非缺血型RVO的疗效观察

目的:探讨地奥司明治疗非缺血型视网膜静脉阻塞(retinal vein occlusion,RVO)的临床疗效。方法:将符合非缺血型RVO诊断的48例48眼随机分为治疗组和对照组。治疗组27例27眼,给予地奥司明0.9g,po,bid,4wk为一疗程,连续三个疗程。对照组21例21眼,先给予丹香冠心注射液16mL加入5g/L葡萄糖注射液(或者9g/L氯化钠注射液)500mL中,iv,qd,1wk后改为丹参片3片,po,tid,连续服用11wk。观察治疗前后最佳矫正视力和眼底病变的动态改变、视网膜电流图的变化、黄斑水肿的发生率及黄斑水肿厚度变化。结果:治疗后4,8,12wk治疗组最佳矫正视力提高均显著高于对照组(P<0.05)。治疗后4wk,治疗组渗出、出血吸收率为63%,高于对照组的33%(P<0.05)。治疗后12wk,治疗组暗适应眼最大电反应的b波振幅(231±39)μV与治疗前(184±65)μV相比明显提高(P<0.05),且与对照组(207±49)μV相比有差异(P<0.05)。治疗组并发黄斑水肿17例,对照组14例,治疗组黄斑水肿的发生率与对照组相比没有明显差异(P>0.05)。治疗后12wk黄斑中心凹厚度,治疗组为298±54μm,低于对照组的369±76μm(P<0.05)。结论:对于非缺血型RVO,地奥司明能够有效的减轻黄斑水肿,降低视网膜的功能损伤,从而改善视功能,效果优于丹参治疗。