Dimeric phthalides from an aqueous extract of the Angelica sinensis root head / 药学学报

Ten dimeric phthalide racemates (1-10) were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, and Sephadex LH-20, together with preparative thin-layer chromatography and reversed phase HPLC. The racemates were further separated into (+)-/(-)-1-(+)-/(-)-10 with chiral HPLC. Their structures including absolute configurations were elucidated by comprehensive analysis of spectroscopic data, combined with electronic circular dichroism (ECD) and NMR calculations as well as single crystal X-ray diffractions. Compounds (+)-/(-)-1-(+)-/(-)-10 are either new structure or new natural product, named (+)-/(-)-angelidipthalidic acids A-H [(+)-/(-)-1-(+)-/(-)-8] and (+)-/(-)-angelidipthalidols A and B [(+)-/(-)-9 and (+)-/(-)-10], respectively. Meanwhile, dimeric phthalide mono- and bis-lactone derivatives with 3.3′a,8.6′- and 3.6′,8.3′a-coupling patterns as well as determination of their relative configurations are discussed.

Neuroprotective Effect of Isobenzofuranones on Hydrogen Peroxide-Mediated Redox Imbalance in Primary Cultures of Hippocampal Neurons

Abstract In live organisms, there is a balance between the production of reactive oxygen species (ROS) and their neutralization. The increased level of these species leads to a condition called redox imbalance. The aim of this study was to evaluate the protective action of isobenzofuranones in primary cultures of hippocampal neurons subjected to redox imbalance. To accomplish this, MTT and LIVE/DEAD assays were initially performed. In the cultures pretreated with isobenzofuranones 1 and 2, there was a higher number of live cells when compared to that in the untreated ones. Regarding redox imbalance, there was a significant increase in the intracellular levels of ROS. The cultures pretreated with isobenzofuranones showed a reduction in ROS levels. Lipid peroxidation caused by oxidative damage was significantly reduced in the cultures pretreated with isobenzofuranones 1 and 2. Taken together, these data show the ability of isobenzofuranones 1 and 2 to significantly minimize cytotoxicity, cell death, intracellular levels of ROS and lipid peroxidation induced by redox imbalance. These results suggest that isobenzofuranones 1 and 2 represent a possible alternative therapy for the neurodegenerative disturbances that are triggered by ROS production increases.

Identification of metabolites of Yaobitong Capsule in rat urine and bile after intragastric administration / 中草药

Objective The main metabolites of Yaobitong Capsule (YC) in rat urine and bile were investigated by UPLC-Q-TOF- MS/MS, and their major metabolic pathways were summarized. Methods To compare with the control samples, the possible metabolites were found. Their structures were speculated by exact mass and fragment ions. Results YC had 31 metabolites in urine and 35 metabolites in bile under positive and negative ion mode. They were mainly the metabolites of ligustilide, 3-butyl-phthalide, osthole, senkyunolide A, sankyunolide A, emodin, decursinol/marmesin/columbianetin, corypalmine/ isocorypalmine, corybulbine/isocorybulbine/coryphenanthrine, allocryptopine, ferulic acid, cryptochlorogenic acid, angelol and so on. Their major metabolic pathways included hydrolysis of the lactone ring, hydroxylation, demethylation, dehydration, dehydrogenation, dehydroxylation, hydrogenation, methylation, methyl oxidation, glucuronidation, sulphate-binding, N-acetylcysteine-binding, cysteine-binding, cysteinyl acid-glycine-binding, glutathione-binding and so on. In addition, three prototype components, namely paeoniflorin, albiflorin, and ginsenosides Rg1, were detected in rats’ bile. Conclusion The established UPLC-Q-TOF-MS/MS method can analyze the metabolites of YC capsule in rat urine and bile. The in vivo metabolic characteristics of YC have been initially clarified. The results provide a foundation for elucidating the in vivo efficacy ingredients of YC.

Clinical Observation of Edaravone Combined with Butyl Phthalide in the Treatment of Acute Ischemic Stroke / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of edaravone combined with butyl phthalide in the treatment of acute ischemic stroke (AIS). METHODS:258 AIS patients were randomly divided into observation group and control group, with 129 cases in each group. Both groups were given routine treatment as antiplatelet,improving microcirculation,controlling blood pressure,lowering blood glucose,regulating blood lipid,keeping plaque stable,nourishing brain cells. Control group was additionally given Butyl phthalide capsules orally,200 mg,tid. Observation group was additionally given Edaravone injection 30 mg added into Sodium chloride injection 100 ml,ivgtt,bid,on the basis of control group. Both groups continuously received 14 days of treatment. The serum inflammatory factor,miR-222 and neurologic impairment score of 2 groups were observed before treatment,7,14 d after treatment. Clinical efficacies and the occurrence of ADR were compared between 2 groups. RESULTS:There was no statistical significance in the serum inflammatory factor,miR-222 and neurologic impairment score between 2 groups before treatment(P>0.05). The serum inflammatory factor and neurologic impairment score of 2 groups were decreased significant-ly 7,14 d after treatment,while serum levels of miR-222 were increased significantly;the observation group was significantly bet-ter than the control group,with statistical significance(P<0.05). Total effective rate of observation group was 92.2%,which was significantly higher than that of control group (69.8%),with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Edaravone combined with butyl phthalide is effective in the treatment of AIS,and can significantly de-crease serum inflammatory factor level,promote the expression of miR-222 and improve neurologic function with good safety.

Research progress of structures and pharmacological activities of phthalides from Angelica sinensis / 中国中药杂志

Angelica sinensis(Umbelliferae)is a worldwide-known medicinal plant and also a famous traditional Chinese medicinal herb. It is recorded to possess the efficacy of enriching the blood and invigorating the circulation of blood of the individual.Danggui was extensively applied to the treatment of gynecological disorders. Modern researches indicate that phthalides are main chemical components related to the bioactivities of A.sinensis, such as anti-tumor, analgesic and neuroprotective effect.The advances in studies on the structures and pharmacological activities of phthalides from A.sinensis are reviewed to provide references for further researches and utilization of their medicinal value.

Antidepression constituents from Angelica Sinensis Radix in Xiaoyao Powder / 中草药

Objective: This current study focused on the identification of active constituents from Angelica Sinensis Radix in Xiaoyao Powder based on UPLC-PDA-guided isolation technique. Methods: The UPLC-PDA chromatogram of Xiaoyao Powder was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra provided by PDA were used in the analyses. The constituents were isolated from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. The structures of the isolates were elucidated by NMR techniques. The antidepression effect was evaluated on glutamate-induced neurons. Results: Five marker peaks of Xiaoyao Powder fingerprint belonged to Angelica Sinensis Radix and they were determined as coniferyl ferulate (1), E-butylidenephthalide (2), ligustilide (3), Z-butylidenephthalide (4), and 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol (5). Compound 5 was isolated from the plants in Umbelliferae for the first time. The treatment with compounds 1, 3, and 4 could protect PC12 and SH-SY5Y cells from glutamate-induced cytotoxicity. Antidepression bioactivity of compound 1 was first investigated. Conclusion: UPLC-PDA-guided isolation technique is confirmed to be a rapid and accurate method to identify the main active constituents from Angelica Sinensis Radix in Xiaoyao Powder.

The effect of butyl phthalide in the treatment of acute cerebral infarction and its influence on serum MCP-1 and vWF / 中国基层医药

Objective To study the relationship of serum monocyte chemotactic factor 1 ( MCP-1) and von willebrand factor (vWF) in patients with acute cerebral infarction and the therapeutic effect of butyl phthalide soft capsule.Methods As the research subjects,160 patients of acute cerebral infarction were randomly divided into two groups,80 cases in the observation group,80 cases in the control group.80 cases of healthy physical examination in our hospital were enrolled as the healthy group.The treatment control group was given conventional treatment,treat-ment observation group on the basis of conventional treatment combined with butyl phthalide soft capsule,0.2g orally, three times a day.They were treated for three months.Serum MCP-1 and vWF were detected.Results Before treat-ment,serum MCP-1 and vWF in the observation group and the control group were significantly higher than those in the healthy group(P<0.01).Before treatment,the serum MCP-1 was (480.2 ±34.2)pg/mL,vWF was (2.70 ± 0.45)μg/L,serum MCP-1 and vWF was positively correlated(r=0.286 2,P<0.05).The two groups after treat-ment serum MCP-1 and vWF were significantly decreased,and compared with the control group,the decrease of ser-um vWF and MCP-1 in the observation group was more obvious(P<0.05).Conclusion Serum MCP-1 and vWF has obvious relationship in acute cerebral infarction,butyl phthalide soft capsule can significantly lower the serum con-centration.

Treating massive cerebral infarction by butyl phthalide:a research on clinical application / 中国生化药物杂志

Objective To explore the effect of butylphthalide on the prognosis of massive cerebral infarction patients.Methods We studied 92 massive cerebral infarction patients hospitalized in the Neurology department of harrison international peace hospital from February 2011 to December 2013 as the researchers.According to the treatment of patients,patients were randomly divided into control group (n=46)and treatment group(n=46),control group was given edaravone.Treatment group was given butylphthalide capsule and edaravone.Two groups were all given 2 weeks treatment continuously.Improvement of symptoms is evaluated by the National Institute of Health stroke scale (NIHSS).The effect of butylphthalide on collateral circulation in ischemic infarction area was evaluated by the standards of collateral vessels grading of susceptibility-weighted imaging(SWI)imaging sequence. Results The symptoms and signs of two groups were improved in a certain extent,but the improvement of patients in treatment group was significantly greater than control group,the difference was statistically significant (P<0.05 ).Degree of NIHSS of treatment group was lower than control group,the difference was also statistically significant (P<0.05).The SWI collateral vessels grading of the two groups were all improved,and the cases of treatment group was higher than control group,the difference was statistically significant (P <0.05 ).The two groups have no obvious adverse reaction.Conclusion Butylphthalide have good effect on massive cerebral infarction.It can effectively improve the nerve function defect,and promote the reconstruction of collateral circulation in ischemic infarction area.

Clinical effects of levodopa benserazide combine with dl-3-butylphthalide capsules on limbs function of patients after stroke / 中国综合临床

Objective To investigate the effects of levodopa benserazide hydrochloride combine with dl-3-butyl phthalide capsule on patient's limbs function after stroke. Methods Ninety patients with stroke were randomly divided into rehabilitation group,treatment group and control group,and 30 cases for each group. Patients in rehabilitation group were treated with exercise therapy,in treatment group were given exercise therapy and levodopa Benserazide and Dl-3-butylphthalide capsules,and in control group were given placebo treatment. Adult hemiplegic motor function score(FMA)and motor function assessment scale(MAS)were used to assess the motor function and lower extremity function before treatment and 8 weeks after treatment. Results Before treatment,FMA and MAS in rehabilitation group,treatment group and control group were(22. 6 ± 3. 6), (23. 1 ± 2. 5)and(20. 3 ± 2. 9),and(1. 6 ± 0. 6),(2. 1 ± 0. 5),(1. 7 ± 0. 9),respectively. There was no significant differences between the two groups( F = 1. 64,P > 0. 05;F = 1. 66,P > 0. 05). After 8 weeks of treatment,FMA and MAS in rehabilitation group and treatment group were(60. 6 ± 3. 5),(14. 6 ± 1. 1),and (75. 7 ± 4. 5),(17. 7 ± 4. 5),significant improved more than that before treatment(t = 1. 738,1,716,1. 732 respectively;P < 0. 05). Meanwhile,patients in the treatment group improved more than that in rehabilitation group(P < 0. 05),and they were superior to patients in control group((31. 0 ± 3. 6),(5. 5 ± 1. 1);P < 0. 05). Conclusion Benserazide combined with dl-3- butyl phthalide capsule can further improve the limbs function.

Effect and safety of butyl phthalide sequential treatment in cerebral infarction of branch sclerosis of arterial congee appearance / 中国综合临床

Objective To value the effect and safety of butyl phthalide sequential treatment in cerebral infarction of branch sclerosis of arterial congee appearance. Methods Sixty patients with acute cerebral infarction were randomly divided into treated group( n = 31)and control group( n = 29). According to the condition of illness,all patients were given aspirin,atorvastatin calcium,and the injection of ozagrel sodium intravenous;controlled the blood pressure,blood sugar,blood lipid,and treated complications posstively;take the early rehabilitation of nerve treatment afte the illness was in stable condition. Butyl phthalide was used in the patients of treated group(100 ml,twice per day,intravenous drip,during 14 days period therapy,and then 0. 2 g oral,third per day),besides the routine therapy. The degree of neural function defect score( NIHSS)and activities of daily living score(BI)between two groups were observed before and after treatment. Corresponding adverse consequences were recorded. Results Compared with pretreatment,the NIHSS of postreatment at the 14th day in treat and control groups were decreased(treated group:(4. 36 ± 3. 11)vs.(11. 42 ± 3. 20);control group:(6. 12 ± 2. 67)vs.(11. 64 ± 3. 43),P < 0. 05,and the treated group was significantly lower than control group(F inner groups = 2. 125,P < 0. 01;F between groups = 18. 63,P < 0. 01;F cross groups = 25. 34,P< 0. 01;P < 0. 05). The BI of postreatment in two group were increased(treated group:(86. 72 ± 8. 44)vs. (26. 54 ± 13. 36);control group:(75. 96 ± 9. 86)vs.(26. 38 ± 13. 02)),and the treated group was significantly lower than control group(F inner groups = 29. 27,P < 0. 01;F between groups = 32. 48,P < 0. 01;F cross groups= 42. 41,P < 0. 01;P < 0. 05). There was no the adverse reactions. Conclusion Butyl phthalide sequential treatment can improve the NIHSS and BI of cerebral infarction of branch sclerosis of arterial congee appearance and have a better therapy effect.