Synthesis of Novel 3-Butylphthalide Derivatives Containing Isopentenylphenol Moiety as Potential Antiplatelet Agents for the Treatment of Ischemic Stroke.

In order to find novel antiplatelet drugs for the treatment of ischemic stroke, a series of 3-butylphthalide derivatives containing isopentenylphenol moiety were designed, synthesized and characterized with spectroscopic analyses. The in vitro antiplatelet activity results indicated that compound 3 better inhibited the arachidonic acid (AA) induced platelet aggregation than aspirin (ASP) and 3-butylphthalide (NBP). Additionally, compared with precursor NBP, compound 3 possessed outstanding antithrombotic activity in the animal experiment model, which could effectively alleviate the formation of tail thrombus and carotid artery thrombus in mice. More importantly, intraperitoneal administration of compound 3 can well protected the rats against ischemia/reperfusion-induced brain injury. Further pharmacokinetic (PK) assay indicated that compound 3 had good absorption characteristics and metabolic stability in vivo. Overall, the present research provides a new candidate compound for the treatment of ischemic stroke caused by platelet aggregation.

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.

Efficacy Observation of dl-3-Butylphthalide in the Sequential Treatment of Acute Middle Cerebral Artery Infarction / 中国药师

Objective:To evaluate the efficacy and safety of dl-3-butylphthalide ( NBP) injection and soft capsules in the treat-ment of acute middle cerebral artery infarction. Methods:Sixty-one patients with acute cerebral infarction in the left middle cerebral artery in 72 hours of onset of ischemic stroke with score of 5-25 according to the national institutes of health stroke scale ( NIHSS) were randomly divided into the observation group (n=31) and the control group (n=30). The control group was treated with the routine treatment, while the observation group was sequentially treated with NBP injection and soft capsules additionally. The treatment course was 90 days. Before the treatment, the NIHSS score was evaluated in both groups to compare the neurologic impairment degree. After the treatment, the daily living skills assessment was performed by Barthel index ( BI) and modified Rankin score ( mRS) , and the ad-verse reactions were recorded. Results:Before the treatment, the NIHSS score in the two groups had no statistical significance ( P>0. 05). After the treatment, the BI in the observation group and the control group was (88. 55 ± 16. 74) and (70. 67 ± 26. 18), and mRS was (1. 87 ± 1. 02) and (2. 53 ± 1. 40), respectively, suggesting the observation group had more favorable outcome than the con-trol group (P≤0. 05). The incidence of adverse reactions had no significant difference between the groups. Conclusion: dl-3-Bu-tylphthalide sequential therapy should be regarded as an effective and safe method for acute cerebral infarction, which can improve the daily living skills and 90-day outcome of patients.

Rapid Determination of Content of 3-Butylphthalide in Angelicae Sinensis Radix by Near-infrared Diffuse Reflection Spectrum / 中国中医药信息杂志

Objective To establish a quantitative model to rapidly determine content of 3-butylphthalide in Angelicae Sinensis Radix based on near-infrared diffuse reflectance spectroscopy (NIR). Methods Totally 145 batches of samples of Angelicae Sinensis Radix from 14 areas of Gansu and Yunnan Provinces were collected and dried in the shade. With the content of 3-butylphthalide determined by RP-HPLC-DAD as reference, the NIR spectra of 145 batches of Angelicae Sinensis Radix were collected by integrating sphere diffuse reflectance, and the PLS (partial least squares) quantitative analysis model was established between 7415-4056 cm-1. Results The Rc (correlation coefficient between actual content and predicted content), RMSEC (the root-mean-square error of calibration), RMSEP (the root-mean-square error of prediction), Rcv (cross-validation correlation coefficient), RMSECV (the root-mean-square error of cross-validation), and average predicted recovery reached 0.976 7, 0.614 3, 0.706 5, 0.897 8, 1.155 4 and 102.08%, respectively. Conclusion This prediction model was accurate, reliable, and can be used to quantitatively determine the content of 3-butylphthalide in Angelicae Sinensis Radix.

Chemical constituents from aerial parts of Ligusticum sinense cv. chaxiong / 中草药

Objective: To study the chemical constituents from the aerial parts of Ligusticum sinense cv. chaxiong. Methods: The chemical constituents were separated and purified by silica gel, ODS column chromatography, and preparative HPLC. Their structures were determined by various of spectroscopic analyses. Results: Fourteen compounds were isolated from the petrol ester and CH2Cl2 fractions of 95% ethanol extract of the aerial parts of L. sinense cv. chaxiong, and their structures were identified as 5-hydroxy-3- butylphthalide (1), 3-hydroxy-octa-1, 5-dien-7-one (2), umbelliferone (3), pumbinernoid A (4), crocinervolide (5), (3R, 6R, 7E)-3- hydroxy-4, 7-megastignadien-9-one (6), senkyunolide G (7), scopoletin (8), (2Z)-3-(3, 4-dihydroxyphenyl)-2-propenal (9), (3S, 5R, 6S, 7E, 9R)-5, 6-epoxy-3, 9-dihydroxy-7-megastigmene (10), vomifoliol (11), dihydroactinidiolide (12), 7-hydroxy-3-butylphthalide (13), and senkyunolide A (14). Conclusion: Compounds 1-13 are isolated from this plant for the first time, compounds 1, 2, 4-6, and 9-13 are found from the plants of genus Ligusticum L. for the first time, and compound 1 is a new natural product.