Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach

Objective: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Methods: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Results: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Conclusion: The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.     

苗药血人参中黄酮类化学成分研究

目的研究苗药血人参(茸毛木蓝Indigofera stachyodes干燥根)中的化学成分。方法采用硅胶、ODS、Sephadex LH-20柱色谱和半制备高效液相色谱技术对血人参中的化学成分进行分离纯化,通过其理化性质和NMR、MS等谱学数据进行结构鉴定。结果从血人参乙醇提取物的醋酸乙酯萃取部位分离鉴定了24个黄酮类化合物,分别鉴定为芒柄花素(1)、7-羟基-3’,4’-二甲氧基异黄酮(2)、染料木素(3)、毛蕊异黄酮(4)、大豆素(5)、farnisin(6)、3’,4’,7-三羟基黄酮(7)、木犀草素(8)、漆黄素(9)、甘草素(10)、erycibenin D(11)、3,4’,7-三羟基二氢黄酮(12)、二氢山柰酚(13)、黄颜木素(14)、6,4’-二羟基-3’-甲氧基橙酮(15)、硫黄菊素(16)、(–)-3,4’,7-三羟基-3’-甲氧基黄烷(17)、儿茶素(18)、表儿茶素(19)、(-)-epicatechin-3-O-p-hydroxybenzoate(20)、美迪紫檀素-3-O-β-D-葡萄糖苷(21)、2’,4’-二甲氧基-3’-羟基异黄烷-6-O-β-D-葡萄糖苷(22)、7-羟基色原酮(23)和5,7-二羟基色原酮(24)。结论化合物2、5～7、11～15、17、20～24为首次从木蓝属植物中分离得到,化合物1、10和16为首次从血人参中分离得到。化合物3、7、8、10、15和16能够抑制LPS诱导巨噬细胞RAW 264.7释放NO,其半数抑制浓度(IC_(50))在7.3～27.3μmol/L。     

A semi-quantitative approach to the design,analysis and operation of a gas target system

Two-level factorial and central composite experimental designs were used to study the influence of operating conditions (pressure and beam current as an example) on gas target design for the production of medical radionuclides. Other aspects of design primarily the foil were analyzed to determine the effect of material properties or the expected performance of the target window. The use of empirical models relating the target's performance to operating conditions provides an adequate method to quantify properties of interest. These models can be readily incorporated into a computer-controlled system capable of updating their parameters, and performing further experiments while ensuring routine production requirements are met. The krypton gas target for the production of ⁸¹Rb was utilized as an example although the models are applicable to gas targets, in general.     

云南沉香果壳的化学成分研究

目的研究云南沉香Aquilaria yunnanensis果壳的化学成分。方法采用硅胶、Sephadex LH-20柱色谱和半制备HPLC技术进行分离、纯化,结合理化性质和波谱数据鉴定化合物的结构。结果从云南沉香果壳的95%乙醇提取物的醋酸乙酯萃取部位中分离得到13个化合物,分别鉴定为trans-linalool-3,6-oxide-7-O-β-D-(6′-O-acetyl)-glucoside(1)、苯乙基-8-O-β-D-(6′-O-乙酰基)-葡萄糖苷(2)、芒果苷(3)、鸢尾酚酮-3,5-C-β-D-二葡萄糖苷(4)、山柰酚-3-O-β-D-葡萄糖苷(5)、木犀草素-7-O-β-D-葡萄糖苷(6)、异鼠李素-3-O-β-D-葡萄糖苷(7)、山柰酚-3-O-β-D-(6″-对-香豆酰基)-葡萄糖苷(8)、香叶醇-1-O-β-D-葡萄糖苷(9)、3-[2-甲酰基-5-(羟甲基)-1H-吡咯-1-基]戊二酸(10)、大麻酰胺D(11)、淫羊藿次苷D_2(12)、松柏苷(13)。结论化合物1为新的单萜苷类化合物,命名为云南沉香苷C,化合物2为新天然产物,7、9～13为首次从沉香属植物中分离得到,所有化合物均为首次从该植物中分离得到。     

Noralashinol B,a norlignan with cytotoxicity from stem barks of Syringa pinnatifolia

One new norlignan, noralashinol B (1), and one new natural product, proposed noralashinol C (2), were isolated in a continuous phytochemical investigation on the stem barks of Syringa pinnatifolia. Their structures were elucidated based on the analysis of spectroscopic data, including mass spectrometry and 1D and 2D NMR spectroscopies, and the absolute configuration was determined by experimental and calculated electronic circular dichroism. Compound 1 showed a weak cytotoxicity against HepG2 hepatic cancer cells with its IC₅₀ value of 31.7 μM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0–80.0 μM.     

紫堇的化学成分研究

目的研究紫堇Corydalis edulis全草的化学成分。方法采用硅胶、Sephadex LH-20、ODS柱色谱和半制备HPLC等色谱方法分离纯化,结合其理化性质和MS、NMR等波谱学数据鉴定化合物的结构。结果从紫堇乙醇提取物的正丁醇萃取部位分离鉴定了15个化合物,分别鉴定为6,7-亚甲二氧基二氢异香豆素(1)、oxohydrastinine(2)、6,7-dimethoyisoquinolin-1(2H)-one(3)、6,7-methylenedioxy-1(2H)-isoquinolinone(4)、(+)-丁香树脂素(5)、梣皮树脂醇(6)、红景天苷(7)、1-(2-羟基苄基)-β-D-吡喃葡萄糖苷(8)、淫羊藿次苷D_2(9)、水杨苷(10)、淫羊藿次苷F_2(11)、淫羊藿次苷B_2(12)、烟酰胺(13)、邻苯二酚(14)和5-羟基-2-羟甲基吡啶(15)。结论化合物1为新天然产物,化合物3、5~12、14和15为首次从紫堇属植物中分离得到,化合物2、4和13为首次从紫堇中分离得到。     

蛇足石杉内生真菌Penicillium chrysogenum MT-12中2个新二苯醚类成分

目的研究蛇足石杉内生真菌Penicillium chrysogenum MT-12经固体发酵培养后的代谢产物。方法利用硅胶、Sephadex LH-20及半制备液相色谱等方法进行分离纯化,根据化合物的理化性质及IR、MS、NMR等光谱数据鉴定化合物的结构;利用体外模型进行抗炎、乙酰胆碱酯酶抑制活性筛选。结果从P.chrysogenum MT-12固体发酵培养后的代谢产物中共分离鉴定8个二苯醚类化合物,分别为黄青霉内酯A(1)、黄青霉内酯B(2)、talaromyone A(3)、isopenicillide(4)、penicillide(5)、hydroxypenicillide(6)、purpactin A(7)、黄青霉内酯C(8)。结论化合物1、2为新化合物,化合物3为首次从青霉属中分离得到,化合物4~8为首次从产黄青霉菌中分离得到;化合物1、2对脂多糖(LPS)诱导的小鼠巨噬细胞RAW264.7的NO产生有一定抑制活性,半数抑制浓度(IC50)值分别为(72.6±2.3)、(41.2±1.4)μmol/L,而所有化合物在100μmol/L时对乙酰胆碱酯酶不显示抑制活性。     

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??OBJECTIVE To study the chemical constituents from the roots of Rubus parvifolius. METHODS Various chromatographic techniques such as silica gel, Sephadex LH-20, and prep-HPLC column chromatography were used. RESULTS Nineteen compounds, including 12 triterpenoids were isolated from the roots of Rubus parvifolius. Based on the analysis of their spectroscopic data, the structures of these 19 compounds were identified as p-hydroxybenzoic acid(1), 4-hydroxy-3,5-dimethoxybenzoic acid(2), 3-methoxy-4-hydroxybenzoic acid(3), ??-sitosterol(4), oleanolic acid(5), ursolic acid(6), 2-oxopomolic acid(7), pomolic acid(8), p-hydroxyphenylethyl alcohol(9), psiguanin A(10), 2??-hydroxyursolic acid(11), tormentic acid(12), 2??,3??,19??,23-tetrahydroxyurs-12-en-28-oic acid(13), L-epicatechin(14), 2??,3??,19??,24- tetrahydroxyolean-12-en-28-oic acid(15), 2??,3??,19??,24-tetrahydroxyurs-12-en-28-oic acid(16), 2??,3??,19??-trihydroxyolean-12-en-23,28-dioic acid(17), suavissimoside R₁ (18), and daucosterol(19), respectively. CONCLUSION Compounds 1-3, 5, 7-10, 12, and 15-17 are isolated from the roots of R. parvifolius for the first time. Compounds 7 and 9 are isolated from the genus Rubus L. for the first time. Compounds 10 and 15-17 are isolated from the family Rosaceae for the first time.