Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 / 中国天然药物

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ

Protective effect of α-asarone and β-asarone on Aβ -induced inflammatory response in PC12 cells and its / 浙江大学学报·医学版

To investigate effects of α-asarone and β-asarone on induced PC12 cell injury and related mechanisms. Aβ toxic injury cell model was induced by Aβ in PC12 cells. PC12 cells were divided into blank control group, model control group, α-asarone group (0.5, 1.0, β-asarone group (6.3, 12.5, vasoactive intestinal peptide (VIP) group, and VIP antagonist control group. Cell survival rate was detected by CCK-8 kit; cell apoptosis rate was detected by flow cytometry. The levels of inflammatory cytokines interleukin (IL)-1, , tumor necrosis factor (TNF)-α, oxidation-related inducible nitric oxide synthase (iNOS), nitric oxide (NO), apoptosis factors caspase-3 and p53 were detected by ELISA method. The expressions of C-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were detected by Western blotting. Compared with model control group, cell survival rates of group, β-asarone group and VIP group increased; the cell apoptosis rate decreased; levels of apoptosis-related factors caspase-3, p53, inflammatory factors IL-1, TNF-α decreased; IL-10 level increased; levels of oxidization-related factors iNOS and NO decreased; the expression of JNK and p38MAPK protein decreased (all 0.05). α-asarone and β-asarone have protective effects on PC12 cell injury induced by Aβ. β-asarone may inhibit inflammatory factors and oxidation-related factors through promoting VIP secretion, regulating JNK/MAPK pathway, and reducing PC12 cell apoptosis; however, the effect of α-asarone may be not related to VIP secretion.

Effect of α-asarone on the Function and Expression of P-glycoprotein in Rat Brain Microvascular Endothelial Cells / 中国医学科学院学报

To investigate the effect of α-asarone on the function and expression of P-glycoprotein(P-gp)in rat brain microvascular endothelial cells(rBMECs). rBMECs were exposed to L-glutamate(100 μmol/L) for 30 mins to induce the overexpression of P-gp/multidrug resistance gene 1a(Mdr1a)on the cell membranes,which mimicked the overexpression of P-gp/Mdr1a in blood brain barrier(BBB) when drug-resistant epilepsy attacked.MTT assay was used to detect the safe range of α-asarone concentration.The model cells were intervened with different concentrations of α-asarone at 12.5,25.0,and 50.0 μg/μl for 24 hours.After the treatment of α-asarone,the expression and the function of P-gp/Mdr1 were measured by Western blotting,real-time PCR,and intracellular rhodamine 123 accumulation assays. The rBMECs,stimulated by glutamine,showed a high expression of P-gp(=1.924,=0.020)/Mdr1a(=1.788,=0.019) compared to the normal rBMECs.The treatment with 25.0(=1.924,=0.025;=1.788,=0.017) and 50.0 μg/μl(=1.924,=0.035;=1.788,=0.026) α-asarone significantly depressed the expression of P-gp/Mdr1a.The treatment with 25.0 and 50.0 μg/μl α-asarone significantly increased intracellular accumulation of Rhodamine 123 by 40% and 60% respectively. α-asarone down-regulates the high expressions of P-gp and Mdr1a mRNA in rBMECs induced by L-glutamate.Moreover and increases intracellular accumulation of rhodamine-123.Thus,α-asarone may reverse drug resistance in P-gp-mediated drug-resistant epilepsy.

Effects of α-asarone on Proliferation and Differentiation of Neural Progenitor Cells / 체질인류학회지

This study investigated whether α-asarone could promote proliferation and differentiation of neural progenitor cells into the neuronal cell types in in vitro and ex vivo studies. For in vitro assay, neural progenitor cells were isolated from fetal cerebral cortex (E15) and checked cell proliferation rate and neural progenitor cell marker in neurospheres. Treatment of α-asarone, particularly at a concentration of 3 µM, promoted the proliferation of neural progenitor cells and effectively differentiated neural progenitor cells into neurons. For ex vivo assay, a hippocampi slice culture system from 7 day postnatal rat fetuses was used. Although slight tissue damage was observed in the hippocampus after the high concentration (100 µM) of α-asarone, however, α-asarone enhanced the proliferation of neural progenitor cells in dentate gyrus region and also effectively differentiated into neuroblast at concentration of 30 µM. Consequently, α-asarone promotes the proliferation of neural progenitor cells and effectively differentiates neural progenitor cells into neurons. Therefore, our results support the therapeutic benefits of α-asarone for treating neurodegenerative diseases.

Effect of α-Asarone on Esophageal Eca-109 Cell Mitochondrial Apoptosis Pathway / 医药导报

Objective To discuss the effect of α-asarone on the expression level of Cyt-c,Smac,Caspase3 mRNA and protein in human esophageal carcinoma Eca-109 cell mitochondria. Methods The Eca-109 cells were cultured in vitro,and divided into the negative control group and the α-asarone treatment groups(final concentration:25,50,100 μg·mL-1).After 48 h,the morphological changes of Eca-109 cells were observed by fluorescence inversion microscope.The total RNA of cells were extracted by TRIzol method,the expressions of Cyt-c、Smac and Caspase3 were measured by RT-PCR and Western blotting. Results After Eca-109 cells were treated with different concentrations of α-asarone for 48 h,and obvious changes in the morphology were observed,the expressions of Cyt-c,Smac and Caspase3 genes and protein were increased significantly compared to the negative control group( P<0.05). Conclusion α-asarone can induce the human Eca-109 cells apoptosis by regulating expressions of mitochondrial apoptosis pathway correlation genes such as Cyt-c,Smac and Caspase3.

Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles / 中国中药杂志

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.

Chemical constituents from branches and leaves of Viburnum sargentii / 中草药

Objective: To study the chemical constituents from the branches and leaves of Viburnum sargentii collected at Mountain Tai. Methods: The chemical constituents were isolated and purified by chromatographic methods, including silica gel, ODS, Sephadex LH-20 columns, and RP HPLC. The structures of the isolated compounds were identified by ESI-MS, 1D-NMR, and 2D-NMR data analyses, and compared with the literature data. Results: Thirteen compounds were obtained from the 95% ethanol extract of branches and the leaves of V. sargentii, and determined as α-amyrin (1), uvaol (2), 3α-ursolic acid (3), 11,12-dehydroursolic acid lactone (4), 3-O-acetyloleanolic aldehyde (5), oleanolic acid (6), betulinic acid (7), magnolin (8), (+)-eudesmin (9), (-)-epieudesmin (10), vibsanol (11), 3,4'-dimethoxylvibsanol (12), and α-asarone (13), respectively. Conclusion: Compound 12 (3,4'- dimethoxylvibsanol) is a new natural product, and compounds 1-11 and 13 are isolated from V. sargentii for the first time.

Research progress and clinical application of α-asarone injection / 中国比较医学杂志

Objective To understand the current state of research and clinical application of α-asarone injection.Method Literature search was conducted and the pharmacology, toxicology, preparation, clinical application and adverse reactions of α-asarone were reviewed.Results α-asarone injection has strong relieving effects on cough and asthma, but the quality of production is varying, adverse reactions are often reported, and the toxicological effects need to be further investigated.Conclusions α-asarone injection has a certain clinical effect, but the reports of related adverse reactions are gradually increased.Its toxicity remains to be further studied, and the product quality standard system and instructions need also to be further improved.

Optimization of solvent-free microwave extraction for Acori Tatarinowii Rhizoma and analysis on volatile components by GC-MS / 中草药

Objective: To study the solvent-free microwave extraction for oils of Acori Tatarinowii Rhizoma and analyze the volatile components. Methods: The paper selected the best technological conditions by L9(34) orthogonal test, with the index of α-asarone, volume of volatile oils, and sum of the percentage, The essential oils in Acori Tatarinowii Rhizoma were analyzed with GC-MS. Results: The percentage of volatile oils was calculated according to peak area normalization method. The results showed similar amount of volatile oil components by two methods, and the extraction rates of α-asarone, β-asarone, and γ-asarone accounted for 4.12%, 55.11%, and 10.54% on the method of solvent-free microwave extraction, while the steam distillation was 5.39%, 47.03%, and 9.15%. To compare with two methods, solvent-free microwave extraction extracted volatile oil 0.235 mL and α-asarone 31.99 mg for 5 min, while steam distillation extracted volatile oil 0.175 mL and α-asarone 29.09 mg for 1 h. The method of solvent-free microwave extraction had the advantage of short reaction time and high yields. Conclusion: Solvent-free microwave extraction is a new method with shorter extracting time and better extracting efficiency.

Experimental study onα-Asarone-induced apoptosis in human esophageal carcinoma Eca-109 cell line I by regulating GADD153 and Smac mRNA expression levels / 医学研究生学报

Objective α?Asarone has the effect of relieving cough and asthma as well as sedative, hypnotic and anticonvul?sive function. Our study was designed to explore the effects of apoptosis induced by α? Asarone on human esophageal carcinoma Eca?109 cell line as well as the expression levels of GADD153 and Smac mRNA. Methods Human esophageal carcinoma Eca?109 cells were cultured in vitro, which were divided into blank control group, 5?FU group( 500μg/mL) andα?Asarone group of different dosages ( 25,50,100μg/mL) . After cultivation, MTT method and Annexin V?PI were used to measure cell proliferation rate and apoptosis rate. Expression levels of GADD153 and Smac protein and mRNA were detected by western blotting and real? time quantitative PCR. Results Compared with blank control group, the cell proliferation rates in other groups decreased significantly (P<0.01), and cell apoptosis rate increased significantly ( P<0.01) . Compared with blank control group, the expression levels of GADD153 and Smac pro?tein and mRNA in other groups increased significantly( P<0.05) . Conclusion α? Asarone can inhibit cell proliferation and induce the apoptosis of human esophageal carcinoma Eca?109 by regulating the expression levels of GADD153 and Smac gene.

Content Determination Method of α-asarone in Dianxianqing Granules / 中国中医药信息杂志

Objective To discuss the content determination method ofα-asarone in Dianxianqing Granules. Methods Kromasil C18 column (250 mm×4.6 mm, 5 μm) was used, with methanol and water as mobile phase of gradient elution. The flow rate was 1.0 mL/min, and the detection wavelength was 257 nm. The column temperature was 25 ℃. Results The sample solution was prepared by reflux extracted with 70% ethanol for 20 min. α-asarone had a good linearity in the ranges of 1.24×10-3-7.44×10-3μg (r=0.999 5). The method was quite good in precision, stability and repeatability, and the average recovery ofα-asarone was 98.14%, with corresponding RSD of 2.5%. Conclusion The experiment provides an accurate and fast analytical method for α-asarone determination in compound preparation of traditional Chinese medicine.