A new protoberberine alkaloid from Corydalis yanhusuo W.T.Wang

A new protoberberine alkaloid, named 5,6-dihydro- 10-hydroxy-2,3,9-trimethoxy- 13-methyldibenzo[α,g]quinoliziniurn （1） was isolated from the 60% ethanol extract of the tubers of Corydalis yanhusuo W. T. Wang, together with a new natural product, 13methylpalmatrubine （2）. Their structures were established by spectroscopic methods. 2009 Xin Sheng Yao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.

Isolation and identification of chemical constituents from the vinegar-prepared Corydalis yanhusuo

Phytochemical investigation of the vinegar-prepared Corydalis yanhusuo led to the isolation of one aristolactam derivative,1,2,8,9-tetramethoxy-5-methyldibenzo[cd,f]indol-4-(5H)-one(1),and seven aporphine alkaloids,including 2,9,10-trimethoxydibenz[de,g]quinolin-7-one(2),1-hydroxy-2,9,10-trimethoxy-7H-dibenzo(de,g)quinoline-7-one(3),oxoglaucine(4),N-methyloxoglaucine trifluoroacetate trifluoroacetate(5),corunine acetate(6),pontevedrine(7),and oxoglaucidaline trifluoroacetate(8).The structures of the isolated compounds were elucidated by extensive spectroscopic data analysis and comparison with the previous reports.Among them,compounds 1 and 2 were obtained as natural products for the first time,and their NMR data were unambiguously assigned.In addition,compound 1 exhibited moderate cytotoxic activity against HepG2 cells with an IC50 value of 16.0±6.4μM.

(+)/(-)-Yanhusuosines A and B, two dimeric benzylisoquinoline-protoberberine alkaloid atropo-enantiomers featuring polycyclic skeletons from Corydalis yanhusuo

(+)/(-)-Yanhusuosines A(1) and B(2), two pairs of trace benzylisoquinoline-protoberberine atropoenantiomeric homodimers featuring an unprecedented 6/7/6/6/6/6 hexacyclic skeleton, were isolated from the tubers of Corydalis yanhusuo. The structures of(+)/(-)-1 and(+)/(-)-2 were elucidated using spectroscopic and quantum-chemical calculation approaches.(+)/(-)-Yanhusuosines A(1) and B(2)represent a new class of alkaloid dimers biogenetically constructed by a molecule of benzylisoquinoline with a unit of protoberberine via an intermolecular [4 + 3] cycloaddition. Their plausible biosynthetic pathways are discussed, and compound 2 exerted moderate inhibitory activity of NO formation in LPS induced RAW264.7 macrophages.

Developing a Novel Single-Marker-Based Method for the Quantitative Evaluation of the Multiple Active Components in Corydalis yanhusuo W. T. Wang

Objective: This study was designed to develop a method for detecting differences in the chemical composition of Corydalis yanhusuo W. T. Wang using high-performance liquid chromatography with a diode array detector technology. Materials and Methods: We established a novel quantitative evaluation method for identifying multiple components in natural extracts using a single-marker method quantitative analysis of multi-components by single marker(QAMS). This method was then validated using eight alkaloid phytochemical markers designed to evaluate C. yanhusuo quality. Results: Our evaluations revealed good linearity(R^(2) ≥ 0.9991) within the range of tested concentrations for all eight alkaloids, with recovery ranging from 95.5% to 101.5%. The evaluations also returned stability results that fell within the acceptable range. Cluster analysis and Heatmap analyses were applied to classify and evaluate alkaloids across 21 different production areas. These results revealed a significant difference in the component profiles between samples from different origins. Conclusions: Thus, these data suggest that in the absence of a material reference, QAMS may help facilitate the stable production of C. yanhusuo. In addition, our data suggest that this method may have value as a promising alternative to common quality evaluations for controlling C. yanhusuo composition.

(+)/(-)-Yanhusamides A-C,three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids,(+)/(-)-yanhusamides A-C(1-3),featuring an unprecedented 3,8-diazatricylco[5.2.2.0^(2,6)]undecane-8,10-diene bridged system.Their structures were exhaustively characterized by X-ray diffraction,comprehensive spectroscopic data analysis,and computational methods.Guided by the hypothetical biosynthetic pathway for 1-3,a gram-scale biomimetic synthesis of(±)-1 was achieved in 3 steps using photoenolization/Diels-Alder(PEDA)[4+2]cycloaddition.Compounds 1-3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages.The in vivo assay showed that oral administration of 30 mg/kg of(±)-1 attenuated the severity of rat adjuvant-induced arthritis(AIA).Additionally,(±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.

不同加工工艺、采收期、存储方法对延胡索质量的影响

通过对延胡索(Corydalis yanhusuo)产地加工工艺的探究,以延胡索乙素、稀乙醇浸出物、乙醇浸出物、黄曲霉毒素含量为指标,考察不同蒸煮工艺、采收期、存储方法对延胡索质量的影响。结果表明,蒸后干燥延胡索整体质量优于煮后干燥处理,其中蒸制3 min的样品质量最佳;采收时期与延胡索乙素含量之间没有明显关联;自然存储和冷库存储5 d以上能明显提高延胡索浸出物含量。建议选择蒸制方式处理延胡索,其中蒸制3 min最佳。采收应在植物茎叶完全枯萎时进行。新鲜采收的延胡索不应立即加工,而应存储一定时间积累有效成分含量。建议自然存储或冷库存储10 d或20 d以上。鲜货存储过程中不易导致黄曲霉素污染,加工后及时干燥可以明显降低黄曲霉毒素超标的风险。

Corydalis Rhizoma as a model for herb-derived trace metabolites exploration:A cross-mapping strategy involving multiple doses and samples

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from representative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to characterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

Effects of Postharvest Processing and Geographical Source on Phytochemical Variation of Corydalis Rhizoma

Objective To assess the relative contributions of postharvest processing and geographical source to phytochemical variation of Corydalis Rhizoma, and rhizome of Corydalis yanhusuo, and to examine what phytochemical components are the most sensitive to the differences of each factor and how they change. Methods HPLC fingerprinting and LC-MS coupled with chemometric approaches were applied. Results The results of principal component analysis(PCA) and hierarchical cluster analysis(HCA) explicitly demonstrated the postharvest processing could produce a greater impact on the phytochemical profiles of Corydalis Rhizoma than geographical source. The contents of most compounds increased after water boiling while decreased after sulphur-fumigation.Protopine, coptisine, and palmatine were the most variable components in processing. Geographical sources also led to a remarkable phytochemical differentiation, in which the environmental variation of the three regions might play a role. Dehydrocorybulbine, coptisine, dehydrocorydaline, and protopine varied most among the three production regions and decreased sequentially in Zhejiang, Shaanxi, and Jiangsu provinces, China. Conclusion Both postharvest processing and geographical source should be enhanced with the priority for the former in the quality control of Corydalis Rhizoma. The application of boiling is supported but the consistency should be improved in practice. Sulphur-fumigation is strongly suggested to be abandoned.

Analgesic Activity of Jin Ling Zi Powder and Its Single Herbs:A Serum Metabonomics Study

Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete random design,including control,model,aspirin(ASP,0.14 g/kg body weight),JLZ(14 g/kg body weight),Corydalis yanhusuo(YHS,14 g/kg body weight),and Toosendan Fructus(TF,14 g/kg body weight)groups,6 mice in each group.The mice in the control and model groups were given the same volume of saline,daily for 2 consecutive weeks.At 30,60,90,and 120 min after the last administration,the pain threshold of mice in each group was measured,and the improvement rate of pain threshold was calculated.Serum endogenous metabolites were analyzed by gas chromatography–mass spectrometry(GC–MS).Results:There was no statistical difference in pain threshold among groups before administration(P>0.05).After 2 weeks of administration,compared with the model group,the pain threshold in JLZ,YHS,TF and ASP groups were increased to varying degrees(P<0.05).JLZ had the best analgesic effect and was superior to YHS and TF groups.A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs.These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism,glycine,serine and threonine metabolism,valine,leucine and isoleucine biosynthesis,aminoacyl-t RNA biosynthesis and inositol phosphate metabolism.Conclusions:The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor,producing post-synaptic potential,reducing the excitability of neurons,and weakening the afferent effect of painful information.