Terpenoids and Phenylpropanoids in Ligularia duciformis, L. kongkalingensis, L. nelumbifolia, and L. limprichtii.[Pubmed: 29186833]

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Proteomic characterization of the possible molecular targets of pyrrolizidine alkaloid isoline-induced hepatotoxicity.[Pubmed: 22885678]

Pyrrolizidine alkaloids (PAs) are distributed in plants worldwide including medicinal herbs or teas. In the present study, we investigated the effects of isoline, which is a retronecine-type PA isolated from traditional Chinese medicinal herb Ligularia duciformis, on mouse liver proteins by using proteomic approaches. Firstly, our results showed that 110mg/kg isoline increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum, and hepatic tissue pathological observation further confirmed isoline-induced liver injury. Proteomic analysis showed that the liver samples from mice of isoline group demonstrated about 13 differentially expressed proteins compared with normal group, and those proteins may be involved in isoline-induced liver injury in mice. Next, all these 13 protein spots were identified by MALDI-TOF-TOF MS or LTQ MS; and among them 9 differentially expressed proteins are involved in the process of oxidative stress or cellular energy metabolism. Further lipid peroxidation analysis and ATPase assay confirmed the existing of oxidative injury induced by isoline and consequent disruption of energy metabolism. Furthermore, an in silico drug target searching program INVDOCK identified 2 potential protein targets of isoline, and the results are in support of proteomic analysis. In summary, the possible signaling molecules related with isoline-induced liver injury were demonstrated in this study.

Chemical and genetic study of Ligularia duciformis and related species in Sichuan and Yunnan Provinces of China.[Pubmed: 22492496]

The chemical constituents of the root extracts and the evolutionarily neutral DNA base sequences were studied for 28 samples of Ligularia duciformis, L. kongkalingensis, and L. nelumbifolia collected in Sichuan and Yunnan Provinces of China. The samples could be classified into four chemotypes (1-4). Sesquiterpenoids having eremophilane and oplopane skeletons were isolated from two (Chemotype 1) and three (Chemotype 2) samples, respectively. Two new oplopane derivatives were isolated and their structures were determined. In 18 samples, phenylpropenoids were the major components (Chemotype 3). In five samples, neither phenylpropenoids nor sesquiterpenoids were found (Chemotype 4). Despite this large chemical variety, no correlation was found between the chemotype and the morphological criteria of species identification. The analysis of the evolutionarily neutral DNA regions also indicated that the samples were not separated into distinct clades and that introgression was extensive.

Involvement of intracellular glutathione in regulating isoline-induced cytotoxicity in human normal liver L-02 cells.[Pubmed: 22474030]

Pyrrolizidine alkaloid isoline is isolated from the traditional Chinese medicine Ligularia duciformis. Our previous reports have already demonstrated isoline-induced liver injury in mice. The present study is designed to observe the involvement of intracellular reduced glutathione (GSH) in isoline-induced cytotoxicity in human normal liver L-02 cells. The results showed that isoline decreased the cellular GSH and the ratio of GSH and oxidized glutathione in a time- and concentration-dependent manner in L-02 cells. l-Buthionine-S-R-sulfoximine (BSO) is reported to inhibit cellular GSH biosynthesis, and further results showed that isoline decreased the cell viability in L-02 cells after pretreated with 25 μM BSO for 24 h. Furthermore, adducts of isoline and GSH were identified in L-02 cells using liquid chromatography/electrospray ionization tandem mass spectrometry (ion trap) for the first time. In conclusion, our study provides the strongest evidence to support the important roles of GSH in regulating isoline-induced cytotoxicity in human normal liver L-02 cells.

3β-Acet-oxy-8β,10β-dihy-droxy-6β-meth-oxy-eremophil-7(11)-en-8,12-olide.[Pubmed: 21588445]

The title compound, C(18)H(26)O(7), is an eremophilenolide which has been isolated from the plant Ligularia duciformis for the first time. The present study confirms the atomic connectivity assigned on the basis of (1)H and (13)C NMR spectroscopy. The mol-ecule contains three fused rings, two six-membered rings in chair confomations and a five-membered ring in a flattened envelope conformation. Two hy-droxy groups are involved in formation of intra- and inter-molecular O-H⋯O hydrogen bonds. The latter ones link mol-ecules into chains propagating in [010].

Pyrrolizidine alkaloid isoline-induced oxidative injury in various mouse tissues.[Pubmed: 19540740]

Isoline is a retronecine-type pyrrolizidine alkaloid (PA) isolated from the traditional Chinese medicinal herb Ligularia duciformis. The present investigation was carried out to evaluate isoline-induced oxidative injury in various important mouse organs. Various tissue samples were collected after mice were administrated with 100mg/kg isoline for 36h, and then lipid peroxidation (LPO) level, total antioxidant capacity, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities were determined to evaluate the oxidative injury. Our results showed that the total antioxidant capacity of liver, brain and lung were all decreased after given isoline, and the LPO level was increased in liver and heart of isoline-treated mice. Further antioxidant-related enzyme activity assays showed that isoline (100mg/kg) decreased GPx activity in liver and heart, increased CAT activity in liver, brain and heart, and decreased the GST activity in lung. Taken together, our results demonstrate that isoline can induce different oxidative injury in various important mouse organs, and of which liver is the most sensitive organ.

Four new alkaloid derivatives from Ligularia duciformis.[Pubmed: 19431014]

Four new alkaloids, named 1-(4'-methylpyridazin-5'-yl)butane-1,2,3,4-tetraol (1), 3,9-dimethyl-5-nitropyrido[3,2,1-ij]quinazoline-1,7-dione (2), N,N-di(1-imine-propanyl)propionamidine (3), and 2,7-bis(isopropylimino)-2H,7H-dicyclopentacyclooctene-4,9-diol (4), were isolated from the rhizomes of Ligularia duciformis. Their structures were elucidated by spectral analysis.