[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Novel indoloquinoline alkaloid glycosides from Cryptolepis sanguinolenta (Lindl.) Schltr.

To explore the phytochemistry of the African ethnomedicinal plant Cryptolepis sanguinolenta (Lindl.) Schltr. (Apocynaceae) for rare indoloquinoline alkaloids, two novel indoloquinoline alkaloid glycosides, namely Cryptospirosanguine A (1) and B (2), were isolated from an ethanolic extract of the root. Their structures were elucidated based on spectral evidence. Furthermore, two known terpenoids were isolated from this plant for the first time.

Discovery of steroidal alkaloid glycosides from the bulbs of Fritillaria unibracteata with anti-inflammatory activities using an in vivo zebrafish model.

Nine undescribed steroidal alkaloid glycosides, unibrasolanosides A-F, unibraverazosides A-B, and unibratomatoside A, were isolated from the bulbs of Fritillaria unibracteata P. K. Hsiao & K. C. Hsia (Liliaceae). Their structures were elucidated by HRESIMS and 1D and 2D NMR data analyses as well as chemical methods and single-crystal X-ray diffraction analyses. Further investigation revealed that eight steroidal alkaloid glycosides displayed moderate anti-inflammatory activity in vivo in a CuSO4-induced transgenic zebrafish model.

Indole alkaloid glycosides from Isatis tinctoria roots.

Isatindigoside A and B (1 - 2), two new indole alkaloid glycosides along with five known ones (3 - 7) were obtained from the roots of I. tinctoria. Their structures were determined as isatindigoside A (1), isatindigoside B (2), isatindosulfonicacid A 3-O-ß-D-glucopyranoside (3), indole-3-acetonitrile 6-O-ß-D-glucopyranoside (4), isatindigobisindoloside A (5), isatindigobisindoloside B (6) isatindigobisindoloside F (7), by physicochemical properties and spectroscopic methods including 1 D, 2 D NMR, IR, HR-ESI-MS data. Nitric oxide (NO) inhibitory activities of all of the isolated compounds (1 - 7) were also evaluated. Compounds 2 and 7 showed inhibitory effects against LPS-stimulated RAW 264.7 cells with IC50 values of 27.6 µM and 18.8 µM, respectively.

Steroidal alkaloid glycosides and phenolics from the immature fruits of Solanum nigrum.

Solanum nigrum L. (also called as European black nightshade) has been traditionally used as folk medicine and food in some regions. Phytochemical investigations of the immature fruits of S. nigrum yielded five steroidal alkaloid glycosides (1-5), including an unprecedented nor-spirosolane type steroidal alkaloid with a five-membered ring A (1) and two novel spirosolane type steroidal alkaloid glycosides (2, 3), together with eight known phenolic compounds (6-13). Their structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, HR-ESI-MS, and GC analyses. Five steroidal alkaloid glycosides were tested for their potential antiproliferative effects against HL-60, U-937, Jurkat, K562, and HepG2 cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 23.4 ±â€¯2.0 µM, compared to positive control indomethacin (IC50, 47.40 ±â€¯4.50 µM). Compound 4 exhibited significant cytotoxicity against all tested cell lines.