3-epi-Pumiloside

Anti-inflammatory effect of the six compounds isolated from Nauclea officinalis Pierrc ex Pitard, and molecular mechanism of strictosamide via suppressing the NF-kappaB and MAPK signaling pathway in LPS-induced RAW 264.7 macrophages.[Pubmed:27989509]

J Ethnopharmacol. 2017 Jan 20;196:66-74.

ETHNOPHARMACOLOGICAL RELEVANCE: Nauclea officinalis Pierrc ex Pitard. is a Chinese medicinal herb that contains high level of alkaloids which is the most abundant and active constituent. Strictosamide isolated from Nauclea officinalis Pierrc ex Pitard. showed significant effects on inflammatory response, compared with pumiloside, 3-epi-Pumiloside, vincosamide, 3alpha,5alpha-tetrahydrodeoxycordifoline lactam and naucleamide A-10-O-beta-D-glucopyranoside of this plant. AIM OF STUDY: we investigated the biological activities of the six compounds mentioned-above, and the underlying molecular mechanism exerted by the most potent one, strictosamide. MATERIALS AND METHODS: The effects of strictosamide and other five compounds on the inhibitory activity of nitric oxide (NO) were screened by Griess test. The contents of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in media were detected by using Enzyme-linked immunosorbent (ELISA) kits. The effects on the mRNA expression of nitric oxide synthase (iNOS), TNF-alpha and IL-1beta of strictosamide were further investigated by RT-qPCR. Western blot assay was conducted to illustrate the effects of strictosamide on iNOS and phosphorylation of p65, inhibitor of NF-kappaB (IkappaB)-alpha, IkappaB-kinase (IKK)-alpha as well as p-extracellular signal-regulated kinase (ERK), p-c-jun N-terminal kinase (JNK) and p-p38 in the protein levels. RESULTS: Strictosamide potently suppressed the productions of NO, TNF-alpha and IL-1beta in LPS-induced RAW 264.7 macrophages, and it dose-dependently alleviated the LPS-simulated protein level of iNOS as well as the mRNA expressions of iNOS, TNF-alpha and IL-1beta. In addition, molecular data revealed that strictosamide markedly decreased the expressions of p-p65, p-IkappaBalpha and p-IKKalpha. Furthermore, strictosamide significantly attenuated LPS-induced the phosphorylation of p38, ERK and JNK. CONCLUSIONS: At present study, the results indicated that the anti-inflammatory activity of strictosamide was associated with the restraint of NO, TNF-alpha and IL-1beta via negative regulation of both NF-kappaB and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells.

New indole glucosides as biosynthetic intermediates of camptothecin from the fruits of Camptotheca acuminata.[Pubmed:25771119]

Fitoterapia. 2015 Jun;103:1-8.

Six new indole glucosides (1-6) and fifteen known alkaloids (7-21) were isolated from the fruit of Camptotheca acuminata. The planar structures of 1-6 were determined on the basis of spectroscopic data analysis and their absolute configurations were established by CD. The isolated indole glucosides showed a clear biosynthetic pathway of camptothecin (7), which started from tryptamine and secologanin and was proposed by synthetic chemists previously. Particularly, compound 1 supplemented the process of the transformation from pumiloside (20) or 3-epi-Pumiloside (21) to camptothecin (7). In addition, camptothecin 10-O-beta-D-glucopyranoside (13) and norcamptothecin (17), synthesized in the early structural modification of 7, were first isolated from the natural resources. The new compounds 1-6 were screened for their in vitro cytotoxicity but they did not show any exciting result.

Simultaneous determination of six alkaloid components in rat plasma and its application to pharmacokinetic study of Danmu preparations by an ultra fast liquid chromatography-electrospray ionization-tandem mass spectrometry.[Pubmed:25612771]

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Mar 1;983-984:10-7.

Danmu injection and Danmu tablet are two widely used traditional Chinese medicine made of Nauclea officinalis (commonly known as Danmu), in which the alkaloids are the major active substances. In this paper, an ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination and the pharmacokinetic characteristics study of six main active alkaloids (naucleamide A-10-O-beta-d-glucopyranosid, naucleamide G, pumiloside, 3-epi-Pumiloside, strictosamide and vincosamide) of the two above-mentioned Danmu preparations in rat plasma. In the course of the experiment, following sample preparation by protein precipitation with methanol-ethyl acetate (2:1, v/v), the nitrogen-dried extraction was reconstituted in methanol and assayed on a C18 column using a gradient elution program with mobile phase consisting of acetonitrile and water containing 0.1% formic acid. The MS detection was performed in positive ionization mode with selected ion transitions. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.32ng/mL in rat plasma and matrix effects ranged from 88.87 to 108.27%. Good linearities of six alkaloids were obtained in respective concentration ranges (r(2)>0.995). The average extract recoveries for each compound at three quality control concentration levels were no less than 79.70%, and the precision and accuracy were within the acceptable limits. The validated method was successfully applied to the pharmacokinetic study of six alkaloid components of Danmu injection and tablet in rat plasma. The obtained results may be helpful to reveal the action mechanism and guide the clinical application of Danmu preparations.

[Chemical constituents of Nauclea officinalis].[Pubmed:23672026]

Yao Xue Xue Bao. 2013 Feb;48(2):276-80.

In order to study the chemical constituents in the water extract of the stem of Nauclea officinalis, column chromatography over D101 macroporous resin and silica gel and an automatic purification system were used to isolate and purify the chemical constituents from the extract. Nine compounds were obtained. By analysis of the physicochemical properties and spectral data, their structures were identified as naucleamide G (1), 3, 4-dimethoxyphenol-beta-D-apiofuranosyl (1-->6)-beta-D-glucopyranoside (2), kelampayoside A (3), 3alpha, 5alpha-tetrahydrodeoxycordifoline lactam (4), naucleamide A-10-O-beta-D-glucopyranoside (5), pumiloside (6), 3-epi-Pumiloside (7), strictosamide (8) and vincosamide (9), separately. Among them, compound 1 is a new compound, compound 2 was found in plants of the genus Nauclea for the first time, and compounds 3 and 4 were isolated from this plant for the first time.