Chemical Composition And Biological Activity Of Dendrobium Nobile

The traditional Chinese medicine "Shi Hu", derived from the dried or fresh stems of several Dendrobium species (Orchidaceae), are widely used as a Yin tonic to nourish the stomach and promote the production of body fluid. Of which, Dendrobium nobile Lindl. is one of the most famous one and has been recorded in the Chinese Pharmacopoeia (2005 Edition) as one of the original materials of "Shi Hu".In our systematical study on the chemical constituents of Dendrobium nobile, 53 compounds were obtained from the 60% ethanol extract of the stems of this plant through various chromatographic techniques. Their structures were elucidated on the basis of physico-chemical property and spectroscopic analysis. The 53 compounds from Dendrobium nobile are dendronobilin A (1)^*, dendronobilin B (2)^*, dendronobilin C (3)^*, dendronobilin D (4)^*, dendronobilin E (5)^*, dendronobilin F (6)^*, dendronobilin G (7)^*, dendronobilin H (8)^*, dendronobilin I (9)^*, 10β,13,14-trihydroxyalloaromadendrane (10), 10,12-dihydroxypicrotoxane (11), 6α,10,12-trihydroxypicrotoxane (12), dendrobiumane A (13), bullatantirol (14), dendrodensiflorol (15), dendrobane A (16), nobilin A (17)^*, nobilin B (18)^*, nobilin C (19)^*, nobilin D (20)^*, nobilin E (21)^*, crepidatin (22), chrysotobibenzyl) (23), dendrobin A (24), chrysotoxine (25), moscatilin (26), gigantol (27), fimbriatone (28), confusarin (29), flavanthrinin (30), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (31), 3,7-dihydroxy-2,4-dimethoxyphenanthrene (32), nobilone (33)^*, dendroflorin (34), syringaresinol (35), pinoresinol (36), medioresinol (37), lirioresinol-A (38), 2-methylanthraquinone (39), nobilate (40)^*, syringic acid (41), 2-hydroxyphenylpropanol (42), vanillin (43), apocynin (44), coniferyl aldehyde (45), syringaldehyde (46), syringylethanone (47), p-hydroxybenzaldehyde (48), 3-hydroxy-4-methoxyphenylethanol (49),α-hydroxysyringylethanone (50), dihydroxyconiferyl alcohol (51), p-hydroxybenzoic acid (52), p-hydroxyphenylpropionic acid (53), respectively. Compounds 1-9, 17-21, 33, 40 are new compounds, compounds 14, 30-31, 38-39, 41-42, 44-53 were isolated for the first time from the Dendrobium genus and compounds 13, 15, 22, 23, 25, 28, 29,32,34-37,43 were isolated from this plant for the first time.All the compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method. The results showed that 24 compounds displayed scavenging activity on different levels. Most of the phenanthrenes, bibenzyls and lignans showed good activity and some of fluorenones and phenolic acids were active in this assay. Almost all the active compounds possessed higher scavenging activity than BHT, which is commonly used in food industry as a synthetical antioxidant. 9 compounds showed activity equivalent to or higher than Vc.At the same time, oxygen radical absorbance capacity method was used to evaluate most of the compounds isolated from Dendrobium nobile. Among the 49 tested compounds, 30 compounds displayed oxygen radical scavenging activity on different levels, most of which showed stronger activity than Vc. The phenanthrenes, bibenzyls, lignans and fluorenones generally possessed good activity and some of phenolic acids were active in this assay.Most of the compounds were assayed against NO production on LPS and IFN-γactivated murine macrophage-like cell line RAW 264.7 by Griess method. Among the 46 tested compounds, 12 compounds displayed inhibitory effects on different levels, 5 of which showed activity equivalent to or higher than positive control resveratrol. Some of lignans and phenolic acids showed week activity and most of the phenanthrenes, bibenzyls and fluorenones were active in this assay.The immunomodulatory activity of most compounds were evaluated. Among the 37 tested compounds, 10 compounds were found to inhibit the proliferation of T lymphocytes of mice induced by Con A, in which compound 29 (confusarin) showed inhibitory activity significantly. The results also showed that glycons of sesquiterpene glycosides were important immunomodulatory activity. And this is the first report of aromatic compounds, such as phenanthrenes, bibenzyls and phenolic acids, with immunosuppressive activity from Dendrobium genus.Some of the compounds on [Ca²⁺]_â…°of Guinea pig's cardiomyocytes increase induced by KCl were also evaluated. The results showed that compounds 11, 22, 25, 41, 45 could inhibit the increase of [Ca²⁺]_â…°mobilized by KCl. It suggested that these compounds could have certain prophylactic and therapeutic effects on such diseases as hypertension, angina pectoris, arrhythmia, myocardical infarction, which have close relationship with calcium channel.On the basis of chemical and bioactive study, this paper confirmed that the antioxidant components from Dendrobium nobile were phenanthrenes, bibenzyls, fluorenones, lignans and phenolic acids, which possessed phenolic hydroxyl groups in their structures, primarily showed that active compounds against NO production on LPS and IFN-γactivated murine macrophage RAW 264.7 were phenanthrenes, bibenzyls and fluorenones, and found new immunosuppressive components, phenanthrenes and bibenzyls. Our study also indicated the above-mentioned compounds in TCM "Shi Hu" could have certain prophylactic and therapeutic effects on many diseases through various modulatory effects, such as scavenging the redundant radicals in the body, inhibiting NO excessive production and inhibiting exorbitant immunoreaction.On the basis of DPPH assay and ORAC assay, the structure-activity relationship was discussed. The number and position of phenolic hydroxyl groups, the number of methoxyl groups substituted in ortho position to the hydroxyl group and the character of side chain in the structure seemed to play an important role in the activity in DPPH assay. But the relativity wasn't obvious between activity and structure in ORAC assay.