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Aging and disease    2017, Vol. 8 Issue (6) : 827-849     DOI: 10.14336/AD.2017.0214
Review |
Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies
Cakova Veronika1,*, Bonte Frederic2, Lobstein Annelise1
1Université de Strasbourg, CNRS, LIT UMR 7200, F-67000 Strasbourg, France
2LVMH Recherche, F-45800 Saint Jean de Braye, France
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Abstract  

Dendrobium represents one of the most important orchid genera, ornamentally and medicinally. Dendrobiums are sympodial epiphytic plants, which is a name they are worthy of, the name coming from Greek origin: "dendros", tree, and "bios", life. Dendrobium species have been used for a thousand years as first-rate herbs in traditional Chinese medicine (TCM). They are source of tonic, astringent, analgesic, antipyretic, and anti-inflammatory substances, and have been traditionally used as medicinal herbs in the treatment of a variety of disorders, such as, nourishing the stomach, enhancing production of body fluids or nourishing Yin. The Chinese consider Dendrobium as one of the fifty fundamental herbs used to treat all kinds of ailments and use Dendrobium tonic for longevity. This review is focused on main research conducted during the last decade (2006-2016) on Dendrobium plants and their constituents, which have been subjected to investigations of their pharmacological effects involving anticancer, anti-diabetic, neuroprotective and immunomodulating activities, to report their undeniable potential for treating age-related pathologies.

Keywords Dendrobium      aging      anticancer      immunomodulatory      neuroprotective      anti-diabetic     
Corresponding Authors: Cakova Veronika   
About author:

These authors contributed equally to this paper.

Issue Date: 01 December 2017
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Cakova Veronika
Bonte Frederic
Lobstein Annelise
Cite this article:   
Cakova Veronika,Bonte Frederic,Lobstein Annelise. Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies[J]. Aging and disease, 2017, 8(6): 827-849.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.0214     OR     http://www.aginganddisease.org/EN/Y2017/V8/I6/827
Figure 1.  Chemical structures of main anticancer compounds from Dendrobium spp.
Dendrobium species
(organ)
Active molecule/type of extractBiological targetActivityRefs.
D. brymerianum
(whole plant)
Methanolic extract
Moscatilin Gigantol Lusianthridin Dendroflorin
Human lung cancer cell line H460Cytotoxic Antimigratory[31]
D. candidum
(whole plant)

Methanolic extract Aqueous extract Not specified
Human colon carcinoma cell line HCT-116, BALB/c mice bearing 26-M3.1 colon carcinoma cells
Azoxymethane- and dextran sulfate sodium-induced colon carcinogenesis in C57BL/6 mice BALB/c mice bearing 26-M3.1 cells Breast cancer cell line MCF-7
Cytotoxic
Anti-metastatic Inhibitory Anti-metastatic Anti-proliferative, induction of cell cycle arrest at G2/M phase
[23]
[55] [54] [17]
D. catenatum
(whole plant)
Protein extract
Peptides
Human liver cancer cell line HepG2, human gastric cancer cell line SGC-7901 and breast cancer cell line MCF-7Cytotoxic, anti-proliferative[26]
D. chrysotoxum
(Not specified)
ErianinHuman mammary gland T47D cells
Human osteosarcoma cells 143B and Saos2, BALB/c-nu mice orthotopically inoculated with 143B cells
Antimigratory, anti-proliferative, induction of apoptosis and cell cycle arrest
Induction of G2/M-phase arrest, apoptosis and autophagy
[41]
[42]
D. draconis
(stems)
GigantolHuman lung cancer cell line H460
Antimigratory, induction of apoptosis through mitochondrial-dependent pathway
Induction of anoikis, attenuation of epithelial to mesenchymal transition (EMT)
[37, 38]
[39, 40]
D. ellipsophyllum
(Not specified)
4,5,4’-trihydroxy-3,3’dimethoxybibenzylHuman lung epithelial cells H292Induction of anoikis, attenuation of EMT, antimigratory[28, 29]
D. falconeri
(aerial parts)
Dendrofalconerol AHuman lung cancer cell line H460 cellsAntimigratory, induction of anoikis
Reduction of the expression of migration-related integrins, suppression of EMT
[43]
[44]
D. fimbriatum
(stems)
Fimbriadimerbibenzyl A, B, E, F, G
Moscatilin 4-(3-hydroxy-4-methoxyphenetyl)-2,6-dimethoxylphenol
Human promyelocytic leukemia cells HL-60, human hepatocarcinoma cells SMMC-7721, lung carcinoma cells A-549, colon cancer cells SW480, breast cancer cells MCF-7Cytotoxic[30]
D. formosum
(leaves)
Ethanolic extractT-cell lymphoma (in vitro)
Dalton’s lymphoma bearing mice
Cytotoxic, induction of apoptosis
Increase of survival time
[24]
D. loddigesii
(Not specified) (stems)
MoscatilinHuman umbilical vein endothelial cells (HUVEC) in vitro
Human lung adenocarcinomic cells A549 xenograft in nude mice Human breast adenocarcinoma MDA-MB-231 cells in vitro and in vivo metastatic model HCT-116 in vitro and xenograft model in vivo Human esophageal cancer cells (squamous and adenocarcinoma)
Anti-proliferative, inhibition of VEGF and bFGF-induced angiogenesis
Inhibition of growth of A549 xenograft Inhibitory and antimigratory Induction of apoptosis Growth suppression, induction of apoptosis
[34]
[57] [35] [36]
D. moniloforme
(stems)
Denbinobin
Moniliformediquinone
Leukemic cells
Human hormone refractory prostate cancer cells PC-3 and DU-145
NF-κB nuclear factor inhibition and apoptosis via ROS generation
Glutathione involved mitochondria stress and DNA damage
[46]
[50]
D. nobile
(stems)
Denbinobin
(+)- denobilone A (-)-denobilone A decumbic acid decumbic acid A decumbic acid B, (-)-decumbic acid, (-)-dendrolactone, (+)-dendrolactone, 4-(3-hydroxyphenyl)-2-butanone 3-hydroxy-1(3-methoxy-4-hydroxyphenyl)-propan-1-one 3’,4’,5’-trimethoxycinnamyl acetate
Human hepatic adenocarcinoma cells SK-Hep-1, human gastric cell line SNU-484 and HeLa cervical cancer cells
Prostatic carcinoma cells PC-3 HeLa, MCF-7 and A549 cells
Cytotoxic
Inhibition of invasion of SNU-484 phenotype via MMP-2/-9 expression Antimigratory Cytotoxic
[47]
[49] [52, 53]
D. officinaleAqueous extractionsMNNG-induced gastric tumorigenesis in ratsAntioxidative effect, modulation of cytokines related to tumorigenesis, induction of apoptosis, chemoprevention for reducing the risk of gastric cancer[56]
D. pulchellum
(stems)
Moscatilin
Moscatilin Chrysotobibenzyl Chrysotoxine Crepidatin
Lung cancer cells H23
Lung cancer cells
Inhibition of cell motility and invasion via suppression of ROS
Anti-metastatic
[32]
[33]
D. signatum
(whole plant)
Dendrosignatol
3,4-dihydroxy-3,4-dimethoxybibenzyl Dendrocandin B Dendrocandin I Dendrofalconerol A
Human breast cancer cells MDA-231, liver hepatocellular carcinoma HepG2, colorectal adenocarcinoma HT-29 cellsCytotoxic[51]
D. sinense
(whole plant)
3,4,3’-trimethoxy-5,4’-dihydroxybibenzyl
Aloifoll 5,3’-dihydroxy-3,4-dimethoxybibenzyl Longicornuol A
Human gastric cancer cells SGC-7901, human hepatoma cells BEL-7402, chronic myelogenous leukemia K562Cytotoxic[27]
D. speciosum
(stems)
Methanolic extractHepG2 cellsAntigenotoxic[25]
Table 1  Dendrobium spp. and their constituents with anticancer properties.
Dendrobium species
(organ)
Active molecule/type of extractBiological targetActivityRefs.
D. auranticum var. denneanum
(stems)
(-)-(7S,8R,7'E)-4-hydroxy-3,3',5,5'-tetramethoxy-8,4'-oxyneolign-7'-ene-7,9,9'-triol 7,9'-bis-O-β-D-glucopyranoside
(-)-syringaresionl-4,4'-bis-O-β-D-glucopyranoside
PC12 cells derived from a pheochromcytoma of the adrenal medullaNeuroprotective activity against glutamate-induced toxicity[66]
D. nobile
(Not specified) (stems)
Alkaloids (DNLA)Primary culture of rat cortical neurons (in vitro)
Rat’s hippocampus Tau protein in rat's hippocampus Aβ25-35-induced spatial learning and memory impairments in mice
Attenuation of neuronal damage on cortical neurons injured by oxygen-glucose deprivation/reperfusion
Inhibition of LPS-induced memory impairment Inhibition of hyperphosphorylation and LPS-induced apoptosis Prevention of Aβ25-35-induced neuronal and synaptic loss
[59]
[16] [58] [61]
D. crepidatum
(stems)
Crepidatol A
Confusarin 3-(2-acetoxy-5-methoxy)-phenylpropanol
PC12 cellsEnhancing activity on NGF-induced neurite outgrowth[65]
D. chrysotoxum
(stems)
Chrisotobibenzyl
Erianin Chrysotoxine Chrysotoxine
AChE and BChE
Bone marrow neuroblastoma cells SH-SY5Y
Enzymatic inhibition
Attenuation of 6-OHDA toxicity cells via mitochondria protection and NF-κB modulation Inhibition of the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP+).
[62]
[63] [64]
Table 2  Dendrobium spp. and their constituents with neuroprotective activities.
Dendrobium species
(organ)
Active molecule/type of extractBiological targetActivityRefs.
D. chrysotoxum
(Not specified) (stems)
Ethanolic extract
Erianin Polysaccharide
Diabetic retinopathy
Alloxan-induced diabetic mice
Amelioration of retinal angiogenesis
Preventing retinal inflammation and tight junction protein decrease Inhibition of high-glucose-induced retinal angiogenesis Inhibition of the increase in blood sugar level
[76]
[77] [78] [18]
D. devonianum
(whole plant)
5-hydroxy-3-methoxy-flavone-7-O-(β-D-apiosyl-(1-6))-β-D-glucoside
Gigantol
α-glucosidase in vitroEnzymatic inhibition[70]
D. huoshanense
(stems)
PolysaccharidesAlloxan-induced diabetic mice
Protein glycation in vitro
Hypoglycemic
Anti-glycation activity
[15]
[73]
D. loddigesii
(stems)
Loddigessinol G-J
Crepidatuol B
α-glucosidase in vitroEnzymatic inhibition[69]
D. nobile
(stems)
PolysaccharidesAlloxan-induced diabetic miceHypoglycemic[15]
D. officinale
(stems)
Polysaccharides
Mixture with other TCM herbs Fresh juice Aqueous extracts (after pre-extraction with petroleum ether and 80% ethanol)
Alloxan-induced diabetic mice
Genome STZ-induced mice
Hypoglycemic
Gene expression of mechanisms involved in type 2 diabetes Cardioprotective potential against diabetic cardiomyopathy STZ-induced diabetic complications, reduction of hypoalgesia and histopathological changes of vital organs induced by hyperglycemia
[15]
[71] [79] [80]
Table 3  Dendrobium spp. and their constituents with anti-diabetic properties.
Dendrobium species
(organ)
Active molecule/type of extractBiological targetActivityRefs.
D. aphyllum
(stems)
Moscatin
Moscatilin Tricetin 3',4',5'-trimethyl ether 7-O-β-glucopyranoside
LPS-stimulated RAW 264.7 cellsInhibition of NO production[109]
D. candidum
(Not specified)
Water liquid extractLabial glands from patients with Sjögren syndromeIncreasing of AQP-5, promotion of secretion of saliva to improve dry mouth symptoms[108]
D. chrysotoxum
(stems)
Polysaccharides DCP-H and DCP-ESpleen cells from BALB/c miceStimulation of splenocyte proliferation[94]
D. huoshanense
(Not specified) (stems)
(Leaves and stems)
(protocorm-like bodies)
Polysaccharides
Polysaccharide HPS-1B23 Polysaccharide DHP Mucilage polysaccharide Polysaccharide DHP-4A
Mouse intestine, spleen and liver (in vivo)
Spleen cells and peritoneal macrophages from BALB/c mice Murine splenocytes RAW264.7 macrophages and peritoneal macrophages C3H/HeN and C3H/HeJ Mouse splenocytes and human peripheral blood mononuclear cells RAW 264.7 macrophage cells
Enhancements in the levels of IFN-γ and IL-4 secretion in spleen and liver by changing the balance of Th1/Th2
Enhancing effect on TNF-α production and IFN-γ secretion Activation of macrophages to release NO, TNF-α and IL-1β, binding of DHP to the surface of macrophages via TLR4 receptor to activate cells via NF-κB, MAPKs and PI3K/Akt signaling pathways Increasing production of IFN-γ, IL-6, IL-10 and IL-1α, induction of hematopoietic growth factors GM-CSF and G-CSF Inducing a panel of cytokines/chemokines in mice in vivo and human in vitro Stimulation of NO, TNF-α, IL-6 and IL-10 secretion via activation of MAPKs (p38, ERK, JNK) and translocation of nuclear NF-κB
[93]
[88] [89] [90] [92] [91]
D. officinale
(Not specified) (stems) (stems) (stems) (stems) (stems) (stems)
Polysaccharides
Polysaccharide fractions DOP-1 and DOP-2 Heteropolysaccharide DOP-1-1 Polysaccharide fraction cDOP and its sufractions DOPa and DOPb Polysaccharide fraction DOP-W3-b Dendronan® Polysaccharide DP
Macrophages function
Murine splenocytes of BALB/c mice Macrophages function THP-1 cells RAW 264.7 macrophages Mouse spleen lymphocytes Bone marrow cells stimulated by the suspension of Peyer’s patch cells of female ICR mice RAW 264.7 macrophages Sjögren's syndrome model mice A253 cell line
Promoting release of NO, phagocytosis, and cytokines IL-1α, IL-6, IL-10 and TNF-α
Enhancing of cellular and nonspecific immunity, increasing IFN-γ production Effects on splenocyte proliferation and NK cytotoxicityn activation of macrophage function Stimulation of cytokine production TNF-α and IL-1β, induction of immune activities via ERK1/2 and NF-κB Enhancing cell proliferation, TNF-a secretion, and phagocytosis Induction of the proliferation Regulation of intestinal mucosal immune activity by changing intestinal mucosal structures, promoting the secretions of cytokines from Peyer’s patches and mesenteric lymph nodes, increasing the production of secretory immunoglobulin A in the lamia propria Enhancing phagocytosis activity, up-regulating NO and influencing cytokine (TNF-α, IL-6 and IL-12) production In vivo promotion of splenocyte proliferation, correction of the imbalance in spleen lymphocyte subsets ratio, reversion of the diminution of cytokine levels, stimulation of the formation of Ig and haemolysin Amelioration of the abnormalities of AQP-5 in saliva secretion Inhibition of TNF-α-induced apoptosis
[83]
[98] [85] [86] [84] [99] [87] [100] [106] [107]
D. nobile
(stems)
Polysaccharide DNP-W5
Rhamnoarabinogalactan DNP-W3 and acetylated galactomannoglucan DNP-W2 Polysaccharide DNP4-2
T- and B-lymphocytes
S180 mice
Enhancing activities
Stimulation of ConA and LPS-induced proliferation Increasing of immune index and promotion of cytokine secretion in vivo
[95]
[96, 97] [102]
D. tosaense
(stems)
Polysaccharide DTPSplenic NK cells, splenocytes in BALB/c miceStimulation of the population of splenic NK cells, cytotoxicity, macrophage phagocytosis, and cytokine induction[101]
Table 4  Dendrobium spp. and their constituents with immunomodulatory activities
Figure 2.  Chemical structures of anti-diabetic compounds of loddigesiinols G-K from D. loddigesi.
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