# Dendrobium officinale Kimura et Migo: A Review on Its Ethnopharmacology, Phytochemistry, Pharmacology, and Industrialization

Authors: Hanxiao Tang; Tianwen Zhao; Yunjie Sheng; Ting Zheng; Lingzhu Fu; Yongsheng Zhang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2017)

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## Abstract

Ethnopharmacological Relevance. Dendrobii Officinalis Caulis, the stems ofDendrobium officinale Kimura et Migo, as a tonic herb in Chinese materia medica and health food in folk, has been utilized for the treatment of yin-deficiency diseases for decades.Methods. Information for analysis ofDendrobium officinale Kimura et Migo was obtained from libraries and Internet scientific databases such as PubMed, Web of Science, Google Scholar, ScienceDirect, Wiley InterScience, Ingenta, Embase, CNKI, and PubChem.Results. Over the past decades, about 190 compounds have been isolated fromDendrobium officinaleKimura et Migo. Its wide modern pharmacological actions in hepatoprotective effect, anticancer effect, hypoglycemic effect, antifatigue effect, gastric ulcer protective effect, and so on were reported. This may mainly attribute to the major and bioactive components: polysaccharides. However, other small molecule components require further study.Conclusions. Due to the lack of systematic data ofDendrobium officinale, it is important to explore its ingredient-function relationships with modern pharmacology. Recently, studies on the chemical constituents ofDendrobium officinale concentrated in crude polysaccharides and its structure-activity relationships remain scant. Further research is required to determine theDendrobium officinale toxicological action and pharmacological mechanisms of other pure ingredients and crude extracts. In addition, investigation is needed for better quality control and novel drug or product development.


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## Body

## 1. Introduction

Dendrobium officinale Kimura et Migo spreads in several countries over the world, such as Japan, United States, and Australia, and it distributes more widely in China [1] (Table 1). Modern pharmacology research has confirmed thatDendrobium officinale and its polysaccharide fraction possess anticancer, hepatoprotective, hypolipidemic, antifatigue, antioxidant, anticonstipation, hypoglycemic, gastric ulcer protective, and antihypertensive effects, immunoenhancement, and so on [2–4].Table 1
The taxonomic classification, names, and distribution ofDendrobium officinale Kimura et Migo.
Synonyms
Dendrobium catenatum Lindl., Gen. Sp. Orchid. Pl.: 84 (1830).
Dendrobium stricklandianumRchb.f., Gard. Chron., n.s., 7: 749 (1877).
Callista stricklandiana (Rchb.f.) Kuntze, Revis. Gen. Pl. 2: 655 (1891).
Dendrobium tosaense Makino, J. Bot. 29: 383 (1891).
Dendrobium pere-faurieiHayata, Icon. Pl. Formosan. 6: 70 (1916).
Dendrobium tosaense var. pere-fauriei (Hayata) Masam., J. Soc. Trop. Agric. 4: 196 (1933).
Dendrobium officinale Kimura & Migo, J. Shanghai Sci. Inst. 3: 122 (1936).
Taxonomic classification
Species 2000 & ITIS Catalogue of Life: Plantae > Tracheophyta > Liliopsida > Asparagales > Orchidaceae > Dendrobium >Dendrobium catenatum Lindl.
IUCN Red List: Plantae > Tracheophyta > Liliopsida > Orchidales > Orchidaceae > Dendrobium >Dendrobium officinale
NCBI Taxonomy: Eukaryota > Viridiplantae > Streptophyta > Streptophytina > Embryophyta > Tracheophyta > Euphyllophyta > Spermatophyta > Magnoliophyta > Mesangiospermae > Liliopsida > Petrosaviidae > Asparagales > Orchidaceae > Epidendroideae > Epidendroideae incertae sedis > Dendrobiinae > Dendrobium >Dendrobium catenatum
Taxonomic Hierarchy of COL-China 2012: Plantae > Angiospermae > Monocotyledoneae > Microspermae > Orchidaceae > Dendrobium >Dendrobium tosaense
Tropicos resource: Equisetopsida C. Agardh > Asparagales Link > Orchidaceae Juss. > Callista Lour. >Callista stricklandianaKuntze
Tropicos resource:Equisetopsida C. Agardh > Asparagales Link > Orchidaceae Juss. > Dendrobium Sw. > Dendrobium officinaleKimura & Migo
Distribution
Japan > Kyushu
United States > Missouri > Saint Louis City
Australia > New South Wales
China > Taiwan, Anhui, Zhejiang, Fujian, Guangxi, Sichuan, Yunnan, Xizang, etc.
Common name
鐵皮石斛 (tiepishihu)
黃石斛 (huangshihu)
Reference
http://www.kew.org/ http://www.theplantlist.org/
http://www.catalogueoflife.org/ http://www.tropicos.org/
http://www.gbif.org/ http://www.eol.org/
http://frps.eflora.cn/
[50][51]
[10]Since 1994, polysaccharides ofDendrobium officinale have been extracted and analyzed [5], and polysaccharides gradually became research focus ofDendrobium officinale. Recently, the chemical compositions and pharmacological effects ofDendrobium officinale have attracted more and more attention. In this review, from substantial data aboutDendrobium officinale, approximately 190 monomer compositions and plenty of pharmacological researches studied in vivo and/or in vitro were summarized. In addition, the development of artificial cultivation ofDendrobium officinale accelerates the promotion of its industrialization in China. Patents and health care products were also improved by the combination of production and research mode.


## 2. Pharmaceutical Botany

Dendrobium, pertaining to the second largest family, Orchidaceae, includes approximately l,400 species worldwide distributed from tropical Asia to Oceania [6]. There are 74 species and 2 variants of genusDendrobium Sw. in China [7]. Some of them can be processed as Dendrobii Caulis (Chinese: 石斛,shihu) of Chinese materia medica [8]. In 2005 Chinese Pharmacopoeia (ChP),tiepishihu (Chinese: 鐵皮石斛) was one species of medicinalshihucalledDendrobium candidum Wall. ex Lindl. [9]; however this Latin name was later disputed and considered the synonym ofDendrobium moniliforme (L.) Sw. [10, 11]. In 2010 ChP,tiepishihu was renamed asDendrobium officinale Kimura et Migo (akaDendrobium officinale, Figure 1(a)). This Latin name was firstly denominated by two Japanese scholars in 1936 when they found the new species ofDendrobium in China [12]. Facilitating the preservation, the fibrous stems ofDendrobium officinale can be twisted into a spiral and dried astiepifengdou (Figure 1(b)) or directly cut into sections and dried as well. What is more, in 2010 ChP,tiepishihu was initially isolated as one single medicine; its processed stem was called Dendrobii Officinalis Caulis (valid botanical name:Dendrobium catenatum Lindl., taxonomic classification and synonyms in Table 1); in the meanwhile,Dendrobium nobileLindl.,Dendrobium chrysotoxum Lindl., Dendrobium fimbriatumHook., and their similar species were collectively referred to asshihu [13].Figure 1
(a)Dendrobium officinale Kimura et Migo; (b)tiepifengdou.
(a)
(b)


## 3. Ethnopharmacological Use

The stems ofDendrobium officinale are mainly used as health food in folk. There are a variety of methods to enjoy its fresh stems, for example, chewing, juicing, decocting, and making dishes [14]. In addition, combining with other tonic Chinese herbs is viable, such as “Panacis Quinquefolii Radix” (xiyangshen, American Ginseng), “Lycii Fructus” (gouqizi, Barbary Wolfberry Fruit), and “Dioscoreae Rhizoma” (shanyao, Rhizome of Common Yam) [15]. As reported, the combination ofDendrobium officinale and American Ginseng could strengthen cell-mediated immunity, humoral immunity, and monocyte-macrophages functions of mice [16].The functions and indications oftiepishihu andshihu are quite similar in traditional Chinese medicine (TCM) [17, 18]. However, TCM physicians useshihu more frequently thantiepishihu. As precious medicinal materials, maybe the high price limits the application oftiepishihu. Because of the output promotion,Dendrobium officinale gradually got more applications, especially in recent decades. Research showed that low-grade fever after gastric cancer operations, atrophic gastritis, mouth ulcers, and diabetes were treated by the freshDendrobium officinale in TCM [19]. Combined with modern medicine,Dendrobium officinale can be used to treat many diseases including Sjögren’s syndrome, gastric ulcer, alcoholic liver injury, chronic obstructive pulmonary disease, diabetes, obesity, rheumatoid arthritis, hypertensive stroke, cataract, weak constitution, or subhealth [2, 20–22]. However, these functions were from an earlier investigation and need further research to probe.


## 4. Phytochemistry

FromDendrobium officinale, at least 190 compounds by far were isolated, mainly including polysaccharides, phenanthrenes, bibenzyls, saccharides and glycosides, essential oils, alkaloids, and other compounds (Table 2).Table 2
Chemical components inDendrobium officinale.
Number
Compounds
PubChem CID
Ref.
Phenanthrenes
1
2,3,4,7-Tetramethoxyphenanthrene
[52]
2
2,5-Dihydroxy-3,4-dimethoxyphenanthrene
[52]
3
1,5-Dicarboxy-1,2,3,4-tetramethoxyphenanthrene
[52]
4
2,4,7-Trihydroxy-9,10-dihydrophenanthrene
21678577
[41]
5
Denbinobin
10423984
[41]
6
Erianin
356759
[53]
7
1,5,7-Trimethoxyphenanthrene-2,6-diol
11779542
[52]
8
3,4-Dimethoxyphenanthrene-2,7-diol
158975
[52]
9
2,4-Dimethoxyphenanthrene-3,5-diol
44445443
[52]
Bibenzyls
10
3,4-Dihydroxy-5,4′-dimethoxybibenzyl
[54]
11
Chrysotobibenzyl
3086528
[53]
12
4′,5-Hydroxy-3,3′-dimethoxybenzyl
[55]
13
3,4′-Dihydroxy-5-methoxybibenzyl
[41]
14
Dendrocandin A
102476850
[56]
15
Dendrocandin B
91017475
[56]
16
Dendrocandin C
25208514
[56]
17
Dendrocandin D
25208516
[56]
18
Dendrocandin E
25208515
[56]
19
Dendrocandin F
[56]
20
Dendrocandin G
[56]
21
Dendrocandin H
[56]
22
Dendrocandin I
101481782
[56]
23
Dendrocandin J
[56]
24
Dendrocandin K
[56]
25
Dendrocandin L
[56]
26
Dendrocandin M
[56]
27
Dendrocandin N
[56]
28
Dendrocandin O
[56]
29
Dendrocandin P
[56]
30
Dendrocandin Q
[56]
31
4,4′-Dihydroxy-3,5-dimethoxybibenzyl
442701
[56]
32
4,4′-Dihydroxy-3,3′,5-trimethoxybibenzyl
176096
[56]
33
3,4,4′-Trihydroxy-5-methoxybibenzyl
[57]
34
Dendromoniliside E
[41]
35
Gigantol
3085362
[54]
Phenols
36
4-(3,5-Dimethoxyphenethyl) phenol
[57]
37
3-(4-Hydroxyphenethyl)-5-methoxyphenol
[57]
38
5-(3-Hydroxyphenethyl)-2-methoxyphenol
[57]
39
4-(4-Hydroxyphenethyl)-2,6-dimethoxyphenol
[57]
40
4-(4-Hydroxy-3-methoxyphenethyl)-2,6-dimethoxyphenol
[57]
Acids
41
p-Hydroxy-coumaric acid
637542
[55]
42
p-Hydroxybenzene propanoic acid
[55]
43
Hexadecanoic acid
985
[41]
44
Heptadecanoic acid
10465
[41]
45
Syringic acid
10742
[58]
46
Vanillic acid
8468
[58]
47
p-Hydroxy-phenylpropionic acid
10394
[58]
48
Ferulic acid
445858
[58]
49
4-Hydroxybenzoic acid
135
[58]
Esters
50
p-Hydroxyl-trans-cinnamic acid myricyl ester
[41]
51
Trans-ferulic acid octacosyl ester
[41]
52
p-Hydroxyl-cis-cinnamic acid myricyl ester
[41]
53
Dihydroconiferyl dihydro-p-cumarate
[58]
54
Cis-3-(4-Hydroxy-3-methoxy-phenyl)-acrylic acid octacosyl ester
[57]
55
Trans-3-(4-Hydroxy-3-methoxy-phenyl)-acrylic acid octacosyl ester
[57]
56
4-[2-(4-Methoxy-phenyl)-ethyl-6]-oxo-6H-pyran-2-carboxylic acid methyl ester
[57]
Amides
57
N-Trans-feruloyltyramine
5280537
[55]
58
cis-Feruloyl p-hydroxyphenethylamine
[55]
59
Trans cinnamyl p-hydroxyphenethylamine
[55]
60
N-p-Coumaroyltyramine
5372945
[58]
61
Dihydroferuloyltyramine
90823368
[58]
62
4-Hydroxy-N-[2-(4-hydroxyphenyl)ethyl]benzenepropanamide
[58]
Saccharides and glycosides
63
4-Allyl-2,6-dimethoxy phenyl glycosidase
[55]
64
Adenosine
60961
[41]
65
Uridine
6029
[41]
66
Vernine
46780355
[41]
67
Apigenin-7-O-β-D-glucoside
5280704
[59]
68
Icariol-A2-4-O-β-D-glucopyranoside
6439218
[59]
69
(+)-Syringaresinol-O-β-D-pyranglucose
[59]
70
Dihydrosyringin
71720642
[58]
71
Vicenin 3
44257698
[55]
72
Isoschaftoside
3084995
[55]
73
Schaftoside
442658
[55]
74
Vicenin 2
442664
[55]
75
Apigenin 6-C-α-L-arabinopyranosyl-8-C-β-D-xylopyranoside
[55]
76
Apigenin 6-C-β-D-xylopyranosyl-8-C-α-L-arabinopyranoside
[55]
77
Vincenin 1
44257662
[55]
78
2-Methoxyphenol-O-β-D-apiofuromosyl-(1→2)-β-D-glucopyranoside
[60]
79
3,4,5-Trimethoxyphenyl-1-O-β-D-apiose-(1→2)-β-D-glucoside
[60]
80
Dictamnoside A
44560015
[61]
81
Leonuriside A
14237626
[60]
82
(1′R)-1′-(4-Hydroxy-3,5-dimethoxylphenyl) propan-1′-ol 4-O-β-D-glucopyranoside
[60]
83
Syringaresinol-4,4′-O-bis-β-D-glucoside
[60]
84
(+)-Syringaresinol-4-β-D-monoglucoside
[60]
85
(+)-Lyoniresinol-3a-O-β-glucopyranoside
[60]
86
3,5-Dimethoxy-4-hydroxylphenyl-1-O-β-D-pyranglucose
[59]
87
7-Methoxycoumarin-6-O-β-D-pyranglucose
[59]
88
Sucrose
5988
[41]
Essential oils
89
Methyl acetate
6584
[44]
90
Carbon disulfide
6348
[44]
91
Hexane
8058
[44]
92
Ethyl acetate
8857
[44]
93
2-Methyl-propanol
6560
[44]
94
3-Methyl-butanal
11552
[44]
95
2-Methyl-butanal
7284
[44]
96
2-Pentanone
7895
[44]
97
Pentanal
8063
[44]
98
3-Pentanone
7288
[44]
99
3-Methyl-1-butanol
31260
[44]
100
2-Methyl-1-butanol
8723
[44]
101
2-Methyl-3-pentanone
11265
[44]
102
1-Pentanol
6276
[44]
103
(Z)-3-Hexanone
[44]
104
2-Hexanone
11583
[44]
105
Hexanal
6184
[44]
106
(E)-2-Hexenal
5281168
[44]
107
(E)-3-Hexanol
[44]
108
(Z)-3-Hexenol
[44]
109
1-Hexanol
8103
[44]
110
Styrene
7501
[44]
111
(E)-2-Heptenal
5283316
[44]
112
Benzaldehyde
240
[44]
113
1-Heptanol
8129
[44]
114
1-Octen-3-one
61346
[44]
115
1-Octen-3-ol
18827
[44]
116
6-Methyl-5-hepten-2-one
9862
[44]
117
2-Pentyl-furan
19602
[44]
118
Decane
15600
[44]
119
Octanal
454
[44]
120
(Z)-3-Hexenyl acetate
5363388
[44]
121
Hexyl acetate
8908
[44]
122
p-Cymene
7463
[44]
123
Limonene
22311
[44]
124
3-Octen-2-one
15475
[44]
125
(E)-β-Ocimene
5281553
[44]
126
(E)-2-Octenal
5283324
[44]
127
Ethyl benzyl ether
10873
[44]
128
1-Phenyl-ethanone
7410
[44]
129
(E)-2-Nonen-1-ol
5364941
[44]
130
1-Octanol
957
[44]
131
Nonanal
31289
[44]
132
2-Heptenyl acetate
85649
[44]
133
(E)-2-Nonenal
5283335
[44]
134
Nonenol
85445514
[44]
135
2-Terpineol
[44]
136
Dodecane
8182
[44]
137
2-Octenyl acetate
[44]
138
Decyl aldehyde
8175
[44]
139
Benzylacetone
17355
[44]
140
(E)-2-Decenal
5283345
[44]
141
1-Dodecanol
8193
[44]
142
Tridecane
12388
[44]
143
α-Cubebene
86609
[44]
144
β-Bourbonene
62566
[44]
145
Tetradecane
12389
[44]
146
α-Cedrene
442348
[44]
147
Zingiberene
92776
[44]
148
Geranyl acetone
19633
[44]
149
2-Methyl tridecane
[44]
150
AR-Curcumene
92139
[44]
151
Pentadecane
12391
[44]
152
β-Bisabolene
403919
[44]
153
(+)-D-Cadinene
441005
[44]
154
5-Phenyl-decane
[44]
155
4-Phenyl-decane
[44]
156
Hexadecane
11006
[44]
157
α-Cedrol
65575
[44]
158
5-phenyl-undecane
[44]
159
4-phenyl-undecane
[44]
160
Heptadecane
12398
[44]
161
Pristane
15979
[44]
162
6-Phenyl-dodecane
17629
[44]
163
5-Phenyl-dodecane
17630
[44]
164
4-Phenyl-dodecane
17631
[44]
165
6,10,14-Trimethyl-2-pentadecanone
10408
[44]
166
Butyl phthalate
3026
[44]
167
Isobutyl phthalate
6782
[44]
168
Sandaracopimaradiene
440909
[44]
169
Hentriacontanol
68345
[62]
170
Citronellol
8842
[55]
171
Citrusin C
3084296
[59]
172
Coniferyl alcohol
1549095
[55]
Others
173
2,6-Dimethoxycyclohexa-2,5-diene-1,4-dione
[63]
174
(24R)-6-β-Hydroxy-24-ethlcholest-4-en-3-one
[63]
175
Dendroflorin
44418788
[63]
176
Friedelin
91472
[63]
177
3-Ethoxy-5-hydroxy-7-methoxy-1,4-phenanthra-quinone
[63]
178
β-sitosterol
222284
[62]
179
5-Hydroxymethyl furfural
237332
[41]
180
Syringaldehyde
8655
[58]
181
3-O-Methylgigantol
10108163
[54]
182
Syringaresinol
332426
[55]
183
5α,8α-Epidioxy-24(R)-methylcholesta-6,22-dien-3β-ol
[63]
184
(−)-Secoisolariciresinol
65373
[60]
185
Aduncin
101316879
[41]
186
β-Daucosterol
5742590
[62]
187
(−)-Loliolide
12311356
[41]
188
Naringenin
932
[61]
189
3′,5,5′,7-Tetrahydroxyflavanone
[61]
190
Dihydrogen resveratrol
[41]


### 4.1. Polysaccharides

Polysaccharides are the main component in driedDendrobium officinale. Extraction and quantitative and qualitative analysis are described as follows, and the pharmacological effects of polysaccharides are in Table 3.Table 3
The pharmacological effects ofDendrobium officinale.
Effect
Tested material
In vivo/in vitro
Adm.
Conc.
Observations
Ref.
Hepatoprotective effect
Arabinose : mannose : glucose : galactose = 1.26 : 4.05 : 32.05 : 3.67
In vivo
Gavage
50, 100, and 200 mg/kg
Increased the weight in mice
[64]
In vivo
Gavage
200 mg/kg
Increased liver coefficient in mice
In vivo
Gavage
50, 100, and 200 mg/kg
Decreased mice serum ALT, AST, ALP activity, and TBIL levels; increased serum HDL-C; decreased LDL-C levels; accelerated metabolism of serum TG and TC; increased liver ADH, ALDH activities; inhibited mRNA expression of P4502E1, TNF-α, and IL-1β
Arabinose : mannose : glucose : galactose = 1.26 : 4.05 : 32.05 : 3.67
In vivo
Gavage
100 and 200 mg/kg
Increased GR activity and GSH-Px activity in mice
[64]
Original extract solution
In vivo
Gavage
3 g/kg
Reduced chronic alcoholic liver injured mice’s serum ALT, AST, and TC levels
[65]
Original extract solution
In vivo
Gavage
6 g/kg
Reduced serum TC level in mice
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45, 0.9, and 1.35 g/kg
Reduced serum AST levels in mice
Original extract solution
In vivo
Gavage
3 g/kg
Increased acute alcoholic hepatic injured mice’s SOD of serum and liver and DSG-Px of liver
[66]
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45, 0.90, and 1.35 g/kg
Increased acute alcoholic hepatic injured mice’s SOD of serum and liver and DSG-Px of liver
Original extract solution
In vivo
Gavage
3 and 6 g/kg
Reduced MDA of serum and liver in mice
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45 and 0.90 g/kg
Reduced MDA of serum and liver in mice
Original extract solution
In vivo
Gavage
9 g/kg
Reduced serum MDA in mice
Anticancer effect
Water extraction by alcohol sedimentation, extraction rate (in dry herb): 19.2%
In vivo
Gavage
10 and 20 g/kg
Increased the level of carbon clearance indexes and NK cells activity of LLC mice (P<0.05)
[67]
In vivo
Gavage
20 g/kg
Improved the LLC mice’s spleen lymphocyte transformation and hemolysin levels (P<0.05)
Water extraction by alcohol sedimentation
In vitro
—
100, 200, and 400μg/mL
Inhibited the growth of human hepatoma cells (HepG2), human lung cancer cells (A549), and human teratoma stem cells (NCCIT)
[68]
In vitro
—
200 and 400μg/mL
Inhibited murine teratoma stem cells (F9) and promoted their apoptosis
In vitro
—
100μg/mL
Promoted the proliferation of mouse spleen cells
Water extraction and alcohol precipitation
In vivo
Gavage
—
Inhibited the growth transplantation tumor (CNE1 and CNE2) of NPC nude mice
[69]
In vitro
—
128 and 256 mg/L
Inhibited the proliferation and induced the apoptosis of CNE1 and CNE2 cells; activated caspase-3; declined Bcl-xL, Mcl-1 protein levels
Hypoglycemic effect
DOP: 2-O-acetylglucomannan consisted of Man, Glc, and Ara in the molar ratio of 40.2 : 8.4 : 1.0
In vivo
Gavage
200, 100, and 50 mg/kg
Decreased levels of fasting blood glucose (FBG) and glycosylated serum protein (GSP); increased level of serum insulin in alloxan induced diabetic mice; attenuated the occurrence of oxidative stress in the liver and kidney of alloxan-induced diabetic mice (decreased MDA levels; increased GSH concentrations and antioxidative enzyme activities)
[70]
Extract, crude drug 1.8 g/g
In vivo
Gavage
0.125 and 0.25 g/kg
Reduced STZ-DM rats’ blood glucose and glucagon levels; enhanced the number of isletβ cells; declined the number of islet α cells
[71]
In vivo
Gavage
0.5 and 1.0 g/kg
Decreased blood glucose and increased liver glycogen content in adrenaline induced hyperglycemia rats
Total polysaccharide: 43.1%, total flavonoids: 19.6%, crude drug 1 g/mL
In vivo
Gavage
TP (total polysaccharides, 100 mg/kg), TF (total flavonoids, 35 mg/kg), and TE (water extract, 6 g/kg)
Significantly downregulated the phosphorylation of JNK (Thr183/Tyr185) and upregulated the phosphorylation of AKT ser473 in rat
[72]
Antifatigue effect
Hot water reflux and cellulase lixiviating extraction
In vivo
Gavage
1.5 and 4.5 g/kg
Increased mice’s glycogen store after exercise fatigue
[73]
Hot water reflux and cellulase lixiviating extraction
In vivo
Gavage
0.75, 1.5, and 4.5 g/kg
Decreased the level of serum urea and lactic acid accumulation; upregulated the expression of CNTF mRNA in mice
Hot water extraction then filtration
In vivo
Gavage
0.75 mg/kg
Increased carbon clearance indexes from 0.025 to 0.034 in mice
[74]
In vivo
Gavage
3 and 6 mg/kg
Extended burden swimming time of mice; reduced serum lactic acids of mice
[74]
Gastric ulcer protective effect
Lyophilization then hot-water extraction, evaporation
In vivo
Gavage
200 mg/kg
Decreased SD rats’ gastric secretion, IL-6, and TNF-α cytokine levels; had 76.6% inhibition of gastric injury rate
[75]
Squeezing then filtration
In vivo
Gavage
0.5 and 2 g/kg
Declined irritable and chemical gastric ulcer model’s ulcer indexes in mice
[76]
Others
Dry powder
In vivo
Gavage
1.5 and 3 g/kg
Reduced ApoE−/− mice’s TG, TCHOL, LDL-C levels, and expression of TNF-α and IL-6 in serum; reduced areas of atheromatous plaque in aortic valve and arch in ApoE−/− mice; then decreased expression of TNF-α and IL-6 in aortic arch
[77]
Aqueous extract
In vivo
Gavage
0.25, 0.5, and 1.0 crude drug g/kg
Extended Stroke-prone spontaneously hypertensive (SHR-sp) rats’ blood pressure, living days, and survival rate
[78]
Water extraction by alcohol sedimentation; mannose : glucose : galactose : arabinose : xylose : glucuronic acid = 10 : 0.25 : 1.2 : 4.7 : 1.3 : 1.4
In vivo
—
20 mg/mL
Inhibited Bax/Bal-2 ratio and caspase-3 expression; decreased expression of cytokines (TNF-α, IL-1β, and IL-6) and activity of MMP-9 in mice
[79]
Water extraction by alcohol sedimentation; mannose : glucose : galactose : arabinose : xylose : glucuronic acid = 10 : 0.25 : 1.2 : 4.7 : 1.3 : 1.4
In vitro
—
0.1, 1.0, and 10μg/mL
Ameliorated the abnormalities of aquaporin-5 (AQP-5) on A-253 cell
[79]
Water extract and alcohol precipitate, extraction rate: 29.87%
In vivo
Smear
5.0 g/L
Increased average score and average quality of hair growth of C57BL/6J mice
[80]
in vitro
—
0.1, 1.0, and 5.0 mg/L
Increased HaCaT cells survival rate and the VEGF mRNA expression level
Dry power decoction then concentration: traditional decoction or dry power steep in hot water: ultra-fine powder decoction
In vivo
Gavage
—
Increased Shannon index and Brillouin index in mice with constipation and improved their molecular diversity of intestinalLactobacillus
[81]


#### 4.1.1. Extraction

Generally, there are three methods that can isolate crudeDendrobium officinale polysaccharides (DOP): a solvent method (water extraction by alcohol sedimentation), a biological method (enzyme extraction), and a physical method (ultrasonic extraction and microwave extraction). Among the three, the solvent method is most popular. The physical method could be combined with the biological and solvent methods to accelerate the extraction process and promote the efficiency [23].Since there are lipids, proteins, pigments, and other impurities after the process of separation of polysaccharides, other separation methods, such as ion-exchange chromatography, gel filtration chromatography, and HPLC, are needed to purify the crude polysaccharides [24]. However, polysaccharides are acknowledged as complex biological macromolecules; the ways and sequences of connections of the monosaccharides determine the difficulty of polysaccharides’ analyses [25].


#### 4.1.2. Quantitative and Qualitative Analysis

The average content of neutral sugar in desiccatedDendrobium officinale is up to 58.3% [26]. Actually, different production origins, processing methods, growing years, and cultivated or wild and different parts ofDendrobium officinale are all related to polysaccharide content. Research showed that there were various polysaccharide contents of the same species cultivated in Guangdong with different origins from Yunnan, Zhejiang, and other provinces [27]. After drying each with different methods, DOP content was arranged as follows: hot air drying > vacuum drying > vacuum freeze drying > natural drying [28]. In addition, amounts of polysaccharide were greater in biennialDendrobium officinale than annual or triennial ones [29], while the wild type contained more content compared to the cultivated type [30]. Research showed that polysaccharides distributing in different parts ofDendrobium officinale varied: middle stem > upper stem > lower stem > roots [31]. Therefore, accurate determination of polysaccharide content is of great significance.Fourier Transform Infrared Spectrometer (FT-IR), Gas Chromatography-Mass Spectrometer (GC-MS), and1H and 13C NMR spectroscopies have been used to analyze the types of monosaccharide residues and the linkage sites of glycosidic bonds [32]. However, the research of polysaccharide’s ratio of mannose to glucose, the existence of branches, and the substitution position of o-acetyl groups was inconsistent [33]. What is more, polysaccharides’ pharmacological activities are strongly linked to the composition and content of their monosaccharides [26]. Therefore, further methods to explore the advanced structures and structure-activity relationships ofDendrobium officinale polysaccharides need to be established. Research showed that O-acetyl-glucomannan, Dendronan® (Figure 2, A), fromDendrobium officinale [34] has been isolated and was affirmed immunomodulatory activity in vitro [35] and in vivo [36], as well as improvement in colonic health of mice [37].Figure 2
Some chemical structure of compounds isolated formDendrobium officinale which have good potentials.


### 4.2. Phenanthrenes

FromDendrobium officinale, nine phenanthrenes(1–9) were isolated.Dendrobium officinale contains a kind of bibenzyl and a kind of phenanthrene identified inD. chrysotoxum before: chrysotobibenzyl(11) and erianin(6). Both chrysotobibenzyl and erianin have antitumor effects. Erianin significantly inhibited the proliferation of HepG2 and Huh7 (human hepatoma cell lines) in vitro [38] and also prevented angiogenesis in human hepatoma Be17402 and human melanoma A375 in vivo [39]. IC50 of P388 murine leukemia cell treated by erianin in MTT assay was 0.11 μM [40].


### 4.3. Bibenzyls

Bibenzyls10–35 were isolated from the stems ofDendrobium officinale. Among these compounds, 17 bibenzyls named Dendrocandins A–Q(14–30) (Figure 2) were extracted by Li et al. from 2008 to 2014. Next, DCET-2(31) could inhibit the proliferation of A2780 (human ovarian cancer cell line) cells, and DCET-12(32) inhibited BGC-823 (human gastric cancer cell lines) and A2780 cells [41]. DCET-18(35) also inhibited the migratory behavior and induced the apoptosis of non-small-cell lung cancer cells (human NCI-H460 cells) [42].


### 4.4. Saccharides and Glycosides

In the last few decades, at least 26 saccharides and glycosides have been found fromDendrobium officinale, (compounds63–88). Among them, Dictamnoside A(80) showed immunomodulatory activity in mouse splenocyte assessed as stimulation of proliferation at 10 umole/L after 44 hours by MTT assay in the presence of Concanavalin A (ConA) [43].


### 4.5. Essential Oils

Compounds89–172, isolated fromDendrobium officinale, comprise essential oils. The content of limonene(123) in the stem is 9.15% for the second; limonene is most abundant in the leaves, accounting for 38% [44]. Limonene contains anticancer properties with effects on multiple cellular targets in preclinical models [45].Dendrobium officinale containing a high content of (E)-2-hexenal(106) shows bactericidal activity againstPseudococcus viburni,Pseudococcus affinis,Bemisia sp., andFrankliniella occidentalis [46].


### 4.6. Alkaloids

Alkaloids are the earliest chemical compounds isolated fromDendrobium genus. Dendrobine, a kind ofDendrobium alkaloid accounting for 0.52%, was isolated initially in 1932 [47]. It was later proved to be the special content ofD. nobile [48]. As reported, the alkaloid inDendrobium officinale belongs to the terpenoid indole alkaloid (TIA) class, with its total content measured at approximately 0.02% [49]. However, the isolation and identification of one single kind of alkaloid have been rarely reported.


### 4.7. Others

Excepting ingredients above, phenols(36–40), acids(41–49), esters(50–56), amides(57–62), and other chemical constituents(173–190) were detected inDendrobium officinale (Table 2), while their pharmacological effects remain to be excavated in the future.


## 4.1. Polysaccharides

Polysaccharides are the main component in driedDendrobium officinale. Extraction and quantitative and qualitative analysis are described as follows, and the pharmacological effects of polysaccharides are in Table 3.Table 3
The pharmacological effects ofDendrobium officinale.
Effect
Tested material
In vivo/in vitro
Adm.
Conc.
Observations
Ref.
Hepatoprotective effect
Arabinose : mannose : glucose : galactose = 1.26 : 4.05 : 32.05 : 3.67
In vivo
Gavage
50, 100, and 200 mg/kg
Increased the weight in mice
[64]
In vivo
Gavage
200 mg/kg
Increased liver coefficient in mice
In vivo
Gavage
50, 100, and 200 mg/kg
Decreased mice serum ALT, AST, ALP activity, and TBIL levels; increased serum HDL-C; decreased LDL-C levels; accelerated metabolism of serum TG and TC; increased liver ADH, ALDH activities; inhibited mRNA expression of P4502E1, TNF-α, and IL-1β
Arabinose : mannose : glucose : galactose = 1.26 : 4.05 : 32.05 : 3.67
In vivo
Gavage
100 and 200 mg/kg
Increased GR activity and GSH-Px activity in mice
[64]
Original extract solution
In vivo
Gavage
3 g/kg
Reduced chronic alcoholic liver injured mice’s serum ALT, AST, and TC levels
[65]
Original extract solution
In vivo
Gavage
6 g/kg
Reduced serum TC level in mice
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45, 0.9, and 1.35 g/kg
Reduced serum AST levels in mice
Original extract solution
In vivo
Gavage
3 g/kg
Increased acute alcoholic hepatic injured mice’s SOD of serum and liver and DSG-Px of liver
[66]
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45, 0.90, and 1.35 g/kg
Increased acute alcoholic hepatic injured mice’s SOD of serum and liver and DSG-Px of liver
Original extract solution
In vivo
Gavage
3 and 6 g/kg
Reduced MDA of serum and liver in mice
Tiepifengdouoriginal extract solution
In vivo
Gavage
0.45 and 0.90 g/kg
Reduced MDA of serum and liver in mice
Original extract solution
In vivo
Gavage
9 g/kg
Reduced serum MDA in mice
Anticancer effect
Water extraction by alcohol sedimentation, extraction rate (in dry herb): 19.2%
In vivo
Gavage
10 and 20 g/kg
Increased the level of carbon clearance indexes and NK cells activity of LLC mice (P<0.05)
[67]
In vivo
Gavage
20 g/kg
Improved the LLC mice’s spleen lymphocyte transformation and hemolysin levels (P<0.05)
Water extraction by alcohol sedimentation
In vitro
—
100, 200, and 400μg/mL
Inhibited the growth of human hepatoma cells (HepG2), human lung cancer cells (A549), and human teratoma stem cells (NCCIT)
[68]
In vitro
—
200 and 400μg/mL
Inhibited murine teratoma stem cells (F9) and promoted their apoptosis
In vitro
—
100μg/mL
Promoted the proliferation of mouse spleen cells
Water extraction and alcohol precipitation
In vivo
Gavage
—
Inhibited the growth transplantation tumor (CNE1 and CNE2) of NPC nude mice
[69]
In vitro
—
128 and 256 mg/L
Inhibited the proliferation and induced the apoptosis of CNE1 and CNE2 cells; activated caspase-3; declined Bcl-xL, Mcl-1 protein levels
Hypoglycemic effect
DOP: 2-O-acetylglucomannan consisted of Man, Glc, and Ara in the molar ratio of 40.2 : 8.4 : 1.0
In vivo
Gavage
200, 100, and 50 mg/kg
Decreased levels of fasting blood glucose (FBG) and glycosylated serum protein (GSP); increased level of serum insulin in alloxan induced diabetic mice; attenuated the occurrence of oxidative stress in the liver and kidney of alloxan-induced diabetic mice (decreased MDA levels; increased GSH concentrations and antioxidative enzyme activities)
[70]
Extract, crude drug 1.8 g/g
In vivo
Gavage
0.125 and 0.25 g/kg
Reduced STZ-DM rats’ blood glucose and glucagon levels; enhanced the number of isletβ cells; declined the number of islet α cells
[71]
In vivo
Gavage
0.5 and 1.0 g/kg
Decreased blood glucose and increased liver glycogen content in adrenaline induced hyperglycemia rats
Total polysaccharide: 43.1%, total flavonoids: 19.6%, crude drug 1 g/mL
In vivo
Gavage
TP (total polysaccharides, 100 mg/kg), TF (total flavonoids, 35 mg/kg), and TE (water extract, 6 g/kg)
Significantly downregulated the phosphorylation of JNK (Thr183/Tyr185) and upregulated the phosphorylation of AKT ser473 in rat
[72]
Antifatigue effect
Hot water reflux and cellulase lixiviating extraction
In vivo
Gavage
1.5 and 4.5 g/kg
Increased mice’s glycogen store after exercise fatigue
[73]
Hot water reflux and cellulase lixiviating extraction
In vivo
Gavage
0.75, 1.5, and 4.5 g/kg
Decreased the level of serum urea and lactic acid accumulation; upregulated the expression of CNTF mRNA in mice
Hot water extraction then filtration
In vivo
Gavage
0.75 mg/kg
Increased carbon clearance indexes from 0.025 to 0.034 in mice
[74]
In vivo
Gavage
3 and 6 mg/kg
Extended burden swimming time of mice; reduced serum lactic acids of mice
[74]
Gastric ulcer protective effect
Lyophilization then hot-water extraction, evaporation
In vivo
Gavage
200 mg/kg
Decreased SD rats’ gastric secretion, IL-6, and TNF-α cytokine levels; had 76.6% inhibition of gastric injury rate
[75]
Squeezing then filtration
In vivo
Gavage
0.5 and 2 g/kg
Declined irritable and chemical gastric ulcer model’s ulcer indexes in mice
[76]
Others
Dry powder
In vivo
Gavage
1.5 and 3 g/kg
Reduced ApoE−/− mice’s TG, TCHOL, LDL-C levels, and expression of TNF-α and IL-6 in serum; reduced areas of atheromatous plaque in aortic valve and arch in ApoE−/− mice; then decreased expression of TNF-α and IL-6 in aortic arch
[77]
Aqueous extract
In vivo
Gavage
0.25, 0.5, and 1.0 crude drug g/kg
Extended Stroke-prone spontaneously hypertensive (SHR-sp) rats’ blood pressure, living days, and survival rate
[78]
Water extraction by alcohol sedimentation; mannose : glucose : galactose : arabinose : xylose : glucuronic acid = 10 : 0.25 : 1.2 : 4.7 : 1.3 : 1.4
In vivo
—
20 mg/mL
Inhibited Bax/Bal-2 ratio and caspase-3 expression; decreased expression of cytokines (TNF-α, IL-1β, and IL-6) and activity of MMP-9 in mice
[79]
Water extraction by alcohol sedimentation; mannose : glucose : galactose : arabinose : xylose : glucuronic acid = 10 : 0.25 : 1.2 : 4.7 : 1.3 : 1.4
In vitro
—
0.1, 1.0, and 10μg/mL
Ameliorated the abnormalities of aquaporin-5 (AQP-5) on A-253 cell
[79]
Water extract and alcohol precipitate, extraction rate: 29.87%
In vivo
Smear
5.0 g/L
Increased average score and average quality of hair growth of C57BL/6J mice
[80]
in vitro
—
0.1, 1.0, and 5.0 mg/L
Increased HaCaT cells survival rate and the VEGF mRNA expression level
Dry power decoction then concentration: traditional decoction or dry power steep in hot water: ultra-fine powder decoction
In vivo
Gavage
—
Increased Shannon index and Brillouin index in mice with constipation and improved their molecular diversity of intestinalLactobacillus
[81]


### 4.1.1. Extraction

Generally, there are three methods that can isolate crudeDendrobium officinale polysaccharides (DOP): a solvent method (water extraction by alcohol sedimentation), a biological method (enzyme extraction), and a physical method (ultrasonic extraction and microwave extraction). Among the three, the solvent method is most popular. The physical method could be combined with the biological and solvent methods to accelerate the extraction process and promote the efficiency [23].Since there are lipids, proteins, pigments, and other impurities after the process of separation of polysaccharides, other separation methods, such as ion-exchange chromatography, gel filtration chromatography, and HPLC, are needed to purify the crude polysaccharides [24]. However, polysaccharides are acknowledged as complex biological macromolecules; the ways and sequences of connections of the monosaccharides determine the difficulty of polysaccharides’ analyses [25].


### 4.1.2. Quantitative and Qualitative Analysis

The average content of neutral sugar in desiccatedDendrobium officinale is up to 58.3% [26]. Actually, different production origins, processing methods, growing years, and cultivated or wild and different parts ofDendrobium officinale are all related to polysaccharide content. Research showed that there were various polysaccharide contents of the same species cultivated in Guangdong with different origins from Yunnan, Zhejiang, and other provinces [27]. After drying each with different methods, DOP content was arranged as follows: hot air drying > vacuum drying > vacuum freeze drying > natural drying [28]. In addition, amounts of polysaccharide were greater in biennialDendrobium officinale than annual or triennial ones [29], while the wild type contained more content compared to the cultivated type [30]. Research showed that polysaccharides distributing in different parts ofDendrobium officinale varied: middle stem > upper stem > lower stem > roots [31]. Therefore, accurate determination of polysaccharide content is of great significance.Fourier Transform Infrared Spectrometer (FT-IR), Gas Chromatography-Mass Spectrometer (GC-MS), and1H and 13C NMR spectroscopies have been used to analyze the types of monosaccharide residues and the linkage sites of glycosidic bonds [32]. However, the research of polysaccharide’s ratio of mannose to glucose, the existence of branches, and the substitution position of o-acetyl groups was inconsistent [33]. What is more, polysaccharides’ pharmacological activities are strongly linked to the composition and content of their monosaccharides [26]. Therefore, further methods to explore the advanced structures and structure-activity relationships ofDendrobium officinale polysaccharides need to be established. Research showed that O-acetyl-glucomannan, Dendronan® (Figure 2, A), fromDendrobium officinale [34] has been isolated and was affirmed immunomodulatory activity in vitro [35] and in vivo [36], as well as improvement in colonic health of mice [37].Figure 2
Some chemical structure of compounds isolated formDendrobium officinale which have good potentials.


## 4.1.1. Extraction

Generally, there are three methods that can isolate crudeDendrobium officinale polysaccharides (DOP): a solvent method (water extraction by alcohol sedimentation), a biological method (enzyme extraction), and a physical method (ultrasonic extraction and microwave extraction). Among the three, the solvent method is most popular. The physical method could be combined with the biological and solvent methods to accelerate the extraction process and promote the efficiency [23].Since there are lipids, proteins, pigments, and other impurities after the process of separation of polysaccharides, other separation methods, such as ion-exchange chromatography, gel filtration chromatography, and HPLC, are needed to purify the crude polysaccharides [24]. However, polysaccharides are acknowledged as complex biological macromolecules; the ways and sequences of connections of the monosaccharides determine the difficulty of polysaccharides’ analyses [25].


## 4.1.2. Quantitative and Qualitative Analysis

The average content of neutral sugar in desiccatedDendrobium officinale is up to 58.3% [26]. Actually, different production origins, processing methods, growing years, and cultivated or wild and different parts ofDendrobium officinale are all related to polysaccharide content. Research showed that there were various polysaccharide contents of the same species cultivated in Guangdong with different origins from Yunnan, Zhejiang, and other provinces [27]. After drying each with different methods, DOP content was arranged as follows: hot air drying > vacuum drying > vacuum freeze drying > natural drying [28]. In addition, amounts of polysaccharide were greater in biennialDendrobium officinale than annual or triennial ones [29], while the wild type contained more content compared to the cultivated type [30]. Research showed that polysaccharides distributing in different parts ofDendrobium officinale varied: middle stem > upper stem > lower stem > roots [31]. Therefore, accurate determination of polysaccharide content is of great significance.Fourier Transform Infrared Spectrometer (FT-IR), Gas Chromatography-Mass Spectrometer (GC-MS), and1H and 13C NMR spectroscopies have been used to analyze the types of monosaccharide residues and the linkage sites of glycosidic bonds [32]. However, the research of polysaccharide’s ratio of mannose to glucose, the existence of branches, and the substitution position of o-acetyl groups was inconsistent [33]. What is more, polysaccharides’ pharmacological activities are strongly linked to the composition and content of their monosaccharides [26]. Therefore, further methods to explore the advanced structures and structure-activity relationships ofDendrobium officinale polysaccharides need to be established. Research showed that O-acetyl-glucomannan, Dendronan® (Figure 2, A), fromDendrobium officinale [34] has been isolated and was affirmed immunomodulatory activity in vitro [35] and in vivo [36], as well as improvement in colonic health of mice [37].Figure 2
Some chemical structure of compounds isolated formDendrobium officinale which have good potentials.


## 4.2. Phenanthrenes

FromDendrobium officinale, nine phenanthrenes(1–9) were isolated.Dendrobium officinale contains a kind of bibenzyl and a kind of phenanthrene identified inD. chrysotoxum before: chrysotobibenzyl(11) and erianin(6). Both chrysotobibenzyl and erianin have antitumor effects. Erianin significantly inhibited the proliferation of HepG2 and Huh7 (human hepatoma cell lines) in vitro [38] and also prevented angiogenesis in human hepatoma Be17402 and human melanoma A375 in vivo [39]. IC50 of P388 murine leukemia cell treated by erianin in MTT assay was 0.11 μM [40].


## 4.3. Bibenzyls

Bibenzyls10–35 were isolated from the stems ofDendrobium officinale. Among these compounds, 17 bibenzyls named Dendrocandins A–Q(14–30) (Figure 2) were extracted by Li et al. from 2008 to 2014. Next, DCET-2(31) could inhibit the proliferation of A2780 (human ovarian cancer cell line) cells, and DCET-12(32) inhibited BGC-823 (human gastric cancer cell lines) and A2780 cells [41]. DCET-18(35) also inhibited the migratory behavior and induced the apoptosis of non-small-cell lung cancer cells (human NCI-H460 cells) [42].


## 4.4. Saccharides and Glycosides

In the last few decades, at least 26 saccharides and glycosides have been found fromDendrobium officinale, (compounds63–88). Among them, Dictamnoside A(80) showed immunomodulatory activity in mouse splenocyte assessed as stimulation of proliferation at 10 umole/L after 44 hours by MTT assay in the presence of Concanavalin A (ConA) [43].


## 4.5. Essential Oils

Compounds89–172, isolated fromDendrobium officinale, comprise essential oils. The content of limonene(123) in the stem is 9.15% for the second; limonene is most abundant in the leaves, accounting for 38% [44]. Limonene contains anticancer properties with effects on multiple cellular targets in preclinical models [45].Dendrobium officinale containing a high content of (E)-2-hexenal(106) shows bactericidal activity againstPseudococcus viburni,Pseudococcus affinis,Bemisia sp., andFrankliniella occidentalis [46].


## 4.6. Alkaloids

Alkaloids are the earliest chemical compounds isolated fromDendrobium genus. Dendrobine, a kind ofDendrobium alkaloid accounting for 0.52%, was isolated initially in 1932 [47]. It was later proved to be the special content ofD. nobile [48]. As reported, the alkaloid inDendrobium officinale belongs to the terpenoid indole alkaloid (TIA) class, with its total content measured at approximately 0.02% [49]. However, the isolation and identification of one single kind of alkaloid have been rarely reported.


## 4.7. Others

Excepting ingredients above, phenols(36–40), acids(41–49), esters(50–56), amides(57–62), and other chemical constituents(173–190) were detected inDendrobium officinale (Table 2), while their pharmacological effects remain to be excavated in the future.


## 5. Pharmacological Effects ofDendrobium officinale

Recently, more and more pharmacological actions ofDendrobium officinale were reported, such as hepatoprotective effect, anticancer effect, hypoglycemic effect, antifatigue effect, and gastric ulcer protective effect (Table 3).


### 5.1. Hepatoprotective Effect

The hepatoprotective capacity ofDendrobium officinale is always related to its antioxidant ability, especially in acute or chronic alcoholic liver injury. Research showed thatDendrobium officinale polysaccharides (DOP) accelerated the metabolism of serum TG and TC, while increased liver ADH and ALDH activities, which recovered disorders of lipid metabolism and accelerated excretion of alcohol and its metabolites [64]. In addition, ALT, AST, and TC ofDendrobium officinale treated mice models with chronic alcoholic liver injury were elevated compared to the normal groups [65]. Besides, compared to the model group of mice with acute alcoholic hepatic injury, freshDendrobium officinale andtiepifengdou groups could increase the SOD and reduce MDA of serum and liver tissue [66].


### 5.2. Anticancer Effect

The anticancer activity ofDendrobium officinale extract has been studied and proved, such as anti-HelaS3, anti-HepG2, and anti-HCT-116 in vitro, as well as anti-CNEl and CNE2 in vivo and in vitro [69]. Besides, DOP has manifested anticancer effects in mice with Lewis lung carcinoma (LLC). Its tumor inhibition rate was 8.5%–18.3% (P>0.05); meanwhile, LLC mice spleen lymphocyte transformation and hemolysin levels (P<0.05) were improved [67]. In cellular experiments, Liu’s morphological analysis showed that DOP can inhibit the growth of human hepatoma cells (HepG2), human lung cancer cells (A549), human teratoma stem cells (NCCIT), and murine teratoma stem cells (F9) and promoted the proliferation of mouse spleen cells in vitro [68]. Research showed that two DOP fractions, DOP-1 and DOP-2, promoted splenocyte proliferation, enhanced NK cell-mediated cytotoxicity, and increased the phagocytosis and nitric oxide production of macrophages significantly (P<0.05) [82]. Therefore, the anticancer effect ofDendrobium officinale may be accompanied by the activity of improving immune system.


### 5.3. Hypoglycemic Effect

Hypoglycemic activity, another important property ofDendrobium officinale, has been studied a lot. Oral administration of DOP decreased levels of fasting blood glucose (FBG) and glycosylated serum protein (GSP) and increased level of serum insulin in alloxan-induced diabetic mice. In addition, DOP attenuated the occurrence of oxidative stress in the liver and kidney of alloxan-induced diabetic mice by decreasing MDA levels, increasing GSH concentrations and antioxidative enzyme activities [70]. Therefore, DOP may regulate blood sugar levels through blood-lipid balance effects and antioxidative damage effects of liver and kidney.Dendrobium officinale exhibited a significant hypoglycemic effect in adrenaline hyperglycemia mice and streptozotocin-diabetic (STZ-DM) rats [71]. In addition, TP (total polysaccharides, 100 mg/kg), TF (total flavonoids, 35 mg/kg), and TE (water extract, 6 g/kg) groups ofDendrobium officinale significantly downregulated the phosphorylation of JNK (Thr183/Tyr185) and upregulated the phosphorylation of AKT ser473 compared with the normal control group, which indicates that effective extracts ofDendrobium officinale have the effects of inhibiting JNK phosphorylation and promoting AKT ser473 phosphorylation [72].


### 5.4. Antifatigue Effect

The antifatigue effect ofDendrobium officinale was illustrated in vivo, when compared with the control groups;Dendrobium officinale could increase the glycogen stored in mice after exercise and decrease the level of serum urea and lactic acid accumulation (P<0.05 or P<0.01). In addition, it could upregulate the expression of ciliary neurotrophic factor (CNTF) mRNA (P<0.05 or P<0.01) [73]. In addition, compared to the control groups,Dendrobium officinale significantly increased carbon clearance indexes and burden swimming time and reduced the serum lactic acids [74]. In general, antifatigue effect ofDendrobium officinal was linked to the TCM use about enriching consumptive diseases, but its mechanism needs to be further clarified.


### 5.5. Gastric Ulcer Protective Effect

Research showed thatDendrobium officinale had a preventive effect of gastric injury caused by 60% ethanol-hydrochloric acid solution (ethanol was dissolved in 150 mM hydrochloric acid). Intragastric administration of SD rats with 200 mg/kg ofDendrobium officinale for two weeks decreased gastric secretion, IL-6 and TNF-α cytokine levels compared with the lower dose groups and the control groups. This concentration (200 mg/kg) had the strongest inhibitory effect of gastric injury (76.6% inhibition of gastric injury rate) [75]. After the successful establishment of the irritable gastric ulcer model (induced by cold water immersion) and chemical gastric ulcer model (indometacin-induced, 40 mg/kg, gavage) the ulcer index was calculated by Guth standard scoring method. Freshly squeezedDendrobium officinale juice (containing crude drugs 0.5, 2 g/kg) showed significant declining irritable and chemical gastric ulcer model ulcer indexes (P<0.01) [76]. However, gastric ulcer is a chronic disease, the security of long-term administration ofDendrobium officinale still uncertain.


### 5.6. Others

It is found thatDendrobium officinale had hypolipidemic and hypotensive effects. The fine powder solution ofDendrobium officinale (1.5, 3 g/kg) can reduce the levels of TG, TCHOL, and LDL-C in serum significantly and reduce the expression of TNF-α and IL-6 in ApoE−/− mice. In addition, it could reduce areas of atheromatous plaque in aortic valve and arch in ApoE−/− mice and then decrease the expression of TNF-α and IL-6 in aortic arch [77]. Research showed that stroke-prone spontaneously hypertensive (SHR-sp) rats’ living days and survival rates were extended by DOP, and hypotensive effect of DOP was significantly better than the nonpolysaccharide ingredients ofDendrobium officinale [78].Moreover,Dendrobium officinale was used to treat Sjögren’s syndrome (SS) with dry eyes and mouth due to impaired lacrimal and salivary glands [80]. Research showed that DOP could suppress the progressive lymphocytes infiltration and apoptosis and balance the disorders of proinflammatory cytokines in the submandibular gland (SG) in vivo. Further, DOP ameliorated the abnormalities of aquaporin-5 (AQP-5) that was supported by in vitro study on A-253 cell line and maintained its function of saliva secretion [79].Meanwhile, research showed that the DOP group demonstrated higher average scores and an improved average quality of hair growth of C57BL/6J mice (5.0 g/L, the solution was ultra-pure water, each 0.2 mL, smeared for 21 d), compared with the control group. Besides, DOP significantly increased HaCaT cells survival rate and the VEGF mRNA expression levels compared with the control group [80].Besides, theDendrobium officinale had an obvious effect on the molecular diversity of intestinalLactobacillus in mice model (irregular diet for 8 d after gavage of folium senna water decoction for 7 d) with constipation resulting from spleen deficiency (TCM syndrome type) [81].Dendrobium officinale also can regulate the digestive function in carbon-induced constipated mice models [83].


## 5.1. Hepatoprotective Effect

The hepatoprotective capacity ofDendrobium officinale is always related to its antioxidant ability, especially in acute or chronic alcoholic liver injury. Research showed thatDendrobium officinale polysaccharides (DOP) accelerated the metabolism of serum TG and TC, while increased liver ADH and ALDH activities, which recovered disorders of lipid metabolism and accelerated excretion of alcohol and its metabolites [64]. In addition, ALT, AST, and TC ofDendrobium officinale treated mice models with chronic alcoholic liver injury were elevated compared to the normal groups [65]. Besides, compared to the model group of mice with acute alcoholic hepatic injury, freshDendrobium officinale andtiepifengdou groups could increase the SOD and reduce MDA of serum and liver tissue [66].


## 5.2. Anticancer Effect

The anticancer activity ofDendrobium officinale extract has been studied and proved, such as anti-HelaS3, anti-HepG2, and anti-HCT-116 in vitro, as well as anti-CNEl and CNE2 in vivo and in vitro [69]. Besides, DOP has manifested anticancer effects in mice with Lewis lung carcinoma (LLC). Its tumor inhibition rate was 8.5%–18.3% (P>0.05); meanwhile, LLC mice spleen lymphocyte transformation and hemolysin levels (P<0.05) were improved [67]. In cellular experiments, Liu’s morphological analysis showed that DOP can inhibit the growth of human hepatoma cells (HepG2), human lung cancer cells (A549), human teratoma stem cells (NCCIT), and murine teratoma stem cells (F9) and promoted the proliferation of mouse spleen cells in vitro [68]. Research showed that two DOP fractions, DOP-1 and DOP-2, promoted splenocyte proliferation, enhanced NK cell-mediated cytotoxicity, and increased the phagocytosis and nitric oxide production of macrophages significantly (P<0.05) [82]. Therefore, the anticancer effect ofDendrobium officinale may be accompanied by the activity of improving immune system.


## 5.3. Hypoglycemic Effect

Hypoglycemic activity, another important property ofDendrobium officinale, has been studied a lot. Oral administration of DOP decreased levels of fasting blood glucose (FBG) and glycosylated serum protein (GSP) and increased level of serum insulin in alloxan-induced diabetic mice. In addition, DOP attenuated the occurrence of oxidative stress in the liver and kidney of alloxan-induced diabetic mice by decreasing MDA levels, increasing GSH concentrations and antioxidative enzyme activities [70]. Therefore, DOP may regulate blood sugar levels through blood-lipid balance effects and antioxidative damage effects of liver and kidney.Dendrobium officinale exhibited a significant hypoglycemic effect in adrenaline hyperglycemia mice and streptozotocin-diabetic (STZ-DM) rats [71]. In addition, TP (total polysaccharides, 100 mg/kg), TF (total flavonoids, 35 mg/kg), and TE (water extract, 6 g/kg) groups ofDendrobium officinale significantly downregulated the phosphorylation of JNK (Thr183/Tyr185) and upregulated the phosphorylation of AKT ser473 compared with the normal control group, which indicates that effective extracts ofDendrobium officinale have the effects of inhibiting JNK phosphorylation and promoting AKT ser473 phosphorylation [72].


## 5.4. Antifatigue Effect

The antifatigue effect ofDendrobium officinale was illustrated in vivo, when compared with the control groups;Dendrobium officinale could increase the glycogen stored in mice after exercise and decrease the level of serum urea and lactic acid accumulation (P<0.05 or P<0.01). In addition, it could upregulate the expression of ciliary neurotrophic factor (CNTF) mRNA (P<0.05 or P<0.01) [73]. In addition, compared to the control groups,Dendrobium officinale significantly increased carbon clearance indexes and burden swimming time and reduced the serum lactic acids [74]. In general, antifatigue effect ofDendrobium officinal was linked to the TCM use about enriching consumptive diseases, but its mechanism needs to be further clarified.


## 5.5. Gastric Ulcer Protective Effect

Research showed thatDendrobium officinale had a preventive effect of gastric injury caused by 60% ethanol-hydrochloric acid solution (ethanol was dissolved in 150 mM hydrochloric acid). Intragastric administration of SD rats with 200 mg/kg ofDendrobium officinale for two weeks decreased gastric secretion, IL-6 and TNF-α cytokine levels compared with the lower dose groups and the control groups. This concentration (200 mg/kg) had the strongest inhibitory effect of gastric injury (76.6% inhibition of gastric injury rate) [75]. After the successful establishment of the irritable gastric ulcer model (induced by cold water immersion) and chemical gastric ulcer model (indometacin-induced, 40 mg/kg, gavage) the ulcer index was calculated by Guth standard scoring method. Freshly squeezedDendrobium officinale juice (containing crude drugs 0.5, 2 g/kg) showed significant declining irritable and chemical gastric ulcer model ulcer indexes (P<0.01) [76]. However, gastric ulcer is a chronic disease, the security of long-term administration ofDendrobium officinale still uncertain.


## 5.6. Others

It is found thatDendrobium officinale had hypolipidemic and hypotensive effects. The fine powder solution ofDendrobium officinale (1.5, 3 g/kg) can reduce the levels of TG, TCHOL, and LDL-C in serum significantly and reduce the expression of TNF-α and IL-6 in ApoE−/− mice. In addition, it could reduce areas of atheromatous plaque in aortic valve and arch in ApoE−/− mice and then decrease the expression of TNF-α and IL-6 in aortic arch [77]. Research showed that stroke-prone spontaneously hypertensive (SHR-sp) rats’ living days and survival rates were extended by DOP, and hypotensive effect of DOP was significantly better than the nonpolysaccharide ingredients ofDendrobium officinale [78].Moreover,Dendrobium officinale was used to treat Sjögren’s syndrome (SS) with dry eyes and mouth due to impaired lacrimal and salivary glands [80]. Research showed that DOP could suppress the progressive lymphocytes infiltration and apoptosis and balance the disorders of proinflammatory cytokines in the submandibular gland (SG) in vivo. Further, DOP ameliorated the abnormalities of aquaporin-5 (AQP-5) that was supported by in vitro study on A-253 cell line and maintained its function of saliva secretion [79].Meanwhile, research showed that the DOP group demonstrated higher average scores and an improved average quality of hair growth of C57BL/6J mice (5.0 g/L, the solution was ultra-pure water, each 0.2 mL, smeared for 21 d), compared with the control group. Besides, DOP significantly increased HaCaT cells survival rate and the VEGF mRNA expression levels compared with the control group [80].Besides, theDendrobium officinale had an obvious effect on the molecular diversity of intestinalLactobacillus in mice model (irregular diet for 8 d after gavage of folium senna water decoction for 7 d) with constipation resulting from spleen deficiency (TCM syndrome type) [81].Dendrobium officinale also can regulate the digestive function in carbon-induced constipated mice models [83].


## 6. The Toxicology ofDendrobium officinale

After acute toxicity test, genetic toxicity test (Ames test, micronucleus test of bone marrow, and sperm shape abnormality test in mice) and 90-day feeding test in rats, the results showed that protocorms ofDendrobium officinale were without toxicity, genetic toxicity and mutagenicity within the scope of the test dose [84]. Furthermore, the 15% decoction ofDendrobium officinale was used for mice sperm malformation test, Ames test, and micronucleus test of bone marrow in mice, and all test results were negative. In addition, the acute oral toxicity test showed that the highest dose was 10 g/kg b.w. which belonged to the actual nontoxic category [85]. However, in the pesticide safety aspect, theDendrobium officinale still need more stringent quality control [86].


## 7. The Industrialization ofDendrobium officinale

Due to the special trophic mode, seed germination ofDendrobium officinale needs the root symbiotic bacteria [87, 88]; the reproduction of wildDendrobium officinale is limited with low natural reproductive rates. The past three decades witnessed excess herb-gathering ofDendrobium officinale destroying much of the wild habitat resource in China [89]. In 1987,Dendrobium officinale was on the list of national third-level rare and endangered plants [90]. However, artificial cultivation based on tissue culture technology significantly prompted the yield ofDendrobium officinale.Recently, increased awareness of the tonic therapeutic effect ofDendrobium officinale has increased the demand and as a consequence the price [91]. However, the high-profit margin ofDendrobium officinale has already led to an increase in the market for counterfeits and adulterants [92] mainly by other confusable species ofDendrobium[91]. The appearance ofDendrobium officinale and other species ofDendrobium is very similar, especially after processing into“tiepifengdou”; it is difficult to distinguish them through morphological identification [93]. It is apparent thatDendrobium officinale germplasm resources’ separation and purification determine its characters and quality [94]. In terms of microscopic identification,Dendrobium officinale could be identified by vascular bundle sheath observed under the fluorescence microscopy and the distribution of raphides under normal light microscopy [95]. In addition, the taxonomy, phylogeny, and breeding ofDendrobium species have made great progress as the advance of molecular markers in the past two decades [96].Under such circumstances, pharmacognosy [97], DNA molecule marker technologies including Amplified Fragment Length Polymorphism (AFLP) [98], Inter Simple Sequence Repeat (ISSR) [99], Start codon targeted (SCoT) and target region amplification polymorphism (TRAP) [100], and sequence related amplified polymorphism (SRAP) analysis [101], and so on have been applied to identifyDendrobium officinale from other Dendrobium species. Further, Yunnan province has completedDendrobium officinale fine gene map and found more than 48,200 protein-coding genes [102]. Therefore, the identification ofDendrobium officinale is more precise due to the gene technology, but genetic fingerprints are difficult to evaluate the quality, so the gene technology combining with the physical and chemical identification is necessary.In recent years, the development ofDendrobium officinale health care products is promising [15]. Many related patented products are being registered or have been authorized, includingDendrobium officinale ingredients such as antiaging compounds [103], lactobacillus drink [104], antiasthenopia eye ointment [105], immunoenhancement compounds [106], hypotensive extractive [107], and hypoglycemic and hypolipidemic compounds [108]. Some of these patents have been put into production like“tiepifengdou,” one of the most famous processed products ofDendrobium officinale [101]. However, there are few medicines ofDendrobium officinale [109] besidestiepishihuof Chinese materia medica in TCM.In summary, the TCM theory and ethnopharmacology could inspire modern researches committed to yield and quality control ofDendrobium officinale, while some standards or laws (such as ISO/TC 249 and CITES) regulated artificial cultivation and protected wildlife resources. Finally, industrialization will drive further researches and is conducive to develop deep-processing products, especially the insufficient new drugs, which will also promote the industrialization and form a virtuous circle simultaneously (Figure 3).Figure 3
The industry and researchstatus quo and future perspectives.


## 8. Conclusion

Dendrobium officinale, one of the most famous species ofDendrobium, has long been regarded as precious herbs and health foods applied in TCM and in folk. In this paper, the ethnopharmacology, phytochemistry, pharmacology, and industrialization ofDendrobium officinale were summarized. In recent years, the interest of exploring ethnopharmacology-based bioactive constituents ofDendrobium officinale has increased considerably. Rapid propagation technology has gradually matured, so yield is no longer the bottleneck ofDendrobium officinaledevelopment. In addition, the confusable identification and uneven quality still exist, and better quality control standards under modern researches are necessary.Consequently, the following points deserve further investigation. (1) Polysaccharides are the main composition inDendrobium officinale with numerous pharmacological researches, but investigation related to its structure-activity relationships remains scant. (2) The pharmacological effects ofDendrobium officinale crude extract and polysaccharide were similar, indicating whether other active ingredients were lost during extraction. (3) There is no enough systemic data about toxicology ofDendrobium officinale. (4) How does TCM theory play a role inDendrobium officinale further in-depth development as theoretical guidance and inspiration source.Over all, further studies at the molecular level are needed to promote the exploration of chemical compositions and pharmacological mechanisms. In addition, the industrialization ofDendrobium officinale not only protected the germplasm resources but also attracted a large quantity of researches in China, which makes the innovation ofDendrobium officinale novel drug and product a promising prospect.



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*Source: 7436259-2017-03-12.xml*