An update on oligosaccharides and their esters from traditional chinese medicines: chemical structures and biological activities.

A great number of naturally occurring oligosaccharides and oligosaccharide esters have been isolated from traditional Chinese medicinal plants, which are used widely in Asia and show prominent curative effects in the prevention and treatment of kinds of diseases. Numerous in vitro and in vivo experiments have revealed that oligosaccharides and their esters exhibited various activities, including antioxidant, antidepressant, cytotoxic, antineoplastic, anti-inflammatory, neuroprotective, cerebral protective, antidiabetic, plant growth-regulatory, and immunopotentiating activities. This review summarizes the investigations on the distribution, chemical structures, and bioactivities of natural oligosaccharides and their esters from traditional Chinese medicines between 2003 and 2013.

1. Introduction

Oligosaccharides and their n class="Chemical">esters, a significant group of phytochemical compounds, are widely distributed in the roots, rhizomes, stems, barks, leaves, aerial, and whole parts of medicinal plants. They not only serve as the energy storage components, but also play a vital role in the treatment of diseases. Before 2003, there have been a number of reviews and reports in respect to the isolation and structure elucidation of oligosaccharides and their esters from Chinese medicinal plants [1-3], but few biological activities such as cancer chemopreventive, and protein kinase C inhibitory activities had been reported [4-6]. With the development of isolation and identification techniques [7-11], a larger number of oligosaccharides and their esters have been endlessly identified from traditional Chinese medicines in the past decades. These compounds have a wide variety of structure types because of the assembly of different monosaccharide units, the combination of various linking styles and the existence of kinds of substituents. And more promising biological activities associated with some of the oligosaccharides and their esters have been discovered. In vitro and in vivo investigations have demonstrated that they displayed antioxidant, antidepressant, anti-inflammatory, neuroprotective, cerebral protective, antidiabetic, cytotoxic, antineoplastic, plant growth-regulatory, and immunopotentiating activities, and so forth. This review aims to provide a systemic summary of the studies on the distribution, chemical structures and biological activities of naturally occurring oligosaccharides and their esters from traditional Chinese medicines in the past decades. Among these compounds, the number of oligosaccharide esters is much greater than that of oligosaccharides, and the disaccharide esters are a very valuable source of active compounds. This information may help readers understand the structure characteristics and therapeutic indications of oligosaccharides and their esters from traditional Chinese medicines and offer clues to the development of new drugs.

2. Chemical Structures

Phytochemical investigations of traditional Chinese medicines have shown that many botanical families, including Polygalaceae, Liliaceae, Asteraceae, Polygonaceae, Smilacaceae, Scrophulariaceae, Asclepiadaceae, Arecaceae, Orobanchaceae, Acanthaceae, Rn class="Chemical">osaceae, Musaceae, Sparganiaceae, Leguminosae, Equisetaceae, Boraginaceae, Iridaceae, Alismataceae, Lamiaceae, Araliaceae, Rubiaceae, Oleaceae, Apocynaceae, Caryophyllaceae, Aspleniaceae and Trilliaceae, are rich in oligosaccharides and their esters. Oligosaccharides show diversified structures because of the type and the number of monosaccharides, as well as the position of glycosidic bonds. And oligosaccharide esters also display distinctive structural diversity largely owing to the number, type, and position of O-substituent units, including phenylpropanoid groups (e.g., coumaroyl, feruloyl, caffeoyl, sinapoyl, 3,4,5-trimethoxycinnamoyl, and cinnamoyl), benzoyl, p-methoxybenzoyl, and p-hydroxybenzoyl groups (Figure 2). Moreover, the double bonds of phenylpropanoid groups possess trans and cis isomeric forms, of which the trans forms widely exist in nature. Hence, according to the number of monosaccharides and the characteristics of chemical structures, these oligosaccharide esters could be categorized into 7 large groups.

Figure 2

2.1. Oligosaccharides

All compounds of this group (Table 1 and Figure 1) merely consist of various monosaccharides without O-substituents. In addition to the well-known n class="Chemical">sucrose, β-D-glucopyranosyl(1→2)-β-D-glucopyranoside (1) was isolated from Camptosorus sibiricus [12]. The oligosaccharides of raffinose (3), stachyose (19), and verbascose (21), all of which belong to the Raffinose family, possess one, two or three galactopyranosyl units linked to sucrose and have been found in the rhizomes and roots of Alisma orientalis [13], Lycopus lucidus [14], Rehmannia glutinosa [15, 16], Salvia miltiorrhiza [17], and Scrophularia ningpoensis [18]. Manninotriose (4) and verbascotetraose (5) consisting of galactopyranosyl units and a glucopyranosyl unit have been isolated from Alisma orientalis [13].

Table 1

Oligosaccharides.

No.	Name	R1	R2	R3	R4	R5	R6	Source	Parts	Reference
22	Perifosaccharide A	OH(e)	OCH3(e)	H	OH(e)	OH	A	Periploca forrestii	Roots	[32]
23	Perifosaccharide B	OH(e)	OCH3(a)	H	OH(e)	OH	A	Periploca forrestii	Roots	[32]
24	Perifosaccharide C	OH(e)	OCH3(e)	H	OH(e)	OCH3	A	Periploca forrestii	Roots	[32]
25	Perifosaccharide D	OAc(e)	OCH3(e)	H	OH(e)	OH	A	Periploca forrestii	Roots	[32]
26	Perisaccharide A	OH(a)	OCH3(e)	OAc	OH(e)	OCH3	A	Periploca sepium	Root barks	[33]
27	Perisaccharide B	OAc(e)	OCH3(a)	H	OH(e)	OH	A	Periploca sepium   Periploca calophylla	Root barks	[33, 34]
28	Perisaccharide C	OH(a)	OCH3(e)	OAc	OCH3(a)	OH	A	Periploca sepium	Root barks	[33]
29	Perisaccharide D	OAc(e)	OCH3(a)	H	OH(e)	OCH3	A	Periploca calophylla	Stems	[34]
30	Perisesaccharide B	OH(a)	OCH3(e)	OAc	OH(e)	OCH3	C	Periploca sepium	Root barks	[35]
31	Perisesaccharide C	OH(a)	OCH3(e)	OH	OCH3(a)	OCH3	C	Periploca sepium	Root barks	[35]
32	Perisesaccharide D	OH(a)	OCH3(e)	OH	OCH3(a)	OH	C	Periploca sepium	Root barks	[35]
33	Perisesaccharide E	OH(a)	OCH3(e)	OAc	OH(e)	OH	C	Periploca sepium	Root barks	[35]
34	Cymaropyranurolactone 4-O-β-D-digitalopyranosyl-(1 → 4)-O-β-D-cymaropyranosyl-(1 → 4)-O-β-D-oleandropyranosyl-(1 → 4)-O-β-D-cymaropyranoside	OH(a)	OCH3(e)	OH	OCH3(e)	OCH3	B	Parabarium huaitingii	Barks	[36]

See Scheme 1.

Figure 1

Five oligosaccharides comprising 1-kestn class="Chemical">ose (6), nystose (7), 1-β-fructofuranosylnystose (8), hexasaccharide (9), and heptasaccharide (10) consisting of fructofuranose and glucopyranose have been isolated from the aerial parts and roots of Gynura divaricata subsp. formosana [19], Morinda officinalis [20-22], Saussurea lappa [23], and Aralia cordata [24]. Two water-soluble oligosaccharides (11, 12) composed of two or three types of monosaccharides including glucopyranose, fructopyranose, and fructofuranose have been obtained from the whole plants of Blumea riparia [25, 26].

Besides, malto-oligosaccharides (17, n = 0~8) consisting of α-D-n class="Chemical">glucopyranosyl residues assembled by (1→4)-linkages and inulo-oligosaccharides (18, n = 1~3) consisting of only fructosyl residues formed by (2→1)-linkages have been found in the roots of Panax ginseng [27, 28] and Morinda officinalis [20], respectively. Three noteworthy oligosaccharides (2, 13, 14) formed by α-D-glucopyranosyl units with (1→6)-linkages and a (1→4)-linkage have been found in the roots of Panax ginseng [28]. And two linear oligosaccharides termed heptasaccharide (15) and octasaccharide (16) consisting of glucose and mannose monomers were identified from the rhizomes of Paris polyphylla var. yunnanensis [29, 30]. A pentasaccharide, stellariose (20) consisting of a raffinose backbone with two galactosyl residues bound to the fructosyl and glucosyl moieties was identified from the stems of Stellaria media [31].

Oligosaccharides (Table 1) are compn class="Chemical">osed of seven kinds of deoxyhexoses including cymaropyranose, canaropyranose, digitoxopyranose, oleandropyranose, digitalopyranose, cymaropyranurolactone, and oleandronic acid-δ-lactone. Oleandronic acid-δ-lactone exhibits the boat and chair conformations. The hydroxyl, methyl, and acetyl groups are located at the equatorial (e) and axial (a) bonds in the chair conformation of deoxyhexoses. These oligosaccharides were isolated from the traditional Chinese medicines including the roots of Periploca forrestii, the root barks of P. sepium, the stems of P. calophylla, and the barks of Parabarium huaitingii.

2.2. Oligosaccharide Esters

2.2.1. Phenylpropanoid-Derived Disaccharide Esters

Phenylpropanoid-derived disaccharide esters (Table 2 and Figure 3) account for a considerable proportion of n class="Chemical">oligosaccharide esters and mainly possess a core of sucrose carrying a varying number of O-substituents, including phenylpropanoid groups, acetyl, benzoyl, p-methoxybenzoyl, and p-hydroxybenzoyl groups. Phenylpropanoid substituents are just present at 1′, 3′, 4′, 6′ positions of β-D-fructofuranosyl unit in compounds 35–97, whereas they appear at 2, 3, 4, 6 positions of α-D-glucopyranosyl moiety in compounds 98–101. Moreover, compounds 76–97 are mainly esterified with acetyl groups along with a phenylpropanoid substituent, coumaroyl, feruloyl, or 3,4,5-trimethoxycinnamoyl group. Interestingly, the phenylpropanoid substituents are only attached to the 3′ position of sucrose. The two sugar rings of compounds 102–128 both possess phenylpropanoid substituents. These oligosaccharide esters have been found in the roots and rhizomes of Polygala tricornis, P. tenuifolia, Fagopyrum tataricum, Scrophularia ningpoensis, Cynanchum amplexicaule, Smilax riparia, Paris polyphylla var. yunnanensis, Smilacis glabrae, Fagopyrum dibotrys, and Sparganium stoloniferum, the underground parts of Trillium kamtschaticum, the stems of Polygonum sachalinensis, P. cuspidatum, P. hydropiper, Smilax china, and Calamus quiquesetinervius, the aerial parts of Polygala sibirica, Smilax bracteata, Heterosmilax erythrantha, and Musella lasiocarpa, the leaves of Persicaria hydropiper and Polygonum hydropiper, the whole plants of Bidens parviflora and Polygala hongkongensis, and the flower buds of Prunus mume.

Table 2

Phenylpropanoid-derived disaccharide esters.  

Number	Name	R1	R2	R3	R4	R5	R6	R7	R8	Source	Parts	Reference
35	Sibiricose A6	H	H	H	H	K	H	H	H	Polygala tricornis  Polygala tenuifolia	Roots   Root barks	[37–40]
36	3′-O-Feruloyl sucrose/Sibiricose A5	H	H	H	H	I	H	H	H	Polygala tenuifolia   Trillium kamtschaticum	Roots   Underground parts	[38–42]
37	Glomeratose A	H	H	H	H	L	H	H	H	Polygala tricornis	Roots	[37]
38	Lapathoside D	H	H	H	H	G	G	H	H	Polygonum sachalinense	Stems	[43]
39	Helonioside A	H	H	H	H	I	I	H	H	Trillium kamtschaticum   Smilax bracteata   Paris polyphylla   var. yunnanensis	Underground  parts  Aerial parts  Roots	[41, 44, 45]
40	Helonioside B	Ac	H	H	H	I	I	H	H	Smilax bracteata   Smilax china  Smilax riparia  Heterosmilax erythrantha	Aerial parts Stems Roots and rhizomes	[44, 46–48]
41	Parispolyside F	H	H	H	H	G	I	H	H	Paris Polyphylla   var. yunnanensis	Rhizomes	[49, 50]
42	Hydropiperoside	H	H	H	H	G	G	H	G	Polygonum sachalinense  Polygonum cuspidatum   Persicaria hydropiper	Stems Leaves	[43, 51, 52]
43	Tricornose B	D	Ac	H	H	L	H	H	H	Polygala tricornis	Roots	[37]
44	Tenuifoliside A	F	H	H	H	L	H	H	H	Polygala tenuifolia  Polygala hongkongensis  Polygala sibirica	Roots Whole plants  Aerial parts	[38, 40, 42, 53–56]
45	Tatariside A	Ac	H	H	Ac	G	G	H	Ac	Fagopyrum tataricum	Roots	[57]
46	Tatariside E	H	H	H	Ac	G	G	H	Ac	Fagopyrum tataricum	Roots	[57]
47	Tatariside G	H	H	H	H	I	G	H	G	Fagopyrum tataricum	Roots	[57]
48	Smiglaside A	Ac	Ac	H	Ac	I	I	H	I	Smilax riparia	Roots and rhizomes	[47]
49	Smiglaside B	Ac	H	H	Ac	I	I	H	I	Smilax riparia	Roots and rhizomes	[47]
50	Smiglaside E	Ac	H	H	Ac	I	I	H	G	Smilax china	Stems	[46]
51	Smilaside A	Ac	Ac	H	H	I	I	H	H	Smilax china	Stems	[46]
52	Smilaside B	H	H	H	Ac	I	I	H	H	Smilax china	Stems	[46]
53	Smilaside C	H	H	H	H	I	I	H	G	Smilax china	Stems	[46]
54	Smilaside D	H	H	H	H	I	I	Ac	G	Smilax china	Stems	[46]
55	Smilaside E	Ac	H	H	H	I	I	H	G	Smilax bracteata  Smilax china	Aerial parts  Stems	[44, 46]
56	Smilaside F	Ac	H	H	Ac	G	I	H	G	Smilax china	Stems	[46]
57	Smilaside G	H	H	H	H	G	I	H	G	Smilax bracteata   Smilacis glabrae	Aerial parts  Rhizomes	[44, 58]
58	Smilaside H	H	H	H	Ac	G	I	H	G	Smilax bracteata	Aerial parts	[44]
59	Smilaside I	Ac	H	H	H	G	I	H	G	Smilax bracteata	Aerial parts	[44]
60	Smilaside J	H	H	H	H	G	I	H	I	Smilax bracteata   Smilacis glabrae	Aerial parts  Rhizomes	[44, 58]
61	Smilaside K	H	H	H	Ac	I	I	H	G	Smilax bracteata	Aerial parts	[44]
62	Smilaside L	H	H	H	H	I	I	H	I	Smilax bracteata  Smilacis glabrae	Aerial parts  Rhizomes	[44, 58]
63	Smilaside M	Ac	H	H	Ac	Cis-feruloyl	I	H	H	Smilax riparia	Roots and rhizomes	[59]
64	Smilaside N	Ac	H	H	Ac	I	Cis-feruloyl	H	H	Smilax riparia	Roots and rhizomes	[59]
65	Smilaside P	H	H	H	Ac	I	I	H	I	Smilax riparia	Roots and rhizomes	[47]
66	3′,4′,6′-O-Tri-feruloylsucrose	H	H	H	H	I	I	I	H	Smilax riparia	Rhizomes and roots	[60]
67	6′-O-Coumaroylsucrose	H	H	H	H	H	G	H	H	Bidens parviflora	Whole plants	[61]
68	1′-O-Coumaroyl-6′-O-feruloylsucrose	H	H	H	H	H	I	H	G	Smilax bracteata	Aerial parts	[44]
69	4-O-Benzoyl-3′-3,4,5-trimethoxycinnamoylsucrose	H	D	H	H	L	H	H	H	Polygala tricornis	Roots	[37]
70	6-O-Benzoyl-3′-O-3,4,5-trimethoxycinnamoylsucrose	D	H	H	H	L	H	H	H	Polygala tricornis	Roots	[37]
71	6-O-Benzoyl-3′-O-sinapoylsucrose	D	H	H	H	K	H	H	H	Polygala tricornis	Roots	[37]
72	6-O-p-Methoxybenzoyl-3′-O-3,4,5-trimethoxycinnamoylsucrose	E	H	H	H	L	H	H	H	Polygala tenuifolia	Roots	[56]
73	2,6-Di-acetyl-3′,6′-di-feruloylsucrose	Ac	H	H	Ac	I	I	H	H	Smilax china  Smilax riparia   Heterosmilax erythrantha	Stems Roots and rhizomes  Aerial parts	[46–48, 59]
74	2,6-Di-acetyl-3′-O-cis-feruloy-6′-trans-feruloylsucrose	Ac	H	H	Ac	Cis-feruloy	I	H	H	Smilax riparia	Roots and rhizomes	[59]
75	2,6-Di-acetyl-3′-O-trans-feruloy-6′-cis-feruloylsucrose	Ac	H	H	Ac	I	Cis-feruloyl	H	H	Smilax riparia	Roots and rhizomes	[59]
76	Regaloside A	Ac	H	H	H	I	H	H	H	Trillium kamtschaticum	Underground parts	[41]
77	Tricornose A	Ac	H	H	H	L	H	H	H	Polygala tricornis	Roots	[37]
78	Mumeose A	H	H	H	Ac	G	H	H	H	Prunus mume	Flower buds	[62, 63]
79	Mumeose B	Ac	H	Ac	H	G	H	H	H	Prunus mume	Flower buds	[62, 63]
80	Mumeose C	Ac	H	Ac	Ac	G	H	H	H	Prunus mume	Flower buds	[62, 63]
81	Mumeose D	Ac	Ac	Ac	Ac	G	H	H	Ac	Prunus mume	Flower buds	[62, 63]
82	Mumeose E	Ac	Ac	Ac	Ac	Cis-coumaroyl	H	H	Ac	Prunus mume	Flower buds	[62, 63]
83	Mumeose F	Ac	Ac	Ac	H	G	H	H	H	Prunus mume	Flower buds	[63]
84	Mumeose G	Ac	H	Ac	H	G	H	Ac	H	Prunus mume	Flower buds	[63]
85	Mumeose H	H	H	Ac	Ac	G	H	Ac	H	Prunus mume	Flower buds	[63]
86	Mumeose I	Ac	Ac	Ac	H	G	Ac	H	H	Prunus mume	Flower buds	[63]
87	Mumeose J	Ac	Ac	Ac	Ac	G	H	Ac	Ac	Prunus mume	Flower buds	[63]
88	Mumeose K	H	H	Ac	Ac	G	H	H	H	Prunus mume	Flower buds	[64]
89	Mumeose L	Ac	H	Ac	Ac	G	H	Ac	H	Prunus mume	Flower buds	[64]
90	Mumeose M	Ac	Ac	Ac	H	G	H	Ac	Ac	Prunus mume	Flower buds	[64]
91	Mumeose N	Ac	Ac	Ac	H	G	Ac	Ac	H	Prunus mume	Flower buds	[64]
92	Mumeose O	Ac	H	Ac	Ac	G	H	Ac	Ac	Prunus mume	Flower buds	[64]
93	1′,2,3,4,6-O-Penta-acetyl-3′-O-trans-coumaroylsucrose	Ac	Ac	Ac	Ac	G	H	H	Ac	Musella lasiocarpa	Aerial parts	[65]
94	1′,2,3,4,6-O-Penta-acetyl-3′-O-cis-coumaroylsucrose	Ac	Ac	Ac	Ac	Cis-coumaroyl	H	H	Ac	Musella lasiocarpa	Aerial parts	[65]
95	1′,2,3,6-O-Tetra-acetyl-3′-O-cis-feruloylsucrose	Ac	H	Ac	Ac	Cis-feruloyl	H	H	Ac	Sparganium stoloniferum	Rhizomes	[66]
96	1′,2,4,6-O-Tetra-acetyl-3′-O-trans-feruloylsucrose	Ac	Ac	H	Ac	I	H	H	Ac	Sparganium stoloniferum	Rhizomes	[66]
97	1′,2,3,6-O-Tetra-acetyl-3′-O-trans-feruloylsucrose	Ac	H	Ac	Ac	I	H	H	Ac	Sparganium stoloniferum	Rhizomes	[67]
98	Sibirioside A	M	H	H	H	H	H	H	H	Scrophularia ningpoensis	Roots	[68]
99	Sibricose A1	K	H	H	H	H	H	H	H	Cynanchum amplexicaule	Roots	[69]
100	6-O-Caffeoylsucrose	J	H	H	H	H	H	H	H	Scrophularia ningpoensis	Roots	[68]
101	Acretoside	I	H	H	H	H	H	H	H	Scrophularia ningpoensis	Roots	[68]
102	Tenuifoliside B	F	H	H	H	K	H	H	H	Polygala tenuifolia	Roots	[42, 56]
103	Tenuifoliside C	K	H	H	H	L	H	H	H	Polygala tricornis  Polygala tenuifolia	Roots	[37, 42, 56]
104	Heterosmilaside	H	H	I	H	H	I	H	H	Heterosmilax erythrantha	Aerial parts	[48]
105	Quiquesetinerviuside A	H	I	H	H	I	I	H	H	Calamus quiquesetinervius	Stems	[70]
106	Quiquesetinerviuside B	Ac	I	H	H	I	I	H	H	Calamus quiquesetinervius	Stems	[70]
107	Quiquesetinerviuside C	H	I	H	Ac	I	I	H	H	Calamus quiquesetinervius	Stems	[70]
108	Quiquesetinerviuside D	Ac	G	H	H	I	I	H	H	Calamus quiquesetinervius	Stems	[70]
109	Quiquesetinerviuside E	H	G	H	Ac	I	I	H	H	Calamus quiquesetinervius	Stems	[70]
110	Vanicoside A	I	H	H	Ac	G	G	H	G	Polygonum sachalinensis   Polygonum cuspidatum  Polygonum hydropiper	Stems  Leaves   Rhizomes	[51, 52, 71, 72]
111	Vanicoside B	I	H	H	H	G	G	H	G	Polygonum sachalinensis   Polygonum cuspidatum   Persicaria hydropiper	Stems   Leaves   Rhizomes	[43, 51, 52, 71, 72]
112	Vanicoside D	G	H	H	H	G	G	H	G	Persicaria hydropiper	Leaves	[51]
113	Vanicoside E	I	Ac	H	Ac	G	G	H	G	Polygonum hydropiper	Stems and leaves	[72]
114	Lapathoside A	I	H	H	H	G	G	H	I	Polygonum sachalinensis   Polygonum cuspidatum   Fagopyrum dibotrys	Stems  Rhizomes	[51, 73]
115	Lapathoside C	I	H	H	H	G	G	H	H	Polygonum sachalinensis  Polygonum cuspidatum	Stems	[43, 52]
116	Diboside A	G	H	H	H	G	I	H	G	Fagopyrum tataricum  Fagopyrum dibotrys	Roots  Rhizomes	[57]
117	Hidropiperoside A	I	H	H	H	H	G	H	G	Polygonum hydropiper	Stems and leaves	[72]
118	Hidropiperoside B	I	H	H	Ac	G	G	H	I	Polygonum hydropiper	Stems and leaves	[72]
119	Tatariside B	I	H	H	Ac	G	G	H	Ac	Fagopyrum tataricum	Roots	[57]
120	Tatariside C	I	Ac	H	Ac	G	G	H	Ac	Fagopyrum tataricum	Roots	[57]
121	Tatariside D	G	H	H	Ac	G	I	H	H	Fagopyrum tataricum	Roots	[57]
122	Tatariside F	G	H	H	H	I	I	H	G	Fagopyrum tataricum	Roots	[57]
123	3′,6-O-Di-sinapoylsucrose	K	H	H	H	K	H	H	H	Polygala tricornis  Polygala hongkongensis  Polygala sibirica  Polygala tenuifolia   Cynanchum amplexicaule	Roots   Root barks  Whole plants  Aerial parts	[37–39, 41, 53–56, 69, 74]
124	6,6′-O-Di-coumaroylsucrose	G	H	H	H	H	G	H	H	Bidens parviflora	Whole plants	[61]
125	1′,3′,6′-O-Tri-coumaroyl-6-feruloylsucrose	I	H	H	H	G	G	H	G	Fagopyrum tataricum	Roots	[75, 76]
126	3′,6′-O-Di-coumaroyl-1′,6-O-di-feruloylsucrose	I	H	H	H	G	G	H	I	Fagopyrum tataricum	Roots	[75, 76]
127	3′-O-Coumaroyl-1′,6′,6-O-tri-feruloylsucrose	I	H	H	H	I	G	H	I	Fagopyrum tataricum	Roots	[75, 76]
128	1′,3′,6′,6-O-Tetra-feruloylsucrose	I	H	H	H	I	I	H	I	Fagopyrum tataricum	Roots	[75, 76]

  See Scheme 2.

Figure 3

Cistanoside F (129) has been found in the stems of n class="Species">Cistanche tubulosa [80] and C. sinensis [81], the barks of Paulownia tomentosa var. tomentosa [82], and the aerial parts of Acanthus ilicifolius [83]. Cistanoside I (130) has also been isolated from the stems of the Cistanche plants [84]. Both of them are composed of glucosyl and rhamnosyl groups connected by a 1→3 glycosidic bond. In addition, 6,6′-sucrose ester of (1α,2α,3β,4β)-3,4-bis(4-hydroxyphenyl)-1,2-cyclobutanedicarboxylic acid (131) with a bis(4-hydroxyphenyl) cyclobutanedicarboxyl group as the acyl unit in the molecule structure was isolated from the whole plants of Bidens parviflora [61].

2.2.2. Fatty Acid-Derived Disaccharide Esters

Eight monosubstituted disaccharide esters (Table 3) with a n class="Chemical">sucrose moiety possess six different types of fatty acid residues which attach to the 6 or 6′ position of sucrose. These fatty acids include linoleic acid, palmitic acid, linolenic acid, myristic acid, hexadeca-7,10,13-trienoic acid, and hexadeca-7,10-dienoic acid. The above sucrose fatty acid esters have been found in the rhizomes of Astragalus membranaceus and the roots of Equisetum hiemale.

Table 3

Fatty acid-derived disaccharide esters.

Number	Name	R1	R2	Source	Parts	Reference
132	6′-O-Linoleylsucrose	H	O	Astragalus membranaceus	Roots	[77]
133	6′-O-Palmitoylsucrose	H	P	Astragalus membranaceus	Roots	[77]
134	6-O-Palmitoylsucrose	P	H	Astragalus membranaceus	Roots	[77]
135	6′-O-Linolenoylsucrose	H	N	Astragalus membranaceus  Equisetum hiemale	Roots Aerial parts	[77, 78]
136	6-O-Linoleylsucrose	O	H	Astragalus membranaceus	Roots	[77]
137	6-O-Myristoylsucrose	Q	H	Astragalus membranaceus	Roots	[77]
138	6-O-[(7Z,10Z,13Z)-Hexadeca-7,10,13-trienoyl]sucrose	H	R	Equisetum hiemale	Aerial parts	[78]
139	6-O-[(7Z,10Z)-Hexadeca-7,10-dienoyl]sucrose	H	S	Equisetum hiemale	Aerial parts	[78]

See Scheme 3.

2.2.3. Lignan-Derived Disaccharide Esters

Six lignan-derived disaccharide esters (Figure 4) contain a n class="Chemical">sucrose core esterified with different lignan residues covalently linked to the 3′ and 6′ positions of β-D-fructofuranosyl unit and have been isolated from the whole parts of Trigonotis peduncularis [85] and the aerial parts of Eritrichium rupestre [86].

Figure 4

2.2.4. Phenylpropanoid-Derived Trisaccharide Esters

In this group, all oligosaccharide esters consist of three n class="Chemical">monosaccharides including glucopyranose, fructofuranose, and rhamnopyranose with O-substituents, which comprise feruloyl, sinapoyl, and 3,4,5-trimethoxycinnamoyl groups. Oligosaccharide esters (146–149) listed in Table 4 as well as kankanose (150), cistantubulose A1/A2 (151), cistansinensose A1/A2 (152), and compound 153 shown in Figure 5 have been found in the roots of Polygala tricornis [37], the stems of Cistanche tubulosa [81, 87] and C. sinensis [80], the whole parts of Boschniakia rossica [88], and the rhizomes of Iris brevicaulis [89].

Table 4

Phenylpropanoid-derived trisaccharide esters.

Number	Name	R1	R2	R3	R4	R5	R6	R7	Source	Parts	Reference
146	Tricornose C	K	H	H	H	H	L	H	Polygala tricornis	Roots	[37]
147	Tricornose D	K	H	H	H	H	K	H	Polygala tricornis	Roots	[37]
148	Tricornose E	K	H	H	H	K	L	H	Polygala tricornis	Roots	[37]
149	Tricornose F	K	H	H	H	I	L	H	Polygala tricornis	Roots	[37]

See Scheme 4.

Figure 5

2.2.5. Phenylpropanoid-Derived Tetrasaccharide Esters

Phenylpropanoid-derived tetrasaccharide esters (154–159) (Table 5) consisting of three n class="Disease">glucopyranosyl units and a fructofuranosyl unit have been identified from the roots of Polygala tricornis. The nonsugar moieties of these oligosaccharides include coumaroyl, feruloyl, sinapoyl, and 3,4,5-trimethoxycinnamoyl groups.

Table 5

Phenylpropanoid-derived tetrasaccharide esters.

Number	Name	R1	R2	R3	Source	Parts	Reference
154	Tricornose G	K	H	K	Polygala tricornis	Roots	[37]
155	Tricornose H	K	K	K	Polygala tricornis	Roots	[37]
156	Tricornose I	K	K	L	Polygala tricornis	Roots	[37]
157	Tricornose J	K	I	L	Polygala tricornis	Roots	[37]
158	Tricornose K	K	I	K	Polygala tricornis	Roots	[37]
159	Tricornose L	K	G	K	Polygala tricornis	Roots	[37]

See Scheme 5.

2.2.6. Phenylpropanoid-Derived Pentasaccharide Esters

As shown in Table 6, oligosaccharide esters (160-179) pn class="Chemical">ossessing a skeleton of five sugar residues have been isolated from the roots of Polygala tenuifolia. The sugar residues are composed of two types of monosaccharides including fructofuranose and glucopyranose, which are esterified with acetyl, benzoyl, rhamnose-substituted/nonsubstituted coumaroyl, and rhamnose-substituted/nonsubstituted feruloyl groups. Other than that, a structure-complex oligosaccharide polyester shown in Figure 5, polygalajaponicose I (180), consisting of a pentasaccharide backbone esterified with feruloyl, coumaroyl, rhamnosyl-coumaroyl, acetyl, and benzoyl groups has been obtained from the roots of P. japonica [90].

Table 6

Phenylpropanoid-derived pentasaccharide esters.

Number	Name	R1	R2	R3	R4	R5	R6	Source	Parts	Reference
160	Tenuifoliose A	G	D	I	Ac	Ac	Ac	Polygala tenuifolia	Roots	[38, 42]
161	Tenuifoliose B	G	D	I	H	Ac	Ac	Polygala tenuifolia	Roots	[42]
162	Tenuifoliose C	G	D	I	H	H	H	Polygala tenuifolia	Roots	[42]
163	Tenuifoliose F	G	D	U	Ac	Ac	Ac	Polygala tenuifolia	Roots	[42]
164	Tenuifoliose G	G	D	U	Ac	H	Ac	Polygala tenuifolia	Roots	[42]
165	Tenuifoliose H	G	D	G	Ac	Ac	Ac	Polygala tenuifolia	Roots	[38, 42, 79]
166	Tenuifoliose I	G	D	G	Ac	H	Ac	Polygala tenuifolia	Roots	[42, 79]
167	Tenuifoliose J	G	D	G	H	Ac	Ac	Polygala tenuifolia	Roots	[42]
168	Tenuifoliose K	G	D	G	H	H	Ac	Polygala tenuifolia	Roots	[42]
169	Tenuifoliose L	G	D	T	Ac	Ac	Ac	Polygala tenuifolia	Roots	[42, 79]
170	Tenuifoliose M	G	D	T	Ac	H	Ac	Polygala tenuifolia	Roots	[42]
171	Tenuifoliose N	I	D	I	Ac	Ac	Ac	Polygala tenuifolia	Roots	[42]
172	Tenuifoliose O	I	D	I	H	Ac	Ac	Polygala tenuifolia	Roots	[42]
173	Tenuifoliose P	I	D	I	H	H	Ac	Polygala tenuifolia	Roots	[42]
174	Tenuifoliose Q	G	D	T	H	Ac	Ac	Polygala tenuifolia	Roots	[79]
175	Tenuifoliose S	G	D	G	H	H	H	Polygala tenuifolia	Roots	[42]
176	Tenuifoliose T	G	D	I	H	H	H	Polygala tenuifolia	Roots	[42]
177	Tenuifoliose V	H	D	I	Ac	Ac	Ac	Polygala tenuifolia	Roots	[42]
178	Tenuifoliose W	I	D	U	Ac	H	Ac	Polygala tenuifolia	Roots	[42]
179	Tenuifoliose X	I	D	I	H	H	H	Polygala tenuifolia	Roots	[42]

See Scheme 6.

2.2.7. Others

Polygalatenosides A–C (181–183) (Figure 6) containing a galactn class="Chemical">osyl unit and a polygolitosyl unit esterified with benzoyl groups at 3, 4 and 6 positions have been found in the roots of Polygala tenuifolia [91]. Three sucrose esters, including polygalatenoside D (190), telephiose F (191), and 6-O-benzoylsucrose (192), possess one benzoyl group, two benzoyl groups, and a p-methoxybenzoyl group, respectively. They were isolated from the roots of P. tenuifolia [91], the whole plants of P. telephioides [92], and the roots of P. tricornis [37]. Six trisaccharide esters, named telephioses A–E and G (184–189) with substituents of acetyl and benzoyl groups, were isolated from the whole plants of P. telephioides [92, 93]. Moreover, a trisaccharide ester (193), pubescenside A from the flowers of Syringa pubescens, possesses a fatty acid residue [94].

Figure 6

3. Biological Activities of Oligosaccharides and Their Esters

The oligosaccharides and n class="Chemical">oligosaccharide esters from Chinese medicinal plants are important products with diversified structures, which have triggered an increasing number of studies carried out on the isolated compounds. And thus diverse pharmacological activities have been proved. Among the isolated compounds, oligosaccharides, phenylpropanoid-derived disaccharide esters and trisaccharide esters, fatty acid-derived disaccharide esters, and others from the families Polygonaceae, Asclepiadaceae, Rubiaceae, Polygalaceae, Liliaceae, Smilacaceae, Arecaceae, Orobanchaceae, Scrophulariaceae, Acanthaceae, Rosaceae, Sparganiaceae, Leguminosae, and Equisetaceae have shown significant pharmacological activities including antioxidant, antidepressant, cytotoxic, antineoplastic, anti-inflammatory, antidiabetic, plant growth-regulatory, neuroprotective, and cerebral protective activities. Lignan-derived disaccharide esters, phenylpropanoid-derived tetrasaccharide esters, and pentasaccharide esters with biological activities have not been reported. Aside from the isolated constituents, oligosaccharide mixtures from Rehmannia glutinosa, Panax ginseng, and Scrophularia ningpoensis were also reported to display diverse pharmacological activities, such as antidiabetic, immunopotentiating, enhanced memory, and antineoplastic activities. These active compounds and mixtures could serve as the valuable candidates to be developed as possible drugs for the treatment and prevention of diseases.

3.1. Antioxidant Activity

The adverse effects of oxidative stress proposed to play significant roles in the pathogenesis of n class="Disease">cardiovascular diseases, atherosclerosis, hypertension, cancer, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, and ageing have become an inevitable and serious issue [95, 96]. Scientists have thus made great efforts to explore antioxidants from medicinal plants by using different kinds of assay methods, which include DPPH radical scavenging assay, hydroxyl radical scavenging assay, superoxide anion scavenging assay, and ABTS radical scavenging method [96].

Lapathosides C and D, n class="Chemical">hydropiperoside, vanicoside B, hidropiperosides A and B, lapathoside A, and diboside A were isolated from the Polygonum, Persicaria, and Fagopyrum genera belonging to the Polygonaceae family. The DPPH test revealed that free radical-scavenging activity of the isolated compounds termed lapathoside C (115), hydropiperoside (42), vanicoside B (111), and lapathoside D (38) increased in turn, and lapathoside D exhibited strongest scavenging ability with an IC50 of 0.088 μM [43]. Hidropiperosides A and B (117, 118) were reported to show obvious antioxidant response to DPPH radicals with the SC50 values of 23.4 and 26.7 μg/mL, respectively, while vanicoside E moderately exhibited the same activity with a SC50 value of 49.0 μg/mL [72]. Lapathoside A (114) and diboside A (116) just showed lower antioxidant activities with the SC50 values of 199.48 and 165.52 μM, respectively [73].

Smiglasides A and B, n class="Chemical">smilaside P, 2,6-di-acetyl-3′,6′-di-feruloylsucrose, helonioside B, smilasides G–L, and heterosmilaside were isolated from the Heterosmilax and Smilax genera. Compared with ascorbic acid (IC50 143.52 μM) used as positive control, smiglasides A and B, and smilaside P (48, 49, 65) (IC50 339.58, 330.66 and 314.49 μM, resp.) showed higher antioxidant activities than 2,6-di-acetyl-3′,6′-di-feruloylsucrose (73) and helonioside B (40) (IC50 631.66 and 518.27 μM, resp.) [47]. Additionally, Nhiem et al. reported that helonioside B, heterosmilaside (104), and 2,6-di-acetyl-3′,6′-di-feruloylsucrose exhibited important DPPH radical scavenging activities with the SC50 values of 9.1, 12.7 and 8.7 μg/mL, respectively [48]. Compared with smilasides G-I (57–59) (ED50 68.5–79.4 μM), smilasides J–L (60–62) showed higher radical scavenging activities with an ED50 value of 26.7–32.7 μM [44].

Five quiquesetinerviusides A–E (105–109) isolated from the Calamus genus showed weak n class="Chemical">DPPH scavenging activities (IC50 60.4–101.8 μM) but exhibited better hydroxyl radical scavenging activities (IC50 3.6–8.4 μM). Moreover, quiquesetinerviuside C showed superoxide anion scavenging activity with an IC50 value of about 184.3 μM [70]. Liu et al. investigated the antioxidant capacity of 3′,6-O-di-sinapoylsucrose (DISS) (123) by using the accelerated senescence-prone, short-lived mice (SAMP) in vivo. The analyses indicated that the activities of antioxidant enzymes of SOD and glutathione peroxidase ascended obviously in SAMP mice when amended with DISS 50 mg/kg. Moreover, DISS could downregulate and even restore the level of malondialdehyde in SAMP model group [97].

From the above studies, it can be concluded that oligosaccharide esters with antioxidant activities have been identified in the Polygonaceae, Liliaceae, Smilacaceae, and Arecaceae families. The results of the antioxidant assays show that the increased number of phenolic hydroxyl groups and n class="Chemical">acetyl groups could produce higher antioxidant activity. Fan et al. indicated that the increased number of phenylpropanoid groups was not beneficial to free radical scavenging activity [43]. Zhang et al. pointed out that oligosaccharide esters with feruloyl groups exhibited better antioxidant activities than those with coumaroyl groups [44].

3.2. Antidepressant Activity

The oligosaccharides obtained from the n class="Species">Morinda genus not only show specific antidepressant and antistress activities but also have no suppression or excitatory effects on central nervous system as well. What is more, they can be taken orally with little toxicity [21]. The inulin-type hexasaccharide (IHS) (9) from Morinda officinalis obviously exhibited cytoprotective activity, which contributed to the antidepressant effect, not only by providing the PC12 with protection against Cort-induced lesion with IHS 0.625 and 1.25 μM, but also by reducing the Cort-induced [Ca2+] overloading with IHS 2.5 and 10 μM. IHS 5 and 10 μM upregulated the nerve growth factor mRNA expression in Cort-induced PC12 cells [22]. Polygalatenosides A (181) and B (182) were isolated from the Polygala genus. They significantly inhibited the isotope-labeled RTI-55 binding to norepinephrine transporter protein with the IC50 values of 30.0 and 6.04 μM, respectively [91].

DISS and tenuifoliside A were isolated from the Polygala and n class="Species">Cynanchum genera. Liu et al. investigated the antidepressant effect of YZ ethanol extract based on the tail suspension test (TST) and forced swimming test (FST), which are the ease-of-use and widely-accepted models for estimating antidepressant activities in mice. The results indicated that YZ-50 fraction at a dose of 200 mg/kg was able to significantly decrease the immobility time in TST. Furthermore, YZ-50 possessed ability to inhibit corticosterone-induced injury of human neuroblastoma SH-SY5Y cells. What is more, DISS (123) and tenuifoliside A (44), two major compounds of YZ-50 fraction, showed effective protective response to the lesion in SY5Y cells [53]. The antidepressant-like effect of DISS at the doses of 5, 10, and 20 mg/kg was also tested in chronically mild stressed rats. DISS was able to exhibit antidepressant activity by upregulating the expression of noradrenergic-regulated plasticity genes including cell adhesion molecule L1, brain-derived neurotrophic factor, laminin, and cAMP response element binding protein factor in hippocampus [98]. DISS improved the reward reaction by increasing sucrose intake and obviously decreased the levels of serum cortisol, adrenocorticotrophic hormone, and corticotropin-releasing factor. Further, DISS played an enhanced role in the expression of mineralocorticoid receptor, together with glucocorticoid receptor mRNA [99].

3.3. Cytotoxic and Antineoplastic Activities

Smilasides A–F and P, n class="Chemical">smiglasides A and B, smilaside P, and helonioside A were isolated from the Smilax, Trillium, and Paris genera. Kuo et al. obtained smilasides A–F (51–56) and evaluated their cytotoxicity against human tumor cell lines comprising human oral epithelium carcinoma (KB), human cervical carcinoma (Hela), human colon tumor (DLD-1), human breast adenocarcinoma (MCF-7), human lung carcinoma (A-549), and human medulloblastoma (Med) cells by MTT assay. Experimental data indicated that all but smilaside C showed cytotoxicity against three to six human tumor cell lines (ED50 = 5.1–13.0 μg/mL), and smilasides D–F (ED50 = 2.7–5.0 μg/mL) displayed strong cytotoxic activities against DLD-1 cells [46]. Wang et al. reported the antitumor constituents of Smilax riparia, including smiglasides A (48) and B (49), 2,6-di-acetyl-3′,6′-di-feruloylsucrose (73), helonioside B (40), and smilaside P (65). Only smiglasides A and B, and smilaside P exhibited cytotoxicity against human tumor cell lines with different inhibitory concentrations comparing with cisplatin and paclitaxel as positive controls [47]. Helonioside A (39) exhibited higher cytotoxicity with the increase of concentration (0.1–100 μg/mL) [45]. Tatarisides A–G (45, 119–121, 46, 122, 47) and diboside A (116) from the Fagopyrum genus exerted cytotoxic activities against different human cell lines, and the cytotoxicity of tatariside C was the most remarkable with the IC50 values ranging from 6.44 to 7.49 μg/mL [57].

1′,2,3,6-O-Tetra-n class="Chemical">acetyl-3′-O-cis-feruloylsucrose (95) from the Sparganium plants exhibited extremely weak cytotoxicity against the growth of mice Lung Adenocarcinoma 795 cell lines with an IC50 value of 116 μg/mL [66]. SnS-2, oligosaccharides mixture, including raffinose (3), stachyose (19), and verbascose (21) from the roots of Scrophularia ningpoensis, had antitumor activity against the growth of Lewis pulmonary carcinoma cells transplanted into mice [18].

Disaccharide esters and n class="Chemical">oligosaccharides mixture from the Liliaceae, Polygonaceae, Sparganiaceae, and Scrpophulariaceae families showed effective cytotoxic and antineoplastic activities. The study results indicated that feruloyl and acetyl groups play an important role in mediating cytotoxicity, which seems to be related to the substitution position of feruloyl groups. The feruloyl groups at C-6 or C-1′ are vital for cytotoxicity. In addition, the increased number of acetyl groups could induce higher tumoricidal activity.

3.4. Anti-Inflammatory Activity

Inflammation, an important basic pathological process, is a defense response of biopsy with vascular system to damage stimuli such as pathogens, impaired cells and tissues, and physical and chemical factors. However, if the process of inflammatory response cannot end normally when cell debris and pathogens were cleared, the biological defence response will become causative factor and bring about many diseases, such as diabetes, n class="Disease">cardiovascular diseases, metabolic syndrome, and cancer [100, 101].

Tenuifoliside A (44) from the Polygala genus exhibited strong anti-inflammatory effect not only by suppressing the production of n class="Chemical">NO, but also by reducing the production of iNOS, prostaglandin E2, cyclooxygenase-2, and proinflammatory cytokines through the inhibition of the mitogen-activated protein kinases pathway and NF-κB pathway [102]. The anti-inflammatory activities of quiquesetinerviusides D (108) and E (109) from the Calamus genus were evaluated in RAW 264.7 cells. Both of them showed significant inhibitory effects against the production of LPS-stimulated NO with the IC50 values of 9.0–29.5 μM [70].

Six disaccharide fatty acid esters (132–137) were isolated from the n class="Species">Astragalus and Equisetum genera. The anti-inflammatory effects of these isolated compounds have also been documented. The activation of NF-κB could upregulate the expression of proinflammatory cytokines inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α). The NF-κB inhibitory activities of compounds 132–137 were tested in HepG2 cells stimulated with TNF-α. All of these compounds could significantly restrain TNF-α-induced NF-κB transcriptional activities with the IC50 values of 4.4–24.7 μM. Li et al. pointed out that olefinic bonds and the length of the fatty acid moieties contributed to the NF-κB inhibitory activity. Furthermore, the inhibition increased significantly with the increase of the number of olefinic bonds on the aliphatic moiety [77]. These results may provide a scientific basis for the development of new anti-inflammatory agents.

3.5. Neuroprotective and Cerebral Protective Activities

As we all know, glutamate works as a major n class="Chemical">excitatory amino acid neurotransmitter in the mammalian central nervous system and plays a crucial role in several physiological processes [103]. However, the accumulation of glutamate induces diverse acute and chronic neurodegenerative diseases, such as epilepsy, ischemic stroke, and Parkinson's disease, as well as Alzheimer's disease [104]. DISS (123) isolated from the Polygala genus exhibited neuroprotective effect against glutamate-induced SH-SY5Y neuronal cell damage. The in vitro test demonstrated that DISS (0.6, 6 and 60 μmol/L) played a critical role in increasing cell viability, controlling lactate dehydrogenase and attenuated apoptosis ranging from 1.95% to 2.58% [105].

Tenuifoliside B (102) from the n class="Disease">Polygala genus was able to significantly shorten the coma time of KCN-induced anoxia mice at the doses of 3 and 10 mg/kg, and it played an important role in ameliorating the scopolamine-induced impairment of performance in passive avoidance task in rats and enhancing the tremors induced by oxotremorine in mice. These results together demonstrated that tenuifoliside B possessed cognitive improving and cerebral protective effects [56].

3.6. Antidiabetic Activity

Diabetes mellitus, a chronic n class="Disease">debilitating metabolic disease, is characterized by high blood glucose content and comprises three types termed type I, type II, and gestational diabetes [106]. Stachyose (19) extract (a part) from Rehmannia glutinosa obviously exhibited the activity of downregulating fasting plasma glucose level and partially keeping from hyperglycemia induced by adrenaline and glucose without obvious dose-dependent effect. Other than that, in vivo tests in rats induced by alloxan revealed that stachyose extract at the dose of 200 mg/kg significantly decreased blood-sugar level [15].

Diboside A, n class="Chemical">lapathosides C and D, vanicosides A and B, and hydropiperoside were isolated from the Fagopyrum, Polygonum, and Persicaria genera belonging to the Polygonaceae family. Diboside A (116) could potentially inhibit α-amylase activity with an IC50 of 26.9 μM and thus retard the starch digestion rate, which is helpful for diabetic individuals in controlling blood sugar level [107]. Lapathoside D (38) exerted stronger activity of α-glucosidase inhibition with an IC50 value of 0.113 mM than acarbose which was chosen as a positive drug for the treatment of type II diabetes [43]. Vanicoside B (111) was reported to have higher β-glucosidase inhibitory activity with an IC50 of 50.5 μM than vanicoside A (110) with an IC50 of 59.9 μM because of the acetyl moiety of the latter possibly decreasing inhibitory activity of vanicoside A [71].

Fujimoto et al. investigated the inhibitory effects of mumeoses F–O (83–92) from the n class="Disease">Prunus genus on aldose reductase and discovered that caffeoyl groups are crucial for the inhibitory effect on aldose reductase. And thus, mumeoses F, G, H, J, K, L, M and N (IC50 = 22–77 μM), with a coumaroyl group and acetyl groups, inhibited moderately aldose reductase from reducing glucose to sorbitol, which is associated with the chronic complications of diabetes [63, 64].

3.7. Elicitors and Regulators

Oligosaccharides are quite propitious for encoding biological information because of diverse n class="Chemical">monosaccharide units and complex molecular structures and they are therefore first described as biological signals in plants [108]. Oligosaccharides from the cell wall fragments of plants and fungi are powerful signal molecules, such as the elicitors of plant defence response and the regulators of plant growth, and they are capable of exerting biological activities at exceedingly low concentrations [109]. Heptasaccharide (HS) (15) and octasaccharide (OS) (16) isolated from the Paris genus possessed plant growth-regulatory activities [29, 30]. The two oligosaccharides significantly promoted the proliferation of Paris polyphylla var. yunnanensis roots at the doses of 2.5–20 mg/L. The octasaccharide had the most obvious effect on the growth of Panax japonicus var. major hairy roots at a dose of 30 mg/L, while the other had the most positive effect on saponin accumulation of Panax japonicus var. major hairy roots at a dose of 10 mg/L [29]. Similarly, Zhou et al. evaluated the stimulating effects of HS and OS on the root growth and saponin production of Panax ginseng hairy roots, which were induced from the plant roots infected with Agrobacterium rhizogenes strain A4. The results showed that there was a maximum effect on the hairy roots growth and saponin accumulation on day 10. Compared with control group, the root biomass dry weight was increased by more than 1.7-fold while the total saponin content of roots increased by more than 1-fold when these two oligosaccharides were added to the hairy root at a dose of 30 mg/L [30]. The above data illustrate that HS and OS could serve as the plant growth-regulators not only in their original species but also in others.

3.8. Immunopotentiating Activity

Macrophages are important targets of investigations on cytophagy, cellular immunity, and molecular immunology. Therefore, they are deemed to play a vital role in host defense comprising phagocytosis, proteolytic processing, pathogenic agent, apoptosis, cytokines production, and foreign antigens presentation [110]. The water-extracted oligosaccharides from Panax ginseng (WGOS) exhibited better immunopotentiating activity by increasing phagocytic function of macrophages and promoting NO, TNF-α and reactive oxygen species production [110]. In addition, Wan et al. have obtained malto-oligosaccharides (17, n = 3~8) and three oligosaccharides (2, 13, 14) from the Panax ginseng roots. The in vitro bioassay pointed out that WGOS could serve as efficacious stimulators of B and T lymphocytes [28]. These studies provided enlightenment that the mixture of oligosaccharides from Chinese herbal medicine exhibits significant effect on immune system.

3.9. Others

Acetylcholinesterase (AChE) inhibitors show good therapeutic effects on n class="Disease">myasthenia gravis, glaucoma, and Alzheimer's disease through reversible enzyme inhibition so as to increase the accumulation of acetylcholine in the synapse and then promote and prolong the function of acetylcholine. Vanicoside B (111) showed AChE inhibitory activity with an IC50 of 0.062 mM, while hydropiperoside (42), and lapathosides C (115) and D (38) just exhibited weak enzyme inhibitory activity [43].

Wang et al. has explored low molecular mass carbohydrate polymer from n class="Species">Panax ginseng roots and obtained 30% ethanol elution (PGO) which included peptides and oligosaccharides (17, n = 0~5) identified as maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose, and maltoheptaose. Pharmacological experiments revealed that PGO could significantly enhance the memory in scopolamine-induced memory deficit rats [27].

Cistanoside F (129) and n class="Chemical">kankanose (150) were isolated from the Cistanche, Paulownia, and Acanthus genera. Pharmacological experiments showed that cistanoside F and kankanose significantly exhibited vasorelaxant effects on the noradrenaline-induced contraction of thoracic aorta from rats [80].

4. Conclusion

Traditional Chinese medicine from natural kingdom plays an indelible role in the treatment of human diseases, and it has aroused the attention of thn class="Chemical">ose who have engaged in medicinal pharmaceutical chemistry. Therefore, scientists have made great contributions day after day to investigate the valid chemicals from traditional Chinese medicines. In the past decades, about 193 oligosaccharides and their esters have been identified from traditional Chinese medicinal plants. On the one hand, only a few oligosaccharides and their mixtures were investigated and just exhibited antidepressant, antineoplastic, antidiabetic, plant growth-regulatory, immunopotentiating, and enhanced memory activities. More exploratory work is still needed to excavate biological and pharmacological activities of oligosaccharides. On the other hand, oligosaccharide esters exhibited multi-advantageous activities. Bioassays have revealed that antioxidant, cytotoxic, antineoplastic, and anti-inflammatory activities are the most notable bioactivities. Of course, to search for the natural products with these activities is a hotpot in the contemporary drug research. Oligosaccharide esters provide a vast treasure trove for medical researchers. After considering the current studies, it should be taken as future directions to make more mechanism of action studies and clinical trials to further evaluate its potential as new drugs. Moreover, the structure-activity relationships discussed in this review will provide reference information for further exploring their relationships and continually discovering the new bioactive oligosaccharide esters.