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Table 1 Biological activities of biomacromolecules based on its traditional efficacy

From: Pharmacodynamic material basis of traditional Chinese medicine based on biomacromolecules: a review

Resources

Polysaccharides/Proteins/miRNA

Molecular weight (KDa)

Compositions/structure

Bioactivities

Effects/mechanisms

Refs.

Panax Ginseng

Glycopeptides (GGP)

6

Rhamnose, arabinose, galactose, glucose (0.46:1.61:1:2.37); contained 1.6–27% polypeptides (consisted of 16 amino acids, Asp, Glu, Pro, and others)

Anti-hyperglycemia

GGP induced the pronounced decreases in blood glucose and liver glycogen levels in both normal and hyperglycemic animals

[30]

Glycopeptides (GMP)

12.38

Arabinose (21.9%), galactose (22.6%), glucose (14.8%), rhamnose (5.8%), uronic acid (32.7%), and protein (2.2%)

Immunoregulatory

GMP increased the lysosomal phosphatase activity and the phagocytic index of peritoneal macrophages and its immunostimulating effects may be due to its ability to stimulate the production of reactive oxygen intermediates

Oligopeptides (GOP)

 < 1

Unknown

GOP enhanced innate and adaptive immune responses in mice by improving cell mediated and humoral immunity, macrophage phagocytosis capacity and NK cell activity

[32]

Polysaccharides (PGP)

Unknown

Unknown

Qi-invigorating and anti-fatigue

PGP inhibited mitochondrial injury and swelling and improved energy metabolism in a concentration dependent manner

[29]

Unknown

α (1 → 6) Glucopyranoside and β (2 → 6) fructofuranoside (5:2)

Immunoregulatory

PGP enhanced the humoral immune response to orally delivered antigen, mediated by CCL3 via cyclooxygenase

[28]

Polysaccharides (Two neutral and six acidic fractions)

3.5–110

Starch-like polysaccharides, pectic arabinogalactans and RG-I-rich and HG-rich pectins

Both the neutral and acidic polysaccharides were potent B and T cell stimulators

[31]

Pseudostellaria heterophylla

Polysaccharides (PRP)

Unknown

Unknown

Anti-fatigue

PRP is beneficial to chronic fatigue syndrome, and the underlying mechanisms of action involve neuroendocrine and immune systems

[34]

Glehniae radix

Polysaccharides (GRP)

13.3

α‑D‑Glucan containing (1 → 6)-linked and (1 → 3)-linked backbone with a branch of one (1 → 6)-linked and terminal glucoses submitting at the C-4 position every fourteen residues

Immunoregulation, anti-inflammatory and anti-tumor

GRP exhibited inhibition against A549 cells proliferation and NO production in RAW264.7 cells, and displayed promotion for proliferation of mouse spleen lymphocytes and RAW264.7 cells

[36]

Astragalus membranaceus

Polysaccharides (APS)

6–20

α-1,4 (1,6) Glucan, arabinose galactose polysaccharides, rhamnose galacturonic acid polysaccharides, and arabinose galactose protein polysaccharide

Immunoregulatory

APS suppressed CD4+ CD25+Treg activity, at least in part, via binding TLR4 on Tregs and triggered a shift of Th2 to Th1 with activation of CD4+ T cells in burned mice

[38]

69

Unknown

Immunoregulatory

APS increased the level of cytokines including TNF-α, GM-CSF and the production of NO. NF-κB protein levels are increased in response to APS. Blocking NF-κB with specific inhibitor resulted in decreased levels of NO and TNF-α

[35]

20.7

α-d-Glucan residues, APS has repeating (1 → 4)-linked backbone with a (1 → 6)-linked branch every 10 residues

Immunoregulatory

APS was able to stimulate activity of purified mouse B cells without promoting T cell proliferation

[37]

11

Rhamnose, glucan, galactose, arabinose (1.19:72.01:5.85:20.95)

Anti-inflammation

APS reduced cell accumulation, swelling and arthritic index of the joints and serum concentrations of TNF-α and IL1-β in a dose-dependent manner in AA rats. Synovial cell apoptosis was elevated by APS and accompanied by increased Bax protein and decreased Bcl-2 protein

[39]

36,300

APS:APS I, II, and III (1.47:1.21:1). APS I consisted of d-glucose, d-galactose, l-arabinose (1.75:1.63:1). Both APS II and APS III are dextrans, the linkage mode o is mainly α-(1 → 4) linkage, and in which α-(1 → 6) linkages are exiguous

Anti-atherosclerosis and anti-diabetes

APS regulated part of the insulin signaling in insulin resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes

[38]

Rhizoma dioscoreae

Polysaccharides (YP-1)

42

Glucose, mannose, galactose (1:0.37:0.11); (1 → 3)-α-glucopyranose as a main chain and -β-galactopyranose-[(1 → 2)-α-mannopyranose]3-(1 → 2)-α-mannopyranose-(1 → 6)-as a side chain

Immunoregulatory

YP-1 stimulated ConA-induced T lymphocyte proliferation and its branches are extremely important for the expression of the enhancement of the immunological activity

[41]

Glycoproteins

Unknown

Unknown

Immunoregulatory

Rhizoma dioscoreae glycoproteins promoted immunity by affecting thymus organ and phagocytic index of mice

[124]

Polysaccharides (DOTP-80)

123

Glucose, galactose, mannose, arabinose (23.7:9.3:17.8:1.0)

Hypoglycemia

DOTP-80 had strong hypoglycemic activity. DOTP-80 increased SOD activity in alloxan induced diabetic mice and increased glucose disposal in diabetic rats

[42]

Ganoderma lucidum

Polysaccharides (Gl-PS)

8.849

Gl-PS consisted of d-glucose with minor amounts of galactose, arabinose and mannose (22.4:1.9:1.0:2.1)

Anti-hyperglycemia

Gl-PS decreased fasting plasma glucose, TC and TG in STZ-induced diabetes rats due to its antioxidant activities and ability to inhibit NO production caused by STZ

[44]

Proteins (Lz 8)

12.722

Lz 8 consisted of 110 amino acid residues with an acetylated amino terminus

Immunoregulatory

Lz 8 induced phagocytosis of macrophages

[43]

Proteins (GCL)

18

Its N-terminal sequence displays slight similarity to a lectin from fungal immunomodulatory proteins

Unknown

[110]

Coriolus versicolo

Polypeptides (PSK); polysaccharide peptides (PSP)

Unknown

PSK consisted of a polypeptide moiety to which polysaccharide β-d-glucan chains are attached; approximately 62% is polysaccharide and 38% is protein. PSP was a closely related protein-bound polysaccharide

Immunoregulatory

PSP and PSK enhanced immunoregulation by inducing production of IL-6, interferons, immunoglobulin-G, macrophages, and T-lymphocytes

[46]

Polysaccharide peptides (PSP)

100

PSP is composed of 74.6% glucose, 4.8% xylose, 2.7% galactose, 2.4% fructose and 1.5% mannose. 18 amino acid were contained

Anti-virus

PSP induced the production of serum interferon and in vitro studies suggested that PSP may be useful against HIV-1 infection

[45]

Licorice

Arabinogalactan proteins

Unknown

contained 65% polysaccharides on the basis of fraction (52% arabinose and 22% galactose were the major neutral sugars together with 6% rhamnose and 2% fucose)

Antitussive

Licorice polysaccharides showed the ability to reduce citric acid-induced cough in awake guinea pigs after oral administration

[49]

miRNA

Unknown

Unknown

Immunoregulatory

miRNA inhibited the differentiation of T cells and the expression of genes related to inflammation and apoptosis

[48]

Schisandra Chinensis

Glycopeptides (SCP)

265

Mannose, glucose, galactose and arabinose (1.32%, 54.41%, 44.10%, 0.17%); glycoprotein, the protein part of SCP consisted of 12 amino acids, Total protein content of SCP was 2.30%

Anti-fatigue

SCP had therapeutic effect on chronic fatigue syndrome was partially related to TCA cycle metabolic pathways and the alanine, aspartate and glutamate metabolism

[51]

Polysaccharides (SCP-IIa)

7.7

Homogeneous polysaccharide without protein and nucleic acid

Immunomodulatory

SCP-IIa increased the thymus and spleen indices, as well as the pinocytic activity of the peritoneal macrophages in immunosuppressed mice

[125]

Polysaccharides (SCFP-1)

31.8

Glucose, arabinose, Rib, rhamnose, xylose, galactose, mannose (302.2:133.6:11.9:2.7:1.7:1.4:1), contained 96.9% carbohydrate and 14.2% uronic acid

Antitussive

SCFP-1 showed remarkable suppressive effects on cough and attenuated inflammatory cells in BALF and some typical characteristics of nonspecific airway inflammation in animals exposed to CS

Polysaccharides (SCP)

Unknown

Unknown

anti-AD

SCP improved the cognition of mice, and it played an anti-AD role by activating the NF-κB/MAPK pathway to alleviate neuroinflammation

[50]

Angelica sinensis

Polysaccharides (AAP)

52

Mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose (0.44:1.00:10.52:7.52:8.19:14.43), where the molar percentage amount of galacturonic acid was 25.0%

Immunomodulatory

AAP improved the mRNA expression of toll-like receptor 4, and the pretreatment of macrophages with anti-TLR4 antibody significantly blocked AAP-induced NO release, TNF-α secretion, and the increase of iNOS activity

[126]

polysaccharide (ASP)

Unknown

Unknown

Hemopoiesis

ASP inhibited the expression of signal transducer and activator of transcription 3/5 and mothers against decapentaplegic proteins 4 in liver and stimulated the secretion of erythropoietin. and is likely to involve the PI3K/AKT pathway

[127]

Polysaccharides (ASPS)

8 and 76

The raw polysaccharides (ASPS) contained ASP I and II (7.41:1); APS I and II consisted of arabinose, galactose, and glucose

The hematopoietic activity was improved by stimulation of IL-6 and GM colony-stimulating factor secretion

[53]

Proteins

17–90

Unknown

Righting and dispeling evil

Angelica decoction proteins can scavenge DPPH free radicals, have a very significant proliferation effect on normal human liver cell line L-02, and an inhibitory effect on human leukemia cell line K562

[54]

Radix Rehmanniae Preparata

Polysaccharides (RRPP)

Unknown

Rehmannan SA and rehmannan SB in RRPP. They were commonly composed of l-arabinose:d-galactose:l-rhamnose:d-galacturonic acid (10:10:1:1) (rehmannan SA) and (14:7:3:8) (rehmannan SB)

Anti-fatigue

RRPP increased the storage of hepatic glycogen and the decrease of the accumulation of SUN and BLA

[55]

Maidong

Liriope spicata polysaccharide (LSP), Ophiopogon japonicus polysaccharide (OJP), Liriope muscari polysaccharide (LMP)

4.742, 4.925 and 4.138

Fruf-(2 → , 2 → 2)-Fruf-(6 → , → 6)-Glcp-(1 → and → 1,2)-Fruf-(6 → with a molar ratio of 5.0:18.2:1.0:5.3 (LSP), 6.8:15.8:1.0:5.8 (OJP), 8.3:12.3:1.0:3.9 (LMP)

Anti-diabetes

LSP, LMP and OJP increased the expression of PI3K, AKT, InsR, PPARγ and decreased the expression of PTP1B in mRNA level and protein level in IR HepG2 cells. Furthermore, glucose consumption was increased after treated with polysaccharides

[58]

Lycium barbarum

Polysaccharides (LBP)

150 (LBPF1-4)、293 (LBPF5)

LBP contains LBPF1, LBPF2, LBPF3, LBPF4 and LBPF5

Immunomodulatory

LBP and LBPF1-5 activated transcription factors NF-κB and AP-1 by RAW264.7 macrophage cells, induced TNF-α, IL-1β, IL-12p40 mRNA expression, and enhanced TNF-α production in a dose-dependent manner

[62]

Polysaccharides (LbGp4)

214.8; carbohydrate content 85.6

Arabinose, galactose, rhamnose, glucose (1.5:2.5:0.43:0.23)

Immunomodulatory

Immunostimulatory effect by activating the expression of NF-jB and activator protein 1 (AP-1)

[61]

Polysaccharides (LBP3p)

157

Galactose, glucose, rhamnose, arabinose, mannose, xylose (1:2.12:1.25:1.10:1.95:1.76)

Immunomodulatory

LBP3p induced immune responses by increasing the expression of IL-2 and TNF-α at both mRNA and protein levels; inhibiting the growth of transplantable sarcoma while increasing macrophage phagocytosis, spleen lymphocyte proliferation and CTL activity

[128]

Glycocojugates LBP-X

23.7 to 214.8

Rhamnose, galactose, glucose, arabinose, mannose, and xylose (4.22:2.43:1.38:1.00:0.95:0.38). LBP-X contained 17 amino acids (8.46%)

Anti-diabetes

Crude LBP and purified polysaccharides fraction reduced the blood glucose levels and serum TC and TG concentrations while increased HDL levels

[59]

Polysaccharides (LBP)

Unknown

Unknown

Enhancing physical strength and ameliorating physical fatigue

LBP prolonged the weight-loaded swimming time, increased the content of hepatic glycogen and prevented the increase of blood lactic acid of mice after swimming

[129]

Polysaccharides (LBP)

Unknown

Unknown

Ameliorating male infertility

LBP attenuated diabetic testicular dysfunction via inhibition of the PI3K/Akt pathway-mediated abnormal autophagy in male mice

[63]

Alpiniae oxyphyllae

Polysaccharides (PAOF)

287

The contents of carbohydrate, protein, sulfated group and uronic acid from PAOF were 95.25%, 4.28%, 6.12% and 3.13%

Anti-urinary incontinence

PAOF reduced the urination volume, Na+, Cl emission and increase K+ excretion of hydruric model rats. And increased the content of aldosterone and antidiuretic hormone. The coefficients of spleen, thymus and adrenal were improved by PAOF

[64]

Cordyceps sinensis

Polysaccharides (CPS-2)

43.9

α-(1 → 4)-d-glucose and α-(1 → 3)-d-mannose, branched with α-(1 → 4,6)-d-glucose every twelve residues on average

Protection of chronic renal failure

CPS-2 relieved renal failure caused by fulgerizing kidney

[71]

Polysaccharides (UM01-S4)

22.559

α-(1 → 2)-Manp core. The side chains were composed of β-(1 → 2)-Galf, β-(1 → 4)-Glcp, α-Galp A, and α-Manp units, which attached to the mannan core at the O-6 position

Immunomodulatory

UM01-S4 exhibited macrophages proliferation, phagocytosis, and release of NO and cytokines. The mechanism of macrophage regulation related to the activation of the MAPK and NF-κB signalling pathways

[65]

Pilose antler

Proteins (PCP)

35.6

PCP was a disulfide-linked heterodimeric glycoprotein subunits with N- and O-glycosylation

Immunoregulatory

Pilose antler proteinase stimulated the proliferation of mouse spleen cells and inhibited the proliferation of T lymphocytes induced by Con A

[73]

Polypeptides

Unknown

The peptide consisted of 34 amino acids

Improving sexual

Pilose antler polypeptide increased the content of LH and T in the plasma of male rats and reduce the content of PRL in the plasma of female rats

[72]

Polypeptides (PSAB)

10–70

PSAB is a mixture of 5 proteins, which contains 17 amino acids

Anti-fatigue

PSAB enhanced the anti-fatigue effect and adrenal function of the body, protected the paint stressed mice, and increased the number of red blood cells and the content of hemoglobin

[75]

Semen cuscutae

Polysaccharides (C-7WR1, C-7WR2 and C-7WR3)

75.9; 32.3 and 22.5

Fructose, mannose (0.02:1) (C-7WR1); fructose, mannose, xylose, arabinose (0.01:1:0.14:0.33) (C-7WR2); fructose, mannose, xylose, arabinose (0.01:1:0.10:0.47) (C-7WR3). They mainly contained mannose and had no nucleic acid and protein

Nourishing kidney

S. cuscutae polysaccharides nourished kidney-yang by increasing the levels of testosterone and estradiol, decreasing the level of blood urea nitrogen, improving immune function, possessing antioxidant effect

[76]

Prunellae Spica

Polysaccharides (PSP-2B)

32

The major sugars of PSP-2B were arabinose, galactose and mannose, glucose and uronic acids. PSP-2B also contained 2.98% protein

Anti-virus

PSP-2B exhibits activity against herpes simplex virus (HSV)

[83]

Lonicera japonica

miR2911

Unknown

Unknown

Anti-virus

miR2911 in Lonicera japonica decoction can be fed into mice by gavage and play a direct role in influenza virus

[78]

Trichosanthis radix

Proteins (TCS)

24

TCS was a single-chain protein with 247 amino acid residues including a 23-amino acid N-terminal signal peptide and a 19-amino acid C-terminal pro-peptide

Anti-virus

TCS inhibited replication of human immunodeficiency virus type 1

[111]

Unknown

Unknown

Selective immunoregulatory

Non-cytotoxic concentrations of TCS suppress the activation, multiplication and differentiation of T and B cells but do not suppress the activation of natural killer cells

[82]

Anemarrhena asphodeloides

Polysaccharides (AABP)

1110

d-Mannose, l-rhamnose, d-galacturonic acid, d-glucose, d-galactose and l-arabinose (1:0.04:0.53:0.11:0.33:0.25)

anti-constipation

AABP could treat constipation by regulating the gastrointestinal hormones and neurotransmitters to improve intestinal motility and water metabolism

[84]

Rehmannia glutinosa

Polysaccharides (RGP)

63.5

Rhamnose, arabinose, mannose, glucose and galactose (1.00:1.26:0.73:16.45:30.40)

Anti-diabetes

RGP meliorated hyperglycemia, hyperlipemia, vascular inflammation and oxidative stress in STZ-induced diabetic mice

[86]

Unknown

Unknown

Immunoregulatory

RGP stimulated lymphocyte proliferation and the growth rate of T cell and IL-2 and IFN-γ production of T lymphocyte were significantly upregulated

[87]

Senna obtusifolia

Proteins

19.7

Its secondary structure has 12.5% α-helix, 55.6% β-sheet, and 31.9% random coil

Cholesterol lowering

Cholesterol-lowering protein inhibited cholesterol biosynthesis in Chinese hamster oocytes

[88]

Earthworm

EFE-III-1

700

Unknown

Thrombolysis

I-labeled fibrinogen showed that EFEs by oral administration had a significant fibrinolytic effect on clots in blood vessels

[92]

Salviae miltiorrhizae

Polysaccharides (SMP1)

550

Galactose, glucose, fucose, rhamnose, arabinose and mannose (1.0:1.2:0.3:1.5:1.3:1.9). SMP1 contained 91.3% of total carbohydrate, 2.81% of uronic acid and 4.34% of protein

Protection of cardiomyocytes

SMP prevented myocardial infarction induced by I/R by improving oxidative stress and inhibiting myocardial cell apoptosis

[93, 94]

Achyranthes bidentata

Polysaccharides (ABPB-3)

77.23

 → 4)-α-d-GalpA-(1 → , → 2,4)-α-l-Rhap-(1 → , → 5)-α-l-Araf-(1 → , → 2,3,5)-α -l-Araf-(1 → , → 3)-β-d-Galp-(1 → , → 3,4,6)-β-d-Galp-(1 → , terminated with α-l-Araf, α-LRhap and β-d-Galp

Anti-osteoporosis

ABP increased the bone mineral density, bone mineral content, trabecular thickness, trabecular number and biomechanical properties of ovariectomized (OVX) rats

[96]

Polysaccharides (ABW70-1)

 

(2 → 1)-linked-β-d-fructofuranosyl (Fruf), (2 → 6)-linked-β-d-Fruf and (2 → 1,6)-linked-β-d-Fruf residues, and terminated with fructose and glucose residue

ABW70-1 stimulated the osteogenic differentiation of MC3T3-E1 cells by promoting cell proliferation, ALP activity, mineral nodules formation and the gene expression of Osx, Ocn and Bsp.

[95]

Polysaccharides (ABP)

Unknown

Unknown

Anti-physical fatigue

ABP had clear anti-physical fatigue effects which extended the exhaustive swimming time of the mice, increased the liver glycogen and muscle glycogen contents and decreased the blood lactic acid and blood urea nitrogen contents

[20]

Gastrodia elata

Polysaccharides (PGEB-3H)

28.8

Glucose; α-1,4-glucan and α-1,4,6-glucan

Neuroprotection

PGEB-3H improved the learning and memory ability of mice with scopolamine-induced memory disorders by increasing the Ach content in brain tissue

[98]

Polysaccharides (PGE)

1540

Glucose; α-1,4-glucan, α-1,3-glucan andα-1,4,6-glucan

PGE was high-molecular-weight polysaccharide which exhibited Angiotensin-I converting enzyme (ACE) inhibitory activity. Its inhibition rate on ACE was calculated as 74.40% and the IC50 value was 0.66 mg/mL

[97]