Table 1.

Biological activities of biomacromolecules based on its traditional efficacy

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]