Table 4.
The bioactivities and mechanisms of polysaccharides from fungal TCM.
| Bioactivity | Compound Name | Source | Subjects | Dose | Effects and Mechanism | Reference |
|---|---|---|---|---|---|---|
| Anti-tumor activity | Pachyman | Poria cocos | HepG2 human liver cancer cell and network pharmacology | 0, 25 and 50 μM | Pachyman exerted an anti-cancer activity by elevating the intracellular level of ALB protein and downregulating the cellular content of VEGFA protein | [85] |
| HPP | Polyporus | BBN-induced Fischer-334 rats and RAW 264.7, TPH-1 and T24 cells | 1, 10 and 100 μg/mL | HPP could inhibit bladder cancer in BBN-induced rats by ameliorating histological damages in bladder; improve the tumor inflammatory microenvironment by regulating TAM polarization and NF-κB/NLRP3 signaling pathway | [76] | |
| HPP | Polyporus | Phorbol myristate acetate-induced THP-1 human leukemic cell | 1, 10 and 100 μg/mL | HPP could confront bladder cancer through inhibiting the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, downregulating the JAK2/NF-κB signaling pathway | [86] | |
| CSP | Cordyceps sinensis | HCT116 cell line | 0–800 μg/mL | CSP could inhibit the proliferation of HCT116 cells by inducing apoptosis and autophagy flux blockage. It might be achieved by modulating PI3K-Akt-mTOR and AMPK-mTOR-ULK1 signaling pathways | [87] | |
| CCP | Cordyceps cicadae | Hela cells | 0, 25, 50, 100, 200, 400, 800 and 1600 μg/mL | CCP could inhibit the expression of Cyclin E, Cyclin A and CDK2, promote the expression of P53, activate Caspase cascade reaction, and up-regulate death receptor and the ratio of pro-apoptotic factor/anti-apoptotic factors to cause the cell cycle arrest and induce the apoptosis | [88] | |
| WCP | Wild Cordyceps | H22 tumor-bearing BALB/c mice | 100 and 300 mg/kg | The large molecular weight polysaccharide could inhibit the proliferation of H22 tumors by improving immune function and promoting the apoptosis of tumor cells, and mainly interfering with IL-10/STAT3/Bcl2 and Cytoc/Caspase8/3 signaling pathways | [89] | |
| WSG | Ganoderma lucidum | LLC1 cells induced lung cancer C57BL/6 mice | 75 mg/kg | WSG significantly prevented tumor growth and the formation of metastatic nodules in the lung tissue, and promoted the apoptotic responses mediated by cisplatin | [90] | |
| WSG | Ganoderma lucidum | Human tongue cancer SAS and HSC3 cells | 0–800 μg/mL | WSG increased subG1 and G2/M populations and elevated Bax/Bcl2 ratio to induce apoptosis; inhibited phosphorylation of EGFR and AKT | [91] | |
| GLPS | Ganoderma lucidum | Mouse RAW 264.7 macrophages and hepatocellular carcinoma cell line Hepa1–6 | 0–200 μg/mL | GLPS markedly prevented the growth of Hepa1–6 allograft; promoted the expression of M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines (IL-12a, IL-23a, IL-27 and TNF-α); blocked macrophage polarization towards the M2 phenotype; reduced the expression of CD206, Arg-1, IL-6 and IL-10; upregulated the phosphorylation of MEK and ERK, IκBα and P65 | [92] | |
| Anti-oxidant activity | PCPP | Poria cocos peels | In vitro | 1–5 mg/mL | PCPP has great anti-oxidant activity by scavenging DPPH radicals and reducing ABST radicals in a dose-dependent fashion | [93] |
| PPS | Polyporus umbellatus | In vitro | 1–8 mg/mL | PPS has the significant scavenging ability of DPPH free radicals and hydroxyl free radicals | [94] | |
| PPS | Polyporus umbellatus | In vitro | 0.5–8 mg/mL | PPS exhibits the significant scavenging ability on DPPH and other free radicals in a dose-dependent manner | [58] | |
| Immunomodulatory activity | CMP | Poria cocos | RAW 264.7 | 12.5, 25, 50, 100, 200 and 400 μg/mL | CMP plays a crucial role in immunoregulation by improving the secretions of iNOS, TNF-α and IL-6 through increasing the expression of iNOS, TNF-α and IL-6 mRNA | [95] |
| AESP-II | Cordyceps militaris | Cyclophosphamide-induced BALB/c mice | 25, 50 and 100 mg/kg | AESP-II could promote the proliferation of spleen T and B lymphocytes, increase the levels of cytokines and immunoglobulin secreted by T and B lymphocytes, and activate the MAPK signaling pathway to involve in the immunomodulatory function | [70] | |
| CSP | Cultured Cordyceps sinensis | Cyclophosphamide-induced female BALB/c mice | 25, 50 and 100 mg/kg | CSP inhibited immunosuppression in mice via stimulating cytokines secretion (IL-12, IFN-γ, IL-4, IL-13, IL-6, IL-10, IL-17, TGF-β3, TNF-α, IL-2, IL-21) and transcription factors production (T-bet, GATA-3, RORγt, Foxp3), upregulating TLRs and NF-κB pathway key proteins | [96] | |
| CCSP-2 | Cordyceps cicadae | Cyclophosphamide-induced immunosuppressive C57BL/6 mice | 50, 100 and 200 mg/kg | CCSP-2 significantly increased spleen and thymus indices, enhanced macrophage phagocytic activity, stimulated splenocyte proliferation, improved natural killer cytotoxicity and bone marrow suppression, regulated the secretion of cytokines and immunoglobulins and modulated antioxidant enzyme system | [97] | |
| Hypolipidemic activity | PCP | Poria cocos | High-fat diet-induced mice | 1.5 g/day | PCP significantly reduced serum and hepatic lipid levels, and altered metabolic pathways including fatty acid metabolism, bile acid metabolism and tricarboxylic acid cycle | [98] |
| CM3-SII | Cordyceps militaris | Heterozygous low-density lipoprotein receptor (LDLR)-deficient hamster | 25, 100 mg/kg | CM3-SII attenuated total plasma cholesterol, non-high-density lipoprotein cholesterol and triglyceride; enhanced the concentration of plasma apolipoprotein A1 and the expression of liver X receptor α/ATP-binding cassette transporter G8 mRNA pathway and suppressed the expression of Niemann-Pick C1-like 1; downregulated sterol regulatory element-binding protein 1c and upregulated peroxisome proliferator-activated receptor α; increased the abundance of Actinobacteria and Faecalibaculum and the ratio of Bacteroidetes/Firmicutes. | [99] | |
| CM1 | Cordyceps militaris | 3T3-L1 cell; LDLR(+/−) hamsters | 100 μg/mL; 100 mg/kg | CM1 alleviated hyperlipidemia by downregulating the plasma level of apolipoprotein B48, modulating the expression of key genes and proteins in liver, small intestine and epididymal fat, and inhibiting preadipocyte differentiation in 3T3-L1 cells by suppressing the key genes involved in lipid droplet formation | [100] | |
| SeCMP | Cordyceps militaris | High-fat diet-fed C57BL/6 mice | 50, 100 and 200 mg/kg | SeCMP-200 showed significantly hypolipidemic activity by decreasing serum triglyceride and low-density lipoprotein cholesterol, ameliorating obese-induced inflammation, decreasing the abundance of Dorea, Lactobacillus, Clostridium, Ruminococcus and increasing mucosal beneficial bacteria Akkermansia | [101] | |
| GLP | Ganoderma lucidum | High-fat diet-induced Kunming mice | 100, 200 and 400 mg/kg | GLP inhibited the body weight gain and excessive lipid levels, ameliorated tissue injury; activated Nrf2-Keap1 and suppressed NF-κB signaling pathway; facilitated cholesterol reverse transport by LXRα-ABCA1/ABCG1 pathway; promoted the expression of CYP7A1 and CYP27A1; inhibited intestinal FXR-FGF15 expressions | [102] | |
| Hypoglycemic activity | EPS-III | Cordyceps militaris | STZ-induced diabetic KM mice | 60, 120 and 225 mg/kg | EPS-III exerted significantly hypoglycemic effect through alleviating weight loss, reducing plasma glucose concentration, improving glucose tolerance, protecting immune organs and repairing dyslipidemia | [69] |
| AEPSa | Cordyceps militaris | High-fat diet and STZ-induced C57BL/6 mice | 400 mg/kg | AEPSa ameliorating diabetes through increasing Allobaculum, Alistipes, Lachnospiracae_NK4A136_group and norank_f_Muribaculaceae and decreasing Enterococcus and Ruminococcus_torques_group, inhibiting TLR4/NF-κB pathway | [103] | |
| SPP | Cordyceps cicadae | HepG2 cells and T2DM KM mice | 100, 200 and 400 mg/kg | SPP significantly increased glucose absorption and alleviated insulin resistance in HepG2 cells; SPP exerted hypoglycemic effect through activating PI3K/Akt signaling pathway to reduce hepatic insulin resistance | [67] | |
| CMP | Cordyceps militaris | High-fat/high-sucrose diet-induced C57BL/6 mice | N/A | CMP played a crucial role in the hypoglycemic effect by promoting the population of next generation probiotic Akkermansia muciniphila in the gut | [104] | |
| F31 | Ganoderma lucidum | High fat diet and STZ-induced type 2 diabetic Kunming mice | 60 and 180 mg/kg | F31 markedly decreased Firmicutes and enhanced the abundance of Bacteroidetes. Specifically, F31 may ameliorate glucose, insulin resistance and inflammation by inhibiting the release of endotoxins into the circulation from intestine, carbohydrate fermentation in gut and activation of intestine–brain axis | [105] | |
| F31 | Ganoderma lucidum | C57BL/c and db/db mice | N/A | F31 ameliorated hyperglycemia through different approaches: decreased adenosine, galactitol and glycerophosphocholine and increased arginine, proline, arachidonic acid, creatine, aspartic acid, leucine, phenylalanine and ornithine to protect kidney function; increased Caspase-3, Caspase-6 and Bax and inhibited Bcl-2 to promote apoptosis in epididymal fat; reduced mitochondrial membrane potential to induce adipocyte apoptosis | [106] | |
| Hepatoprotective activity | PCP-1C | Poria cocos | Alcohol-induced C57BL/6N mcie | 25, 50 and 100 mg/kg | PCP-1C exerted a hepatoprotective action by decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and ameliorating intestinal barrier injury | [107] |
| GLP | Ganoderma lucidum | C57BL/6 mice and rat HSC-T6 hepatic stellate cell line | 150 and 300 mg/kg; 0, 1.25, 2.5, 5, 7.5 and 10 mg/mL | GLP dramatically ameliorated hepatic fibrogenesis and inflammation by TLR4/NF-κB/MyD88 signaling pathway; blocked HSCs activation by reducing collagen I and a-SMA expressions; suppressed cell cycle; induced S phase arrest; inhibited the ECM-receptor interaction-associated molecule expressions (ITGA6 and ITGA8); restrained TGF-β/Smad signaling pathway in mice; decreased TGF-β1, Smad2 and Smad3 phosphorylation and promoted Smad7 expression in HSC-T6 cells | [108] | |
| Modulation on gut microbiota | WIP | Wolfporia cocos | Alcohol-induced C57BL/6 mice | 1 g/kg | WIP significantly enhanced the ratio of Firmicutes to Proteobacteria, increased the abundance of Lachnospiraceae and inhibited the ethanol-induced fungal overgrowth. It activated the PPAR-γ signaling pathway and facilitated a hypoxic state that suppressed the overgrowth of fungi and Proteobacteria in the gut | [109] |
| PCP | Poria cocos | High-fat diet-induced nutritionally obese SD rats | 50, 100 and 200 mg/kg | PCP could regulate intestinal flora structure by increasing the relative abundance of Prevotella, Bacteroides and Sutteralla, and decreasing the ratio of Firmicutes/Bacteroidetes and the relative abundance of Morganella | [110] | |
| CSP | Cultured Cordyceps sinensis | Cyclophosphamide-induced female BALB/c mice | 25, 50 and 100 mg/kg | CSP regulated gut microbiota through recovering SCFAs levels, improving microbial community diversity, modulating the overall structure of gut microbiota, increasing the abundance of probiotics (Lactobacillus, Bifidobacterium and Bacteroides) and decreasing pathogenic bacteria (Clostridium and Flexispira) | [96] | |
| CMP | Cordyceps militaris | High-fat diet-induced C57BL/6 mice | 200 and 400 mg/kg | CMP significantly improved the high-fat diet-induced gut microbiota dysbiosis, increased the abundance of Alloprevotella, Parabacteroides, Butyricimonas and Alistipes, and decreased the abundance of Negativebacillus | [111] | |
| GLP | Ganoderma lucidum | C57BL/c mice | N/A | GLP elevated the abundances of probiotic bacteria including Lachnospiraceae NK4A136, Ruminococcaceae UGG-014, Lactobacillus and Parabacteroides. | [112] | |
| BSGLP | Sporoderm-broken spores of Ganoderma lucidum | C57BL/6J mice | 100 and 300 mg/kg | BSGLP improved gut microbiota dysbiosis; maintained intestinal barrier function; promoted short-chain fatty acid production and GPR43 expression; inhibited serum lipopolysaccharide level; augmented ileum expression of tight junction proteins and antimicrobial peptides; inhibited TLR4/MyD88/NF-κB signaling pathway in adipose tissue | [113] | |
| Anti-inflammatory activity | PCP | Poria cocos | Arteriosclerosis in ApoE−/− mice | 100, 200, 400 mg/kg | The serum inflammatory mediators and lipids were inhibited; the pathological changes of the aorta were improved and the activation of TLR4/NF-κB pathway of the aorta was inhibited | [115] |
| PPs | Poria cocos | Chronic nonbacterial prostatitis in SD rats | 100, 250, 500 mg/kg | PPs plays the role of anti-chronic nonbacterial prostatitis via alleviating inflammation and oxidative stress, regulating hormone production, modifying gut microbiota and remodeling the DNA methylome | [117] | |
| PPs | Poria cocos | Chronic nonbacterial prostatitis in SD rats | 250 mg/kg | PPs alleviates the chronic nonbacterial prostatitis by improving the histological damages in the inflamed prostate, inhibiting inflammation and regulating the gut microbiota by targeting Ruminococcaceae NK4A214 group | [118] | |
| PPs fermentation broth | Poria cocos | Chronic nonbacterial prostatitis in SD rats | 250 mg/kg | It is proved that the metabolites of PPs 7-ketodeoxycholic acid and haloperidol glucuronide may be the signal molecules of the “gut-prostate axis” | [119] | |
| CMP | Poria | Ulcerative colitis in ICR female mice | 300 mg/kg | CMP alleviated ulcerative colitis in mice through inhibiting colonic shortening and inflammation in colonic tissues, and regulating gut microbiota | [120] | |
| PCP | Poria cocos | Nonalcoholic steatohepatitis in C57BL/6 mice | 150 and 300 mg/kg | The mechanism of PCP in preventing the development of NASH may be associated with the modulation of intestinal microbiota and the downregulation of the NF-κB/CCL3/CCR1 axis | [121] | |
| PCP | Poria cocos | Nonalcoholic steatohepatitis in C57BL/6 J mice and zebrafish | 50, 100 and 200 mg/kg | PCP could slow down weight gain, hyperlipidemia and liver steatosis induced by high-fat diet; reduce the destruction of the gut-vascular barrier and the translocation of endotoxins; inhibit intestinal pyroptosis by regulating PARP-1 | [122] | |
| CM1 | Cordyceps militaris | Low-density lipoprotein receptor knockout (LDLR−/−) mice | 25, 50 and 100 mg/kg | CM1 could reduce plasma lipid level and formation of atherosclerotic plaques through multiple pathways, enhanced plasma level of apolipoprotein A-I, decreased the levels of triglyceride, apolipoprotein B and total cholesterol, inhibited sterol regulatory element binding protein 1c, increased the liver X receptor α/ATP-binding cassette G5 pathway, inhibited PPAR-γ and adipose triglyceride lipase in epididymal fat | [116] | |
| GLPs | Ganoderma lucidum | High-fat diet-induced Japanese big-ear white rabbits | 300 mg/kg | GLPs could prevent the progression of atherosclerosis through improving endothelial dysfunction and inflammatory polarization of macrophages, accelerating the apoptosis of foam cells | [123] | |
| GLP | Ganoderma lucidum | AOM/DSS-induced C57BL/6 mice | 200 and 300 mg/kg | GLP ameliorated microbiota dysbiosis; promoted short-chain fatty acid production; inhibited TLR4/MyD88/NF-κB signaling pathway; increased numbers of goblet cells, MUC2 secretion, tight junction protein expressions; inhibited macrophage infiltration and IL-1β, iNOS, COX-2 expressions; inhibited the activation of MAPK | [23] | |
| Other activities | PCPP | Poria cocos peels | AML-12 liver cell/60Co-γ induced KM mice | 50–400 μg/mL/5, 10 and 20 mg/kg | PCPP exerts a significantly radiation protection effect through ameliorating the damage of spleen and liver, improving the damage of hematopoietic system by regulating erythrocytes, platelets and hemoglobin and decreasing the degree of oxidative damage | [93] |
| PPS | Polyporus | Bleomycin-induced lung fibrosis C57BL/6 mice and human lung fibroblasts cell line | 100 mg/kg; 1 mg/mL | PPS significantly improved bleomycin-induced lung fibrosis in mice through ameliorating pathological damages of lung tissues; it exerted antifibrotic effects in vitro via inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, repressing lung fibroblast proliferation and migration, suppressing TGF-1β-induced Smad2/3 activating | [125] | |
| RLSP | Lasiophaere fenzlii | In vitro | 0.1, 0.01 and 0.001 mg/mL | RLSP possessed an inhibitory effect on both Staphylococcus aureus and Escherichia coil | [126] | |
| CPA-1 and CPB-2 | Cordyceps cicadae | High fructose/high fat diet induced obesity and metabolic disorders rats | 100 and 300 mg/kg | These two polysaccharides regulated metabolic disorders through inhibiting insulin and glucose tolerance, serum insulin and glucose levels, reducing serum and hepatic lipid profiles, liver function enzymes and pro-inflammatory cytokines, suppressing hepatic oxidative stress and hepatic lipid accumulation | [127] | |
| CMP | Cordyceps militaris | Ovalbumin-induced allergic asthma BALB/c mice | 50, 100 and 200 mg/kg | CMP showed significantly anti-allergic asthma effects through improving inflammatory cytokine levels, ameliorating the histopathological damages, regulating oxidative and inflammatory pathways, reversing gut dysbiosis and improving microbiota function | [128] | |
| CMP | Cordyceps militaris | High-fat diet-induced C57BL/6 mice | 400 mg/kg | CMP showed a promising ability to protect mice from obesity through ameliorating systematic inflammation, restoring the phylogenetic diversity of gut microbiota, increasing the relative abundance of short-chain fatty acid-producing bacteria, down-regulating the level of bacteria, which were positively related to the development of obesity | [129] | |
| CMPB | Cordyceps militaris | ICR mice | 400 and 800 mg/kg | CMPB significantly decreased fatigue metabolites and oxidative stress, increased the expression level of BDNF, PI3K, Nrf2 and HO-1 in the hippocampus | [130] | |
| GLP-1 | Ganoderma lucidum | Chronic cerebral hypoperfusion mice | N/A | GLP-1 improved cognitive impairment mice by elevating the levels of Foxp3+ Treg cell and inhibiting energy metabolism disorder | [26] | |
| GLP | Ganoderma lucidum | C57BL/6 mice and CD1 mice | 1, 5 and 12.5 mg/kg | GLP inhibited the expression of IL-1β and TNF-α; promoted the expression of IL-10 and BDNF; prevented the activation of microglia and proliferation of astrocytes in hippocampus; increased the expression of GluA1 S845 phosphorylation as well as GluA1 and GluA2 expression levels | [131] | |
| GLPs | Ganoderma lucidum | Ethanol-induced acute gastric injury SD rat | 100, 200 and 400 mg/kg | GLPs diminished the gastric injury in a dose-dependent manner through regulating anti-oxidation, inhibiting inflammation and decreasing the expression of histamine in serum | [132] | |
| GLP | Ganoderma lucidum | LPS-induced sepsis C57BL/6J mice | 25 mg/kg | GLP could elevate the expression of SIRT1, decreased inflammatory factors in serum and inflammatory cells in heart tissues, blocked apoptosis and facilitated proliferation of myocardial tissues | [133] | |
| Liz-H | Ganoderma lucidum | Cisplatin plus docetaxel induced cachexia C57BL/6J mice | 250 mg/mouse | Liz-H could block weight loss, muscle atrophy and neutropenia; downregulate muscle protein degradation-related genes (MuRF-1 and Atrogin-1); increase myogenic factors (MyoD and myogenin); restore the abundance of Ruminococcaceae and Bacteroides to normal levels | [134] | |
| GLP | Ganoderma lucidum | D-galactose-induced C57BL/6J mice | N/A | GLP increased the expression levels of AQP5, AQP4, AQP1; blocked the release of inflammatory factors; upregulated core clock genes and proteins; restored the co-localized expression of CLOCK and AQP5 | [135] | |
| GLP | Ganoderma lucidum | LPS-induced C57BL/6N mice | 25, 50 and 100 mg/kg | GLP inhibited inflammatory cell infiltration; reduced the expression levels of GM-CSF, IL-6, IL-1β, TNF-α and Saa3; blocked the activation of NRP1; promoted the expression of Bcl2/Bax and LC3; decreased the ratio C-Caspase 3/Caspase 3 and P62 expression | [124] | |
| GLP5 | Ganoderma lucidum | Human acute T cell leukemia cell line | 25 and 50 mg/L | GLP5 notably suppressed the proliferation of Jurkat cells; increased the expression levels of Caspase3; regulated the expression levels of Bax and Bcl-2 | [136] | |
| CSP | Cordyceps sinensis | Dextran sodium sulfate-induced C57BL/6J mice | N/A | CSP significantly increased the colon length; improved colon tissue damage; inhibited the activation of NF-κB pathway; decreased the expressions of inflammatory cytokines; augmented the number of goblet cells; regulated the expressions of intestinal tight junction proteins (Occludin and Claudin-1); promoted the formation of IgA-secretory cells and sIgA contents | [137] | |
| CMPS-80 | Cordyceps militaris | Apolipoprotein E-deficient mice | N/A | CMPS-80 dramatically blocked formation of atherosclerotic lesions and plasma lipid profiles; regulated multiple lncRNA-microRNA-mRNA axes | [138] |