Table 4. Pharmacology of CK.
| Biological activities | Models | Targets | Description | Ref. |
|---|---|---|---|---|
| Anti-inflammatory and anti-allergic effects | LPS-induced RAW264.7 and HEK293 | iNOS, COX-2 | CK inhibited the production of NO and PGE2 | (11) |
| Dectin-1,ROS | CK inhibited the production of systemic inflammatory cytokines | (96) | ||
| IRAK-1, IKK-β, NF-κB | CK inhibited the production of proinflammatory cytokines | (97) | ||
| AKT1 | CK inhibited the production of IL-1β, IFN-β, and TNF-α | (98) | ||
| Oxazolone-induced mouse dermatitis | COX-2, Th cells | CK inhibited the production of IFN-γ, and IL-4 | (12) | |
| LPS-induced lethal shock | TLR4/LPS, NF-κB, MAPK | CK reduced the levels of systemic inflammatory cytokines in mice and reversed the fatal sequelae of sepsis | (99) | |
| Collagen-induced arthritis | CCL21/CCR7 | CK suppressed T-cell priming | (100) | |
| β-arrestin1, AP2 | CK inhibited the activity of B cells | (101) | ||
| β-arrestin2, Gαi, TLR4, NF-κB | CK regulated macrophage function | (102) | ||
| TCR, CD28, CTLA-4, PD-1 | CK suppressed the abnormal activation of T lymphocytes | (103) | ||
| Adjuvant-induced arthritis | memory B cells, T cells | CK downregulated memory B cells | (104) | |
| TNF-α, TNFR 2, GR | CK inhibited proliferation, migration, and secretion of FLS | (105) | ||
| T cells | CK suppressed T cell activation (T cell proliferation, CD25 and IL-2) | (106) | ||
| B cells, macrophages | CK affected the function of immune cells and effector cells (FLS) to attenuate inflammatory responses | (107) | ||
| DSS-induced colitis rats | PXR/NF-κB | CK targeted PXR/NF-κB interactions to cause anti-inflammatory effects without damaging PXR function in healthy rats | (108) | |
| NF-κB | CK promoted the recovery of the progression of colitis and inhibited pro-inflammatory cytokine production | (109) | ||
| IMQ-induced psoriasis mice | REG3A/RegIIIγ | CK inhibited keratinocyte proliferation and ameliorated psoriasis-like hyperkeratosis | (110) | |
| TNF-α-induced astroglial cells | NF-κB, JNK | CK inhibited the production of VCAM-1 induced by TNF-α | (111) | |
| U937, RAW264.7 cells | NF-κB, AP-1 | CK had an immunomodulatory role in innate immune responses | (63) | |
| Anti-diabetic effects | db/db mice | plasma adiponectin | CK enhanced insulin secretion | (10,112) |
| MIN6 pancreatic β-cells | GLUT2 | CK enhanced insulin secretion | (113) | |
| HFD/STZ-induced T2DM, HepG2 | PEPCK, G6Pase | CK suppressed gluconeogenesis | (114) | |
| PI3K/Akt | CK suppressed insulin resistance | (115) | ||
| AMPK | CK suppressed gluconeogenesis | (116) | ||
| High glucose-induced 3T3 adipocytes | ER stress, NLRP3 inflammasome | CK improved insulin signaling | (117) | |
| 3T3-L1 adipocytes | GLUT4, AMPK, PI3K | CK stimulated glucose uptake | (118) | |
| Palmitate-induced damage of MIN6 cells | AMPK/JNK | CK protected pancreatic islet cells against apoptosis | (119) | |
| NCI-H716 | bile acid receptor, GLP-1, TGR5 | CK stimulated GLP-1 secretion | (120) | |
| High-fat diet/streptozotocin-induced diabetic mice | NLRP3 inflammasome, NF-κB/p38 | CK had a protective effect on diabetic nephropathy | (121) | |
| Neuroprotective effects | LPS-induced microglia, Sepsis and cerebral ischemia mouse models | NF-κB /AP1 | CK reduced the volume of ischemic cerebral infarction and inhibited microglial cell activation | (16) |
| CCH rats | pser9-gsk-3, IDE PKB/Akt | CK attenuated cognitive deficits | (122) | |
| Primary astrocytes | mTOR | CK enhanced autophagy to promote Aβ-clearance | (123) | |
| Scopolamine hydrobromide-induced memory impaired mouse | Nrf2/Keap1, Aβ | CK reduced oxidative damage to neurons, inhibited neuronal apoptosis, and improved memory function | (65) | |
| HT22 cells | GLUT, ATP | CK adjusted energy metabolism to inhibit neuronal damage | (124) | |
| Behavioral despair model and CUMS model in mice or rats | 5-HT, DA, BDNF, NGF | CK enhanced antioxidant capacity and increased neurotrophic protein expression | (125) | |
| CA3 pyramidal neurons | GABA | CK inhibited the transmission of CA3 pyramidal neurons, affected hippocampal mediated physiological functions | (27) | |
| African xenopus oocytes | GABAC Receptor | CK inhibited GABA-induced introverted peak current (IGABA) | (126) | |
| Pentylenetetrazole or lithium chloride-rutin-induced epilepsy rats | GABA, GABAAR | CK promoted the release of GABA and enhanced GABAA-mediated inhibitory synaptic transmission | (127) | |
| Menopausal depressive-like state in female mice | 5-HT2A | CK improved depressive-like state | (128) | |
| Anti-angiogenesis effects | bFGF-induced HUVECs | p38, AKT | CK inhibited bFGF-induced angiogenesis | (13) |
| S1P-induced HUVECs | SPHK1, MMP | CK inhibited HUVECs migration | (129) | |
| TNF-α-induced monocyte-endothelial cells | VCAM-1, NF-κB | CK blocked leukocyte endothelial interactions and transport. | (130) | |
| ox-LDL-induced injury in HUVECs | NF-κB, p38MAPK, JNK | CK prevented inflammation and apoptosis | (131) | |
| PDGF-BB-induced VSMC | CDK2, CDK4, cyclinE, cyclinD1, MMP-2, MMP-9 | CK inhibited abnormal VSMC proliferation and migration | (132) | |
| I/R-induced mice | Akt/PI3K, eNOS | CK induced cardiac protection | (133) | |
| I/R-induced H9C2 cells | PI3K/Akt | CK inhibited autophagy-mediated apoptosis | (134) | |
| Anti-aging effects | HaCaT cells, hairless mice | HAS2 | CK increased the production of HA | (14) |
| TNF-α-stimulated dermal fibroblasts | MMP-1, c-Src, ERK, AP-1 | CK inhibited collagen degradation | (135) | |
| UV- irradiated HaCaT cells | XPC, ERCC1 | CK suppressed apoptosis by inducing DNA repair | (136) | |
| UVB- irradiated NIH3T3 cell | MMP-1, COX-2, HAS-1 and -2 | CK increased the production of HA and type I procollagen | (67) | |
| UVA-irradiated fibroblasts | MMP-1 | CK up-regulated the production of type I procollagen | (137) | |
| Hepatoprotective effects | APAP-induced liver injury in rats | JNK | CK alleviated hepatotoxicity | (15) |
| SVP-induced hepatotoxicity in rats | sHE, iron homeostasis | CK alleviated hepatotoxicity | (68) |
CK, Ginsenoside compound K; TNF, tumor necrosis factor; iNOS, inducible nitric-oxide synthase; COX-2, cyclooxygenase; AKT, Serine/threonine protein kinase; IRAK, interleukin-1 receptor-related kinase; IKK-β, inhibitor of nuclear factor kappa-B kinase; TLR, toll like receptor; CCL, CC chemokine ligand; CCR7, chemokine receptor; AP2, adaptor protein 2; LPS, lipopolysaccharide; IL, interleukin; IFN, interferon; Gαi, guanine nucleotide-binding protein subunit alpha; TCR, T cell receptor; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CD28, cluster of differentiation 28; PD-1, programmed cell death protein 1; TNFR 2, tumor necrosis factor receptor; GR, glucocorticoid receptor; FLS, fibroblast-like synovial; PXR, progesterone X receptor; GLUT2, glucose transporter protein 2; PEPCK, phosphoenolpyruvate carboxy kinase; G6Pase, glucose 6-phosphatase; ER stress, endoplasmic reticulum stress; NLRP3, NOD-like receptors; GLP-1, glucagon-like peptide-1; TGR5, G protein-coupled receptor 5; Nrf2, nuclear factor E2-related factor 2; Keap1, Keleh-like ECH-associated protein l; GABA, gamma-aminobutyric acid; 5-HT, serotonin; GABAAR, gamma-aminobutyric acid-A receptor; S1P, sphingosine-1-phosphate; Ox-LDL, oxidized low density lipoprotein; PDGF-BB, platelet-derived growth factor; SPHK1, sphingosine kinase 1; VCAM-1, vascular cell adhesion molecule 1; HA, hyaluronic acid; HAS, hyaluronic acid synthase; XPC, Xeroderma pigmentosum-C; ERCC1, excision repair cross-complementation group 1; APAP, acetaminophen; SVP, sodium valproate.