Table 2 Functional effects of BG in vitro, in vivo and human studies
From: The functional evolution of Korea ginseng: black ginseng
Function | Model | Treatments (Dose/Period) | Target/Mechanisms | References |
|---|---|---|---|---|
Antioxidant | Whole embryo culture | BG EtOH (1, 10, 100ug/ml;2 days) | mRNA antioxidant enzymes (GPx) ▲ | [46] |
PERK & XBP1 KO MEF cells | BG Ext with high Rb1, Rg3 & Rk1 (0, 10, 50, 100, 200 ug/ml) | H2O2-induced ROS, NO, INOS ▼ | [43] | |
Zebrafish | BG (0, 1, 10, 50, 100, 200 µg/mL) | H2O2-induced ROS, ▼ | [43] | |
NAFLD mice | Rb1, Rg3 and Rk1-rich-BG (0.5,1, 2%) | ER stress markers ▼ Glutathione, catalase ▲ | [44] | |
H2O2- -induced AML-12 hepatocytes | Rg3/CpK/Rg5-rich BG | BG enhanced antioxidant activity with ROS scavenging compared to WG and RG, and inhibited apoptosis | [41] | |
Chemical assay | RK3, Rh4, 20(S)/(R)-Rg3 rich BG (0-10 mg/ml) | DPPH scavenging activity ▲ | [112] | |
Human embryonic kidney (HEK)-293 cells | Rk1-rich BG | GSH, lipid peroxidation (MDA) ▼ Nrf2, HO-1 ▲ Bax, cleaved caspase-3/caspase-9 ▼ | [47] | |
Hepatotoxic mice | Rg5 (10 or 20 mg/kg, 7 days) | With 4-HNE/CYP2E1 expression, oxidants removed in acetaminophen (APAP)-induced hepatotoxic mice (COX-2/iNOS)▲ Bax, cleaved caspase-3/caspase-9 ▼ | [44] | |
AlCl3 Induced Osteoporosis rat | Rg3-rich BG | ROS, MDA ▼ GPx and SOD activities ▲ Bone formation▲ (with Ca, P, type I collagens, osteocalcin, bone alkaline phosphatase) | [48] | |
Anti-inflammation | LPS-induced RAW 264.7 | High-Rg1/Rb1-RG and high-Rg5 -BG | BG decreases iNOS & COX-2 and pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α | [54] |
CS/LPS-exposed animals | BG Ext (20,50, 100 mg/Kg) | Smoking-induced inflammation markers (TNF-α, IL-6, MCP-1, elastase, TAK-1) ROS ▼ | [55] | |
NAFLD mice | Rb1, Rg3 and Rk1-rich-BG (0.5,1, 2%) | IL-6, CCAAT/CHOP, binding immunoglobulin protein (BiP) ▲ | [43] | |
SD-rats with heat stress | JP5(100,300 mg/Kg)/BG1(100,300 mg/Kg) | ROS and catalase, GR, GPx, SOD2 감소 JNK-MAPK signals (Caspase1, BCl2) ▼ p-NF-κB/TNF-α and NLRP3 inflammasome ▼ | [52] | |
Heat-stressed HepG2 cells | Rg5/Rk1 (1,25,50ug/ml) | |||
Human (n = 180) | BG Ext (KGR-BG1 1500 mg 6 wks) | No significant differences were observed in the head, face and body temperature No changes on inflammation, glucose metabolism and lipid metabolism | [56] | |
Human leukemia THP-1 (monocytic) and EoL-1 (eosinophilic) | BG extract (radix/leaf) | IL-6, IL-8 and MCP-1 secretion ▼ in D. pteronissinus-induced THP-1 and EoL-1 cells Effective in atopic dermatitis | [58] | |
Chemo-prevention | 6 human cancer cell lines | Rg5 &Rg3-rich BG | BG was higher cytotoxicity than RG in all six cell lines higher efficacy in Rg5 than Rg3 | [61] |
Ovarian cancer cells (SKOV-3) bearing mice | Rg3 (0.3–3.0 mg/kg) IP injection (tumor-bearing mice) | Tumor-induced angiogenesis ▼ (by reduction of MMP-9 expression_ | [65] | |
Colon26-M 3.1 cells/macrophages | WG (2000ug/ml) Rg3, Rh1 and Rh2-rich BG (800ug/ml) | Antitumor & anti-inflammatory effects (TNF-α, IL-1β and IL-6) ▲ | [66] | |
10 types of cancer; in vitro & in vivo | CK | Apoptosis, autophagy, antiangiogenesis ▲ in 10 types of cancer such as lung, liver, breast, colorectal, brain, leukemia, bladder, nasopharyngeal, ovarian and renal cancer | [67] | |
A375-S2 human melanoma cells | Rh2 | Cell growth▼ G-Rh2-induced apoptosis is partially dependent on caspase-8 and caspase-3 pathway | [68] | |
Leukemia cells (THP-1) | Rh1/Rh2 vs Rg3 | PPD/PPT aglycone (Rh1/Rh2) increases apoptosis with releasing LDH, not in Reg3 | [69] | |
14 cancer cell lines (Hela cervical) | Rh2 | Caspase-8 and caspase-9 ▲ Death receptors Fas and TNFR1 ▲ P53-dependent Fas involved in apoptosis process via capase-8/-9 activation | [70] | |
Human MCF-7 breast cancer cells | 2-Deoxy-Rh2 (LC50; 32.6uM) vs 20(S)Rh2 (IC50; 45.22uM) | Deoxy-Rh2 Apoptosis, ROS production ▲ - Glucose uptake & intracellular ATP production, cellular O2 consumption ▼ | [71] | |
SD rats | Rg5 and 20(S)-Rg3-rich BG 28 days | Set up NOAEL of BG extract 2000 mg/Kg | [72] | |
Anti obesity | 3T3-L1 | Rg-rich BG (30, 50, 100 uM) | PPAR-γ, CEBPa, FAS, FABP4, perilipin▼ | [78] |
DIO-beagle dogs | HF + BG (12 Ws) | Nine obesity genes (NUGGC, EFR3B, RTP4, ACAN, HOXC4, IL17RB, SOX13, SLC18A2 and SOX4) ▼ Gut microbiome regulation | [75] | |
Rats | Rg3-rich BG (100 mg/Kg/d for 3wks) | Weight gain, epididymal/abdominal fats and plasma TG▼ More effective than WG & RG | [77] | |
3T3-L1 & High fat diet-induced obesity (DIO) rats | Rh1(20 mg/kg) | PPAR-γ, C/EBP-α, FAS and aP2▼ Weight gain, epididymal/abdominal fats and plasma TG▼ F4/80, CD68, TNF-α, IL-6 and IL-1β▼ | [79] | |
3T3-L1 | Rb1-rich BG | Adipogenic genes (C/EBPα, SREBP-1c) ▼ Browning markers (PRDM16, PGC-1α, & UCP1) ▲ | [80] | |
3T3-L1/RAW 264.7 or Stem cells | Rh1, Rg2 and Rb1-rich BG EtOH | PPAR-γ, C/EBPα and pAMPK regulation IL-10 ▲ MCP-1 ▼ Doubling time of stem cells in subcutaneous fat ▲ Ratio of M1/M2 macrophages ▼ | [20] | |
Circulation (glucose & lipid metabolism) | Rattus beta cells | Rg3, Rb1, Rg1, Rg5 and CK | Activation insulin secretion with increasing AMPK | [87] |
HIT-T15, & MIN6 cells | CK | Activation insulin secretion in a beta cell line and Mouse Insulinoma MIN6 pancreatic β-cell | ||
db/db mice | BG EtOH GBG05-FF(300, 900 mg/Kg for 4 wks) | Plasma lipids ▼ Glucose homeostasis & glucose uptake ▲ HbA1c ▼ Lipid accumulation/liver damage ▼ p-AMPK (liver), GLUT2( liver), GLUT4 (muscle) ▲ | [91] | |
C2C12 myotubes | BG EtOH GBG05-FF | Increased glucose uptake via AMPK, Sirt1 and PI3-K pathway | [92] | |
STZ-induced diabetic mice | BG EtOH GBG05-FF | PEPCK, G6Pase, LG, GS expression ▼ GLUT1, GLUT4, ACO CPT1a MCAD ▲ | [92] | |
STZ-induced insulin-deficient diabetic mice | BG-High Rg5 & CKs(200 mg/kg) | Hyperglycemia ▼ Insulin/glucose ratio and β-cell function by NFkB suppression ▲ Better than RG for antidiabetic effect | [90] | |
High fat/STZ-induced diabetic nephropathy mice | BG-High Rg5 (30, 60 mg/kg/d) | Rg5 is a potential compound to prevent or control diabetic renal injury Biomarkers for insulin resistance, oxidative stress, renal histopathology and inflammation ▼ | [93] | |
Type 2 db/db mice | BG-High Rh4, Rg5 and Rk1 (100,900 mg/kg BW) | Antihyperglycemic & hypolipidemic effects Insulin resistance, ROS, adipogenesis, GLUT-4 &-2 ▼ | [95] | |
Heart failure rats | BG saponins (30, 60, 120 mg/Kg BW) | p-Akt/Akt & p-mTOR/mTOR ▲ Beclin1, p62 & LCII/LC3I ▼ | [97] | |
High-cholesterol diet SD rats | BG EtOH(200 mg/kg) | TC and LDL levels ▼ Lipogenesis genes; CoA acetyltransferase, HMG-CoA reductase, SREBP2 ▼ | [97] | |
Anti aging | C2C12 myoblasts | BG (0.1, 1, 10,20 ug/ml) | Akt/mTOR/p70S6K activation. ▲ Myoblast differentiation and myotube hypertrophy | [103] |
B16F10, HaCa, HDF cells | Fermented BG by Aspergillus niger KHNT-1 | Antimelanogenesis in B16F10 murine melanoma cells ▲ Elastase in human dermal fibroblast (HDF) cells ▼ Antioxidation in H2O2-induced HaCat human epidermal keratinocyte cells ▲ | [104] | |
Human subjects (n = 23) | 1% BG cream formulation (2/day for 8 ws) | Antiwrinkle and skin-whitening ▲ Same effects on human CCD-986sk and mouse B16F1 cells Collagenase/matrix metalloproteinase -1 (MMP-1) ▲ | [27] | |
18-month aged mice | BG (200 mg/Kg/d for 16 wks) | DNA damage in brain ▼ Choline acetyltransferase, acetylcholine transporter, growth-associated protein 43, synaptosomal-associated protein 25, NGF and BDNF expression ▲ | [28] | |
10-month aged mice | BG-Low(10 g/kg) or BG-High (30 g/Kg) | Cognitive decline by aging ▼ Antioxidant system ▲ | [112] | |
Chemical assay | RK3, Rh4, 20(S)/(R)-Rg3 rich BG (0-10 mg/ml) | Aetylcholinesteras (AChE) and butyrylcholinesterase (BChE) ▼ | [111] | |
Rat and BV2 microglial cells | BG-enriched CMT | DNA damage in brain ▼ Improved the learning behavior▲ Oxidative and inflammatory stress (COX-2, lL-1β) related to MAPK- NF-kB pathway. ▼ | [112] |