Ginger as a nutraceutical shield: Counteracting acrylamide-induced liver injury

Table 1 Major bioactive compounds of Zingiber officinale with hepatoprotective effects and their associated signaling mechanisms

Phytochemical components	Biological effects	Signaling pathways	Ref.
6-gingerol	Inhibits invasion and metastasis; blocks angiogenesis; induces apoptosis; exhibits hepatoprotective effect	NF-кB decrease, STAT3 decrease, MAPK decrease, PI3K/AKT-P21 increase, AMPK increase, BAX increase	[33-35]
8-gingerol	Exhibits antiemetic activity; reduces ROS production; modulates autophagy; inhibits proliferation and migration; induces apoptosis	Nrf2-HO-1 increase, 5-hydroxytryptamine 3 antagonist; neurokinin-1 antagonist modulates EGFR/STAT/ERK signaling, PI3K/AKT/mTOR and MAPK pathways	[33,34,38,39,41,43-45]
10-gingerol	Reduces cell division and induces S-phase cell cycle arrest and apoptosis; exhibits anti-neuroinflammatory and antioxidant activity	AKT decrease, PI3K/p38 MAPK decrease, EGFR increase, NF-кB decrease, AMPK increase, mTOR pathway modulation	[34,36,41]
6-shogaol	Increases antioxidant enzyme levels; inhibits tumor invasion; prevents TNF-α-induced barrier loss	MMP-9 expression decrease, PI3K/AKT decrease, NF-кB decrease, MAPK decrease, Nrf2 increase	[33-35,37]
10-shogaol	Exhibits anti-inflammatory and anti-cancer activity; reduces lipid accumulation	AMPK increase, NF-кB decrease	[33,39,41]
Zingerone	Exhibits antioxidant and anti-inflammatory effects, antiemetic activity and cytoprotective effect	NF-кB decrease, IL-1β decrease, 5-hydroxytryptamine 3 antagonist	[33,34,41,44]
Paradols (6-, 8-, 10-)	Exhibits anti-proliferative, antioxidant, anti-inflammatory activity	PI3K/AKT/mTOR decrease, NF-кB decrease	[39,41,44]
Gingerenone A	Exhibits anti-tumor, pro-apoptotic and anti-inflammatory activity	JAK2/STAT3 decrease	[33,34,40,41]
β-sesquiphellandrene	Exhibits antioxidant, antimicrobial and anti-inflammatory activity	NF-кB decrease, MAPK decrease	[33,41]
Geraniol	Promotes autophagy; exhibits antioxidant activity	AMPK increase, mTOR decrease	[33,34,42]
Phenolic acids (gallic, ferulic, caffeic, ellagic, hydroxybenzoic acid)	Scavenges reactive species; modulates inflammation and lipid metabolism	NF-кB decrease, PI3K/MAPK decrease, AMPK increase, Nrf2/HO-1 increase	[33,41,43]
Minor flavonoids (quercetin, rutin, naringenin)	Exhibits antioxidant and anti-inflammatory activity	NF-кB decrease, Nrf2 increase	[33,41]

NF-кB: Nuclear factor kappa-light-chain-enhancer of activated B cells; STAT: Signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; PI3K/AKT: Phosphatidylinositol 3-kinase/protein kinase B; BAX: BCL2-associated X protein; ROS: Reactive oxygen species; HO-1: Heme oxygenase-1; EGFR: Epidermal growth factor receptor; ERK: Extracellular regulated protein kinases; mTOR: Mechanistic target of rapamycin; TNF-α: Tumor necrosis factor-α; Nrf2: Nuclear factor erythroid 2-related factor 2; MMP: Matrix metalloproteinases; IL-1β: Interleukin-1β; JAK: Janus kinase.