Table 1.

Overview of the studies describing the biological role of curcumin. This table shows all metabolic pathways (insulin resistance, oxidative stress, lipid metabolism, inflammation, gut microbiota, and hepatic fibrogenesis) and the physiological effects that curcumin exerts both in animal models than in vitro.

Animal/In Vitro Models	Physiological Effects	Dose of Curcumin	Duration of Treatment	Reference
Insuline resistence
Animal model: C57BL/6J mice	Improvement of glucose levels	4 g/kg	2 days/week	Shao W et al., 2012 [38]
Animal model: C57BL/6 mice	Downregulation of CD36 expression. Decrease in flux of FFAs. Inhibition of DAG-PKCε and G6P-α and PCK1 pathway	50 mg kg−1	10 days	Wang L et al., 2016 [39]
Animal model: C57BL/6 mice In Vitro: HSCs	Inhibition the secretion of TIMP-1, MCP-1 and α-SMA	25 μg 20 μM	Weekly intervals for 10 weeks 30 min	Vizzutti F et al., 2010 [40]
Animal model: Sprague Dawley rats	Increase in GSH, GS, HO-1 and glutamate cysteine ligase. Deregulation of ChREBP and SREBP1-c	50 mg/kg	6 weeks	Li B et al., 2016 [41]
Animal model: C57BL/6J mice	Decrease in CYP2E1 and C/EBPβ. Attenuation of Nrf2. Inhibition of HMGB1-NF-κB translocation	100 mg/kg/day	4 weeks	Afrin R et al., 2017 [42]
Animal model: Sprague Dawley rats	Nrf2 traslocation. Increase in HO-1, GCLC, NAD(P)H and NQO-1. Decrease in MDA. Inibition of IkBs. Reduce of NF-κB activation	30, 60, 120 mg/kg	3 days	Xie YL et al., 2017 [43]
Animal model: Female Wistar rats	Increase in SOD1.	~100 mg/kg of body weight per day	8 weeks	Cunningham RP et al., 2018 [44]
Animal model: C57BL/6J mice In Vitro: AML12 cells	Induce of SIRT1. Decrease in ROS. Deregulation of ChREBP and SREBP1-c. Inhibition of O-GlcNAcylation and NF-κB	100 mg/kg 0.3, 3 μM	3 weeks 12 h	Lee DE et al., 2019 [45]
Animal model: Sprague Dawley rats In Vitro: BNL CL.2 cells	Inhibition of the EMT procession	100, 200, 400 mg/kg 10, 20, 30 μM/L	8 weeks 24 h	Kong D et al., 2020 [46]
Animal model: Male albino Wistar rats	Decrease in MDA and increase in GPx	60 mg/kg	16 weeks	Mahmouda, Ahmed M.M et al., 2021 [47]
Lipid metabolism
Animal model: C57BL/6 mice In Vitro: Primary liver cells	Upregulation of CYP7A1 and CYP3A through the regulation of Nrf2/FXR/LXRα pathway	50, 100 mg/kg 10 μM	4 weeks 24 h	Yan C et al., 2018 [48]
Animal model: Male Sprague Dawley rats	Upregolation of PPAR-α. Downregulation of ACC and FAS. Downregulation of Notch signaling and NF-κB	100, 200 mg/kg/day	8 weeks	Zhao NJ et al., 2018 [49]
In Vitro: HepG2 cells	Reduction in AMPK and the inhibition of SREBP-1c	1, 5, 10, 25, 50 µM	24 h	Kang OH et al., 2013 [50]
Animal model: C57BL/6N mice	Targeting HMG-CoA and ACAT	theracurmin (500, 1000, 2000 mg/kg) curcumin (150, 300, 600 mg/kg)	12 weeks	Wang, J.W et al., 2019 [51]
Animal model: Male Syrian Golden Hamsters In Vitro: Caco-2; HepG2 cells	Downregulation of SREBP-2/HNF1α pathway	0.1% w/w	12 weeks 24 h	Yang, J et al., 2023 [52]
Inflammation
Animal model: ApoE−/− mice with a C57/BL6 genetic background	Downregulation of TLR4 and NF-κB. Up-regulation of ZO-1 and occludin	0.1% w/w	16 weeks	Feng D et al., 2019 [53]
Animal model: Male C57BL/6 mice In Vitro: RAW264.7 cells	Reduciton of IL-1β, TNF-α and M1 macrophages	100 mg/kg 0, 2.5, 5, 10 μM	8 weeks 3 h	Tong C et al., 2021 [54]
Animal model: Sprague Dawley male rats In Vitro: LSECs	Modulation of NF-κB and PI3K/Akt/HIF-1α pathway	25, 50, 100 mg/kg 1, 2, 4, 8, 10 μM	8 weeks 24 h	Wu J et al., 2023 [55]
Gut microbiota
Animal model: CD-1 male mice	Restoration of ZO-1 and occluding. Reduction in TLR4/NF-κB.	0.1% w/w	24 weeks	Hong T et al., 2022 [56]
Animal model: Sprague Dawley male rats	Restoration of ZO-1 and occluding. Regulation of LPS-binding protein and TNFα. Suppression of NF-κB and TLR4 up-regulation	200 mg/kg	12 weeks	Feng W et al., 2017 [57]
Animal model: Sprague Dawley male rats	Reduction in the Firmicutes/ Bacteroidetes ratio	200 mg/kg/day	14 weeks	Li R et al., 2021 [58]
Animal model: Male C57BL/6 mice	Reduction in the Firmicutes/Bacteroidetes ratio and desulfovibrio bacteria. Enrichment of oxidative phosphorylation, FFAs metabolism, glycolysis/gluconeogenesis, and biliary secretion	1.2 g	10 weeks	Li, S et al., 2021 [59]
Hepatic fibrogenesis
In Vitro: HSCs	Enhancement of PPARγ activity. Inhibition of PDGF-b	20 μM	24 h	Lin J et al., 2008 [60]
Animal model: ICR mice In Vitro: Human LX-2 cells	Expression of Nrf2	100, 200, 400 mg/kg 10, 20, 40 μM	4 weeks 24 h	Lu C et al., 2017 [61]
Animal model: Albino Sprague Dawley	Expression of Nrf2	50 mg/kg/day	16 weeks	Abd El-Hameed NM et al., 2021 [62]
In Vitro: HSCs	Interruption of leptin signaling pathway	100 ng/m	24 h	Tang Y et al., 2009 [63]

Abbreviations: α-SMA, α-Smooth muscle actin; ACAT, acetoacetyl-CoA Thiolase; ACC, acetyl-CoA carboxylase; AKT, serine/threonine kinase 1; AML12, alpha mouse liver 12 cells; AMPK, AMP-activated protein kinase; BNL CL.2, embryonic liver cell line; C/EBPβ, CCAAT/enhancer binding proteins; CD36, cluster of differentiation; ChREBP, carbohydrate response element binding protein; CYP2E1, cytochrome P450 2E1; CYP3A, cytochrome P450 3A; CYP7A, cholesterol 7 alpha-hydroxylase; DAG-PKCε, diacylglycerol-protein kinase C; EMT, epithelial–mesenchymal transition; FAS, fatty acid synthase; FFAs, free fatty acids; FXR, farnesoid X receptor; G6P-α, glucose-6-phosphate dehydrogenase; GCLC, glutamate-cysteine ligase; GPx, glutathione peroxidase; GS, glutathione synthase; GSH, glutathione; HepG2, human hepatoma cells; HIF-1, hypoxia-inducible factor-1; HMG-CoA, hydroxymethylglutaryl-CoA synthase; HMGB1-NF-κB, high mobility group box 1- nuclear factor kappa B; HNF1α, hepatocyte nuclear factor 1 homeobox alpha; HO-1, heme oxygenase-1; HSCs, hepatic stellate cells; ICR, imprinting control region; IkBs, inhibitors of NF-κB; IL-1β, interleukin-1β; LPS, lipopolysaccharides; LSECs, human liver sinusoidal endothelial cells; LXRs, liver X receptors; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NQO1, NAD(P)H quinone oxidoreductase 1; NRF2, nuclear factor erythroid 2-related factor 2; PCK1, phosphoenolpyruvate carboxykinase 1; PI3K, phosphoinositide 3-kinases; PDGF-B, platelet-derived growth factor B; PPAR-α, peroxisome proliferator activated receptor alpha; ROS, reactive oxygen species; SIRT1, silent information regulator sirtuin 1; SOD1, superoxide dismutase 1 gene; SREBP1c, sterol regulatory element binding protein 1c; TIMP-1, metallopeptidase inhibitor type 1; TLR4, Toll-like receptor 4; TNF, tumour necrosis factor; ZO-1, zonulin. Curcumin concentration in animal models has been reported as g/kg, mg/kg·min, μg/kg or based on animal weight (0.1% w/w [weight/weight]); for in vitro models, the dosage of curcumi used is reported in μM, μM/L or ng/m.