Table 1.

Main characteristics of the included studies in the current review.

Author, year (ref)	Animal model	Experimental subject	Assays	Sepsis induction	Treatment	Results	Main conclusions
Memis et al., 2008 [28]	Rats Wistar albino (male)	Group I: control Group II: CUR (1.2 g/kg) Group III: LPS+placebo Group IV: LPS+CUR	Histopathological examination	LPS (1 mg in 500 μL of sterile saline) i.p.	CUR (1.2 g/kg) through an orogastric tube, daily for 7 days after LPS administration	CUR attenuated hepatocellular hydropic degeneration, sinusoidal dilation, necrosis areas, and inflammatory infiltration in the liver; reduced inflammation, hyperemia, and mucosal ulceration in the small bowel; attenuated inflammation and necrosis of the proximal tubules in the kidney	CUR reduced organ dysfunction in rats with experimental sepsis
Vachharajani et al., 2010 [31]	Mice C57Bl/6 (male)	Group I: sham Group II: CLP Group III: CLP+CUR (100 mg/kg)	Intravital fluorescent video microscopy technique Evans blue (EB) leakage method Dual radiolabeling technique Survival rate	CLP	CUR (100 mg/kg) in saline i.p. pretreated with 48 h before CLP P<0.05	CUR significantly attenuated leukocyte and platelet adhesion in cerebral microcirculation, EB leakage in the brain tissue, and improved survival in mice with CLP. P-selectin expression in mice with CLP+CUR was significantly attenuated. CUR reduced platelet adhesion via modulation of the endothelium	CUR modulates leukocytes and platelet adhesion and blood-brain barrier (BBB) dysfunction in mice with CLP via P-selectin expression
Xiao et al., 2012 [27]	Rats Sprague-Dawley specific pathogen-free (male)	Group I: sham Group II: CLP Group III: CLP+DMSO Group IV: CLP+CUR (50 mg/kg) Group V: CLP+CUR (200 mg/kg)	Measurement of lung W/D ratio Measurement of lung injury in bronchoalveolar lavage fluid (BALF) Histopathological examination of the lung Measurement of MPO, MDA, and SOD activity Measurement of inflammatory cytokines Survival rate	CLP	CUR (50 mg/kg or 200 mg/kg) dissolved in 1% DMSO i.p. at 2 h and 12 h post-CLP	Treatment with CUR significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary myeloperoxidase (MPO) activity. CUR significantly increased superoxide dismutase (SOD) activity with a significant decrease in malondialdehyde (MDA) content in the lung. Caused downregulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung, and CUR improved the survival rate of rats by 40%–50% with CLP-induced acute lung injury (ALI)	CUR protects against sepsis-induced acute lung injury in rats by reducing inflammatory cell infiltration, reactive oxygen species (ROS) generation, and regulating cytokine effects
Savcun et al., 2013 [29]	Rats of Wistar albino (both genders)	Group I: control Group II: CLP Group III: CLP+CUR (200 mg/kg)	Histopathological analyses Measurement of TNF-α and IL-1β levels Hepatic and renal tissues MDA and glutathione (GSH) levels MPO and Na+/K+-ATPase activities	CLP	CUR (200 mg/kg i.p.) in two equal doses just after surgery and at the 12-hour post-CLP	Serum TNF-α and IL-1β and tissue MDA and MPO values were higher, whereas tissue GSH and Na+/K+-ATPase values were lower, in the CLP group as compared to the sham group. These values in the CLP+CUR group were the inverse of those in the CLP group. As compared to the sham group, histopathological evaluation of the CLP group showed damaged hepatocytes, glomeruli, and tubules, whereas the damage was significantly reduced in the CLP+CUR group as compared to the CLP group	CUR has antioxidant and anti-inflammatory effects against the tissue damage likely caused by free oxygen radicals and lipid peroxidation induced by experimental sepsis in rats
Xu et al., 2013 [24]	Sprague-Dawley rats (male)	Group I: control Group II: sham Group III: CLP Group IV: DMSO Group V: CUR (200 mg/kg)	Lung wet/dry weight ratio Transmission electron microscopy Histopathological examination RNA isolation and analysis Real-time reverse transcription-polymerase chain reaction Enzyme-linked immunosorbent assay Protein determination Western blot analysis	CLP	CUR (200 mg/kg, 2 days, in DMSO, was administered i.p. 2 h and 12 h post-CLP	CUR treatment was found to significantly reduce lung wet/dry weight ratio in the sepsis-induced acute lung injury in rats at both 24 and 48 h. 24 h after the initial treatment, real-time PCR and Western blot analysis showed that the expression of TGF-β1 and SMAD3-dependent signaling pathway was significantly decreased in the CUR-treated group than other control groups (P b 0.05). In the CUR group, exudation of fibrin in the alveolar space and cell necrosis were less prominent, and there was no exudation of erythrocytes. CUR treatment prevented some sepsis-induced damage	CUR played a protective role in sepsis-induced ALI, possibly through the inhibition of the expression of the TGF-β1/SMAD3 pathway
Yang et al., 2013 [25]	Sprague-Dawley rats (male)	Group I: sham Group II: CLP Group III: CLP+CUR (200 mg/kg/d)	Determination of cardiac function by cardiac ultrasound, morphological changes of myocardial tissues and contents of cTnI, SOD, and MDA in plasma	CLP	CUR (200 mg/kg/d, 3 days) was administered i.p. in two equal doses just after the perforation and at twelve-hour postperforation	Treatment of rats with CUR significantly decreased the elevated cardiac troponin I (cTnI) levels and MDA in plasma and increased the levels of SOD after CLP. Moreover, CUR enhanced the myocardial contractility by increasing the decreased ejection fraction (EF) and fractional shortening (FS) in rats with sepsis-induced by CLP. In addition, CUR could alleviate the myocardial inflammation and structural damage of myocardial cells in sepsis induced by CLP	CUR has the protective effects on cardiac function in rats with sepsis
Zhao et al., 2016 [22]	Mice C57BL/6 (male)	Group I: control Group II: CLP Group III: CLP+CUR (100 mg/kg)	Evaluation of survival rate BBB permeability TUNEL-apoptosis kit for staining mitochondria and cytosolic fraction isolation Mitochondrial membrane potential (MMP) Measurement of mitochondrial ROS production Mitochondrial complex I activity measurement Western blot	CLP	CUR (100 mg/kg) dissolved in 1% DMSO (in normal saline) was administrated i.p. of each time, at 3-, 12-, and 24-hour post-CLP	CUR improved survival rate, attenuates brain edema, enhanced BBB integrity, decreased apoptosis, and attenuated mitochondrial dysfunction in septic mice	CUR improved the survival of mice with sepsis and ameliorated brain injury
Zhong et al., 2016 [23]	Mice C57BL/6 (male)	Group I: control Group II: LPS Group III: LPS+CUR (20 mg/kg) Group IV: LPS+CUR (40 mg/kg) Group V: LPS + CUR (80 mg/kg)	Biochemical hepatic function examination Measurement of liver O2− and H2O2 levels and intracellular ROS production Measurement of TNF-α, IL-1β and IL-18 levels Liver histological analysis Semi-quantitative RT-PCR analysis Western blot	LPS (5 mg/kg) i.p.	CUR (20, 40, and 80 mg/kg) o.a. once daily for 4 weeks before LPS administration	CUR lowered IL-1β, IL-6, and TNF-α and improved liver apoptosis by suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting cyclic AMP-responsive element-binding protein (CREB)/caspase expression and decreased oxidative stress-associated protein-expressing. CUR regulated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as SOD, catalase (CAT), GSH, and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats	CUR exhibited protective effects in LPS-induced mice by inhibiting inflammatory signaling pathway through IKK/NF kappa B pathway suppression and proinflammatory cytokine reduction and limiting PI3K/AKT-related signaling pathway
Kumari et al., 2017 [30]	Mice Swiss albino	Group I: control Group II: LPS Group III: LPS+CUR (20 mg/kg) Group IV: LPS+CUR (10 mg/kg) Group V: LPS+DMSO (vehicle) Group VI: LPS+DEX (dexamethasone -1 mg/kg)	LPS-induced ROS measurement in BALF Nitrite level measurement TNF-a level determination MPO activity in lungs Assessment of capillary leakage Inflammation determination of hydroxyproline (Hyp) content as collagen marker in lungs Histopathological determination of lung fibrosis Survival rate	LPS (10 mg/kg) i.p.	CUR (20 mg/kg, i.p. and 10 mg/kg, i.n.) dissolved in DMSO an hour before LPS administration	CUR ameliorates oxidative damage caused by LPS-induced ROS and nitrite level. LPS-induced TNF-a level was ameliorated by CUR. CUR suppresses neutrophil infiltration and lung inflammation. CUR protects against LPS-induced histopathology and capillary damage. CUR ameliorates LPS-induced collagen deposition in the lungs and liver. CUR ameliorated LPS-induced TGF-β1, TLR-4, and iNOS expression in the lungs. CUR protects against LPS- induced lethality	CUR at a lower dose (20 mg/kg, i.p.) can inhibit inflammation, oxidative damage, and fibrotic changes in murine models
Liu et al., 2017 [26]	Rats albino healthy (male)	Group I: control Group II: CLP Group III: CLP+CUR (50 mg/kg) Group IV: CLP+CUR (100 mg/kg)	Measurement of lung W/D ratio Measurement of lung injury in BALF Histopathological examination of the lung Measurement of MPO, MDA, SOD, and catalase enzyme activities Measurement of inflammatory cytokines	CLP	CUR (50 mg/kg or 100 mg/kg) dissolved in saline o.a. The dose was continued for 45 consecutive days	CUR administration significantly reduced CLP-induced inflammation, pulmonary edema, and chronic lung injury (CLI). CUR treatment significantly reduced MPO activity and inflammatory cell accumulation in the BALF, and also protein level, MDA, SOD, and W/D ratio were significantly reduced in the lung tissues. Also, CUR reduced the expression of IL-1b, TNF-a, and MIF levels in the lung tissues	CUR can ameliorate CLP-induced CLI in male albino rats
Maa et al., 2017 [20]	Mice C57BL/6 (male)	Group I: control (carboxymethylcellulose solution) Group II: LPS Group III: LPS+CUR (20 mg/kg)	Histopathological analyses Biochemical levels of serum aspartate transaminase (AST) and blood urea nitrogen (BUN) Detection of F4/80+CD11c+ cells by flow cytometry Western blotting for detection of miR-155	LPS (10 mg/kg) i.p.	CUR (20 mg/kg) in 0.5% carboxymethylcellulose o.a. for 3 days before LPS administration	CUR effectively protected mice from sepsis as evidenced by decreasing histological damage, reducing AST and BUN levels, and the proportion of macrophages in the spleen (31.1% vs. 13.5%). MicroRNA-155 levels and cytokines were also reduced in CUR-treated mice	CUR improves the histopathological and biochemical responses of sepsis and the LPS-induced inflammatory response is mediated by miR-155 expression
Chen et al., 2018 [21]	Mice BALB/c (male)	Group I: sham Group II: CLP Group III: vehicle (CLP+corn oil) Group IV: CLP+CUR (50 mg/kg) Group V: CLP+CUR (100 mg/kg) Group VI: CLP+CUR (200 mg/kg)	Magnetic isolation of CD4+ T and Treg cells Cytokine measurements RT-qPCR Western blotting Flow cytometry Histopathological examination	CLP	CUR (50, 100, 200 mg/kg). Twelve-hour post-CLP was induced, via administration intragastric	CUR significantly alleviated inflammatory injury of the lung and kidney in septic mice and improved survival after CLP. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with CUR. TNF-α and IL-6 levels were reduced in septic mice treated with CUR	CUR attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs

CLP: cecal ligation and puncture; LPS: lipopolysaccharide; i.p.: intraperitoneal; i.n.: intranasal; o.a.: oral administration; EB: Evans blue; BBB: blood-brain barrier; BALF: bronchoalveolar lavage fluid; MPO: myeloperoxidase; SOD: superoxide dismutase; MDA: malondialdehyde; ALI: acute lung injury; ROS: reactive oxygen species; GSH: glutathione; cTnI: cardiac troponin I; EF: ejection fraction; FS: fractional shortening; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphatase; CAT: catalase; GSH-px: glutathione peroxidase; BUN: blood urea nitrogen; CLI: chronic lung injury; iNOS: inducible nitric oxide synthase; cytokines: IL-1b, IL-4, IL-6, IL-10, TNFα, IFN-γ, MIP-1a, TGF-β.