Table 1.

Summary of in vitro or animal models studies on the effect of curcumin and its analogs on the individual parameter of MS.

Compound	Model	Dose	Mechanism of action	References
Curcumin	3T3-L1 preadipocytes	High dose: >30 μM	High dose curcumin generates preadipocyte apoptosis in a time- and dose-dependent manner and caspase-dependent pathways (3-, 8-, and 9-)	(58)
		Low dose: <15 μM	Low dose curcumin suppresses adipocyte differentiation via modulation of cell cycle regulator expression, downregulating PPAR, and CCAAT/enhancer-binding protein (C/EBP) expression, blocking differentiation medium-induced catenin downregulation and lowering lipid accumulation
Curcumin	Male Wistar rats with diet-induced MS	High dose: curcumin suspension 100 mg/Kg/day	High dose curcumin nanoparticles may reduce cardiac injury and improve inflammation of ventricular fibrosis	(59)
		Low dose: curcumin nanoparticles 5 mg/Kg/day	Low dose curcumin nanoparticles lower blood pressure, target Uncoupling Protein (UCP) 2 and induce vascular tone and the predisposition to vascular disease; reduce inflammation in white adipose tissue and increase energy expenditure via activation of brown adipose tissue
Curcumin	Obese C57BL/6 J mice	After 16 weeks of a Western-style diet, curcumin accumulates in eWAT (299 ± 113 pmol/g)	Curcumin accumulates in eWAT and inhibits eukaryotic translation initiation factor 2 (eIF2) phosphorylation, which is triggered by ER stress, macrophage accumulation, NF-KB p65, and leptin but not TNF- and IFN- levels. Curcumin reduces lipogenesis and lipolysis by suppressing the expression of glycerol-3-phosphate acyltransferase 1 and adipose triglyceride lipase, resulting in a decrease in diacylglycerols (DAGs) and DAG-derived glycerophospholipids.	(60)
Curcumin	Skeletal muscle C2C12 cells	5, 20, and 40 μM	Curcumin exhibits anti-inflammatory activity in C2C12 cells via suppressing the JNK and NF-KB pathways and reducing oxidative stress	(61)
Curcumin	PCOS -induced Wistar rats	100 and 300 mg/Kg	Curcumin modifies the lipid profile and increases insulin sensitivity	(62)
Curcumin	High fructose diet-induced adult male Sprague Dawley rats	200 mg/Kg/day	Curcumin exhibits antioxidant, antiinflammatory, antihyperglycemic, anti-hypercholesterolemic, anti-hypertriglyceridemic, and antihyperuricemic, weight loss, and blood pressure-lowering effects in high fructose diet-induced rats via the activation of antioxidants, such as malondialdehyde and serum catalase, and suppression of inflammatory factors, such as TNF-α and NF-KB	(63)
Curcumin	Fructose diet and STZ-induced diabetes in adult male Wistar rats	1 g/Kg	Curcumin pre-treatment improves metabolic changes (hyperglycemia, hypercholesterolemia, hypertriglyceridemia) and oxidative stress in rats induced by both fructose-induced MS and STZ-induced diabetes, as well as lowering systolic blood pressure due to its ability to reverse oxidative stress	(64)
Curcumin	Male Sprague Dawley rats	200 mg/Kg/day	Curcumin competitively inhibits human and rat 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), with selectivity against 11β-HSD2. In high-fat-diet-induced obese mice, curcumin lowered serum glucose, cholesterol, triglycerides, and low density lipoprotein levels. Inhibition of 11β-HSD1 is substantially more potent with four curcumin derivatives and (1E,4E)-1,5-bis(thiophen-2-yl) penta-1,4-dien-3-one (compound 6), has a much lower IC50 compared to the parent compound.	(65)
Curcumin with piperine and quercetin	Albino female Wistar rats	100 mg/Kg/day	Curcumin combined with piperine and quercetin enhances peripheral glucose utilization to decrease blood glucose levels, possibly via inhibition of glucosidase enzyme, and can also increase the pancreatic insulin output	(66)
Curcumin	Caco-2 cells	40–50 μM	Curcumin reduces cholesterol absorption via suppression of Niemann-Pick C1-Like 1 (NPC1L1) expression	(67)
Curcumin analog (Curcumin5-8)	High-fat diet-induced obesity C57BL/6 mice	100 mg/Kg/day	Compared to the parent curcumin, curcumin5-8 inhibits fatty acid synthesis and lipid droplet formation to inhibit fatty liver formation. The improved NAFLD and hepatic triglyceride levels are not associated with increased autophagy, as oxidative stress is suppressed consequently reducing the risk of metabolic diseases, such as obesity, fatty liver, and diabetes. Compared to the untreated group, curcumin 5–8 significantly improves insulin resistance and shows a hepatoprotective effect against lipid toxicity and apoptosis, with decreased serum alanine aminotransferase levels	(68)