Table 2.

The main properties of different natural compounds.

Plant	Bioactive Component	Properties	In vitro/in vivo Models	Clinical Trials	References
Rosmarinus officinalis Salvia officinalis	Carnosic acid	↓ Body weight ↑ Insulin sensitivity ↓ Serum Glucose, TG, TC ↓ ALT, AST ↓ MDA, IL-1β, IL-6, TNF-α ↑ Bcl-2 ↓ Bax, MMP-9	- HFD fed mice		[34,35]
Cinnamonium verum Cinnamomum cassia	Cinnamaldehyde Polyphenols	Anti-inflammatory and antioxidant effects Insulin-like activity ↓ Fasting blood glucose and blood pressure ↑ IRβ, GLUT-4, TTP, GLP-1, PPAR-γ	- mouse 3T3-L1 adipocytes - High Fructose Diet fed mice - STZ-induced diabetic rats	- Pre-diabetes - MetS - T2DM	[36,37,38,39]
Capsicum genus	Capsaicin	↓ Fasting glucose ↑ Insulin sensitivity ↓ TG, Leptin ↑ Adiponectin ↓ Gluconeogenesis ↑ Glycogen synthesis ↓ TNF-α, MCP-1, IL-6 ↑ LXR, PDX-1 ↑ TRPV-1, GLUT-4, IRS-1 ↑ PPAR-α/PGC-1α	- TRPV1-KO mice fed with HFD - HFD fed mice - STZ-induced diabetic rats		[40,41,42,43,44]
Curcuma longa	Polyphenols	Anti-inflammatory and antioxidant effects ↑ Insulin sensitivity ↓ BMI, body fat, systolic blood pressure ↓ Plasma glucose ↓ NF-κB, COX-2, VEGF ↓ MCP-1, MCP-4, ILs, TNF-α ↓ JNK, ERK1/2, P38MAPK ↓ Wnt/β-catenin pathway ↓ TG, TC, Leptin ↑ Adiponectin ↓ Malondhyaldeide ↑ PPAR-γ, Catalase activity	- mouse 3T3-L1 adipocytes - rat hepatic stellate cells - HFD fed mice - ob/ob C57BL/6J mice - Balb/c mice - HFD fed rats - STZ-induced diabetic rats fed with HFD	- MetS	[45,46,47,48,49,50,51,52,53,54,55,56]
Rhizoma Coptidis	Berberine	Anti-inflammatory and antioxidant effects ↑ Insulin sensitivity ↓ Fasting glucose Plasma glucose, systolic blood pressure ↓ TG, TC, LDL-C ↑ HDL-C ↓ Leptin, adiponectin ↓ hs-CRP, IL-6, TNF-α, MCP-1 ↓ Macrophage recruitment ↑ Thermogenesis ↓ PPARγ2, C/EBPα, ↑ AMPK and GLUT-4	- mouse 3T3-L1 adipocytes - rat L6 myotubes - HFD fed mice - C57BLKS/J Leprdb-Leprdb mice - HFD fed rats	- T2DM -Hyperlipemia -Hypertension - MetS	[57,58,59,60,61,62,63]
Citrus bergamia Risso et Poiteau	BEO-NVF BPF	↓ SMC proliferation, LOX-1, p-PKB ↓ ROS, TBARS, MDA, Nitrotyrosine ↓ Serum glucose, TG, TC, LDL-C, VLDL-C ↑ HDL-C Re-arrangement of lipoprotein particles ↓ ALT, AST, γ-GT, ↓ Hs-CRP, TNF-α, JNK, p-P38 MAPK, ↓ Caspase-3, Cleaved- PARP ↑ Lipid transfer protein system ↓ Fibrogenic activity ↓ pCEH↓ Steatohepatitis, hepatocellular ballooning ↓ Sinusoidal fibrosis	- rat neointimal hyperplasia - hypercholesterolemic diet fed rats - NAFLD mice	-Hyperlipemia - MetS - NAFLD - T2DM	[66,67,68,69,70,71,72]
Cynara cardunculus	Cynaropicrin	↓ TNF-α, MDA ↓ ALT, AST, γ-GT, ALP ↓ Liver fibrosis ↑ SOD, GPx		- NAFLD - T2DM	[73]
Brassicaceae family Gramineae family	Coenzyme Q10	Antioxidant capacity, nephroprotective effect ↓ TG, TC, LDL-C, serum insulin ↑ β-cell Function ↑ Glucose metabolism	- db/db and dbH mice model of type 2 diabetic nephropathy - STZ-nicotinamide induced diabetic rats	- T2DM - MetS	Zozina V. I. et al. 2018 [74]
Vitis vinifera	Resveratrol	↓ BMI, waist circumference, insulin secretion ↓ Hs-CRP, TNF-α ↓ Malondhyaldeide ↓ Leptin, RAAS modulation ↓ Lipogenesis ↑ Lipolysis	- SGBS preadipocytes - human preadipocytes - adipose stem cells - high Fructose Diet fed rats - high Sucrose Diet fed rats - high–fat/cholesterol diet fed swine - IH-induced metabolic dysfunction in mice - insulin-resistant KKAy mice	- MetS	Hou C.Y. et al. 2019 [75]
Vaccinium myrtillus Fragaria ananassa	Anthocyanins	Anti-inflammatory and antioxidant effects Hypocholesterolemic effects ↓ TG, body weight, fat mass ↓ α-amylase and α-glucosidase activities ↓ Leptin ↓ MCP-1, ICAM-1, VCAM-1, NF-κB B ↑ PPARs	- HK-2 cells - HUVEC cells - STZ- induced diabetic rats - STZ- induced diabetic mice - db/db mice fed with HFD - obese Zucker rats - Dahl Salt-Sensitive rats	- MetS	Naseri R. et al. 2018 [76]
Oleaceae family (Olea europaea Linn.)	Oleuropein	Antioxidant effect ↑ Insulin sensitivity, glucose tolerance ↓ TG, TC, LDL-C ↑ SOD, GPx ↓ LpL, PPARγ, C/EBPα, SREBP-1c ↓ Leptin ↑ AMPK UCP-1 TRPV-1	- MSC from human bone marrow - 3T3-L1 adipocytes - C2C12 cells - Alloxan-induced diabetic rats - HFD fed mice and rats - PPARα null mice - BPA-induced hyperlipidemia and liver injury in rats	-Hyperchole sterolemia - Overweight	Ahamad J.et al. 2019 [77]

↑: Increased, ↓: Decreased. ALP, Alkaline Phosphatase; ALT, Alanine Aminotransferase; AMPK, 5’ AMP-activated Protein Kinase; AST, Aspartate Aminotransferase; Bax, Bcl-2-like protein 4; Bcl-2, B-cell lymphoma 2; BEO-NVF, Non-Volatile Fraction of the Bergamot Essential Oil; BMI, Body Mass Index; BPA, Bisphenol A; BPF, Bergamot Polyphenolic Fraction; C/EBPα, CCAAT-Enhancer-Binding Protein-α; COX-2, Cyclooxygenase-2; ERK1/2, Extracellular signal-Regulated Kinase 1/2; GLP-1, Glucagon-Like Peptide-1; GLUT-4, Glucose Transporter Type 4; GPx, Glutathione Peroxidase; GSK-3β; Glycogen Synthase Kinase-3β; HDL-C, High Density Lipoprotein Cholesterol; HFD, High Fat Diet; Hs-CRP, High sensitivity C-Reactive Protein; ICAM-1, Intercellular Adhesion Molecule 1;IH, Intermittent Hypoxia; IL-1β (Interleukin-1β); IL-6, Interleukin.6; IRS-1, insulin receptor substrate-1; IRβ, Insulin Receptor- β; JNK, c-Jun N-terminal Kinase; LDL-C, Low Density Lipoprotein Cholesterol; LOX-1, Lectin-type Oxidized LDL receptor 1; LpL, Lipoprotein Lipase; LXR, Liver X Receptor; MCP-1, Monocyte Chemoattractant Protein-1; MDA, Malonildialdehyde; MetS, Metabolic Syndrome; MM-9, Matrix Metalloproteinase-9; NAFLD, Non Alcoholic Fatty Liver Disease; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PARP, Poly(ADP-ribose) Polymerase; pCEH, pancreatic Cholesterol Ester Hydrolase; PDX-1, Pancreatic Duodenal homeobox-1; PGC-1α, PPAR-γ coactivator-1α; PPAR-γ, Peroxisome Proliferator-Activated Receptor- γ; p-PKB, phospho-Protein Kinase B; p-38 MAPK, p-38 Mitogen-Activated Protein Kinases; RAAS, Renin Angiotensin Aldosterone System; ROS, Reactive Oxygen Species; SMC, Smooth Muscle Cell; SOD, Superoxide Dismutase; SREBP-1c, Sterol Regulatory Element-Binding Protein-1c; STZ, Streptozotocin; TBARS, Thiobarbituric Acid Reactive Substances; TC, total Cholesterol; TG, Triglycerides; TNF-α, Tumor Necrosis Factor-alpha; TRPV-1, Transient Receptor Potential cation channel subfamily V member 1; TTP, Tristetraprolin; T2DM, Type 2 Diabetes Mellitus; UCP-1, Uncoupling Protein-1; VCAM-1, Vascular cell adhesion protein 1; VEGF, Vascular Endothelial Growth Factor; VLDL-C, Very-Low-Density Lipoprotein Cholesterol; γ-GT, Gamma-Glutamyl Transferase.