Table 2. Characteristics of the studies selected for the systematic review separated by categories of anti-inflammatory agents, revealing the outcomes to answer the question: What are the mechanisms of action of anti-inflammatory agents in adipose tissue?.
| Author | Compound/Dose and frequency | Time | Animals/Species | Outcomes |
|---|---|---|---|---|
| Drugs | ||||
| Hsieh et al. [45] | Colecoxib—30 mg/kg/day | 12 weeks | Sprague-Dawley Rats | × COX-2 ↓ Adipocyte hypertrophy ↓CD68 ↓TNF-α ↓PPAR-γ and CEBP-α |
| Ma et al. [46] | Dextran– 5 mg/kg/day | 24 h | C57BL/6J mice | ↓CLS ↓MCP-1 ↓TNF-α, IL-6 ↓NF-kB |
| Ndisang & A. Jadhav [47] | Hemin—30 mg/kg/day | 8 weeks | Zucker‐lean (ZL) and ZDF rats | ℗ AMPK ↓℗ JNK ↓ Serum levels of inflammatory cytokines ↓MCP-1 ↑ LPL, IRS-1, GLUT-4, PKB/AKT, Adiponectin |
| Furuya et al. [12] | Atorvastatin—0,1% chow (wt/wt) | 4 weeks | CD1 mice | ↓TNF-α, IL-6, NF-kB, IKK-α/β ↑GLUT-4 |
| Okada et al. [48] | Pioglitazone (TZD) - 0,001% chow | 4 weeks | KKAy mice | ↑LXB4, IL-10, IL-13 e Arg-1 ↓Prostaglandin 2 |
| Xu et al. [49] | Empagliflozin (TZD) - 3 or 10 mg/kg/day | 16 weeks | C57BL/6J mice | ◊ AMPK ↑Adiponectin, UCP-1 ↓F4/80, leptina, CLS × SGLT2 |
| Prabhu et al. [50] | Dextran– 0,1, 0,7, or 5 mg/kg/day | 4 weeks | C57BL/6J mice | ↓CLS, TNF-α, IL-6, IL-1β, CD68, CD11c, CCR2, CCR5, F4/80, CCL3 and CCL5 ↑ CD206 |
| Zhou et al. [51] | (EX-4)2-Fc, an GLP-1 receptor agonist—1,8 mg/kg-1 | 14 days | C57BL/6 mice | ↓ IL-1β, TNF-α, IL-6 e MCP-1 ↓ CD11b, F4/80, iNOS, ↑ CD206 ℗ NF-kB, p38, AMPK |
| Natural | ||||
| Lee et al. [52] | Metabolaid® (MetA), verbena and hibiscus—50 or 100 mg/kg/day | 8 weeks | C57BL/6 mice | ↓PPAR-γ e CEBP-α ↓SREBP1c and FAS ↓TNF-α ↑ UCP1 and UCP2 ℗ AMPK |
| Fenni et al. [53] | Lycopene and tomato powder supplementation—10 mg/kg of chow/day | 12 weeks | C57BL/J6 mice | ↓℗ p65 and IKB ↓NF-kB and PPAR ↓SREBP-1c and FAS ↓TNF-α, IL-6, CCL2 and CCL5 |
| Abu Bakar et al. [54] | Celastrol—1 or 3 mg/kg/day | 8 weeks | Sprague-Dawley rats | ↓IL-6, TNF-α, MCP-1, NF-kB, iNOS, CD11c ↑ Arg1 |
| Alsaggar et al. [55] | Silibinin– 50 mg/kg twice a week | 8 weeks | C57BL/6 mice | ↓F4/80, CD11c, TNF-α, IL-1β ↑IL-10, adiponectin |
| Han et al. [56] | Berberine– 1,5 mg/kg/day | 12 weeks | C57BL/6 mice | ↓ F4/80, IL-6, MCP-1 ↑IL-4, CD206, ARG1, CD163 ↑ M1/M2 reason |
| Choi, et al. [57] | Indole-3-carbinol (I3C) - 0,1% (wt/wt) | 10 weeks | C57BL/6N mice | ↑SIRT-1, PGC-α, UCP1 and UCP3 ×℗ERK ↓℗TLR2 and 4 and PPARγ2 ↓TNFα, IFNβ and IL-6 |
| Ma et al. [58] | Spermidine– 20 mg/kg | 8 weeks | C57BL/6J mice | ↓CLS, F4/80 ↓SREBF1c, FAS, PPARγ, IL-1β, IL-6, iNOS, MCP-1, CCL5, leptin ℗ p38 AMPK, p65 NF-kB |
| Wei et al. [59] | EPA e DHA– 1, 2 and 4% chow (w/w) | 12 weeks | C57BL/6J mice | ↓IL-6, TNFα, MCP-1, CD11c, FAS, UCP-1 ↓GPR120, PPARγ |
| Cho et al. [60] | Carvacrol—0,1% chow (w/w) | 10 weeks | C57BL/6N mice | ↓TNFα, IFNα ↓TLR2, TLR4, Tirap, TRAF6, IRF5, MyD88 and TRIF |
| Lee et al. [61] | Black Raspberry Seed Oil—50 ou 100% chow | 10 weeks | C57BL/6 and C57BL/KsJ‐db/db mice | ↓TLR4, NF-κB ↓TNFα and IL-6 ↓F4/80, CD68 and MCP-1 |
| Kim et al. [62] | Resveratrol—0,4% ~400 mg/kg | 10 weeks | C57BL/6J mice | ↓TNFα, IFNα, INFβ and IL-6 ↓TLR2, TLR4, MyD88, Tirap, TRIF, TRAF6, IRF5, pIRF3 and NF-kB |
| Oliveira et al. [63] | α-linolenic (ω3) or oleic (ω9) fatty acids - 10% chow | 8 weeks | Swiss Mice | ↓IL-1β, IL-6 and TNFα ↓℗ IKK, IκBα and JNK ↑IL-10 ◊ GRP120 |
| Ye et al. [64] | Berberine—50 mg/kg/day | 14 days | C57BL/6 mice | × Macrophage polarization M1 ↓MCP-1, IL-6 and TNF-α ↓℗ JNK, IKKβ and AKT ↓ NF-kB ↓F4/80, CD206 ↑CD11c |
| Gao et al. [65] | Rutin—50 mg/kg twice a week | 8 weeks | C57BL/6J mice | ↓ Adipocyte hypertrophy and CLS ↓TNF-α ↓MCP-1 ↓F4/80, CD11c and CD68 ◊ CD206 and Arg1 |
| Kang et al. [66] | Capsaicin—0,015% chow | 10 weeks | C57BL/6J mice | ↓MCP-1, TNFα, IL-6, leptin ↑Adiponectin |
| Veeramani et al. [67] | Lavatera critica (LC) - 50, 100 or 200 mg/kg/day | 5 weeks | C57BL/6J mice | ↓TNF-α, IL-1β, IL-6, MCP-1 and CD11c ↓iNOS ↑Ym1, arginase and clec7a |
| Yang et al. [68] | Bitter melon—1 or 3% chow | 6 weeks | OLETF rats | ↓TNF-α and IL-6 ↓CCL2 ↓JNK and NF-kB |
| Ying et al. [69] | Interfeton tau—8 μg/kg/day | 8 weeks | C57BL/6J mice | ↓JNK, NF-kβ and p65 ↓IL-1β, IL-6, TNF-α and macrophage M1 ↑IL-10 and macrophage M2 |
| Zhou et al. [70] | Catalpol—100 mg/kg/day | 4 weeks | C57BL/6J mice | ↓ Adipocyte size and CSL ↓IL-1β, IL-6, TNF-α ↓MCP-1, iNOS and CD11c ↓JNK, NF-kB and IKKβ ↑IL-10 ↑MGL1, clec7a and MMR |
| Subramanian et al. [71] | Terminalia chebula Fruit Extract– 50 mg/kg/day | 9 weeks | C57BL/6 mice | ↓ TNF-α, IL-6, PPARα, CPT-1α, FAS, adiponectin ↑leptin |
| Yu et al. [72] | Sarsasapogenina– 40 or 80 mg/kg/day | 6 weeks | C57BL/6J mice | ↓ TNF-α, IL-1β, IL-6, MCP-1, Nos2, COX2, adiponectin, F4/80 and CD68 ↑Arg1, Ym1, Fizz1 and IL-10 |
| Bashir et al. [73] | Fish oil—4, 8 or 16 mg/kg | 4 weeks | C57BL/6 mice | ↓IL-1β, IL-2, TNF-α and IFN-γ ↓NF-kB, TLR4 ↓CD86 |
| Bettaieb et al. [74] | Flavan-3-ol (−)-epicatechin—20 mg/kg/day | 15 weeks | C57BL/6J mice | ↓TNF-α, MCP-1 and F4/80 ↓pIKK, IκB, p65 and NF-κB ↓NOX4, p47 |
| Guo et al. [75] | Cianidin-3-glucoside—0,2% chow | 5 weeks | C57BL/6J, C57BL/Ks db/db and db/+ mice | ↓TNF-α and IL-6 ↓F4/80, CD11c and MCP-1 ↓JNK and FoxO1 |
| Kwon et al. [76] | Coptidis Rhizoma– 200 or 400 mg/kg/day | 10 weeks | C57BL/6 mice | ↓CD11c, TNF-α, F4/80, CCL2, CCL4 and CCL5 ↑CD206, |
| Lee et al. [77] | Broussonetia papyrifera root bark extract—40 mg/kg/day | 7 days | C57BL/6 mice | ↓NF-kB, IL-1β, iNOS ↑AMPK |
| Perdicaro et al. [78] | Quercetin– 20 mg/kg/day | 6 weeks | Sprague Dawley rats | ↑PPARγ/CEBPα, FAS, adiponectin ↓TLR4, CD68, MCP-1, JNK |
| Ramalho et al. [79] | Eicosapentaenoic Acid– 36 g/kg chow | 11 weeks | C57BL/6 mice | ↓Alox5, Myd88, Stat1, Ccr5, Card11 and LTB4 ↓miR-146b, miR-125b-5p, miR-30a-5p and miR-143-3p |
| Synthetics | ||||
| Dinh et al. [80] | Bardoxolone methyl (BARD) - 10 mg/kg/day | 21 weeks | C57BL/6J mice | ↓TNF-α and F4/80 ↓ Adipocyte size and CSL ↓STAT3, AKT, ERK, JNK |
| Wang et al. [81] | Sodium buryate—1 g/kg every two days | 6 weeks | C57BL/6J and C57BL/6J db/+ mice | ↓TNF-α, IL-1β, IL-6 and INF-γ ↓CD68, F4/80 ↓MCP-1, NLRP3 and caspase 1 |
| Bak et al. [82] | Licochalcones—10 mg/kg/day | 3 weeks | C57BL/6J mice | ↓ Adipocyte size, CSL ↓TNF-α ↓CD68, MCP-1 e p38 ↑AKT |
| Gambaro et al. [83] | Spexin—29 μg/kg/dia | 10 days | Swiss Mice | ↓ TNF-α, IL-6, IL-1β, M1a Ly6C-, CD11c, CD11b ↑CD206 ↑M1/M2 reason |
| Chen et al. [84] | Sea cucumber saponin liposomes—0,45 mg/mL | 8 weeks | C57BL/6J mice | ↓ Infiltration of macrophages ×℗ ERK ↓TNF-α and IL-6 |
↑ Increase ↓ Decrease × Inhibit ◊ Stimulate ℗ Phosphorylation
COX2: cyclooxygenase enzyme. TNF-α: tumor necrosis factor alpha. PPAR-γ/2: peroxisome proliferator-activated gamma receptors. CEBP-α: CCAAT-enhancer-binding proteins. SREBPc: sterol regulatory element binding proteins. TLR2/4: toll-like receptors. MyD88: myeloid differentiation primary response gene 88. JNK: c-Jun N-terminal kinases. iNOS: induced nitric oxide synthase. MGL-1: macrophage galactose-type lectin 1. NOX4: NADPH oxidase 4. FoxO1: Forkhead Box O1. STAT3: signal transducer and activator of transcription 3. NLRP-3: NLR family pyrin domain containing 3. FAS: Fas cell surface death receptor. INFα/β: interferons. IL-1, IL- 6, IL-10, IL-13: interleukins. MCP-1: monocyte chemoattractant protein-1. NF-kB: nuclear factor kappa B. CLS: crown-like structures. LPL: lipoprotein lipase. IRS-1: insulin receptor substrate 1. GLUT-4: glucose transporter. LXB4: lipoxin A4. ARG-1: arginase 1. AMPK: AMP-activated protein kinase. UCP-1/2/3: uncoupling protein. SGLT2: sodium/glucose cotransporter 2