Could Pomegranate Juice Help in the Control of Inflammatory Diseases?
Abstract
:1. Introduction
2. Search Strategy
3. Results and Discussion
3.1. Findings Related to Pomegranate Products Consumption and CID in Humans
3.2. Evidence of Anti-Inflammatory Effects of Pomegranate or Pomegranate-Derived Products in Different Animal Models of CID
3.3. In Vitro Anti-Inflammatory Activity of Pomegranate Extracts or Pomegranate-Derived Bioactive Compounds
4. Conclusions and Future Directions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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CID | Human Clinical Trials (No. of Subjects) | Animal Model Studies | Cell Culture Studies |
---|---|---|---|
Asthma and COPD | - | 3 [17,18,19] | - |
IBD | - | 8 [20,21,22,23,24,25,26,27] | 2 [28,29] |
Immune system | - | - | 2 [30,31] |
Metabolic and cardiovascular disorders § | 7 (51 [32], 13 [33], 31 [34], 30 [35], 101 [36], 24 [37], 27 [38]) | 14 [39,40,41,42,43,44,45,46,47,48,49,50,51,52] | - |
Neurodegenerative diseases | - | 8 [53,54,55,56,57,58,59,60] | 4 [53,61,62,63] |
Psoriasis | - | - | - |
RA | 1 (55 [64]) | 1 [65] | 1 [66] |
Other disorders §§ | - | 3 [67,68,69] | 1 [70] |
Study Design | Population | Subjects (Gender, No., Age) | Intervention | Control/Comparator | Duration | Outcomes | Reference |
---|---|---|---|---|---|---|---|
Double-blind, placebo-controlled, randomised | Dyslipidaemic patients | F & M: 51, 42–64 years | Pomegranate seed oil 400 mg/day × 2 | Paraffin 400 mg/day × 2 | 4 weeks | ↓ TG, ↓ HDL-C, ↓ TG/HDL-C ratio, ↔ TNF-α | Asghari et al., 2012 [32] |
Pre- and post-test | Hypertensive patients | M: 13, 39–68 years | Pomegranate juice 150 mL/day | - | 1 day | ↓ SBP, ↓ DBP, ↔ CRP, ↔ ICAM-1, ↔ VCAM-1, ↔ IL-6, ↔ E-selectin | Asgary et al., 2013 [33] |
Pre- and post-test | Type 2 diabetic patients | F: 16, M: 15, 38–54 years | Concentrated pomegranate juice 50 g/day | - | 4 weeks | ↔ SBP, ↔ DBP, ↑ TC, ↑ HDL-C, ↔ TG, ↔ LDL-C, ↔ glycaemia, ↓ IL-6, ↔ TNF-α, ↔ CRP, ↓ adiponectin, ↑ TAC | Shishehbor et al., 2016 [34] |
Double-blind, placebo-controlled, randomised crossover | Patients with metabolic syndrome | F: 16, M: 14, 42–62 years | Pomegranate juice 500 mL/day | Placebo 500 mL/day | 1 week | ↓ SBP, ↓ DBP, ↓ CRP, ↑ TG, ↑ VLDL-C | Moazzen & Alizadeh 2017 [35] |
Double-blind, placebo-controlled, randomised | Haemodialysis patients | F: 46, M: 55, 55–81 years | Pomegranate juice 100 mL/day | Placebo 100 mL/day × 1 | 12 months | ↓ IL-6, ↓ TNF-α, ↓ MPO, ↓ AOPP, ↓ oxidised fibrinogen, ↓ MDA | Shema-Didi et al., 2012 [36] |
Pilot, open, randomised crossover | Haemodialysis patients | F: 13, M: 11, 47–75 years | Pomegranate juice 100 mL/day; Pomegranate extract POMxTM 1050 mg/day (both containing 650 mg GAE) | - | 4 weeks | ↔ SBP, ↔ DBP, ↔ CRP, ↔ IL-6, ↔ F2-isoprostanes, ↔ isofurans, TG, ↔ TC, ↔ HDL-C, ↔ LDL-C | Rivara et al., 2015 [37] |
Double-blind, placebo-controlled, randomised, parallel-arm | Haemodialysis patients | F: 10, M: 17, 49–59 years | Pomegranate extract POMxTM 1 g/day (containing 600–755 mg GAE) | Placebo 1 pill/day | 6 months | ↓ SBP, ↓ DBP, ↔ CRP, ↔ IL-6, ↔ TC, ↔ HDL-C, ↔ LDL-C, ↔ TG, ↔ ORAC, ↔ AOPP, ↔ 8-OHdG, ↔ ox-LDL, ↔ arylesterase activity, ↔ lactonase activity, ↔ PON activity | Wu et al., 2015 [38] |
Double-blind, placebo-controlled, randomised | RA patients | F & M: 55, 37–61 years | Pomegranate extract POMxTM 250 mg/day × 2 | Placebo (cellulose) 250 mg/day × 2 | 8 weeks | ↔ CRP, ↔ MMP3, ↔ MDA, ↑ GPx, ↓ ESR, ↓ DAS28, ↓ HAQ, ↓ swollen joints, ↓ tender joints, ↓ pain intensity, ↓ morning stiffness | Ghavipour et al., 2017 [64] |
clintrials.gov Identifier | Study Focus | Study Design, Duration | Sponsor | Estimated Enrolment | Study Start Date | Estimated Completion Date |
---|---|---|---|---|---|---|
NCT02093130 | Memory in older adults | Double-blind, placebo-controlled, parallel arm, randomised, 12 months | University of California (Los Angeles, CA, USA) | 212 | January 2014 | December 2017 |
NCT02258776 | Ageing and inflammation of the skin | Single-blind, placebo-controlled, parallel arm, randomised, 12 weeks | University of California (Los Angeles, CA, USA) | 15 | October 2015 | January 2018 |
NCT03000101 | Inflammation in IBD | Double-blind, placebo-controlled, parallel arm, randomised, 12 weeks | St. Orsola-Malpighi Hospital (Bologna, Italy) | 36 | December 2016 | June 2018 |
Disease Model | Animal Model | Tested Product(s), Vehicle, Duration | Disease Induction | Effects | Reference |
---|---|---|---|---|---|
Respiratory diseases | BalbC mice | Pomegranate peel aqueous extract (200 mg/kg b.w.) via intraperitoneal injection for 2 days | LPS-induced lung inflammation | ↓ total cells in BAL, ↓ neutrophils in BAL | Bachoual et al., 2011 [17] |
BalbC mice | Encapsulated pomegranate leave extract (10 mg/mL) or non-encapsulated pomegranate leave extract (20 mg/kg b.w.) via nostril for 4 days | Ovalbumin-induced asthma | ↓ leukocytes, neutrophils, and eosinophils in BAL, ↓ macrophages in BAL (non-encapsulated extract only), ↔ lymphocytes in BAL, ↓ IL-1β and IL-5 in BAL | de Oliveira et al., 2013 [18] | |
C57BL/6J mice | Pomegranate juice (80 μmol/kg b.w.) via bottle for 1 week or 1 month or 3 months | Cigarette smoke-induced lung stress | ↓ IL-1β and IL-6 expression in lung (1 week only), ↓ TNF-α expression in lung | Husari et al., 2016 [19] | |
IBD | Wistar rats | Punicic acid (400 mg/0.5 mL PBS) or pomegranate seed oil (0.5 mL) via oral administration for 10 days | TNBS-induced colitis | Punicic acid: ↓ Wallace and Ameho scores, ↓ MPO activity in colon, ↓ F2-isoprostane in colon; Pomegranate seed oil: ↓ Wallace and Ameho scores | Boussetta et al., 2009 [20] |
Swiss albino mice | Pomegranate flower hydro-alcoholic extract (100 or 200 mg/kg b.w.) or EA-rich fraction of pomegranate flower (100 or 200 mg/kg b.w.) via oral administration for 7 days | DSS-induced colitis | ↓ macroscopic and histopathological changes in colon, ↓ colon MPO activity, ↓ histamine content in colon, ↓ MDA level in colon, ↓ superoxide anion production in colon | Singh et al., 2009 [27] | |
Fischer rats | Pomegranate extract (250 mg/kg b.w.) or urolithin A (15 mg/kg b.w.) via chow for 10 days | DSS-induced colitis | ↓ colon tissue damage (urolithin A only), ↑ FRAP (pomegranate extract only), ↓ MDA in colon (pomegranate extract only), ↓ COX-2 gene and protein expression in colon, ↓ iNOS expression in colon, ↓ PGE2 and NO levels in colon (pomegranate extract only), ↓ PTGES protein expression in colon | Larrosa et al., 2010 [22] | |
Wistar rats | EA (10 and 20 mg/kg b.w.) via oral gavage for 48, 24 and 1 h prior to the induction of colitis and 24 h later | TNBS-induced colitis | ↓ colon macroscopic damage, ↓ b.w. loss, ↓ colon weight/length, ↓ histological damage in colon, ↓ colon MPO activity, ↓ iNOS and COX-2 protein expression in colon, ↓ JNK and ERK phosphorylation in colon, ↓ NF-κB activation in colon | Rosillo et al., 2011 [25] | |
Wistar rats | Pomegranate extract (250 or 500 mg/kg feed) or EA (10 mg/kg feed) or EA-enriched pomegranate extract (pomegranate extract 250 mg/kg feed + EA 10 mg/kg feed) via chow for 30 days prior to the induction of colitis and 14 days later | TNBS-induced colitis | ↓ colon macroscopic damage, ↓ b.w. loss (all treatments, apart from extract 250 mg/kg), ↓ colon weight/length (EA and EA-enriched extract only), ↓ colon MPO activity, ↓ TNF-α level in colon, ↓ iNOS and COX-2 protein expression in colon, ↓ JNK and ERK phosphorylation in colon, ↓ NF-κB activation in colon, ↔ colon PPAR-γ protein expression | Rosillo et al., 2012 [24] | |
C57BL/6 mice | EA (0.5% w/w, equivalent to 25 mg/mouse) via chow for 56 days | DSS-induced colitis | ↓ disease symptoms, ↓ DAI, ↓ iNOS and COX-2 protein expression in colon, ↓ JNK and ERK phosphorylation in colon, ↓ NF-κB activation in colon, ↓ IL-6 gene expression in colon, ↓ STAT3 phosphorylation in colon | Marín et al., 2013 [23] | |
Sprague-Dawley rats | Pomegranate beverage (containing 2504.74 mg/L GAE) ad libitum for 3 weeks prior to the induction of colitis and 7 weeks later | DSS-induced colitis | ↓ colonocyte proliferative index, ↓ expression of hs-CRP, TNF-α, IL-1β, and IL-6 in intestinal mucosa, ↓ IL-1β and IL-6 levels in serum, ↑ IL-10 level in serum, ↓ p-p70-S6K/p70-S6K, ↓ p-rpS6/rpS6 | Kim et al., 2016 [21] | |
Sprague-Dawley rats | Pomegranate juice (400 mg/kg b.w.) or pomegranate powder (4 mg/kg b.w.) via oral administration for 18 days | DNBS-induced colitis | ↔ histopathological scores, ↓ CMDI and DAI, ↓ MDA in colon (juice only), ↔ colon MPO activity, ↓ colon NO production, ↓ colon SOD activity, ↓ serum cortisol level, ↓ IL-1β, IL-18, TNF-α, and NF-κB expression in colon | Shah et al., 2016 [26] | |
Metabolic and cardiovascular disorders | Zucker rats | Concentrated pomegranate juice or pomegranate fruit extract (6.25 mL/L) via drinking water or pomegranate seed oil (1 mL/L) via chow for 5 weeks | Obese metabolic syndrome model | ↔ TC, ↔ LDL-C, ↔ HDL-C, ↑ TG (seed oil only), ↔ daytime MAP, ↔ BPM, ↔ motor activity, ↓ arterial TSP-1 protein expression, ↑ eNOS protein expression (apart from oil), ↓ arterial TGF-β1 protein expression (except oil), ↓ nitrate and nitrite levels (apart from oil), ↔ insulin and glucose levels | de Nigris et al., 2007 [43] |
db/db mice | Pomegranate seed oil (1 g/100 g feed) via chow for 30 days | Diabetes and obesity model | ↓ glycaemia, ↓ blood insulin, ↑ expression of genes PPAR-α, CD36, and FABP4 in adipose tissue, ↔ expression of genes PPAR-γ, ACAD, and SCD1 in adipose tissue, ↑ expression of genes PPAR-γ, CD36, FABP4, ACAD, and SCD1 in muscle, ↔ expression of genes PPAR-α in muscle, ↓ TNF-α expression and NF-κB activation in adipose tissue and liver | Hontecillas et al., 2009 [46] | |
CD-1 mice | Pomegranate juice (12.5 mL/L juice diluted in water, equivalent to 0.35 mmol polyphenols) via drinking water for 4 months | Streptozotocin-induced diabetes | ↑ hepatic PON-1 expression and activity, ↓ glycaemia, ↔ blood TC and TG levels | Betanzos-Cabrera et al., 2011 [41] | |
Sprague-Dawley rats | Pomegranate juice (100 μL) via gastric gavage for 10 weeks | Streptozotocin-induced diabetes | ↔ GSH in lung, ↑ SOD activity in lung, ↓ protein carbonyl content in lung, ↓ serum sialic acid, ↓ eNOS protein in lung | Çukurova et al., 2012 [42] | |
SR-BI/apoE double knockout mice | Pomegranate extract (307.5 ml/L) via drinking water for 2 weeks | Coronary heart disease model | ↑ TC, ↔ serum apoA and apoB, ↓ atherosclerosis, ↔ SAA and serum MCP-1, ↓ MCP-1 in plaques, ↓ lipid accumulation, macrophage infiltration, and MCP-1 levels in heart, ↓ myocardial fibrosis, cardiac enlargement, and ECG abnormalities | Al-Jarallah et al., 2013 [40] | |
BalbC mice | Pomegranate peel extract (0.2% w/v diluted in water, equivalent to 6 mg per mouse) via drinking water for 4 weeks | High-fat diet-induced obesity and hypercholesterolaemia | ↔ body weight gain, ↔ adiposity, ↔ glycaemia and insulin response, ↓ serum TC and LDL-C, ↔ serum HDL-C and TG, ↔ hepatic TC and TG, ↔ IL-1β, IL-6, and COX-2 expression in liver, ↔ IL-1β expression in colon, ↓ IL-6 and COX-2 expression in colon | Neyrinck et al., 2013 [47] | |
Wistar rats | EA (0.8 g/kg feed) via chow for 8 weeks after the induction of metabolic syndrome | High-fat and high-carbohydrate diet-induced metabolic syndrome | ↑ retroperitoneal, epididymal, omental, and total abdominal fat, ↔ whole-body fat mass, ↓ whole-body lean mass, ↓ glycaemia, ↓ plasma TG, TC, NEFA, uric acid, urea, and CRP, ↓ plasma ALT, AST, ALP, and LDH activity, ↔ plasma albumin and bilirubin, ↓ SBD, ↑ coronary endothelial-dependent relaxation, ↔ Nrf2 protein expression in heart, ↑ Nrf2 protein expression in liver, ↓ NF-κB expression in heart and liver, ↑ CPT1 expression in heart and liver | Panchal et al., 2013 [49] | |
Wistar Albino Glaxo rats | Pomegranate extract (300 mg/kg b.w.) via chow for 8 weeks | High-fat diet-induced metabolic syndrome | ↔ weight of epididymal adipose tissue, ↔ glycaemia, ↓ LDL-C, ↔ TC, HDL-C, TG, and FFA, ↔ SBP, ↓ serum corticosterone, ↔ adrenal corticosterone, ↓ serum IL-6 and TNF-α, ↓ TG in liver | Dushkin et al., 2014 [44] | |
Sprague-Dawley rats | PUNI-enriched pomegranate extract (150 mg/kg b.w.) via oral gavage for 8 weeks | High-fat diet-induced NAFLD | ↓ body weight gain, ↓ serum TG, HDL-C, and LDL-C, ↔ serum C, ↓ serum insulin, leptin, and adiponectin, ↓ HOMA-IR, ↓ serum ALT level, ↓ liver tissue weight, ↓ hepatic TG and TC, ↓ expression of SREBP-1c precursor protein, ↔ expression of SREBP-1c mature protein, expression of FA biosynthesis-related genes (↓ SREBP-1c, ↓ FAS, ↓ ACC1, ↓ SCD1), expression of TG biosynthesis-related genes (↓ ACLY, ↔ GPAM, ↑ DGAT-1 and-2), ↓ serum CRP level, IL-1β, IL-4, IL-6, and TNFα, ↓ serum IgA, IgG, and IgM, ↓ protein carbonyl content in liver tissue and liver mitochondria, ↓ lipid peroxidation in liver, ↑ hepatic total SOD activity, ↓ hepatic GSH and GSSG levels, ↑ GSH/GSSG ratio, ↓ Nrf2, HO-1, NQO-1, and UCP2 protein expression in liver, ↑ ATP content in liver, ↑ activities of mitochondrial complexes I, II, and IV in liver, ↑ expression of genes PGC-1-α and PPAR-α in liver, ↔ expression of PGC-1β gene in liver, ↑ PGC-1α protein expression in liver, ↑ expression of genes CPT1A, CPT1B, and ACAD in liver | Zou et al., 2014 [52] | |
Pigs | Pomegranate extract Pomanox® (625 mg equivalent to 200 mg punicalagins) via chow for 10 days | High-fat diet-induced coronary endothelial dysfunction | ↑ coronary endothelial-dependent relaxation, ↑ Akt and eNOS phosphorylation in coronary artery, ↔ MCP-1 gene expression in coronary artery, ↓ MCP-1 protein content in coronary artery, ↓ coronary DNA oxidative damage, ↓ LDL-C oxidation | Vilahur et al., 2015 [51] | |
Sprague-Dawley rats | Pomegranate juice concentrate (equivalent to 80 μmol polyphenols/mL) via drinking water for 5 weeks | Cigarette smoking-induced cardiac hypertrophy | ↔ DBP and SBP, ↓ ROS in aortic tissue, ↓ heart to body weight ratio, ↓ fibrotic marker (ObR and Fn1) and kinin receptor (Bdkrb1 and Bdkrb2) expression in aorta, ↓ IL-1β expression in aorta, ↔ TNF-α expression in aorta | Al Hariri et al., 2016 [39] | |
C57Bl/6 mice | Pomegranate peel (250 mg/kg b.w.) or Pomegranate flower extract (250 mg/kg b.w.) or Pomegranate seed oil (2 mL/kg b.w.) for 6 weeks | High-fat and high-sugar diet-induced obesity | ↔ b.w. gain, ↓ glycaemia (28 days- seed oil treatment only), ↔ plasma insulin level, ↔ plasma TC, HDL-C, and TG, ↔ hepatic ALT and AST, ↔ hepatic TG, ↑ plasma IL-2 (peel extract only), ↓ plasma IL-6 (apart from flower extract), ↑ plasma IL-10 (flower extract only), ↓ plasma TNF-α (apart from peel extract), ↑ IFN-γ (seed oil only) | Harzallah et al., 2016 [45] | |
Sprague-Dawley rats | Pomegranate juice (60 mL) via drinking water for 7 weeks | High-fat and high-sugar diet-induced NAFLD | ↓ plasma ALT and AST, ↔ plasma GGT and ALP, ↓ glycaemia and insulin, ↓ plasma TG, ↔ plasma TC, HDL-C, and LDL-C, ↓ hepatic IL-1β, IL-6, TNF-α, and TGF-β1 expression, ↑ hepatic IL-10 expression, ↔ GSH level, TBARS level, GR activity, CAT activity, SOD activity in liver, ↑ hepatic GPx activity, ↓ hepatic steatosis and ballooning, ↓ lobular and portal inflammation in liver | Noori et al., 2017 [48] | |
Sprague-Dawley rats | Pomegranate juice (1 mL) or pomegranate seed extract (100 mg/mL) via oral administration, by force-feeding for 21 days | Streptozotocin-nicotinamide induced type 2 diabetes | ↔ b.w. gain, ↔ glycaemia and plasma insulin level, ↓ TC and TG (juice only), ↔ LDL-C and HDL-C (juice only), ↑ TC, LDL-C, and HDL-C (seed extract only), ↔ TG (seed extract only), ↓ plasma IL-6 and NF-κB levels, ↓ plasma TNF-α level (juice only), ↑ number and size of Islets of Langerhans (juice only) | Taheri Rouhi et al., 2017 [50] | |
Neurodegenerative diseases | APPswe/PS1dE9 mice | Pomegranate extract (6.25 mL/L) via drinking water for 3 months | Transgenic model overexpressing APP, developing amyloid plaques and progressive cognitive deficits | ↑ behavioural performance, ↓ TNF-α in spleen and brain, ↓ NFATc1 activation in spleen and brain, ↑ p-NFATc2/NFATc2 ratio in brain, ↓ p-IκB/IκB ratio in brain, ↓ plaques in brain | Rojanathammanee et al., 2013 [59] |
Lewis rats | Pomegranate juice (juice diluted 1:40 in water, equivalent to ~0.6–0.7 mg polyphenols) via drinking water for 2 weeks | Rotenone-induced degeneration of neurones | ↓ rearing behaviour, ↔ postural instability, ↔ catecholamine levels, ↓ dopamine fibres in striatum, ↓ nigral dopaminergic neurones, ↑ nitrotyrosine in substantia nigra, ↑ iNOS induction, ↑ NF-κB activation, ↑ caspase activation, ↔ IL-1β, TNF-α, and COX-2 protein expression | Tapias et al., 2014 [60] | |
C57BL/6 mice | Pomegranate seed oil as emulsified nanodroplets (10 μL) via gavage for 10 days | MOG-induced experimental autoimmune encephalomyelitis | ↓ demyelination and oxidation of brain lipids, ↓ MDA in brain | Binyamin et al., 2015 [54] | |
APPsw/Tg2576 mice | Pomegranate fruit (4% w/w) via chow for 15 months | Transgenic model overexpressing APP, developing amyloid plaques and progressive cognitive deficits | ↓ IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and eotaxin levels in serum, ↓ Aβ-1 40 and 42 levels in brain, ↑ ATP levels the cortex and hippocampus, ↓ IL-1β, IL-6, TNF-α levels in cortex and hippocampus | Essa et al., 2015 [56] | |
APPsw/Tg2576 mice | Pomegranate fruit (4% w/w) via chow for 15 months | Transgenic model overexpressing APP, developing amyloid plaques and progressive cognitive deficits | ↓ expression of genes IL-1β, IL-10, TNF-α, IGF-1, iNOS, and CCL2, ↑ BDNF gene expression, ↑ PSD-95, Munc18-1, SNAP25, and synaptophysin protein expression, ↑ p-CaMKIIα/CaMKIIα protein expression, ↑ p-CREB/CREB protein expression, ↑ BECN1 protein expression, ↑ LC3-I and LC3-II protein expression, ↑ Akt and mTOR protein expression, ↑ p70-S6K protein expression, ↔ APP and CTF-α protein expression, ↓ BACE-1, CTF-β, and sAPP-β protein expression, ↔ ADAM-10 and ADAM-17 protein expression | Braidy et al., 2016 [55] | |
Wistar rats and mice | EA (10, 30, and 100 mg/kg b.w.) via intraperitoneal injection in a single administration | Scopolamine- and diazepam-induced cognitive impairments | ↓ amnesia in EPM and PA tests in mice ([EA] ≥ 30 mg/kg), ↓ amnesia in EPM test in rats ([EA] ≥ 30 mg/kg) | Mansouri et al., 2016 [57] | |
C57Bl/6 mice | Pomegranate peel extract as microparticles (800 mg/kg b.w.) via oral administration for 35 days | Amyloid-β peptide-induced neurodegeneration | ↔ locomotor activity in an activity cage, ↔/↑ spatial memory in the Barnes maze, ↓ senile plaques, ↑ BDNF level in cortex and hippocampus, ↓ acetylcholinesterase activity in cortex and hippocampus, ↓ MDA in liver, ↔ SOD activity in hippocampus, cortex and serum, ↓ TNF-α in cortex, ↔ TNF-α in serum | Morzelle et al., 2016 [58] | |
ICR mice | PUNI (1.5 mg/kg b.w.) via drinking water for 4 weeks | LPS-induced cognitive impairment | ↓ Aβ and BACE-1 protein expression, ↓ GFAP and AIF-1 protein expression, ↓ IL-1β, IL-6, and TNF-α release, ↑ GSH/GSSG ratio, ↓ ROS level, ↓ MDA, ↓ IκB phosphorylation, ↓ p50 and p65 protein expression | Kim et al., 2017 [53] | |
RA | DBA/1 Lac J mice | POMxTM extract (13.6 or 34 mg/kg b.w.) via oral gavage for 10 days | Collagen-induced arthritis with chicken CII (Chondrex) | ↓ incidence and delay of arthritis, ↓ synovitis, ↓ pannus formation, ↓ joint degradation, ↓ IL-1β expression in ankle joints (13.6 mg/kg only), IL-6 expression in ankle joints, ↓ TNF-α expression in ankle joints (34 mg/kg only) | Shukla et al., 2008 [65] |
Hepatocellular carcinoma | Sprague-Dawley rats | Pomegranate emulsion (1 or 10 g/kg b.w.) via oral gavage for 4 weeks prior to the DENA exposure and 18 weeks later | DENA-induced hepatocarcinogenesis | ↓ cyclin D1 expression (10 g/kg only), ↑ Bax/Bcl-2 ratio (10 g/kg only), ↓ β-catenin expression (10 g/kg only), ↑ GSK-3 expression (10 g/kg only) | Bhatia et al., 2013 [67] |
Prostatic hyperplasia | Sprague-Dawley rats | Pomegranate fruit extract (25, 50, and 100 mg/kg b.w.) via oral gavage for 4 weeks | Testosterone-induced prostatic hyperplasia | ↓ prostate weight, ↓ PAP activity, ↑ GSH, ↔ total glutathione, ↑ SOD activity (100 mg/kg only), ↔ CAT activity, ↓ MDA, ↓ iNOS and COX-2 expression, ↔ AR, NF-κB, ER-α, and p-Akt expression | Ammar et al., 2015 [68] |
Prostate cancer | Athymic nude mice | Pomegranate fruit extract (0.1% and 0.2% w/v) via oral administration for 28–51 days (until the implanted tumour reached to a volume of 1200 mm3) | Implantation with androgen-responsive CWR22Rn1 cells | ↓ PSA secretion | Malik & Mukhtar 2006 [69] |
Cell Model | Primary Cell/Cell Line | Tested Compound(s), Dose, Duration | Pro-Inflammatory Treatment | Biological Effects | Reference |
---|---|---|---|---|---|
Intestinal cells | CCD18-Co | Uro-A (40 μM) + Uro-B (5 μM) + EA (1 μM) for 12–48 h in concomitant exposure with pro-inflammatory stimulus | IL-1β (1 ng/mL) or TNF-α (50 ng/mL) | ↓ IL-8 release, ↓ PGE2 release (only upon IL-1β stimulus), ↓ PAI-1 release, ↔ ICAM-1 and VCAM-1 release, ↔ MCP-1, ↓ cell migration and adhesion | Giménez-Bastida et al., 2012 [28] |
Caco-2 | Pomegranate husk extract (containing 8.1 μM PUNI and 7.9 μM EA) or PUNI (50 μM) for 1 h as pre-treatment and 24 h in concomitant exposure with pro-inflammatory stimulus | basolateral side: IL-1β (25 μg/L) + TNF-α (50 μg/L) + IFN-γ (50 μg/L); apical side: LPS (1 mg/L) | ↓ IL-6 and MCP-1transcription, ↔ IL-8 transcription, ↓ IL-6, IL-8, and MCP-1 secretion | Hollebeeck et al., 2012 [29] | |
Immune cells | KU812 | POMxTM extract (20, 40, and 100 μg/mL) for 2 h prior to pro-inflammatory stimulus | PMA (40 nM) + A23187 (1 μM) | ↓ IL-6 and IL-8 transcription, ↓ IL-6 and IL-8 secretion, ↓ JNK and ERK phosphorylation, ↓ NF-κB activation | Rasheed et al., 2009 [31] |
Primary HGE | EA (12.5, 25, 50, and 100 μM) for 18 h | - | ↓ IL-8 transcription ([EA] ≥ 25 μM), ↑ BD2 transcription ([EA] ≥ 25 μM), ↑ SLPI transcription, ↓ CCL20 transcription ([EA] ≥ 50 μM), ↓ CXCL5 transcription ([EA] ≥ 50 μM), ↔ IL-1β secretion, ↑ IL-2 secretion ([EA] = 12.5 μM), ↓ IL-2 secretion ([EA] = 50 μM), ↔ IL-4, IL-6, and TNF-α secretion, ↓ IL-8 secretion ([EA] = 50 μM), ↔ MCP-1 secretion, ↑ CCL5 secretion ([EA] ≥ 12.5 μM), ↑ BD2 secretion ([EA] = 100 μM), ↔ SLPI secretion | Promsong et al., 2015 [30] | |
Neuronal cells | PC12 | Pulp aqueous extract (6.25–800 μg/mL), pulp hydro-alcoholic extract (6.25, 12.5, 25, 50, 100, 200, 400, and 800 μg/mL), PJ extract (6.25, 12.5, 25, 50, 100, 200, 400, and 800 μg/mL) for 2 h prior glucose deprivation | Serum glucose deprivation | ↓ DNA damage ([PJ] ≥ 400 μg/mL) | Forouzanfar et al., 2013 [61] |
BV-2 | Pomegranate seed oil (25 μg/mL) for 24 h | LPS (1 mg/mL) | ↓ NO production, ↓ TNF-α release, ↓ iNOS induction, ↓ caspase 3 activation | Račková et al., 2014 [62] | |
SK-N-SH | PJ extract (25, 50, 100, and 200 μg/mL) for 24 h | IL-1β (10 U/mL) | ↓ PGE2 release, ↓ COX-2 protein expression, ↓ BACE-1 ([PJ] ≥ 50 μg/mL), ↓ amyloid-β ([PJ] ≥ 100 μg/mL), ↓ IκBα phosphorylation ([PJ] ≥ 50 μg/mL) | Velagapudi et al., 2016 [63] | |
Primary astrocytes and BV-2 | PUNI (10, 20, and 50 μM) for 1 h | LPS (1 mg/mL) | ↓ iNOS and COX-2 protein expression, ↓ APP and BACE-1 protein expression, ↓ IκBα phosphorylation | Kim et al., 2017 [53] | |
Rheumatoid arthritis cells | MH7A | Delphinidin (10 and 30 μM) for 24 h or 2 h (for ELISA) | TNF-α (20 ng/mL) | ↓ IL-1β and IL-6 expression, ↓ COX-2 expression, ↓ p65 acetylation, ↓ NF-κB DNA binding activity | Seong et al., 2011 [66] |
Cancer cells | DU145 and PC3 | PJ (1% or 5%) for 18 h | - | ↓ IL-6 and IL-12 secretion, ↓ IL-1β secretion (DU145 only), ↓ CCL5 secretion (PC3 only) | Wang et al., 2011 [70] |
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Danesi, F.; Ferguson, L.R. Could Pomegranate Juice Help in the Control of Inflammatory Diseases? Nutrients 2017, 9, 958. https://doi.org/10.3390/nu9090958
Danesi F, Ferguson LR. Could Pomegranate Juice Help in the Control of Inflammatory Diseases? Nutrients. 2017; 9(9):958. https://doi.org/10.3390/nu9090958
Chicago/Turabian StyleDanesi, Francesca, and Lynnette R. Ferguson. 2017. "Could Pomegranate Juice Help in the Control of Inflammatory Diseases?" Nutrients 9, no. 9: 958. https://doi.org/10.3390/nu9090958