The effect of immunomodulatory properties of naringenin on the inhibition of inflammation and oxidative stress in autoimmune disease models: a ... View Full Text


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Article Info

DATE

2022-07-08

AUTHORS

Mina Alimohammadi, Rebar N. Mohammad, Ali Rahimi, Fatemeh Faramarzi, Reza Alizadeh-Navaei, Alireza Rafiei

ABSTRACT

Background/objectiveNaringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis.MethodsUp until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-α, IL-6, IL-β, IFN-γ, NF-κB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI).ResultsWe excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-κB (SMD − 3.77, 95% CI [− 6.03 to − 1.51]; I2 = 80.1%, p = 0.002), IFN-γ (SMD − 6.18, 95% CI [− 8.73 to − 3.62]; I2 = 53.7%, p = 0.115), and NO (SMD − 3.97, 95% CI [− 5.50 to − 2.45]; I2 = 73.4%, p = 0.005), IL-1β (SMD − 4.23, 95% CI [− 5.09 to − 3.37]; I2 = 0.0%, p = 0.462), IL-6 (SMD − 5.84, 95% CI [− 7.83 to − 3.85]; I2 = 86.5%, p < 0.001), and TNF-α (SMD − 5.10, 95% CI [− 6.34 to − 3.86]; I2 = 74.7%, p < 0.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I2 = 79.9%, p = 0.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I2 = 90.5%, p < 0.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I2 = 86.6%, p = 0.001) and decreasing the levels of MDA (SMD − 3.65, 95% CI [− 4.80 to − 2.51]; I2 = 69.4%, p = 0.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [− 1.11 to 4.89]; I2 = 93.6%, p < 0.001).ConclusionOverall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin. More... »

PAGES

1127-1142

References to SciGraph publications

  • 2014-03-26. SYRCLE’s risk of bias tool for animal studies in BMC MEDICAL RESEARCH METHODOLOGY
  • 2017-04-13. Anti‐inflammatory and anti‐arthritic properties of naringenin via attenuation of NF‐κB and activation of the heme oxygenase ﴾HO﴿‐1/related factor 2 pathway in PHARMACOLOGICAL REPORTS
  • 2009-10-13. Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-β in JOURNAL OF NEUROINFLAMMATION
  • 2014-09-26. Effects of Naringenin on Inflammation in Complete Freund’s Adjuvant-Induced Arthritis by Regulating Bax/Bcl-2 Balance in INFLAMMATION
  • 2004-01. Do Vitamin E and Selenium Have Beneficial Effects on Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in DIGESTIVE DISEASES AND SCIENCES
  • 2008-12-03. Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-κB activation in experimental colitis in INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
  • 2022-06-04. The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence in INFLAMMOPHARMACOLOGY
  • 2009-09-23. Protective Effects of Selenium and Vitamin E Combination on Experimental Colitis in Blood Plasma and Colon of Rats in BIOLOGICAL TRACE ELEMENT RESEARCH
  • 2018-10-28. Naringenin mitigates titanium dioxide (TiO2)-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB in INFLAMMATION RESEARCH
  • 2012-03-27. Effect of Boswellia serrata on Antioxidant Status in an Experimental Model of Colitis Rats Induced by Acetic Acid in DIGESTIVE DISEASES AND SCIENCES
  • 2011-11-23. Protective Effect of Naringenin Against Lead-Induced Oxidative Stress in Rats in BIOLOGICAL TRACE ELEMENT RESEARCH
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    http://scigraph.springernature.com/pub.10.1007/s00011-022-01599-7

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        "description": "Background/objectiveNaringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis.MethodsUp until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-\u03b1, IL-6, IL-\u03b2, IFN-\u03b3, NF-\u03baB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI).ResultsWe excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-\u03baB (SMD \u2212\u00a03.77, 95% CI [\u2212\u00a06.03 to \u2212\u00a01.51]; I2\u2009=\u200980.1%, p\u2009=\u20090.002), IFN-\u03b3 (SMD \u2212\u00a06.18, 95% CI [\u2212\u00a08.73 to \u2212\u00a03.62]; I2\u2009=\u200953.7%, p\u2009=\u20090.115), and NO (SMD \u2212\u00a03.97, 95% CI [\u2212\u00a05.50 to \u2212\u00a02.45]; I2\u2009=\u200973.4%, p\u2009=\u20090.005), IL-1\u03b2 (SMD \u2212\u00a04.23, 95% CI [\u2212\u00a05.09 to \u2212\u00a03.37]; I2\u2009=\u20090.0%, p\u2009=\u20090.462), IL-6 (SMD \u2212\u00a05.84, 95% CI [\u2212\u00a07.83 to \u2212\u00a03.85]; I2\u2009=\u200986.5%, p\u2009<\u20090.001), and TNF-\u03b1 (SMD \u2212\u00a05.10, 95% CI [\u2212\u00a06.34 to \u2212\u00a03.86]; I2\u2009=\u200974.7%, p\u2009<\u20090.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I2\u2009=\u200979.9%, p\u2009=\u20090.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I2\u2009=\u200990.5%, p\u2009<\u20090.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I2\u2009=\u200986.6%, p\u2009=\u20090.001) and decreasing the levels of MDA (SMD \u2212\u00a03.65, 95% CI [\u2212\u00a04.80 to \u2212\u00a02.51]; I2\u2009=\u200969.4%, p\u2009=\u20090.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [\u2212\u00a01.11 to 4.89]; I2\u2009=\u200993.6%, p\u2009<\u20090.001).ConclusionOverall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin.", 
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    28 schema:description Background/objectiveNaringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis.MethodsUp until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-α, IL-6, IL-β, IFN-γ, NF-κB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI).ResultsWe excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-κB (SMD − 3.77, 95% CI [− 6.03 to − 1.51]; I2 = 80.1%, p = 0.002), IFN-γ (SMD − 6.18, 95% CI [− 8.73 to − 3.62]; I2 = 53.7%, p = 0.115), and NO (SMD − 3.97, 95% CI [− 5.50 to − 2.45]; I2 = 73.4%, p = 0.005), IL-1β (SMD − 4.23, 95% CI [− 5.09 to − 3.37]; I2 = 0.0%, p = 0.462), IL-6 (SMD − 5.84, 95% CI [− 7.83 to − 3.85]; I2 = 86.5%, p < 0.001), and TNF-α (SMD − 5.10, 95% CI [− 6.34 to − 3.86]; I2 = 74.7%, p < 0.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I2 = 79.9%, p = 0.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I2 = 90.5%, p < 0.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I2 = 86.6%, p = 0.001) and decreasing the levels of MDA (SMD − 3.65, 95% CI [− 4.80 to − 2.51]; I2 = 69.4%, p = 0.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [− 1.11 to 4.89]; I2 = 93.6%, p < 0.001).ConclusionOverall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin.
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