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

1-16

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
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  • 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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    17 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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    21 schema:keywords AD model
    22 Cochrane Library
    23 ConclusionOverall
    24 EMBASE
    25 English language
    26 GPx
    27 GSH
    28 I2 statistic
    29 IFN
    30 IL
    31 IL-1β
    32 IL-6
    33 MDA
    34 MethodsUp
    35 NF-κB
    36 OS biomarkers
    37 PubMed
    38 ResultsWe
    39 SOD
    40 SOD activity
    41 Scopus
    42 TNF
    43 Web
    44 Web of Science
    45 activity
    46 address
    47 alternative treatment
    48 animal models
    49 animal studies
    50 assessment
    51 autoimmune disease models
    52 autoimmune disorders
    53 autoimmune-related diseases
    54 biological processes
    55 biomarkers
    56 cats
    57 checklist protocol
    58 clinical setting
    59 clinical studies
    60 clinical trials
    61 comprehensive literature search
    62 conditions
    63 confident interval
    64 control group
    65 data
    66 database
    67 differences
    68 different parameters
    69 disease
    70 disease models
    71 disorders
    72 dosage range
    73 effect
    74 effect of naringenin
    75 effective alternative treatment
    76 efficacy
    77 efficacy of naringenin
    78 electronic databases
    79 eligible studies
    80 evidence
    81 experiment study
    82 factors
    83 family
    84 findings
    85 flavonoid family
    86 future
    87 group
    88 heterogeneity test
    89 immunomodulatory activity
    90 immunomodulatory potential
    91 immunomodulatory properties
    92 inflammation
    93 inflammatory biomarkers
    94 inflammatory diseases
    95 inflammatory mediators
    96 inhibition
    97 inhibition of inflammation
    98 initial safety profile
    99 interval
    100 investigation
    101 language
    102 large-scale clinical studies
    103 levels
    104 levels of CAT
    105 levels of MDA
    106 library
    107 limitations
    108 literature search
    109 mean difference
    110 mediators
    111 members
    112 model
    113 naringenin
    114 naringenin group
    115 nitric oxide
    116 oxidative stress
    117 oxide
    118 parameters
    119 parameters of inflammation
    120 pathological conditions
    121 pharmacokinetic investigations
    122 potential
    123 preclinical evidence
    124 preclinical models
    125 process
    126 profile
    127 properties
    128 protocol
    129 quality assessment
    130 quantitative synthesis
    131 random-effects model
    132 range
    133 recent research
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    139 series
    140 setting
    141 statistically difference
    142 statistics
    143 stress
    144 strong preclinical model
    145 study
    146 subjects
    147 synthesis
    148 systematic review
    149 test
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