Interleukin‐6 inhibitory effect of natural product naringenin compared to a synthesised monoclonal antibody against life‐threatening COVID‐19

AmeliMojarad, Melika; AmeliMojarad, Mandana

doi:10.1002/rmv.2445

Cited by 3 publications

(4 citation statements)

References 130 publications

(225 reference statements)

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“…Naringin has been shown to significantly reduce the infiltration of inflammatory cells induced by lipopolysaccharide and decrease the production of macrophage nitrogen monoxide (NO) and IL-6 [ 169 ]. In critically ill COVID-19 patients, naringenin also showed excellent IL-6 inhibition compared to synthetic monoclonal antibodies [ 46 ]. In a paraquat-induced acute lung injury model, naringin not only decreased the production of the inflammatory cytokines TNF-α and TNF-β1 but also inhibited oxidative stress by activating the expression of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and heme oxygenase 1) and regulated collagen formation by modulating the ratio of tissue inhibitors of metalloproteinases-1 (TIMP-1) to MMP-9, thereby preventing lung fibrosis [ 170 ].…”

Section: Therapeutic Potential Of Naringin and Naringenin In Long Covidmentioning

confidence: 99%

“…The efficacy of naringin and naringenin is due to anti-inflammatory [ 41 ], anticancer [ 42 ], antioxidant properties [ 43 , 44 ], treatment of cardiovascular disease [ 45 ], antiviral [ 36 ] and immune-modulation effects [ 41 ], which may play an effective role in treating long COVID. The anti-inflammatory and antioxidant effects of naringenin can effectively counteract the cytokine storm induced by SARS-CoV-2, especially targeting and inhibiting interleukin(IL)-6, the main pro-inflammatory factor of COVID-19 [ 46 ]. Moreover, numerous molecular docking studies reveal that naringenin binds to viral spiking proteins, viral major proteases, host receptors, and host viral transport channels and has multiple antiviral effects against SARS-CoV-2 [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

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Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Liu,

Zhong,

et al. 2024

Microorganisms

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Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.

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Section: Therapeutic Potential Of Naringin and Naringenin In Long Covidmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Liu,

Zhong,

et al. 2024

Microorganisms

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“…After NAR enters the body, its active metabolite naringenin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP pathway [12]. Most notably, NAR has shown effectiveness in repairing inflammatory damage in the respiratory tract, and reducing sputum secretion and inflammatory infiltration in lungs [13]. NAR can improve lung inflammation by inhibiting the release of interleukin (IL)-8, leukotriene B4, tumour necrosis factor (TNF)-α, and persistent neutrophilic infiltration due to infection [14].…”

Section: Introductionmentioning

confidence: 99%

“…Porcine alveolar macrophages (PAM) are widely distributed on the alveolar and bronchial surfaces, forming a vital defence barrier for innate lung immunity [16]. When APP invades, pathogen-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP) in PAM are activated, causing it to release an excess of inflammatory cytokines [13,16]. When lung tissue is overloaded with inflammatory factors, it activates the NLRP3 inflammatory vesicle classical/non-classical pathway in turn, which mediates apoptosis as well as cellular pyroptosis via the caspase-1, caspase-8, and caspase-9 pathways, further exacerbating inflammation [17,18].…”

Section: Introductionmentioning

confidence: 99%

Naringin’s Alleviation of the Inflammatory Response Caused by Actinobacillus pleuropneumoniae by Downregulating the NF-κB/NLRP3 Signalling Pathway

Huang,

Li,

Jing

et al. 2024

IJMS

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Actinobacillus pleuropneumoniae (APP) is responsible for causing Porcine pleuropneumonia (PCP) in pigs. However, using vaccines and antibiotics to prevent and control this disease has become more difficult due to increased bacterial resistance and weak cross-immunity between different APP types. Naringin (NAR), a dihydroflavonoid found in citrus fruit peels, has been recognized as having significant therapeutic effects on inflammatory diseases of the respiratory system. In this study, we investigated the effects of NAR on the inflammatory response caused by APP through both in vivo and in vitro models. The results showed that NAR reduced the number of neutrophils (NEs) in the bronchoalveolar lavage fluid (BALF), and decreased lung injury and the expression of proteins related to the NLRP3 inflammasome after exposure to APP. In addition, NAR inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in porcine alveolar macrophage (PAMs), reduced protein expression of NLRP3 and Caspase-1, and reduced the secretion of pro-inflammatory cytokines induced by APP. Furthermore, NAR prevented the assembly of the NLRP3 inflammasome complex by reducing protein interaction between NLRP3, Caspase-1, and ASC. NAR also inhibited the potassium (K+) efflux induced by APP. Overall, these findings suggest that NAR can effectively reduce the lung inflammation caused by APP by inhibiting the over-activated NF-κB/NLRP3 signalling pathway, providing a basis for further exploration of NAR as a potential natural product for preventing and treating APP.

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Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway

Huang,

Zhao

et al. 2024

BMC Vet Res

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Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

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Interleukin‐6 inhibitory effect of natural product naringenin compared to a synthesised monoclonal antibody against life‐threatening COVID‐19

Cited by 3 publications

References 130 publications

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Naringin’s Alleviation of the Inflammatory Response Caused by Actinobacillus pleuropneumoniae by Downregulating the NF-κB/NLRP3 Signalling Pathway

Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway

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