TABLE 1.

Summary of studies evaluating antiviral and anti‐inflammatory effects of naringenin

Articles	Type of study	Reference	Samples	Study design	Main results
Viral‐related articles	In vitro	Paredes, Alzuru, Mendez, & Rodriguez‐Ortega, 2003	BHK‐21 were infected with NSV	Administration of naringenin: 25 μg/ml	Inhibition of viral replication up to 80%
	In vitro, In vivo	Nahmias et al., 2008	Huh7.5.1human hepatoma cell line were infected with HCV; male mice were infected with HCV	Administration of naringenin: 200, 1,000, and 5,000 μM	Silencing apoB100 messenger RNA, a 70% reduction in the secretion of both apoB100 and HCV, a 80% reduction in HCV secretion in infected cells, a decrease in TG levels following injection
	In vitro	Goldwasser et al., 2011	Huh7.5.1 human hepatoma cell line infected with HCV	Administration of naringenin: 200 μM	A dose‐dependent inhibition of HCV production without affecting intracellular levels of the viral RNA or protein, inhibition of the assembly of intracellular infectious viral particles, a rapid 1.4 log reduction in HCV similar to 1,000 U of interferon
	In vitro	Zandi et al., 2011	Vero cells infected with DENV‐2	Administration of Naringenin: 50 μg/ml	A decrease in the DENV‐2 RNA level by 50% with naringenin compared to the non‐treated virus inoculum
	In vitro	Ahmadi et al., 2016	BHK‐21 were infected with CHIKV; Vero cells were infected with CHIKV	Administration of naringenin: Up to 500 μM	Reduction of the CHIKV intracellular replication efficiency and downregulation of the production of viral proteins involved in replication
	In vitro	Frabasile et al., 2017	Huh7.5 cells were infected with DENV; primary human monocytes were infected with DENV	Administration of naringenin: 250 μM	Inhibition of DENV replication with an efficiency similar to IFN‐α 2A and ribavirin, a reduction in the number of DENV‐infected cells
	In vitro	Cataneo et al., 2019	Human A549 cells were infected with ZIKV; primary human monocyte‐derived dendritic cells were infected by ZIKV	Administration of naringenin: 15.6, 31.25, 62.5 and 125 μM	Inhibition of viral replication or assembly of viral particles
	Human	Goncalves et al., 2017	43 adult patients with chronic HCV	Supplementation with 500 ml/day orange juice containing 2.7 mg naringenin	Protection against harmful effects of HCV by an increase in antioxidant capacity and a decrease in inflammation
	Quantitative analysis	Alam, Parvez, Arbab, & Al‐Dosari, 2017	Guiera senegalensis	Sensitive RP‐/NP‐HPTLC methods	Exhibiting anti‐HBV activity of Guiera senegalensis including naringenin
Inflammation‐related articles	In vivo	Fouad, Albuali, & Jresat, 2016	Induced‐lung injury rats	Administration of naringenin: 50, 100 mg/kg	Attenuating the production of inflammatory cytokines, pulmonary edema, neutrophil recruitment, myeloperoxidase activity, and reduction of oxidative/nitrosative stress markers
	In vivo	Ali et al., 2017	Rats with lung damage	Administration of naringenin: 100 mg/kg	Downregulation of the expression of NF‐κB and COX2
COVID‐19 related articles	Molecular docking analysis	Cheng et al., 2020	Citrus fruit flavonoids including naringenin	Docking analysis	Reduction of ACE2 receptor activity through the binding of naringenin to ACE2 with binding site proline, leucine, and lysine
	Molecular docking analysis	Khaerunnisa, Kurniawan, Awaluddin, Suhartati, & Soetjipto, 2020	6 LU7 and native ligands including naringenin	Docking analysis	Inhibition of COVID‐19 main protease through the interaction of naringenin with amino acids histidine, glutamic acid, aspartic acid, and threonine in the CoV main protease active site

Abbreviations: ACE2, angiotensin‐converting enzyme 2; apoB100, apolipoprotein B100; BHK‐21, baby hamster cells 21 clone 15; CHIKV, chikungunya virus; DENV, dengue virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IFN‐α 2A, interferon‐alpha 2A; NSV, sindbis neurovirulent strain; PR‐/NP‐HPTLC, reverse phase−/normal phase‐high performance; TG, triglyceride; Vero cells, african green monkey kidney cells; ZIKV, zika virus.