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. Author manuscript; available in PMC: 2023 Jun 1.
Published in final edited form as: J Nutr Biochem. 2022 Feb 18;104:108967. doi: 10.1016/j.jnutbio.2022.108967

Table 1.

Lipids lowering effects of naringin, naringenin, and its enriched food sources

Model Flavonoid Key Findings Mechanism Reference
In vitro study Pancreatic lipase activity assay Naringin (0.6 mM) Synergistically inhibited PL activity with 0.6 mM emodin PL inhibition [45]
Hela cells Naringenin (0.01–100 μM for 24 h) Decreased ABCA1 mRNA expression Antagonist of LXRs [48]
Human THP-1 macrophages Naringenin (100 μM for 18 h) Enhanced cholesterol efflux; Increased RCT Increased NR1H3, ABCA1, and ABCG1 mRNA and protein expression [50]
Murine RAW 264.7 macrophages Naringenin (10–50 μM for 24 h) Enhanced cholesterol efflux; Increased RCT Increased Nr1h3, Abca1, and Abcg1 mRNA and protein expression; Decreased ATF6, GRP78, XBP-1 protein levels [49]
Human HepG2 cells Naringin (12.5 μM-50 μM for 24 h) Dose dependently increased LDLR and CYP7A1 mRNA expression and protein level SREBP-2 and PPARγ activation [52]
Obesity-induced dyslipidemia In vivo - mice Diet-induced obese male C57BL/6 mice; (n=10 per group) Naringin 25–100 mg/kg for 8 weeks Decreased body weight, liver weight, plasma LDL-C level, and hepatic TG and TC levels Up-regulated hepatic Ldlr mRNA expression; Up-regulated hepatic p-AMPK α level; Reduced hepatic Srebp-1, Srebp-2, Pcsk9 mRNA expression [53]
In vivo - mice Ovariectomized obese C57BL/6 female mice (n=4–10 per group) Naringenin 3% (WT/WT) for 11 weeks No changes in serum and hepatic TG and TC levels; Decreased body weight, intraabdominal adiposity, and blood glucose levels; Decreased DAG levels in muscle Decreased Fasn and Scd1 mRNA expression in muscle [55]
In vivo - humans Class 1 obese patients with hypercholesterole mia (n=28) Naringin 450 mg/d for 90 days Decreased body weight, plasma TG, TC, and LDL-C levels Undetermined [56]
Diabetic dyslipidemia In vivo - rats high fat-low streptozocin model of T2DM rats (n=5 per group) Naringin 50–200 mg/kg bw/d for 9 weeks Decreased plasma TC and TG, and hepatic TC levels; Increased hepatic HDL-C and HDL3-C levels; No changes in liver TG levels Increased hepatic CPT activity; Increased paraoxonase activities in HDL; Increased hepatic Scarb1, Ahr, Lipc, and Lcat mRNA expression [60]
Simple dyslipidemia without other metabolic diseases In vivo - mice Lean male Ldlr −/− C57BL/6 mice; (n=12 per group) Naringenin 3% (WT/WT) for 8 weeks Decreased body weight, epididymal white fat weight, plasma TG, LDL-C, VLDL-C, and liver TG levels; Increased plasma betahydroxybutyrate level Enhanced hepatic Pnpla2, Cpt1a mRNA expression [63]
In vivo - humans Moderately hypercholesterole mic men and women (n=194) Naringin 500 mg/d for 4 weeks No changes in serum TG, HDL-C, and LDL-C level Undetermined [64]
Bergamot extracts with other nutraceuticals In vivo - humans Patients with moderate dyslipidemia (n=11) F105 (Bergamot fruit extract (BFP, 500 mg/d) with other 9 phytoextracts (220 mg/d) for 12 weeks Decreased plasma TC, LDL-C, non-HDL-C, and C/HDL; Decreased TG, oxLDL, LDL/HDL, TG/HDL, oxLDL/HDL, and PAI levels in a subgroup of subjects with abnormal HbA1C, HOMA-IR score, or TG levels Undetermined [70]
In vivo - humans Participants (n=50) with higher serum cholesterol (<500 mg/dl) 1 tablet/d (whole bergamot extracts (200 mg), omega-3 (400 mg), trivalent chromium (10 μg), and red yeast rice (100 mg)) for 6 weeks Decreased plasma TG, TC, LDL-C levels; Increased plasma HDL level Undetermined [71]
In vivo - humans Older adults with moderate dyslipidemia (n=98) 1 tablet contains whole bergamot extract (250 mg), plant sterol esters (410 mg), orange oil, vitamin C (25 mg), Vitamin B6 (10 mg), Vitamin B12 (1000 μg), and folic acid (400 μg). 2 tablets/day for 12 weeks Decreased body weight, circumstances, BMI, plasma TG, TC, and LDL-C levels Undetermined [72]
Citrus Sinensis (Orange) In vivo - rats Diet-induced hyperlipidemic Male Wistar rats (n=10 per group) Orange juice (2–8 ml/kg bw/day) Decreased serum TG, TC, and LDL-C; Increased HDL-C level Undetermined [75]
In vivo - humans Overweight/obese participants (n=100) Orange juice with normal (299 mg) or high (745 mg) content of polyphenols (500 ml/d) for 12 weeks Reduced body weight, BMI, waist circumference, plasma TG, ApoB levels by both juices; Increased plasma ApoA-1 level only by the juice with high polyphenols Undetermined [76]
In vivo - humans Obese participants (n=78) Orange juice 500 ml/d combined with a reduced-calorie diet for 12 weeks Reduced plasma TC and LDL-C levels in addition to the benefits by only a reduced-calorie diet Undetermined [77]
In vivo - humans Overweight or obese men (n=36) Orange juice 250 ml/d compared to an energy and sugar content matched control drink for 12 weeks Decreased plasma TG in the subjects with elevated TG at base line Undetermined [78]
In vivo - humans Healthy women (n=10) Orange juice 300 ml/d for 60 days Decreased serum TG, TC, and LDL-C levels; Increased Lactobacillus and Bifidobacterium in fecal samples; Increased acetic acid and decreased NH4+ level in fecal samples. The relative abundance of Akkermansia is negatively correlated with serum TG and LDL-C, but positively correlated with HDL-C Improved gut microbiota [39], [79]
In vivo - humans Healthy participants (n=15) Orange juice 500 ml/d for 2 weeks No changes in plasma glucose, TG, TC, LDL-C, and HDL-C levels; Decreased medium and long-chain acylcarnitine level; Increased short-chain acylcarnitine level Undetermined [80]
In vivo - humans Normal weight (n=17); or overweight/obese subjects (n=12/6) Red orange juice 750 ml/d for 8 weeks Decreased TC and LDL-C levels but no changes of TG in both normal weight and overweight/obese group; Decreased HDL-C and ApoA1 only in the normal weight group Undetermined [82]
In vivo - humans Obese women (n=11) Red orange juice 500 ml/d for 12 weeks Decreased plasma TC and LDL-C levels; No changes in body weight and TG level Undetermined [83]
In vivo - humans Obese participants (n=41) Red orange juice 500 ml/d for 4 weeks No changes in plasma TC, TG, LDL-C, and HDL-C levels Undetermined [84]
In vivo - mice Healthy lean male OF1 mice (n=8 per group) Orange beverage for 12 weeks (fermentedpasteurized) 1:10 diluted in tap water, equal to 250 ml/d in human Decreased TC, TG, LDL-C, and oxidized LDL levels; Increased HDL, total and reduced glutathione level Anti-oxidation; [87]
In vivo - humans Participants with moderate hypercholesterolemia (n=18) Orange beverage 500 ml/d for 2 weeks (fermentedpasteurized) Decreased plasma TC, TG, LDL-C, and LDL/HDL ratio and other cardiovascular risk factors Undetermined [88]
In vivo - humans Healthy participants (n=26) Orange juice (20% of energy requirement) with or in between three meals; for 2 weeks in a 4-week cross-over study Decreased fat mass and serum gamma-glutamyl transferase when taking orange juice with meals; Increased fat mass and a trend of increased postprandial insulin sensitivity when taking between the meals; No changes in body weight and TG level Undetermined [89]
Other citrus fruits In vivo - mice Diet-induced obese C57BL/6J mice (n=8 per group) Citrus junos Tanaka peel extract 5% w/w for 10 weeks Decreased plasma TC and LDL-C level PPARα activation; Increased CPT1 level [90]
In vivo - mice Diet-induced obese C57BL/6J mice (n=8 per group) Immature Citrus reticulata (mandarin) dry fruits extracts

1% w/w for 11 weeks		 Decreased body weight, epidydimal fat pad weight, serum TG and TC level; Decreased adipocyte size and hepatic steatosis; Improved cold tolerance Increased mRNA expression of Ucp1 and thermogenic genes in inguinal WAT [91]
In vivo - mice Diet-induced obese C57BL/6J mice (n=8 per group) Citrus aurantium (bitter orange) blossoms extract 50 –200 mg/kg bw/d for 12 weeks Decreased body weight, serum TG, TC, LDL-C, LPS, and leptin level; Improved liver oxidation damage and steatosis Enhanced mitochondrial fatty acid beta-oxidation; Inhibited chronic low-grade inflammation; Reversed gut dysbiosis; [92]
In vivo - mice Diet-induced obese C57BL/6J mice (n=7–8 per group) Citrus tumida peel extract 5% w/w for 4 weeks Decreased body weight, epidydimal, perirenal, and subcutaneous fat pad weight; Decreased serum TG and TC level Undetermined [93]
In vivo - hamsters Diet-induced hyperlipidemic Hamsters (n=80) Citrus changshan-huyou peel extract 25–100 mg/kg bw/d for 4 weeks Decreased serum TG, TC, and LDL-C level; Increased SOD activity and decreased MDA level; Decreased serum and hepatic TNF-a and IL-6 level PPARα/γ activation; Increased hepatic CYP7A1 content; Decreased oxidative stress and inflammation [94]