Biological Mechanisms and Related Natural Inhibitors of CD36 in Nonalcoholic Fatty Liver

Figures & data

Figure 1 The mechanisms of CD36 in NAFLD. (A). Molecular mechanisms by which CD36 palmitoylation promotes FAO and NAFLD. (B). Molecular mechanisms by which CD36 palmitoylation promotes β-oxidation and inflammation. (C). Molecular mechanisms by which CD36 inhibits autophagy. (D). Molecular mechanisms by which CD36 promotes De novo lipogenesis.

Abbreviations: NAFLD, nonalcoholic fatty liver disease; CD36, differentiated cluster 36; LCFA, long chain fatty acid; ACSL, long-chain acyl-CoA synthetase; FAO, free fatty acid oxidation; TG, triglycerides; LKB1, live kinase B1; JNK, c-JUN N-terminal kinase; AMPK, AMP-activated protein kinase; Lyn, the kinase Lck/Yes-related novel protein tyrosine kinase; FA, Fatty acid; AhR, aryl hydrocarbon receptor; PXR, Pregnane X receptor; PPARγ: peroxisome proliferator-activated receptorγ; LXR, liver X receptor; PCSK9, proprotein convertase subtilisin/kexin type 9; mTOR, mechanistic target of rapamycin; UCK1, uridine-cytidine kinase 1; LDs, lipid droplets; ER, endoplasmic reticulum; SCAP, SREBP cleavage-activating protein; INSIG2, insulin-induced gene-2; SREBP1, sterol regulatory element-binding protein 1.

Table 1 Natural products which treat NAFLD through CD36

Name	Classification	Sources	Type of Study	Dosage	Medical Effects	References
Berberine	Alkaloids	Coptis chinensis	In vivo	blended into the ^AHFD at 1.4 g/kg	↓ Protein levels of CD36	[81]
			In vivo and in vitro	In vitro:10 µM In vivo:10 mg/kg/day	In vitro: ↑ mRNA expression and protein levels of CD36 transcriptional activation of CD36 In vivo: ↑ mRNA expression and protein levels of CD36	[82]
Curcumin	Phenols	Turmeric	In vivo	50 mg/kg and 100 mg/kg	↓ mRNA Expression of CD36	[86]
β-patchoulene	Terpenoids	Pogostemonis Herba or “Guang-Huo-Xiang”	In vivo	10, 20 and 40 mg/kg	↓ Hepatic CD36 expression	[91]
Naringin	Flavonoids	Grapefruit and oranges	In vivo	In vitro:10 μM	↓ mRNA expression and protein levels of CD36	[94]
The extract of Syzygium simile leaves	Extracts	Syzygium simile leaves	In vitro	50 and 100 µg/mL	↓ mRNA and Protein Expression of CD36 in Huh7 cells ↓ the expression of CD36 in both macrophage and enterocyte cells	[95]
Siphonaxanthin	Carotenoid	Green algae such as Codium fragile, Umbraulva japonica, and Caulerpa lentillifera	In vitro	0.5, 1.0, and 2.0 μM	↓ The transcriptional levels of CD36	[96]
Dolichos lablab water extract	Extracts	Dolichos lablab Linne	In vitro	1, 10, 100, and 250 μM	↓ mRNA level of CD36	[97]
Cinnamic acid	Phenylpropanoids	Citrus fruits and grape and vegetables	In vivo and in vitro	In vitro:25, 50, and 100 μM In vivo: 20 mg/kg	In vitro: ↓ The mRNA expression of CD36 In vivo: ↓ the mRNA expression of CD36	[101]
Alisol B	Triterpenoids	Alisma orientalis	In vivo and in vitro	In vitro:10 µM In vivo: 100 mg/kg	In vivo: ↓ mRNA and protein level of CD36 In vivo: ↓ mRNA and protein level of CD36	[102]
Quercetin	Flavonoids	Flowers, leaves, and fruits of many plants, particularly alfalfa.	In vivo	100 mg/kg·bw	↓ The mRNA and protein expression of CD36	[103]
Gypenosides	Triterpenoids	Gynostemma pentaphyllum, perennial vines widely grown in Asian	In vivo	300 mg/kg	↓ The mRNA levels of CD36	[104]
Raw Bowl Tea polyphenols	Phenols	Bowl Tea	In vivo	In vivo: 50 and 100 mg/kg	↓ The mRNA and protein expression of CD36	[105]
The aqueous extract of the aerial part of Angelica tenuissima Nakai	Extracts	Angelica tenuissima Nakai	In vivo and in vitro	In vitro:50, 100, and 200 µg/mL In vivo: 10 or 50 mg/kg	In vivo: ↓ The mRNA and protein expression of CD36 In vitro: ↓ The protein expression of CD36	[106]
Piceatannol	Phenols	Grapes, whites tea, passion fruit, and Japanese knotweed	In vitro	100 μM	↓ The mRNA expression of CD36	[107]
Magnolol	Lignans	Magnolia officinalis	In vivo and in vitro	In vitro: 8 µg/mL In vivo: 10 mg/kg	In vivo: ↓ The mRNA expression of Cd36 In vitro: ↓ The protein and mRNA expression of cd36	[108]
A pomegranate fruit extract	Extracts	Pomegranate	In vivo	In vivo: 1%	↓ CD36	[109]
Cordycepin	Alkaloids	Cordyceps militaris.	In vivo	In vivo: 50 mg/kg	↓ The mRNA and protein expression of CD36	[110]
Liriope platyphylla root ethanolic extract	Extracts	Liriope platyphylla	In vivo and in vitro	In vitro: 50, 100 µg/mL In vivo: 100, and 250 mg/kg	In vivo: ↓ The protein expression of CD36 In vitro: ↓ The protein expression of CD36	[112]
Sweroside	Iridoids	Swertia pseudochinensis Hara	In vivo	In vivo: 60, 120, 240 mg/kg	↓ The mRNA levels of CD36	[113]
Ginsenoside Rg1	Triterpenoids	Ginseng	In vitro	In vitro: 25, 50μM	↓ The mRNA and protein expression of CD36	[114]
Extracts of Ficus hirta Vahl.	Extracts	Ficus hirta Vahl.	In vivo and in vitro	In vivo: 5, 10 mg/kg In vitro: 15, 30mg/mL	In vivo: ↓ The mRNA and protein levels of CD36 In vitro: ↓ The mRNA and protein levels of CD36	[115]
Betaine	Alkaloids	Beta vulgaris	In vivo	In vivo:1% (w/v)	↓ The mRNA and protein levels of CD36	[116]
Abelmoschus esculentus subfractions	Extracts	Abelmoschus esculentus	In vitro	In vitro: 1, 2.5, and 5 µg/mL	↓ The mRNA and protein levels of CD36	[118]
Hydroethanolic extract of Dillenia indica leaf	Extracts	Dillenia indica leaf	In vitro	5, and 10 μg/mL	↓ The protein levels of CD36	[120]
Salvianolic acid B	Phenylpropanoids	The root of Salvia miltiorrhiza	In vivo	10 and 20 mg/kg/d	↓ The mRNA levels of CD36	[122]
Puerarin	Flavonoids	The root of Pueraria lobata	In vivo	0.1% and 0.2%	↓ The mRNA levels of CD36	[124]
Gallic acid	Phenols	Fruits and nuts	In vitro	In vitro: 50, 100, and 200 µM	↓ The mRNA and protein levels of CD36	[126]
Theobromine	Alkaloids	A variety of plants such as Theobroma cacao, Cola aluminate, Paullinia cupana, and Ilex aquifolium.	In vivo and in vitro	In vitro: 0, 10, 100 μM In vivo: 100 mg/kg/d	In vivo: ↓ The protein expression of CD36 In vitro: ↓ The protein expression of CD36	[129]

Abbreviations: ^AHFD, high-fat diet.

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