Table 1.

Natural products targeting cholesterol metabolism and mechanisms of action.

	Ingredients	Structure	Effect	Mechanism	Ref.
Targeted cholesterol biosynthesis	Artesunate		Anti-glioblastoma	Affecting SREBP2 nuclear localization, disrupting SREBP2-p53 interactions and inducing p21 expression.	[20]
	Gypenoside L		Anti-hepatoma	Inhibiting the expression of HMGCS1, HMGCR and MVK, enhancing the immune response of CD8+ T cells and promoting the release of pro-inflammatory immune factors IL-2, IL-6, IFN-γ.	[21]
	Emodin		Anti-hepatoma	Down-regulating SREBP2 to inhibit the expression of HMGCS1, HMGCR, FDPS, DHCR7 and DHCR24.	[23]
	Osthole		Anti-hepatoma	Down-regulating SREBP2 and HMGCR to inhibit cholesterol biosynthesis and increase sensitivity of doxorubicin to hepatocellular carcinoma.	[24]
	Alpinumisoflavone		Anti prostate cancer	Down-regulating HMGCR to inhibit cholesterol biosynthesis.	[29]
	Quercetin		Anti-glioma	Inhibiting SREBP and ChREBP transcription to downregulate HMGCR and ACC1, thereby inhibiting cholesterol and fatty acid synthesis.	[30]
	Genkwadaphnin		Anti-hepatoma	Targeting DHCR24 to block cholesterol biosynthesis.	[39]
Targeted cholesterol uptake	Curcumin		Anti-colorectal cancer	Activating TRPA1 and downregulating NPC1L1 to reduce cholesterol absorption.	[44]
	Platycodon D		Anti-glioblastoma	Upregulating LDLR level to inhibit autophagy.	[48]
	Pseurotin A		Anti-prostate and breast cancer	Inhibiting PSCK9 to upregulate LDLR level.	[55, 56]
	Tanshinone IIA		Anti-hepatoma	Inhibiting PSCK9 to upregulate LDLR level through FoxO3a and HIF-1α pathways.	[57]
Targeted cholesterol efflux	Isoliquiritigenin		Anti colorectal cancer	Downregulating ABCA1 to inhibit cholesterol efflux thereby inhibiting EMT by weakening the interaction between YY1 and PGC-1α.	[9]
	Celastol		Anti-renal clear cell carcinoma	Upregulating ABCA1 to promote cholesterol efflux to inhibit tumor growth and migration by activating LXR expression.	[66]
	SR9243		Anti-clear cell renal cell carcinoma	Downregulating the synthesis of SREBP-1c, FASN, and SCD1 to decrease intracellular FA content and induce apoptosis.	[75]
	LXR623		Anti-clear cell renal cell carcinoma	Activating LXR by inhibiting the expression of LDLR and upregulating the expression of ABCA1.	[75]
	Bergapten		Anti-hepatoma	Regulating LXR/PI3K/Akt and IDOL/LDLR pathways to inhibit lipid accumulation.	[76]
	GW3965		Anti- glioblastoma	Regulating the LXR/LDLR/IDOL pathway and increasing ABCA1 expression to promote glioblastoma death.	[77]
	Lycopene		Anti prostate cancer	Activating PPARγ-LXRα-ABCA1 pathway to inhibit proliferation.	[79]
Targeted cholesterol esterification	Avasimibe		Anti-melanoma	Targeting ACAT1 to inhibit cholesterol esterification in T cells, leading to increased plasma membrane cholesterol levels and enhanced T cell receptor aggregation and signal transduction in CD8+ T cells.	[87]
			Anti-prostate cancer	Blocking Wnt/β-catenin pathway to inhibit cholesterol esterification.	[88]
	K604		Anti-glioblastoma	Inhibiting cell proliferation and downregulating Akt and extracellular signal-regulated kinase activation by inhibiting ACAT1.	[89]
	Manzamine A		Anti-uterine fibroids	Targeting ACAT2 to inhibit the nuclear localization of β-catenin and the activation of its downstream target genes reduces the acetylation level of Wnt3a, further blocking its secretion and disrupting Wnt signaling activity.	[91]