Abstract
Medicinal plants show important therapeutic value in chronic disease treatment. However, due to their diverse ingredients and complex biological effects, the molecular mechanisms of medicinal plants are yet to be explored. By means of several high-throughput platforms, here we show hawk tea extract (HTE) inhibits Niemann–Pick C1-like 1 (NPC1L1)-mediated free cholesterol uptake, thereby inducing the transcription of low-density lipoprotein receptor (LDLR) downstream of the sterol response element binding protein 2 (SREBP2) pathway. Meanwhile, HTE suppresses hepatocyte nuclear factor 4α (HNF4α)-mediated transcription of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), thereby decreasing the production of very-low-density lipoprotein. The catechin EGCG ((−)-epigallocatechin gallate) and the flavonoids kaempferol and quercetin are identified as the bioactive components responsible for the effects on the NPC1L1-SREBP2-LDLR axis and HNF4α-MTP/APOB axis, respectively. Overall, hawk tea works as a previously unrecognized cholesterol-lowering agent in a multi-target and multi-component manner.
Highlights
Medicinal plants show important therapeutic value in chronic disease treatment
The effects of hawk tea extract (HTE) on Niemann–Pick C1-like 1 (NPC1L1)-sterol response element binding protein 2 (SREBP2)-low-density lipoprotein receptor (LDLR) axis and hepatocyte nuclear factor 4α (HNF4α)-microsomal triglyceride transfer protein (MTP)/apolipoprotein B (APOB) axis can be attributed to the catechin Epigallocatechin gallate (EGCG) ((−)-epigallocatechin gallate) and the non-catechin flavonoids kaempferol and quercetin, respectively
We confirmed that kaempferol and quercetin decreased MTP protein amount and suppressed APOB secretion from HepG2 cells (Fig. 7h, i). These results suggest that the flavonoids kaempferol and quercetin are bioactive components that mediate the inhibitory effects of HTE on the assembly and secretion of very-low-density lipoprotein (VLDL) in HepG2 cells
Summary
Medicinal plants show important therapeutic value in chronic disease treatment. due to their diverse ingredients and complex biological effects, the molecular mechanisms of medicinal plants are yet to be explored. By means of several high-throughput platforms, here we show hawk tea extract (HTE) inhibits Niemann–Pick C1-like 1 (NPC1L1)-mediated free cholesterol uptake, thereby inducing the transcription of low-density lipoprotein receptor (LDLR) downstream of the sterol response element binding protein 2 (SREBP2) pathway. HTE suppresses hepatocyte nuclear factor 4α (HNF4α)-mediated transcription of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), thereby decreasing the production of very-low-density lipoprotein. The catechin EGCG ((−)-epigallocatechin gallate) and the flavonoids kaempferol and quercetin are identified as the bioactive components responsible for the effects on the NPC1L1-SREBP2-LDLR axis and HNF4α-MTP/APOB axis, respectively. Hawk tea extract (HTE) inhibits Niemann–Pick C1-like 1 (NPC1L1)-mediated hepatic-free cholesterol uptake, thereby inducing sterol response element binding protein 2 (SREBP2)mediated low-density lipoprotein receptor (LDLR) expression. The effects of HTE on NPC1L1-SREBP2-LDLR axis and HNF4α-MTP/APOB axis can be attributed to the catechin EGCG ((−)-epigallocatechin gallate) and the non-catechin flavonoids kaempferol and quercetin, respectively
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